Atlas Of Bone Pathology.pdf

Shi Wei Gene P. Siegal

Atlas of Bone Pathology

123

Atlas of Anatomic Pathology Series Editor

Liang Cheng

Available Volumes Atlas of Spleen Pathology, Atlas of Genitourinary Pathology Upcoming Volumes Atlas of Medical Renal Pathology

Shi Wei • Gene P. Siegal

Atlas of Bone Pathology

Shi Wei, MD, PhD Assistant Professor of Pathology University of Alabama at Birmingham

Medical Director, Immunohistochemistry Laboratory UAB Hospital Birmingham, AL USA

Gene P. Siegal, MD, PhD R.W. Mowry Endowed Professor of Pathology Director, Division of Anatomic Pathology Executive Vice-Chair - Pathology, UAB Health System Department of Pathology University of Alabama at Birmingham Birmingham, AL USA

ISBN 978-1-4614-6326-9 ISBN 978-1-4614-6327-6 DOI 10.1007/978-1-4614-6327-6 Springer New York Heidelberg Dordrecht London

(eBook)

Library of Congress Control Number: 2013933857 © Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

This book is dedicated to all those who have taught us and continue to teach us each day: our teachers, our colleagues, and our students—our parents, our children, and our spouses—it’s time to pass the knowledge forward! Shi Wei Gene Siegal

Series Preface

One Picture Is Worth Ten Thousand Words – Frederick Barnard, 1927

Remarkable progress has been made in anatomic and surgical pathology during the last 10 years. The ability of surgical pathologists to reach a definite diagnosis is now enhanced by immunohistochemical and molecular techniques. Many new clinically important histopathologic entities and variants have been described using these techniques. Established diagnostic entities are more fully defined for virtually every organ system. The emergence of personalized medicine has also created a paradigm shift in surgical pathology. Both promptness and precision are required of modern pathologists. Newer diagnostic tests in anatomic pathology, however, cannot benefit the patient unless the pathologist recognizes the lesion and requests the necessary special studies. An up-to-date Atlas encompassing the full spectrum of benign and malignant lesions, their variants, and evidence-based diagnostic criteria for each organ system is needed. This Atlas is not intended as a comprehensive source of detailed clinical information concerning the entities shown. Clinical and therapeutic guidelines are served admirably by a large number of excellent textbooks. This Atlas, however, is intended as a “first knowledge base” in the quest for definitive and efficient diagnosis of both usual and unusual diseases. The Atlas of Anatomic Pathology is presented to the reader as a quick reference guide for diagnosis and classification of benign, congenital, inflammatory, nonneoplastic, and neoplastic lesions organized by organ systems. Normal and variations of “normal” histology are illustrated for each organ. The Atlas focuses on visual diagnostic criteria and differential diagnosis. The organization is intended to provide quick access to images and confirmatory tests for each specific organ or site. The Atlas adopts the well-known and widely accepted terminology, nomenclature, classification schemes, and staging algorithms. This book Series is intended chiefly for use by pathologists in training and practicing surgical pathologists in their daily practice. It is also a useful resource for medical students, cytotechnologists, pathologist assistants, and other medical professionals with special interest in anatomic pathology. We hope that our trainees, students, and readers at all levels of expertise will learn, understand, and gain insight into the pathophysiology of disease processes through this comprehensive resource. Macroscopic and histological images are aesthetically pleasing in many ways. We hope that the new Series will serve as a virtual pathology museum for the edification of our readers. Liang Cheng, MD, Series Editor

vii

Preface

Now that this monograph has been “put to bed,” we thank the series editor, Dr. Liang Cheng, for providing us this opportunity to add to this exciting series of atlases focused on the modern classification of pathologic conditions by organ type. We had been able to turn aside multiple other competing requests, but his charm and reputation for high-quality publications swayed us to undertake this challenge, and in the end we are glad that we did deliver the product before you. We were also inclined to undertake this project because of the positive experience we had with the publisher, Springer, who graciously published our Bone volume for the Frozen Section Library series in 2011. We now see these two texts as companion works, one for the other. Attempting to remain true to the spirit of this series, this book does not attempt to be encyclopedic, as many fine such books already exist by us and others, and we try to acknowledge many of them in the Suggested Reading section. Rather, we have sought to highlight, with high-quality images, the histopathologic features of the many conditions of bone, emphasizing the neoplastic ones. Where appropriate, we have supplemented these images with clinical and gross pathology photographs. As radiologic evaluation is critical in virtually every facet of bone pathology diagnosis, we also have included representative conventional radiographs as well as CT and MRI images. For completeness, immunophenotyping of key entities also has been included along with a reference to advances in cytogenetics and molecular genetics in the purposely truncated text. As a “quick reference guide,” this book is organized along classic lines in some one dozen chapters. Although we have had the opportunity to publish many papers in the peer-reviewed literature, we have made a special effort to provide never-before-seen images that we hope will be aesthetically pleasing but, more importantly, highly informative. In cases in which previously published images were needed, permission was obtained from the publishers, and we thank them collectively. As with the Atlas of Genitourinary Pathology, most of the entities will be familiar to the seasoned pathologist, but we hope that everyone, be they wizened masters or young novices, will see one or more bits of exotica that they can add to their mental libraries for future use to benefit their patients. Birmingham, AL Birmingham, AL

Shi Wei Gene P. Siegal

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Acknowledgments

As the authors, we greatly acknowledge the contributions of our many colleagues who gave graciously of their intellectual capital to assure the successful completion of this book. We wish to personally acknowledge the following physicians, who provided source material from their personal collections and allowed this material to be published: Dr. Michael J. Pitt, Emeritus Professor of Radiology, University of Alabama at Birmingham (UAB) Dr. Philip H. Lander, Professor of Radiology, UAB Dr. Ona Faye-Petersen, Professor of Pathology, UAB Dr. Michael J. Klein, Pathologist in Chief, Hospital for Special Surgery, and Professor of Pathology, Weill Medical College of Cornell University Dr. Brian Rubin, Cleveland Clinic Dr. Patricia DeVilliers, Assistant Professor of Oral Pathology, UAB Dr. Kristopher McKay, Assistant Professor of Dermatology and Pathology, UAB Dr. Keith Harrison, Children’s Hospital of Alabama We also acknowledge with gratitude the critical support of Mr. Erik (Scott) Young, Ms. Patricia F. Lott, Dr. Dezhi (Annie) Wang, and Ms. Cassandra (Sandy) B. Cummings.

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Contents

1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Normal Bone Histology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Callus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Chest Wall Hamartoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Chondroid Hamartoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 2 11 16 20

2

Bone-Forming Tumors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Osteoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Osteoid Osteoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Osteoblastoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Conventional Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Telangietatic Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Small Cell Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.7 Low-Grade Central Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.8 Parosteal Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.9 Periosteal Osteosarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.10 High-Grade Surface Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.11 Secondary Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

23 24 26 29 38 67 71 78 81 89 93 97

3

Cartilage-Forming Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Osteochondroma (Exostosis) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Chondroma (Enchondroma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Periosteal Chondroma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Enchondromatosis (Including Ollier Disease and Maffucci Syndrome) . . 3.5 Chondroblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6 Chondromyxoid Fibroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7 Synovial Chondromatosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8 Conventional Chondrosarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9 Secondary Chondrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10 Dedifferentiated Chondrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11 Clear Cell Chondrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.12 Mesenchymal Chondrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

101 102 109 115 117 122 127 132 134 144 146 150 152

4

Fibrous and Fibrohistiocytic Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Nonossifying Fibroma (Metaphyseal Fibrous Defect, Fibrous Cortical Defect). . . . . . . . . . . . . . . 4.2 Benign Fibrous Histiocytoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Desmoplastic Fibroma (Desmoid Tumor) . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Fibroma of Tendon Sheath . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Fibrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6 Malignant Fibrous Histiocytoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

157 158 163 167 169 171 175

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Contents

5

Fibro-osseous Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Fibrous Dysplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Osteofibrous Dysplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 Central Ossifying Fibroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4 Liposclerosing Myxofibrous Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

179 180 193 196 203

6

Giant Cell–Rich Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1 Giant Cell Tumor of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2 Giant Cell Reparative Granuloma of Gnathic Bones . . . . . . . . . . . . . . . . . 6.3 Malignant Giant Cell Tumor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.4 Tenosynovial Giant Cell Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.5 Hyperparathyroidism (Brown Tumor) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.6 Cherubism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

207 208 216 218 222 228 235

7

Small, Round Cell Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1 Benign, Reactive, Inflammatory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.1 Osteomyelitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.2 Langerhans Cell Histiocytosis (Histiocytosis X, Eosinophilic Granuloma). . . . . . . . . . . . . . . . . . . 7.1.3 Mastocytosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.4 Sinus Histiocytosis with Massive Lymphadenopathy (Rosai-Dorfman Disease) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.5 Sarcoidosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.6 Xanthoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 Malignant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.1 Lymphoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.2 Plasmacytoma/Plasma Cell Myeloma . . . . . . . . . . . . . . . . . . . . . . . 7.2.3 Ewing Sarcoma/Primitive Neuroectodermal Tumor (PNET) . . . . .

237 238 238

8

Cysts ......................................................... 8.1 Aneurysmal Bone Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2 Unicameral Bone Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.3 Ganglion Cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

283 284 295 298

9

Vascular Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.1 Hemangioma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2 Hemangioendothelioma and Epithelioid Hemangioendothelioma. . . . . . . 9.3 Hemangiopericytoma/Solitary Fibrous Tumor . . . . . . . . . . . . . . . . . . . . . . 9.4 Angiosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

301 302 305 312 314

10

Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors . . . . . . . . . . . 10.1 Leiomyoma of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2 Leiomyosarcoma of Bone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.3 Rhabdomyosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4 Lipoma of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.5 Myxoma of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6 Paraganglioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.7 Neurilemmoma/Schwannoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.8 Malignant Peripheral Nerve Sheath Tumor . . . . . . . . . . . . . . . . . . . . . . . . 10.9 Ependymoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.10 Adamantinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.11 Ameloblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.12 Chordoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.13 Synovial Sarcoma of Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

321 322 323 326 331 332 333 334 338 340 342 349 353 364

246 251 253 257 258 259 259 266 274

Contents

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11

Tumor-like Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.1 Avascular Necrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2 Bone Infarct . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3 Osteochondral Body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.4 Gout . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.5 Calcium Pyrophosphate Dihydrate Disease . . . . . . . . . . . . . . . . . . . . . . . . 11.6 Bizarre Parosteal Osteochondromatous Proliferation. . . . . . . . . . . . . . . . . 11.7 Subungual Exostosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.8 Myositis Ossificans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

373 374 379 381 383 387 391 397 399

12

Reactive, Metabolic, and Developmental Conditions . . . . . . . . . . . . . . . . . . . . . 12.1 Osteoarthritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.2 Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.3 Detritic Synovitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.4 Gaucher Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.5 Osteogenesis Imperfecta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.6 Osteomalacia/Rickets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.7 Osteopenia/Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.8 Osteopetrosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.9 Paget Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.10 Phosphaturic Mesenchymal Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

405 406 412 415 418 420 425 426 428 429 434

13

Metastases to and from Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.1 Metastases to Bone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.2 Metastases from Bone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

441 442 463

Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

467

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

469

1

Introduction

Human skeletons can be classified based on their position, shape, and structure (Table 1.1). In long bones, the epiphysis is the section between the expanded end of bone and its growth plate (also known as the physis or epiphyseal plate). The physis disappears by 20 years of age. The epiphysis consists of a hyaline cartilage joint surface, compact exterior (cortex), and spongy interior (medulla), and it is the region of secondary ossification. The diaphysis is the central shaft of the long bone with compact bone surrounding marrow cavity, and it is the region of primary ossification. The metaphysis is the junctional portion lying between the growth plate and the diaphysis. Cartilage is composed of chondrocytes embedded in a prominent ground substance of extracellular matrix, which is made of proteoglycan aggregates in hyaluronic acid. The varying proportions of collagen types and elastic fibers embedded within the ground substance give rise to three types of cartilage: hyaline cartilage, fibrocartilage, and elastic cartilage (Table 1.2).

Table 1.1 Classification of human skeletons Basis of classification Region

Type of bone Axial skeleton

Appendicular skeleton Shape

Long bone Short bone

Flat bone

Irregular bone

Structure

Sesamoid bone (bone embedded in a tendon) Compact bone Cancellous bone/trabecular bone

Examples/locations Skull, vertebral column, sternum, and ribs Limbs and girdles of limbs Limb bones such as humerus Wrist and ankle bones such as cuboid Skull, sternum, scapula, and pelvis Vertebrae, acetabulum, and base of skull Patella Cortex Medulla

Table 1.2 Classification of cartilage Type Hyaline cartilage Fibrocartilage

Elastic cartilage

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_1, © Springer Science+Business Media New York 2013

Examples/locations Large bone joints (hip, elbow, knee) Intervertebral disks, pubic symphysis, meniscus, and temporomandibular joints External ear, larynx, and epiglottis

1

2

1.1

1

Normal Bone Histology

Fig. 1.1 Gross anatomy of long bone. Each long bone may be divided into three regions. (1) The epiphysis (E) is the rounded end covered by articular cartilage. (2) The metaphysis (M) is the triangular zone adjacent to the growth plate (GP) in children and next to the epiphysis in adults, in whom the growth plate has closed. (3) The diaphysis (D) corresponds to the cylindrical shaft of the bone. The proximal femur of a growing child has two growth plates—one associated with the epiphysis of the femoral head and the other associated with the apophysis (A) of the greater trochanter

Introduction

1.1

Normal Bone Histology

Fig. 1.2 Lamellar bone. This type of bone is the dominant form in adults; it is organized in layers (lamellae), either concentrically arranged (e.g., compact bone, as illustrated in this image) or in parallel (cancellous bone). The inorganic composition (mineral) of bone is principally derived from crystallized hydroxyapatite (Ca10[PO4]6[OH]2). The organic portion of bone (matrix) is composed mainly of type I collagen. The compact bone is of intramembranous origin and constitutes 90 % bone

Fig. 1.3 Lamellar bone. Polarized microscopy of the section shown in Fig. 1.2. The concentric lamellae are more easily recognized in polarized light

3

and 10 % space by volume. The osteocytes situated in the lacunae are terminally differentiated bone cells originating from osteoblasts. They communicate with their neighboring cells and contact them via an intricate cell process network called canaliculi. The osteon (also known as the haversian system), the fundamental functional unit of compact bone, consists of concentric layers (lamellae) that surround a central canal (the haversian canal), which contains the nerve and blood supplies

4 Fig. 1.4 Lamellar bone. This photomicrograph illustrates cancellous (trabecular, medullary) bone of endochondral origin. The coarse cancellous bone is only 25 % bone and 75 % marrow space by volume. Unlike compact bone, the cancellous bone does not have osteons. Again, mature osteocytes are located in the lacunar spaces

Fig. 1.5 Lamellar bone. The same field as Fig. 1.4 viewed with polarized light, which emphasizes the regular parallel alignment of the lamellae

1

Introduction

1.1

Normal Bone Histology

Fig. 1.6 Woven bone. The central portion of the bone represents woven bone, which is newly formed immature bone characterized by a haphazard organization of collagen fibers (left), best illustrated with polarized light, as in the right image). Therefore, it is mechanically weak compared with lamellar bone, which has an organized parallel arrangement

5

of collagen fibers. Any woven bone present after the third year of life represents an abnormality, unless it lies on the metaphyseal side of the growth plates. Note the basophilic lines known as reversal (cement) lines in the left image, which are rich in inorganic matrix and are evidence of active bone remodeling

6

Fig. 1.7 Reversal line. The reversal lines are produced by osteoblasts on a surface previously resorbed by osteoclasts, and their amount corresponds to the extent of remodeling that has occurred. The cement line

1

Introduction

in normal bone remodeling is usually straight and long (left), whereas an irregular line or mosaic pattern typically indicates an accelerated remodeling process caused by a pathologic condition (right)

1.1

Normal Bone Histology

Fig. 1.8 Osteoblasts and lining cells. The bone-forming osteoblasts are derived from bone marrow – derived mesenchymal stem cells governed by the transcription factor Cbfa1/Runx2. These cells are located on the surface of the bone (or osteoid) and are responsible for synthesizing the organic components of the bone matrix. The active osteoblasts are plump, basophilic cells with eccentrically located nuclei and perinuclear cytoplasmic halos, whereas the flattened-shaped lining cells are thought to be osteoblasts in their inactive phase. Osteoblasts do not divide. They give rise to osteocytes when surrounded by newly deposited organic matrix or, alternatively, become quiescent bone-lining cells

Fig. 1.9 Osteoclasts. This image illustrates three osteoclasts actively resorbing bone. Osteoclasts are multinucleated giant cells derived from hematopoietic stem cells. They are formed by fusion of mononuclear precursors of the monocyte/macrophage lineage under the influence of the specific osteoclastogenic cytokine, receptor activator of NF-kB ligand (RANKL), expressed on osteoblasts and bone marrow stromal cells. These cells are rich in lysosomes that contain tartrate-resistant acid phosphatase (TRAP). Osteoclasts have a much shorter life span (a few days) than osteoblasts and are rarely seen in routine normal bone sections. Increased osteoclast activity is indicative of conditions or diseases with increased bone turnover. Note also the active bone formation by osteoblasts in this image

7

8 Fig. 1.10 Articular cartilage. Articular cartilage refers to the hyaline cartilage on the articular surface of both the short and long bones. The adult articular cartilage is not covered by perichondrium (vessel-containing fibrous membrane), unlike the cartilage in fetal/embryonic life or that of nonskeletal sites in adults (i.e., ears and nose). In hyaline cartilage, the structural collagen (mainly type II) becomes denser toward the external surface and less dense internally. The articular cartilage contains a deep calcified zone near the subarticular bone in the mature skeleton (seen very near the bottom of this image), and is known as the tidemark

Fig. 1.11 Articular cartilage. The mature cartilage cells (chondrocytes) are situated in the lacunae embedded in a large amount of bluish extracellular matrix and tend to be clustered in groups. The cells are characterized by granular basophilic cytoplasm and small nuclei with dispersed chromatin. Binucleation or multinucleation occasionally may be seen but is more common in degenerative or neoplastic conditions

1

Introduction

1.1

Normal Bone Histology

Fig. 1.12 Fibrocartilage. Predominantly found in the intervertebral disks and the pubic symphysis, fibrocartilage consists of a mixture of fibrous and cartilaginous tissue in various proportions; thus it contains type I collagen in addition to the normal type II. The chondrocytes, also located within the lacunae, are far less cellular and more widely separated than those in hyaline cartilage

Fig. 1.13 Growth plate. This image illustrates an active growth plate with ongoing endochondral ossification. The growth plate, located between the epiphysis and the metaphysis, can be divided into five zones in the direction of the diaphysis as follows: (1) resting (reserve) zone, (2) proliferative zone, (3) hypertrophic zone, (4) calcified zone (zone of mineralization), and (5) primary spongiosa (ossification zone). The chondrocytes die in zone 4, where bone deposition on calcified cartilage starts

9

10 Fig. 1.14 Primary spongiosa. The bone spicules are made up of acellular calcified cartilage cores, and the immature bone is deposited at the periphery of the calcified cartilage

Fig. 1.15 Periosteum. A fibrous membrane that covers the outer surface of the bone, the periosteum is composed of two cell populations: the outer fibrous layer that contains fibroblasts, and the inner cambium (or “osteogenic”) layer that contains osteoblasts and progenitor cells. The cambium layer is responsible for intramembranous ossification and is essential to the healing process (callus formation) after a bone fracture. The periosteum is connected to the bone by Sharpey (or perforating) fibers, part of the outer fibrous layer that enters the bone. Sharpey fibers also are used to connect muscle to the periosteum. Endosteum is the thin fibrous layer that lines the inner surface of long bones (not shown)

1

Introduction

1.2

1.2

Callus

Callus

Fig. 1.16 Callus. The healing of a fracture occurs in a continuum, beginning with hemorrhage and hematoma formation that provides mechanical stability to the fracture site and causes osteoblast and chondrocyte precursors to produce matrix. This is followed by the formation of immature reparative connective tissue called fracture callus that bridges the fracture gap. The histologic features at the earliest stage are nonspecific and may mimic those of granulation tissue, as seen in the illustration

Fig. 1.17 Callus. This image shows a fracture callus formed at about 2 weeks post injury. The bone matrices are lacelike or sheetlike, or both, and some are organized into microtrabeculae. These microtrabeculae, along with the hypercellular stroma and reactive atypia, may closely resemble an osteosarcoma histologically. Both intramembranous and endochondral ossification may occur at the fracture site

11

12 Fig. 1.18 Callus. Fibrocartilage undergoing endochondral ossification within a fracture callus

Fig. 1.19 Callus. Mineralization of the callus results in bony callus. Note the residual cartilage. The progression from cartilage to bone is orderly and is sometimes misidentified under the term chondro-osseous metaplasia

1

Introduction

1.2

Callus

Fig. 1.20 Callus. Late in the reparative reaction, the pattern of bone is organized into an arrangement of trabeculae with a cellular fibrous stroma. The cartilage disappears. Note the appositional osteoblasts lining on the bone surface, which represents a common histologic thread regardless of time

Fig. 1.21 Callus. Another example of well-formed bony callus showing organized trabeculae interconnected by a fine latticework. The stroma is more vascular and less fibrous

13

14 Fig. 1.22 Nonunion. Nonunion refers to the healing of a fracture site with collagen-rich soft tissue instead of bone. This image illustrates an example of nonunion showing vascularized fibrous tissue adjacent to reparative bone

Fig. 1.23 Nonunion. Dystrophic ossification, although not specific, is not an uncommon finding in nonunion

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Introduction

1.2

Callus

Fig. 1.24 Nonunion. Infected nonunion typically shows reactive bone, marrow fibrosis, and chronic inflammation; thus it is histologically indistinguishable from chronic osteomyelitis

15

16

1.3

1

Chest Wall Hamartoma

Fig. 1.25 Chest wall hamartoma. An axial CT image of a 4-month-old boy showing bilateral chest wall masses with a rightward mediastinal shift. Chest wall hamartoma, also known as mesenchymal hamartoma of the chest wall, is a nonneoplastic lesion composed of mesenchymal tissue, predominantly cartilage. The lesion is remarkable for its development during fetal life and its occurrence in neonates or during infancy. It typically appears as an intrathoracic and/ or an extrapleural mass and arises almost exclusively from the posterior or lateral portions of the rib. The lesion is often large and partially mineralized radiographically

Fig. 1.26 Chest wall hamartoma. The histologic appearance of this lesion varies from region to region and typically consists of solid and cystic components. The solid area is composed primarily of islands of mature hyaline cartilage

Introduction

1.3

Chest Wall Hamartoma

Fig. 1.27 Chest wall hamartoma. In this lesion, the cartilage often undergoes endochondral ossification. Note the irregular islets of cartilage. The abundant spicules of osteoid rimmed by plump osteoblasts on the left may result in confusion with chondroblastic osteosarcoma

Fig. 1.28 Chest wall hamartoma. Longstanding lesions typically have mature bone formation

17

18 Fig. 1.29 Chest wall hamartoma. The solid cartilage components may have intermixed cystic areas filled with blood, thereby resembling an aneurysmal bone cyst

Fig. 1.30 Chest wall hamartoma. A higher-power view of the cyst wall shows fibroblastic proliferation, osteoid formation, and abundant osteoclast-like multinucleated giant cells; these features are typical of aneurysmal bone cysts. It thus is evident that analyzing the clinical presentation, demographic information, and radiologic and pathologic findings all together allow one to reach the right diagnostic conclusion

1

Introduction

1.3

Chest Wall Hamartoma

Fig. 1.31 Chest wall hamartoma. A high-power view of proliferating cells demonstrates a mixture of spindled fibroblasts/ myofibroblasts and immature, chondroblast-like cells with abundant eosinophilic cytoplasm and occasional nuclear grooves

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1.4

1

Chondroid Hamartoma

Fig. 1.32 Chondroid hamartoma. An axial CT image shows a 2-cm solitary pulmonary nodule in the right lower lobe without cavitation or calcification. Chondroid hamartoma, also known as chondroma, adenochondroma, or mesenchymoma, is typically located in the lung parenchyma just beneath the pleura but may rarely be endobronchial. More commonly, this lesion demonstrates a “popcorn” pattern of calcification radiographically

Fig. 1.33 Chondroid hamartoma. A low-power view of chondroid hamartoma of the lung. The tumor is typically made up of predominantly nodular hyaline or fibrocartilage admixed with fat and smooth muscle and is lined with respiratory epithelium. This lesion had been thought to be a tumor-like malformation and therefore was designated as a “hamartoma,” whereas more recent studies argue that it likely is neoplastic owing to nonrandom cytogenetic abnormalities in a significant proportion of cases

Introduction

1.4

Chondroid Hamartoma

Fig. 1.34 Chondroid hamartoma. A higher-power view of a pulmonary hamartoma showing normal-appearing cartilage with focal myxoid degeneration. Note the minor fat and smooth muscle components at the periphery. The cartilage may undergo calcification and, rarely, ossification, thus giving it the popcorn pattern of calcifications noted previously. The combination of pulmonary chondromas, gastrointestinal stromal tumors, and paragangliomas is known as the Carney triad

21

2

Bone-Forming Tumors

Bone-forming tumors represent a broad spectrum of neoplasms that arise within or on the surface of bone and may rarely occur in extraskeletal sites. The hallmark of these tumors is that the neoplastic cells produce the organic components of bone or bone matrix that may or may not be mineralized. Osteoma is usually solitary but in rare cases may be multiple. The latter is seen typically in association with Gardner syndrome. Osteoid osteoma and osteoblastoma are terms used to describe benign bone-forming tumors with essentially identical histologic features, thus preventing their distinction from one another solely on histomorphologic grounds. They differ in size, anatomic sites, and clinical manifestations. Osteosarcoma is the most common primary malignant tumor of bone, exclusive of hematologic malignancies. Although the tumor may occur at any age with a slightly male predilection, it has a bimodal age distribution, with a propensity to develop predominantly in adolescents and young adults. This is followed by a smaller second peak in the elderly, frequently with conditions known to predis-

pose to osteosarcoma, including Paget disease and prior radiation. Most osteosarcomas demonstrate multiple acquired genetic abnormalities; however, none is specific to this tumor. It is important to note that although conventional osteosarcoma historically has been divided into osteoblastic, chondroblastic, and fibroblastic subtypes, depending on the predominant type of extracellular matrix, this separation is largely artificial because most tumors are mixed, there is no difference in the treatment strategy, and there is no statistical significance in the outcomes. Similarly, all other histologic forms of conventional osteosarcoma are not associated with a specific biological behavior that differs from the major subtypes. The prognostic significance of osteosarcoma largely depends on the tumor grade. The so-called secondary osteosarcomas refer to bone-forming sarcomas that result from malignant transformation within a benign process. The most common of these processes are Paget disease and irradiation, and rarely other preexisting conditions, including a bone infarct, prosthesis placement, and fibrous dysplasia.

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_2, © Springer Science+Business Media New York 2013

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24

2.1

2

Bone-Forming Tumors

Osteoma

Fig. 2.1 Osteoma. Coronal (left) and axial (right) CT images show an osteoma in the right frontal sinus. Osteomas have a propensity to involve craniofacial bones (skull, jaw, and sinuses), although they may be seen rarely in the vertebral columns and periosteum of long, tubular

Fig. 2.2 Osteoma. This CT image shows an example of the cancellous variant of osteoma

bones. Radiographically, the tumor typically is a round to ovoid, welldemarcated mass of cortical-type bone, with a stalk (but sometimes a broad base) connecting to the surface of its parental bone

2.1 Osteoma Fig. 2.3 Osteoma. Histologically, the tumor is sharply circumscribed and is composed of entirely compact bone. Insert: A highpower view shows admixture of lamellar and woven bone

Fig. 2.4 Osteoma of cancellous variant. A section from the lesion shown in Fig. 2.2 exhibits trabecular bone with intervening fatty bone marrow

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26

2.2

2

Bone-Forming Tumors

Osteoid Osteoma

Fig. 2.5 Osteoid osteoma. CT scan of the left tibia of a 15-year-old girl. The tumor is demonstrated as a small radiolucency (corresponding to the histologic nidus), which elicits extensive surrounding sclerosis and a cortical reaction. Commonly seen in patients in their teens and twenties, the tumor typically arises in the diaphyseal and metaphyseal regions of long tubular bones, especially the femur. Osteoid osteoma frequently originates in the cortex. By definition, the tumor is less than 2 cm. The patient typically presents with localized pain of increasing severity that worsens at night and is relieved with aspirin

Fig. 2.6 Osteoid osteoma. Axial CT images of the lesion seen in Fig. 2.5. Note the central ossification within the nidus (top). Given its characteristic clinical and radiologic features, the primary therapeutic modality is radiofrequency ablation or cryotherapy of the nidus via a percutaneous approach (bottom), a procedure frequently performed prior to pathologic confirmation of the diagnosis. Unfortunately, tissue obtained from these procedures often show markedly fragmented nonviable bone (sometimes referred to as “bone dust”) that is nondiagnostic histologically

2.2 Osteoid Osteoma Fig. 2.7 Osteoid osteoma. Low-power view of the tissue obtained from radiofrequency ablation. The nidus of osteoid osteoma is typically well-circumscribed, consisting of variably mineralized bony trabeculae arranged in a haphazard manner in a vascular-rich, loose connective tissue background. Note the surrounding sclerotic bone at the lower margin

Fig. 2.8 Osteoid osteoma. A closer view shows the nidus as characterized by irregular osteoid trabeculae with prominent osteoblastic rimming. Note also the markedly increased osteoclast activity

27

28 Fig. 2.9 Osteoid osteoma. Another example of a nidus showing an inter-anastomosing network of woven bone trabeculae with intervening richly vascularized connective tissue

Fig. 2.10 Osteoid osteoma. A higher magnification of the nidus. The irregularity of the osteoid/woven trabeculae and the pleomorphism of the proliferating osteoblasts may closely resemble an osteosarcoma. Thus, clinical and radiologic correlations are crucial

2

Bone-Forming Tumors

2.3

2.3

Osteoblastoma

29

Osteoblastoma

Fig. 2.11 Osteoblastoma. CT scan from a 36-year-old man shows a well-defined lytic lesion in the right pedicle of T12. An osteoblastoma is larger than 2 cm by definition (originally termed giant osteoid osteoma) and more frequently involves the spine. Local pain may be the presenting symptom and is usually dull, of long duration, and unresponsive to nonsteroidal anti-inflammatory drugs

Fig. 2.13 An osteoblastoma with secondary aneurysmal bone cyst formation. A sagittal CT image of this 24-year-old woman reveals a 2.4-cm lytic lesion in the epiphysis of her left ulna. The lesion has a sclerotic geographic border with a narrow zone of transition. There is no cortical reaction or associated soft tissue mass

Fig. 2.12 Osteoblastoma. This lesion was discovered incidentally in a 16-year-old boy during workup for a football injury. This sagittal CT image demonstrates a lytic lesion located within the distal sacrum with cortical destruction and soft tissue extension. There are punctate calcifications within the lesion. The radiographic features of osteoblastoma may be specific but more commonly are not, and they may have features suggestive of a malignancy. The margins may be well-demarcated, poorly defined, or indefinite. An osteoblastoma usually does not induce a marked periosteal reaction, as illustrated in this case

30

Fig. 2.14 Osteoblastoma. Magnetic resonance (MR) images of the lesion shown in Fig. 2.13. The subchondral epiphyseal lesion is isointense to the adjacent muscle on a T1-weighted sequence (left), with a multilocular brighter and heterogeneous T2 signal (right). The differential diagnosis includes chondroblastoma, chondromyxoid fibroma,

Fig. 2.15 Osteoblastoma. Note first the well-defined margin separating the neoplasm from the surrounding bone. The presence of numerous irregular bony trabeculae in a background of fibrovascular connective tissue is typical of an osteoblastoma

2

Bone-Forming Tumors

osteoblastoma, aneurysmal bone cyst, and giant cell tumor of bone. The pathologic examination revealed an osteoblastoma with secondary aneurysmal bone cyst formation (see Fig. 2.20). Like several other bone tumors, a secondary aneurysmal bone cyst is not infrequently associated with an osteoblastoma

2.3

Osteoblastoma

Fig. 2.16 Osteoblastoma. Scanning power of another osteoblastoma involving the vertebral column. Although the tumor has a well-circumscribed periphery, cortical destruction is evident

Fig. 2.17 Osteoblastoma. Higher magification reveals variably mineralized bony trabeculae rimmed by plump osteoblasts. The lesion is essentially indistinguishable from an osteoid osteoma histologically. In some lesions, the osteoblasts and stromal cells may have a variable degree of cytologic atypia, thus simulating osteosarcoma. Thus, attention should be paid to the histologic features at low-power magnification and the radiologic appearnce of the lesion to avoid an incorrect diagnosis of malignancy. The cellularity may be variable but typically the osteoblasts do not entirely fill the intertrabecular spaces

31

32 Fig. 2.18 Osteoblastoma. A closer view demonstrates uneven mineralization of the trabeculae and the abundantly present osteoclast-type multinucleated giant cells. Taken out of context, this image could easily be mistaken for an osteosarcoma

Fig. 2.19 Osteoblastoma. This photomicrograph illustrates variable ossification and the transition from a relatively cellular, less ossified area and (left and top) to a hypocellular, heavily ossified region (center and right)

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Bone-Forming Tumors

2.3

Osteoblastoma

Fig. 2.20 Osteoblastoma with secondary aneurysmal bone cyst formation. Histologic section of the lesion shown in Fig. 2.13

Fig. 2.21 “Cellular” osteoblastoma. At times, an osteoblastoma may be significantly more cellular, containing sheets of tumor cells, and the lesional cells may be epithelioid. In addition, the osteoid may be less easily discernible. However, significant nuclear pleomorphism is generally lacking in the conventional forms of this neoplasm, a feature helpful in distinguishing an osteoblastoma from an osteoblastoma-like osteosarcoma. It should be noted that there is a histologic continuum between conventional osteoblastoma and osteosarcoma, with the osteoblastoma variants in the middle

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34

Fig. 2.22 Aggressive osteoblastoma. A conventional radiograph of a 12-year-old girl demonstrates a well-circumscribed expansile lytic lesion in the medullary cavity of the femoral diaphysis. An intense periosteal reaction is noted

2

Bone-Forming Tumors

2.3

Osteoblastoma

Fig. 2.23 Aggressive osteoblastoma. Coronal CT with contrast (left) and T1-weighted MRI (right) of the lesion shown in Fig. 2.22 demonstrate intense enhancement of this 5.7-cm lesion

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36

2

Bone-Forming Tumors

Fig. 2.24 Aggressive osteoblastoma. A technetium bone scan of the lesion shown in Fig. 2.22. Note the intense uptake at the site of the lesion

Fig. 2.25 Aggressive osteoblastoma. Histologic appearance of the lesion seen in Fig. 2.22. The histologic section shows a cellular lesion composed of bland, large, polygonal cells that were producing densely calcified osteoid (“spiculated blue bone”) within a vascularized fibrous stroma

2.3

Osteoblastoma

Fig. 2.26 Aggressive osteoblastoma. A high-magnification view exhibits a sheet-like growth pattern of “epithelioid osteoblasts” characterized by eccentrically positioned, round-to-oval vesicular nuclei containing a single nucleolus and an abundantly clear or finely granular eosinophilic cytoplasm. Mitoses may be discernible, but atypical forms are not present. It should be noted that there is continuing debate in the literature as to whether these lesions represent benign, locally aggressive, or early but fully transformed (osteosarcoma) tumors. Thus, radiologic–pathologic correlation must be performed to determine the correct diagnosis for each case, and review by experts may be indicated

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2.4

2

Conventional Osteosarcoma

Fig. 2.27 Conventional osteosarcoma. There is a large, poorly defined mixed lytic/ sclerotic lesion in the distal tibia extending to the subchondral bone plate as assessed by conventional radiography (left). There is subtle irregular periosteal reaction as well as lateral cortical destruction. No definite soft tissue mass is identified. The gross features (right) correspond well to the convential radiograph. The tumor is solid, tan-white, and hemorrhagic. Osteosarcoma may arise in any bone of the body but more commonly affects long, tubular bones that contain the most proliferative growth plates, especially those in the distal femur, proximal tibia, and proximal humerus. The favored site within the long bone is the metaphysis, but the tumor also may occur in the diaphysis and, rarely, the epiphysis

Fig. 2.28 Conventional osteosarcoma. Coronal (left) and axial (right) CT scans demonstrate a 7-cm aggressive-appearing mixed lytic and sclerotic lesion centered within the medullary cavity of the proximal tibial metadiaphysis. There is endosteal thinning of the cortex, with a surrounding soft tissue component containing bony ossific matrix. A pathologic fracture also is present. In general, the radiographic appearance of an osteosarcoma is highly variable. There may be lytic, blastic, or mixed bone destruction and production

Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.29 Conventional osteosarcoma. Anteroposterior (left) and lateral (right) views of an osteosarcoma in a 13-year-old girl. The destructive lesion in the distal left tibial metaphysis is demonstrated by a permeative appearance and an aggressive periosteal reaction. A periosteal reaction also is seen in the distal fibula, along with a large surrounding soft tissue mass

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40

Fig. 2.30 Conventional osteosarcoma. MR images (left, sagittal T1 turbo spin-echo; right, coronal short T1 inversion recovery [STIR]) of the tumor seen in Fig. 2.29. There is marrow enhancement extending from the distal physis cranially 14.5 cm to the mid-diaphysis. There is a large soft tissue component showing heterogeneous enhancement with underlying destruction of the adjacent tibial cortex

2

Bone-Forming Tumors

Fig. 2.31 Conventional osteosarcoma. The characteristic “sunburst” sign of osteosarcoma involves the left mandible. The periosteal reaction may be solid or lamellated. If the lesion grows rapidly, the periosteum may not have enough time to lay down even a thin shell of bone. In such cases, the Sharpey fibers (the fibers connecting the periosteum to the bone) may become stretched out perpendicular to the bone and produce a sunburst or “hair-on-end” pattern of periosteal reaction

2.4

Conventional Osteosarcoma

41

Fig. 2.32 Chondroblastic osteosarcoma. Cross-section of a tumor involving the clavicle in an 18-year-old girl. The prominent chondroid matrix produced by the tumor closely resembles a high-grade chondrosarcoma

Fig. 2.33 Chondroblastic osteosarcoma. Although it is subtle, one can still appreciate the focal chondroid matrix in this tumor of the distal femur. Also note the cortical destruction

Fig. 2.34 Conventional osteosarcoma. Amputated specimen after chemotherapy for an extensive chondroblastic osteosarcoma involving the distal femur. Although there is significant residual viable tumor upon microscopic examination, no gross features remain, which would suggest that the tumor had cartilaginous differentiation

42 Fig. 2.35 Osteoblastic osteosarcoma. Microscopic examination of the tumor involving the proximal tibia revealed minimal response to chemotherapy

2

Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.36 Conventional osteosarcoma. A sclerosing type of conventional osteosarcoma involving the proximal humerus shows an extensive chemotherapeutic effect. The histologic section reveals 95 % tumor necrosis

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2

Bone-Forming Tumors

Fig. 2.37 Conventional osteosarcoma. Radiograph of the corresponding specimen in Fig. 2.36

Fig. 2.38 Conventional osteosarcoma. A mixed fibroblastic and chondroblastic osteosarcoma involving the proximal humerus in a 31-yearold woman. This represents another tumor with a minimal therapeutic response

2.4

Conventional Osteosarcoma

Fig. 2.39 Osteoblastic osteosarcoma. Even at this scanning power, abundant tumor osteoid imparting a basket-weave appearance can be visualized

Fig. 2.40 Osteoblastic osteosarcoma. A low-power view of a core needle biopsy specimen shows compact, blueish, variably mineralized bone matrix. Note the permeation of preexisting bone by tumor osteoid

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46 Fig. 2.41 Osteoblastic osteosarcoma. Intermediate magnification demonstrates haphazardly arranged, partly mineralized osteoid trabeculae rimmed by cellular osteoblastic tumor cells

Fig. 2.42 Osteoblastic osteosarcoma. This section shows lacelike osteoid production, a frequent finding in osteoblastic osteosarcomas. Note the binucleated and multinucleated tumor cells and a tripolar mitotic figure

2

Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.43 Conventional osteosarcoma. A closer view shows anaplastic tumor cells embedded in a background of osteoid matrix. Note the frequent mitotic activity. Osteosarcoma typically is hypercellular. However, some tumors (or a portion of tumor) may undergo degeneration and appear hypocellular

Fig. 2.44 Conventional osteosarcoma. This section exhibits a lacelike yet thickened osteoid network

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48 Fig. 2.45 Conventional osteosarcoma. This osteosarcoma has a more subtle osteoid production. Osteoid is unmineralized bone matrix that typically is homogeneously eosinophic. There is no minimal amount of bone matrix necessary when diagnosing an osteosarcoma. The presence of any tumor osteoid/ bone is reason enough to render a diagnosis of osteosarcoma in the setting of a malignant neoplasm

Fig. 2.46 Conventional osteosarcoma. This needle biopsy specimen shows a hypocellular osteosarcoma with prominent mineralized bone matrix. In contrast to the previous image, there are a minimal number of lesional cells but abundant bone formation as a result of mineralization. The newly formed bone may vary in color from dark blue to light pink, largely depending on the degree of mineralization or the duration of calcification, or both

2

Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.47 Conventional osteosarcoma. Fine-needle aspiration of an osteoblastic osteosarcoma. Note the pleomorphic tumor cells. A Diff-Quik stain (Polysciences, Inc., Warrington, PA) showing metachromatic osteoid is diagnostic but may not always be apparent

Fig. 2.48 Conventional osteosarcoma. Histomorphology of an osteosarcoma with prominent plasmacytoid morphology. The neoplastic cells in benign or malignant boneforming tumors may express CD138 in a membranous fashion. In the setting of minimal tumor osteoid, this may lead to a mistaken diagnosis of plasmacytoma or multiple myeloma

49

50 Fig. 2.49 Conventional osteosarcoma. Note the prominent osteoid production reminiscent of amyloid. This, along with the plasmacytoid cytologic appearance of the tumor cells seen in the previous image, again may result in a misinterpretation of plasmacytoma or multiple myeloma

Fig. 2.50 Conventional osteosarcoma. Note the filigree osteoid that forms a delicate “chicken-wire” pericellular network

2

Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.51 Conventional osteosarcoma. This tumor shows a prominent “staghorn” vasculature imparting a solitary fibrous tumor/hemangiopericytoma-like pattern. Note the highly pleomorphic histomorphology and the subtle, eosinophilic intercellular osteoid production in the stroma, leading to the correct diagnosis

Fig. 2.52 Chondroblastic osteosarcoma. The chondroid matrix and the lacelike pattern of osteoid production, more prominent at the left upper corner, help characterize this lesion as a chondroblastic osteosarcoma

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52 Fig. 2.53 Chondroblastic osteosarcoma. Note the thick osteoid seams produced by the tumor cells

Fig. 2.54 Chondroblastic osteosarcoma. This section shows delicate chicken-wire pericellular osteoid production. The histomorphologic features are otherwise that of a high-grade chondrosarcoma. Once again, the presence of tumor osteoid, regardless of amount, identifies the tumor as an osteosarcoma

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Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.55 Chondroblastic osteosarcoma. The chondroid matrix is prominent. The matrix in a chondroblastic osteosarcoma tends to be high-grade hyaline cartilage intimately associated with randomly arranged osteoid/ bone, which may be inconspicuous in some cases

Fig. 2.56 Chondroblastic osteosarcoma. The bone-forming nature of this tumor can be appreciated even at a low-power view

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54 Fig. 2.57 Conventional osteosarcoma. A mixed osteoblastic and chondroblastic type

Fig. 2.58 Chondroblastic osteosarcoma. Vascular invasion of the tumor in the form of a tumor embolus is seen. The vascular wall is seen stretching across the top of the image

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Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.59 Fibroblastic osteosarcoma. This subtype of osteosarcoma typically presents as a high- grade spindle-cell malignancy with minimal amounts of osseous matrix. Intermixed chondroblastic and/or osteoblastic elements are not uncommon findings

Fig. 2.60 Conventional osteosarcoma. This tumor has a prominent alveolar growth pattern mimicking an alveolar rhabdomyosarcoma. Other areas show obvious tumor osteoid

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56 Fig. 2.61 Conventional osteosarcoma. An epithelioid variant of osteosarcoma. A bone biopsy of a specimen with such cytologic characteristics and minimal osteoid production may result in an erroneous interpretation of metastatic carcinoma, especially in elderly patients

Fig. 2.62 Sclerosing osteosarcoma. A sclerosing variant of osteoblastic osteosarcoma is illustrated. The production of osseous matrix is in excess to the proportion of tumor cells. The latter have been largely immersed in the newly formed bone

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Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.63 Sclerosing osteosarcoma. This section illustrates “normalization” of nuclei. The tumor cells become incorporated into the bone matrix and resemble normal osteocytes

Fig. 2.64 Sclerosing osteosarcoma. The tumor has produced so much matrix that it has markedly compressed the tumor cells. In some cases, the produced bone matrix may be so excessive that the cellular component of the tumor is difficult to identify. A purely sclerosing osteosarcoma is difficult to diagnose in a small biopsy specimen. The tumor cells often are most obvious at the advancing edge of the lesion

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58 Fig. 2.65 Osteosarcoma resembling an osteoblastoma (osteoblastoma-like osteosarcoma). Although the radiographic appearance is that of a malignant tumor, histologically the lesion is composed of arborizing microtrabecular bone rimmed by osteoblastic cells in a background of a vascular-rich stroma, thus simulating an osteoblastoma

Fig. 2.66 Chondroblastoma-like osteosarcoma. A CT scan from a 69-year-old woman shows an aggressive left scapular leson

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Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.67 Chondroblastoma-like osteosarcoma. A biopsy of the lesion seen in Fig. 2.66 shows a cellular lesion with chondromyxoid islands and focal calcification, mimicking a chondroblastoma

Fig. 2.68 Chondroblastoma-like osteosarcoma. A high-power view shows the neoplastic cells to have indistinct cell membranes, eosinophilic cytoplasm, and minimal nuclear atypia, thus closely resembling chondroblasts

59

60 Fig. 2.69 Chondroblastoma-like osteosarcoma. Areas with emerging tumor osteoid production are seen

Fig. 2.70 Chondromyxoid fibroma-like osteosarcoma. Note the lobular growth pattern with a zonal distribution of tumor cells in a background of high-grade hyaline cartilaginous stroma. Other areas show obvious osteoid production

2

Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.71 Giant cell–rich osteosarcoma. Note the abundant unmineralized bone matrix. Approximately one fourth of osteosarcomas contain benign osteoclast-type multinucleated giant cells. Rarely, an osteosarcoma may contain so many giant cells that the malignant elements in the background may be obscured. In such cases, the lesion may be mistaken histologically for a giant cell tumor of bone

Fig. 2.72 Giant cell–rich osteosarcoma. There is obvious bone matrix produced by tumor

61

62 Fig. 2.73 Malignant fibrous histiocytoma (MFH)-like osteosarcoma. The histologic features of tumor cells are those of an MFH. However, the abundant newly formed bone identifies it as an osteosarcoma. Also note the destruction of the preexisting lamellar bone

Fig. 2.74 MFH-like osteosarcoma. Occasionally the tumor osteoid may be minimal and/or subtle. Careful examination of all sections is crucial to correctly categorize this group of lesions. It is important to note that all these aforementioned unusual histologic forms are not associated with a specific biological behavior that differs from the conventional form

2

Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.75 Dedifferentiated osteosarcoma. The tumor is composed of spindle-shaped cells with abundant eosinophilic cytoplasm forming whorling fascicles and nuclear atypia, which are characteristic of a leiomyosarcoma. The tumorproduced bone matrix distinguishes it from a primary bone leiomyosarcoma

Fig. 2.76 Osteosarcoma with leiomyosarcomatous dedifferentiation. Identification of subtle, granular bone matrix such as this may be challenging. One should bear in mind that a primary bone leiomyosarcoma is far less common than a dedifferentiated osteosarcoma

63

64 Fig. 2.77 Osteosarcoma post chemotherapy. This represents a complete response to chemotherapy. The variably collagenized stroma devoid of tumor cells is a common pattern of osteosarcoma following chemotherapy

Fig. 2.78 Osteosarcoma post chemotherapy. This illustrates another common pattern of chemotherapeutic response. The tumor bone matrix remains, although there are no viable tumor cells

2

Bone-Forming Tumors

2.4

Conventional Osteosarcoma

Fig. 2.79 Osteosarcoma post chemotherapy. This section shows a chemoresistant mixed osteoblastic and chondroblastic osteosarcoma

Fig. 2.80 Osteosarcoma post chemotherapy. This represents another example of an osteosarcoma that failed to respond to chemotherapy. Sometimes therapeutic agents may cause marked nuclear pleomorphism, similar to that seen in carcinomas

65

66 Fig. 2.81 Osteosarcoma post chemotherapy. The interface between an osteosarcoma with chemoresponsive (lower right) and nonresponsive (upper left) regions. Of additional importance is the knowledge that chemotherapy may cause a phenomenon similar to the normalization effect (referred to as maturation), as the residual viable tumor illustrated in this image, along with necrosis

2

Bone-Forming Tumors

2.5

2.5

Telangietatic Osteosarcoma

67

Telangietatic Osteosarcoma

Fig. 2.82 Telangiectatic osteosarcoma. Sagittal (left) and axial (right) CT images demonstrate a large lytic lesion in the left femoral neck of a 16-year-old boy. Note the cortical destruction and soft tissue mass

Fig. 2.83 Telangiectatic osteosarcoma. An axial T2-weighted MR image of the lesion seen in Fig. 2.82. There is high-signal intensity with several cystic foci and fluid–fluid levels, similar to what can be seen in an aneurysmal bone cyst

68 Fig. 2.84 Telangiectatic osteosarcoma. The tumor contains large blood-filled spaces without endothelial lining, thus bearing a striking resemblance to an aneurysmal bone cyst. There is a solid component consisting of sheets of tumor cells (upper left)

Fig. 2.85 Telangiectatic osteosarcoma. As seen in this image, random fields at high magnification of a telangiectatic osteosarcoma may be histologically indistinguishable from those of an aneurysmal bone cyst. Although the production of bone or osteoid by tumor helps considerably in formulating the diagnosis, frequently there is little extracellular matrix to evaluate, making the distinction of these two entities extremely challenging. The distinguishing feature is the permeative growth pattern in such scenarios and the cytomorphology of the “osteoblasts”

2

Bone-Forming Tumors

2.5

Telangietatic Osteosarcoma

Fig. 2.86 Telangiectatic osteosarcoma. This section illustrates cortical destruction in the presence of remarkable new bone formation. The newly formed bone in a telangiectatic osteosarcoma typically is laid down in the form of haphazardly arranged microtrabeculae similar to those seen in a conventional osteosarcoma. In contrast, there commonly is a thin shell of osteoid/bone formation along the wall of an aneurysmal bone cyst

Fig. 2.87 Telangiectatic osteosarcoma. This image exhibits an area of telangiectatic osteosarcoma simulating a solid aneurysmal bone cyst. Destruction of medullary bone is evident

69

70 Fig. 2.88 Telangiectatic osteosarcoma. The presence of abundant osteoclast-like multinucleated giant cells is a common finding in a telangiectatic osteosarcoma and is similar to that seen in aneurysmal bone cyst. This may focally resemble a giant cell tumor of bone. In addition, giant cell–rich osteosarcoma seems to be associated with telangiectatic osteosarcoma at a more than random rate. Thus, one or more molecules present at higher locoregional concentrations may serve as common stimulator(s) of multinucleation in these conditions

Fig. 2.89 Telangiectatic osteosarcoma. This image demonstrates a telangiectatic osteosarcoma on the left with a coexisting sclerosing variant of conventional osteosarcoma on the right. The presence of other histologically identifiable osteosarcomatous elements often helps in reaching the correct diagnosis and emphasizes the importance of examining the entire lesion

2

Bone-Forming Tumors

2.6

2.6

Small Cell Osteosarcoma

71

Small Cell Osteosarcoma

Fig. 2.90 Small cell osteosarcoma. A coronal T1-weighted MR image shows an aggressive heterogeneous enhancing mass in the medial metaphysis of the distal right femur of this 14-year-old girl. The lesion extends into the epiphysis and has a medial extraosseous component. There is surrounding soft tissue and periosteal edema

Fig. 2.91 Small cell osteosarcoma. Gross pathologic features of the small cell osteosarcoma seen in Fig. 2.90

72

2

Bone-Forming Tumors

Fig. 2.92 Small cell osteosarcoma. This tumor arose in the femoral diaphysis of a 73-year-old man and showed a minimal therapeutic response on histologic examination

Fig. 2.93 Small cell osteosarcoma. A pelvic CT image shows a lytic lesion in the left ilium of a 22-year-old man. Small cell osteosarcomas reportedly all have a lytic component but may have associated radiodense areas. The radiologic features are not consistently typical for osteosarcoma because often this tumor produces very little mineralized matrix Fig. 2.94 Small cell osteosarcoma. A coronal STIR MR image of the tumor shown in Fig. 2.93 after chemotherapy. There is an enlarged lobulated soft tissue mass emanating from the left iliac crest

2.6

Small Cell Osteosarcoma

Fig. 2.95 Small cell osteosarcoma. The gross features of the tumor removed from the patient seen in Fig. 2.94. Sectioning through the mass reveals a dark-red hemorrhagic cut surface with multiple blood-filled cystic clefts and areas of necrosis

Fig. 2.96 Small cell osteosarcoma. The histomorphologic features of small cell osteosarcoma combine those of osteosarcoma and Ewing sarcoma. A small cell osteosarcoma should be diagnosed only if osteoid/bone matrix is seen, as illustrated on the right of this photomicrograph. Of importance as well is that tumor cells may be immunoreactive with CD99. Thus, the latter should not be used for distinction of small cell osteosarcoma and Ewing sarcoma

73

74 Fig. 2.97 Small cell osteosarcoma. The cells constituting a small cell osteosarcoma are round and, less frequently, short spindles. The latter finding is not characteristic of Ewing sarcoma. A mixture of both cell types also may be seen

Fig. 2.98 Small cell osteosarcoma. All cells have scanty cytoplasm and generally are hyperchromatic. The nuclei of the round cell type are round to oval with fine to coarse chromatin. The size of nuclei may vary from smaller ones equivalent to those of Ewing sarcoma or small cell lymphoma, to larger ones comparable to those of large cell lymphoma. Nucleoli may be present but typically are small and not a constant feature. A perivascular growth pattern, such as that seen in a subset of Ewing sarcoma cases, is not uncommon

2

Bone-Forming Tumors

2.6

Small Cell Osteosarcoma

Fig. 2.99 Small cell osteosarcoma. At higher magnification, there is a mixture of round and spindle cells. The latter cell type has short, oval to spindle nuclei with more homogeneous chromatin. As illustrated here, mitotic figures, some of which are atypical, are variably present

Fig. 2.100 Small cell osteosarcoma. Note the subtle osteoid production in a lacelike pattern. This finding should not be confused with the fibrin deposits more commonly seen among Ewing sarcoma cells

75

76 Fig. 2.101 Small cell osteosarcoma. This photomicrograph shows relatively hypocellular areas with scanty, lacelike, variably mineralized osteoid matrix

Fig. 2.102 Small cell osteosarcoma. A prominent hemangiopericytoma-like growth pattern, which is present in about one third of cases, is shown

2

Bone-Forming Tumors

2.6

Small Cell Osteosarcoma

Fig. 2.103 Small cell osteosarcoma post chemotherapy. Note that the histologic features illustrated here are those of a conventional osteoblastic osteosarcoma. Thus, although the tumor is chemoresistant, the therapeutic agents induce further differentiation of the tumor cells, a maturation phenomenon

77

78

2.7

2

Low-Grade Central Osteosarcoma

Fig. 2.104 Low-grade central osteosarcoma. Note the markedly illdefined cloud of density in the distal femoral diaphysis by conventional radiography. As the name implies, low-grade central osteosarcomas typically arise from the medullary cavity of long bones (Photograph courtesy of Dr. Michael Pitt)

Fig. 2.105 Low-grade central osteosarcoma. The tumor is characterized histologically by a hypo- or moderately cellular fibroblastic stroma with variable amounts of bone/osteoid matrix. The spindle cells usually are arranged in fascicles or interlacing bundles. The histologic appearance may closely resemble fibrous dysplasia or osteofibrous dysplasia and essentially is identical to that seen in parosteal osteosarcoma

Bone-Forming Tumors

2.7

Low-Grade Central Osteosarcoma

Fig. 2.106 Low-grade central osteosarcoma. This section shows permeation of adjacent cortex. Destruction of preexisting bony trabeculae commonly is seen. Thus, it is extremely informative if sections include the interface of the lesion with normal bone. Findings such as fibrous tissue within haversian canals or between mature medullary trabeculae are reassuring signs of occult malignancy in the proper clinical and radiologic environment

Fig. 2.107 Low-grade central osteosarcoma. In areas with densely collagenized stroma where bone formation is scant, there also may be a histologic resemblance to desmoplastic fibroma of bone

79

80 Fig. 2.108 Low-grade central osteosarcoma. In more cellular areas of this osteosarcoma, there may be moderate nuclear enlargement and hyperchromasia, along with intermixed epithelioid tumor cells. Significant cytologic atypia or increased mitotic activity, or both, generally are not present

2

Bone-Forming Tumors

2.8

2.8

Parosteal Osteosarcoma

81

Parosteal Osteosarcoma

Fig. 2.109 Parosteal osteosarcoma. An anteroposterior radiograph (left) and a coronal CT image (right). There is an exophytic bony lesion arising from the cortex/periosteum of the mid-femoral diaphysis.

Parosteal osteosarcoma most commonly involves the distal posterior femur in young adults, with a slight female predominance

82

2

Bone-Forming Tumors

Fig. 2.111 Parosteal osteosarcoma. A coronal CT image shows a large, heterogeneous, exophytic, cortical-based mass arising from the proximal humeral metaphyseal cortex and extending into the soft tissues

Fig. 2.110 Parosteal osteosarcoma. An axial CT image of the lesion shown in Fig. 2.109. The tumor shows heterogeneous ossification without internal structure. Cortical thickening is evident. In contrast to an osteochondroma, there typically is no continuity of the surface of the mass with the cortex of the parental bone in parosteal osteosarcoma, and its “inside” is not in continuity with the underlying medullary cavity. That being said, parosteal osteosarcomas occasionally may invade the medullary cavity

Fig. 2.112 Parosteal osteosarcoma. An axial CT image of the tumor seen in Fig. 2.111 demonstrates invasion of the adjacent cortex and tumor extension into the bone marrow

2.8

Parosteal Osteosarcoma

83

Fig. 2.113 Parosteal osteosarcoma. Gross pathologic features of the tumor seen in Fig. 2.109. The midportion of the femur is involved by a bulky soft and bony mass surrounding approximately 75 % of the femoral shaft. The external surface of the mass is tan and bosselated

Fig. 2.114 Parosteal osteosarcoma. An axial cross-section of the tumor shown in Fig. 2.113. The cut surface reveals a tan-pink to mottled white bony matrix with focal areas that are soft, tan-white, and glistening. The lesion arises from the cortex and does not appear to directly involve the medullary space. The mass mostly has a bony consistency, whereas the remaining volume is white, fleshy, and granular-appearing

84

2

Bone-Forming Tumors

Fig. 2.115 Parosteal osteosarcoma. The tumor in the distal femur is densely ossified and shows a stuck-on appearance. No medullary involvement is present

Fig. 2.116 Parosteal osteosarcoma. Gross appearance (left) and corresponding specimen radiograph (right) of a parosteal osteosarcoma involving the femoral shaft. The bony mass comprises a cancellous type of bone mimicking the medullary bone normally present in the marrow

2.8

Parosteal Osteosarcoma

Fig. 2.117 Parosteal osteosarcoma. A low-power view shows bony trabeculae arranged in a parallel manner (“streamers of woven bone”), a common finding in parosteal osteosarcoma. The bony trabeculae formed by the tumor are mature-appearing, simulating normal bone, with or without osteoblastic rimming. The tumor is typically composed of hypocellular to moderately cellular bland spindle cells within a fibrous stroma

Fig. 2.118 Parosteal osteosarcoma. Different from the previous image, this section shows irregular bone trabeculae arranged haphazardly. Thus, the features present an appearance closely reminiscent of fibrous dysplasia and are indistinguishable histologically from those of a low-grade central osteosarcoma, as previously noted

85

86 Fig. 2.119 Parosteal osteosarcoma. The bone spicules may become thickened at the base of the lesion, but there usually is little maturation of the matrix into a lamellar architecture

Fig. 2.120 Parosteal osteosarcoma. In areas with immature bone formation, the bony spicules may have a “psammoma body”–like appearance. The spindle cells show miminal cytologic atypia, whereas the background stroma is densely collagenized. These features closely resemble those seen in fibromatosis

2

Bone-Forming Tumors

2.8

Parosteal Osteosarcoma

Fig. 2.121 Parosteal osteosarcoma. In areas with increased cellularity, there may be mild to moderate cytologic atypia. Significant nuclear pleomorphism is not a common feature

Fig. 2.122 Parosteal osteosarcoma. Cartilaginous differentiation is not an uncommon finding and is reported in up to 50 % of the tumors, either within the lesion or as a cartilage cap on the surface. The latter may result in the pathologic misinterpretation of this lesion as an osteochondroma or a Nora lesion of long bones

87

88 Fig. 2.123 Parosteal osteosarcoma. This image shows a focus with medullary invasion. Such findings do not affect the patient’s prognosis if the tumor remains low grade

2

Bone-Forming Tumors

2.9 Periosteal Osteosarcoma

2.9

89

Periosteal Osteosarcoma

Fig. 2.124 Periosteal osteosarcoma. A conventional radiograph shows cortical thickening with peripheral amorphous calcification in the midfemoral diaphysis (Photograph courtesy of Dr. Michael Pitt)

Fig. 2.125 Periosteal osteosarcoma. An axial CT image of the lesion shown in Fig. 2.124. Note the heavily ossified mass arising from the cortex (Photograph courtesy of Dr. Michael Pitt)

90 Fig. 2.126 Periosteal osteosarcoma. The histologic features are those of an intermediate- to high- grade chondroblastic osteosarcoma, characterized by lobules of malignant-appearing cartilage with ossification in the center or at the periphery of the lobules

Fig. 2.127 Periosteal osteosarcoma. Some tumors show regions of spindle cell proliferation between or adjacent to the cartilaginous lobules. In such lesions, the histologic differential diagnosis also includes a highgrade surface osteosarcoma

2

Bone-Forming Tumors

2.9 Periosteal Osteosarcoma Fig. 2.128 Periosteal osteosarcoma. At the periphery of the cartilage lobules, the tumor tends to exhibit a condensation of spindle cells and the cartilaginous elements display greater cellular pleomorphism

Fig. 2.129 Periosteal osteosarcoma. This image shows a haphazard arrangement of irregular cartilage lobules, spindle-cell elements, and bone formation

91

92 Fig. 2.130 Periosteal osteosarcoma. A high-power view of the spindle cells exhibits moderate cytologic atypia. Mitotic activity may be present but is not brisk. Note the small bone spicules forming directly from the spindle cell stroma

2

Bone-Forming Tumors

2.10

2.10

High-Grade Surface Osteosarcoma

93

High-Grade Surface Osteosarcoma

Fig. 2.131 High-grade surface osteosarcoma. An axial CT image from a 29-year-old man shows a 8.0-cm, partially mineralized mass on the surface of the proximal right femoral metaphysis extending into the soft tissue

Fig. 2.132 High-grade surface osteosarcoma. The bone scan of the patient seen in Fig. 2.131 shows a defined region of increased tracer uptake

94 Fig. 2.133 High-grade surface osteosarcoma. The histologic appearance is within the same spectrum of anaplastic change as is seen in a conventional osteosarcoma. Osteoblastic, chondroblastic, or fibroblastic differentiation may dominate in various regions of the lesion

Fig. 2.134 High-grade surface osteosarcoma. Zones of chondroid differentiation. High-grade cytologic atypia is invariably seen in all tumors

2

Bone-Forming Tumors

2.10

High-Grade Surface Osteosarcoma

Fig. 2.135 High-grade surface osteosarcoma. Note the bone spicules characteristic of osteoblastic osteosarcoma

Fig. 2.136 High-grade surface osteosarcoma. Areas of spindle cell proliferation and lacelike osteoid production. The latter reportedly is always identifiable

95

96 Fig. 2.137 High-grade surface osteosarcoma. Areas of dense collagenized stroma are similar to those seen in the sclerosing variant of conventional osteosarcoma

2

Bone-Forming Tumors

2.11

2.11

Secondary Osteosarcoma

Secondary Osteosarcoma

Fig. 2.138 Secondary osteosarcoma. Gross photograph of a recurrent osteosarcoma of the right forearm in a 44-year-old woman with a history of Mazabraud and McCune-Albright syndromes. The patient’s history was complicated by osteosarcoma arising in a background of fibrous dysplasia in the right proximal radius and distal humerus. She had undergone wide resection 2 years earlier

Fig. 2.139 Secondary osteosarcoma. Gross phograph of the bisected specimen shown in Fig. 2.138. In both the distal humerus and proximal ulna, there is loss of the normal spongy appearance, and the medullary canal has been replaced by firm, solid, white tumoral tissue admixed with fibrous dysplasia

Fig. 2.140 Secondary osteosarcoma. Radiograph of the specimen shown in Fig. 2.139 similarly reveals replacement of the normal medullary architecture by mixed lytic and sclerotic lesions that are mostly fibrous dysplasia

97

98 Fig. 2.141 Secondary osteosarcoma. Gross specimen of an above-the-knee amputation showing osteosarcoma secondary to Paget disease

Fig. 2.142 Secondary osteosarcoma. The histologic appearance of secondary osteosarcomas generally is that of conventional osteosarcomas. A section of the tumor in Fig. 2.138 shows pleomorphic cells with ill-defined tumor osteoid

2

Bone-Forming Tumors

2.11

Secondary Osteosarcoma

Fig. 2.143 Secondary osteosarcoma. This tumor arose in the humerus of a patient with a metallic prosthesis. The histologic appearance is that of an osteoblastic osteosarcoma

Fig. 2.144 Secondary osteosarcoma. The section depicts an osteosarcoma arising in Paget disease of the skull

99

3

Cartilage-Forming Tumors

All tumors that engage in chondroid matrix production are traditionally grouped together, regardless of their histogenesis. Cartilage tumors account for most nonhematologic primary bone tumors and encompass a broad spectrum of lesions, ranging from completely benign to highly malignant. As in most types of bone tumors but in contrast to bone-forming tumors, benign cartilaginous lesions are far more common

than malignant ones. As for all bone lesions, evaluation of cartilage tumors necessitates adequate correlation with radiographic and demographic findings. This is extremely important in differentiating chondromas from chondrosarcomas, because benign lesions may have worrisome cytohistologic features, and conversely, high-grade lesions may possess foci of benign-appearing cytologic characteristics.

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_3, © Springer Science+Business Media New York 2013

101

102

3.1

3

Cartilage-Forming Tumors

Osteochondroma (Exostosis)

Fig. 3.1 Osteochondroma. This conventional radiograph shows an osteochondroma in the distal femur of a 12-year-old girl. Osteochondroma, the most common benign tumor of bone, is characterized by a hyaline cartilage–capped bony projection on the surface of bone. The tumor develops only in bones of endochondral origin and thus predominantly arises from the metaphysis of long bones, especially around the knee. It most commonly affects adolescents and young adults, and has a peak incidence in the second decade of life. Osteochonromas are mostly solitary but also are seen as part of hereditary osteochondromatosis, an autosomal dominant disease thought to be caused principally by germline loss-of-function mutations in either the EXT1 or EXT2 gene

Fig. 3.2 Osteochondroma. A sagittal CT image shows a large (14-cm) left proximal femoral osteochondroma in a 46-year-old woman with hereditary osteochondromatosis. On imaging, the osteochondroma demonstrates continuity of marrow and cortex with the underlying bone. The cartilage cap of the exophytic mass points away from the nearest joint. The tumor may be sessile or pedunculated and is attached to the parent bone by a bony stalk

3.1

Osteochondroma (Exostosis)

Fig. 3.3 Osteochondroma. A sagittal T1-weighted magnetic resonance (MR) image of the lesion shown in Fig. 3.2. Note the continuity of marrow between the tumor and the underlying skeleton and a large adventitial bursa associated with the tumor (bursa exostotica). The cartilage cap of the lesion measures 1.8 cm at its widest point

103

Fig. 3.4 Osteochondroma. A conventional radiograph shows deformity of the proximal half of the left humerus, which is consistent with multiple sessile osteochondromas

104

3

Cartilage-Forming Tumors

Fig. 3.5 Osteochondroma. A chest CT image demonstrates a cartilaginous lesion of the scapula that has resulted in remodeled expansion. The body of the scapula is grossly deformed. Osteochondromas occasionally develop from the skeleton other than in long, tubular bones, including the pelvis, scapula, and ribs. The lesions in these sites typically are sessile and have short stalks

Fig. 3.7 Osteochondroma. In this intact excisional specimen, the lesion shows a prominent cartilage cap with a smooth, glistening, bluish and somewhat transparent surface. Underlying the cap is benignappearing cortical and medullary bone viewed on cross-section. Sessile lesions show a broad base. The cartilage cap usually is less than 1 cm and decreases in thickness with age. A thick and irregular cap (>2 cm) may be indicative of malignancy but also may be seen in benign lesions in skeletally immature individuals

Fig. 3.6 Osteochondroma. An axial CT image demonstrates a sclerotic bordered expansile lesion of the right pedicle and posterior aspect of the T6 vertebral body of this 19-year-old boy. There is osseous density within the lesion. No associated soft tissue mass or cortical disruption is seen. Although the features also suggest osteoblastoma on imaging, the histologic examination of the lesion demonstrated an osteochondroma. Central osteochodromas involving the skull base and spine may cause neurologic sequelae such as cranial nerve deficits, spinal stenosis, cauda equina syndrome, and myelomalacia

3.1

Osteochondroma (Exostosis)

Fig. 3.8 Osteochondroma. Gross pathologic features of a pedunculated lesion demonstrating a white-tan, polypoid mass with a cauliflower-like appearance

105

106 Fig 3.9 Osteochondroma. A cross-section of the lesion seen in Fig. 3.8. Note the cancellous bone in the center of the mass and the thin cartilaginous cap (0.5 cm in thickness) at the periphery. This pedunculated lesion had a bony stalk measuring 12.0 cm

Fig. 3.10 Osteochondroma. On low-power view, the surface of the lesion is represented by hyaline cartilage with a striking resemblance to an epiphyseal or growth plate. Degenerative changes also may be present. The cartilage is covered by a thin fibrous membrane (perichondrium), which usually is not present in mimicking lesions such as the Nora lesion of long bones. Beneath the cartilage cap is cancellous bone with intertrabecular spaces filled by mostly fatty or fibrous marrow and a few hematopoietic elements

3

Cartilage-Forming Tumors

3.1

Osteochondroma (Exostosis)

Fig. 3.11 Osteochondroma. At higher magnification, the chondrocytes are arranged in an orderly fashion and undergo endochondral ossification at the bone/cartilage interface in the manner identical to that seen in a growth plate

Fig. 3.12 Osteochondroma. Focal myxoid change, increased cellularity, and hyperchromasia in the cartilage cap are not infrequent features and are not indicative of malignant transformation by themselves

107

108

Fig. 3.13 Osteochondroma. Osteochondroma rarely may arise in flat bones. This CT scan from a 3-year-old boy demonstrates a nodular bony projection on the posterior skull showing continuity from the underlying skull. A is anterior and P is posterior

Fig. 3.14 Osteochondroma. A histologic section of the lesion seen in Fig. 3.13 shows a small evolving osteochondroma. Although the location is extremely uncommon, the radiographic findings and histologic features are mostly consistent with an osteochondroma

3

Cartilage-Forming Tumors

3.2

3.2

Chondroma (Enchondroma)

109

Chondroma (Enchondroma)

Fig. 3.16 Chondroma. There is a minimally expansile lytic lesion in the proximal left clavicle. No aggressive radiologic features are present

Fig. 3.15 Chondroma. This conventional radiograph demonstrates an elongated lucent lesion in the right fifth metatarsal with no aggressive features. The findings are mostly consistent with an enchondroma. Chondromas are benign neoplasms of hyaline cartilage. They typically occur in bones of endochondral origin. When arising in the medullary cavity, they are referred to as enchondromas. The favored sites of involvement are small tubular bones of the hands and feet followed by long tubular bones, particularly the humerus and femur

110 Fig. 3.17 Chondroma. Hyaline cartilage lesions have a characteristic bluish matrix rich in proteoglycans. Chondromas of long, tubular bones usually are hypocellular, as illustrated in this femoral lesion. Chondromas typically are avascular tumors, and nutrients are diffused through the matrix, as occurs in normal cartilage

Fig. 3.18 Chondroma. The architecture may be confluent or multinodular with reactive new bone formation at the periphery of the nodules, as depicted in the section. This should not be interpreted as a chondroblastic osteosarcoma. Focal myxoid changes may be seen in chondromas, but only if they constitute a minor component (<10 %) of the tumor

3

Cartilage-Forming Tumors

3.2

Chondroma (Enchondroma)

Fig. 3.19 Chondroma. Sometimes the lesional cells are arranged in clusters similar to those in mature cartilage

Fig. 3.20 Chondroma. At high magnification, the chondrocytes are situated in the lacunar spaces and have small round or slightly irregular nuclei with condensed chromatin and clear, vacuolated to eosinophilic cytoplasm. Binucleated forms may be seen but are rare. Mitotic activity is not discernible

111

112 Fig. 3.21 Chondroma. Shown is an enchondroma present in a finger. In contrast to tumors of long bones, chondromas of small, tubular bones of the hands and feet typically have increased cellularity, binucleation, and cellular pleomorphism

Fig. 3.22 Chondroma. The tumor typically is wellcircumscribed but may erode the endosteal surface. Chondromas do not invade the haversian system

3

Cartilage-Forming Tumors

3.2

Chondroma (Enchondroma)

Fig. 3.23 Cartilaginous tumor of indeterminate biological potential. CT scan of the mid-femoral diaphyseal lesion shows worrisome features, including larger size, endosteal scalloping, and cortical thickening; however, it does not otherwise appear aggressive

Fig. 3.24 Cartilaginous tumor of indeterminate biological potential. The histologic appearance of the lesion is shown in Fig. 3.23. This section shows a hypercellular cartilage tumor (in the context of a long bone lesion) with increased binucleated forms and myxoid changes. Features of overt malignancy, such as significant cytologic atypia or permeation of preexisting bone by tumor, are not present. Thus, neither the radiologic findings nor the histologic features fulfill the requirements for a low-grade chondrosarcoma, nor do they allow one to simply assume a chondroma is present

113

114

Fig. 3.25 Cartilaginous tumor of indeterminate biological potential. The conventional radiograph of this 62-year-old woman demonstrates a large (approximately 7 cm) proximal humeral intramedullary dense lesion with ring and arc type calcifications. However, aggressive features, such as a periosteal reaction or cortical breakthrough, are not seen

Fig. 3.26 Cartilaginous tumor of indeterminate biological potential. A section of the curetted specimen from the lesion shown in Fig. 3.25. The histologic features are similarly borderline and the curettings have no preserved geographic relationship to the adjacent normal cancellous bone. In such cases, a diagnosis of “cartilaginous tumor of indeterminate biological potential” is appropriate and close follow-up is recommended

3

Cartilage-Forming Tumors

3.3

3.3

Periosteal Chondroma

Periosteal Chondroma

Fig. 3.27 Periosteal chondroma. MR images demonstrate a T1 hypointense (left, axial) and peripheral enhancing (right, coronal postcontrast) mass adherent to the periosteum of the fifth proximal phalanx. The periosteum appears mostly intact but is focally involved. Periosteal chondromas are rare. They usually involve the long bones around the knee but also may affect the small bones of the hands and feet

115

116 Fig. 3.28 Periosteal chondroma. The histologic features of periosteal chondromas closely resemble those of enchondromas of the small bones in the hands and feet. Histologically, the tumor typically shows a lobulated growth pattern and appears extremely hypercellular. Focal myxoid changes also may be seen. However, the tumor does not permeate haversian canals or the medulla

Fig. 3.29 Periosteal chondroma. At higher magnification, cellular pleomorphism, hyperchromasia, and binucleation are not uncommon. These features, along with the hypercellularity and myxoid changes, closely resemble a grade 1 or even a grade 2 chondrosarcoma if taken out of context

3

Cartilage-Forming Tumors

3.4

3.4

Enchondromatosis (Including Ollier Disease and Maffucci Syndrome)

117

Enchondromatosis (Including Ollier Disease and Maffucci Syndrome)

Fig. 3.30 Enchondromatosis in Ollier disease. Multiple enchondromas involving the metacarpals and phalanges of the hand in a 29-year-old man. Ollier disease is a developmental disorder caused by failure of normal endochondral ossification, thus resulting in multiple enchondromas and varying degrees of bone deformity. Maffucci syndrome is characterized by the combined features of enchondromatosis and hemangiomas of the surrounding soft tissue. Both conditions are associated with a significantly increased risk of secondary chondrosarcoma, with the risk of Maffucci syndrome said to reach 100 % over a lifetime

Fig. 3.31 Enchondromatosis. The patient is a 24-year-old man with a history of Ollier disease. A conventional radiograph demonstrates multiple enchondromas throughout the right hand. The largest two exophytic masses originating from the index and long fingers are worrisome for sarcomatous transformation

118

3

Cartilage-Forming Tumors

Fig. 3.32 Enchondromatosis. An axial T1-weighted MR image of the lesions shown in Fig. 3.31. Postcontrast imaging demonstrates that the two largest lesions involve the proximal phalanx of the long and index fingers (10.5 and 5.5 cm, respectively)

Fig. 3.34 Enchondromatosis. The patient is a 31-year-old woman with Maffucci syndrome. Conventional radiograph demonstrates multiple expansile, exostotic lesions around the knee. The lesions appear to have arc-like calcifications in their matrix

Fig. 3.33 Enchondromatosis. An axial CT image shows innumerable expansile cartilaginous lesions involving the proximal right humerus, right scapula, and multiple ribs

3.4

Enchondromatosis (Including Ollier Disease and Maffucci Syndrome)

Fig. 3.35 Multiple hemangiomas in a patient with Maffucci syndrome. There are widespread soft tissue calcifications (phleboliths) around the elbow consistent with multiple thrombosed hemangiomas

119

120

Fig. 3.36 Enchondromatosis. Gross pathologic features of the long finger lesion shown in Fig. 3.31. There is a bulky lobulated firm mass between the middle joint and the metacarpal phalangeal joint (left). Sectioning

Fig. 3.37 Enchondromatosis. Histologic appearance of the larger lesion shown in Fig. 3.36. Increased cellularity and myxoid change are typical of the cartilaginous lesions in patients with Ollier disease and Maffucci syndrome, especially in the fingers and toes. This lesion shows somewhat greater cellularity than that seen in many solitary chondrosarcomas of long bone

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Cartilage-Forming Tumors

through the mass reveals a cartilaginous tumor that is tan-white to mottled pink, glistening, and thinly rimmed by calcified bony tissue at the periphery, with scattered calcified matrix in the center (right)

3.4

Enchondromatosis (Including Ollier Disease and Maffucci Syndrome)

Fig. 3.38 Enchondromatosis. Binucleation and mild cytologic atypia frequently are seen. Mitotic activity is not evident as found in other benign cartilage tumors. Its presence should prompt the pathologist to seek other features of malignancy

Fig. 3.39 Enchondromatosis. A representative section of the soft tissue lesions seen in Fig. 3.35, which shows a hemangioma with organizing thrombus and phleboliths

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Chondroblastoma

Fig. 3.40 Chondroblastoma. The CT scan shows a lytic lesion in the epiphysis of the proximal tibia in a 14-year-old boy. There are spotty matrix calcifications and sclerosis at the periphery, the latter attesting to the lesion’s slow growth. Chondroblastoma usually arises in skeletally immature patients, mostly affecting bones around the knee, followed by the proximal humerus. The tumor has a striking predilection for the epiphysis (or its equivalents in the acetabulum and ilium) but may extend into the metaphysis. Other usual sites include the skull, scapula, ribs, patella, and bones of the feet

Fig. 3.41 Chondroblastoma. Lateral radiograph of a right foot showing a lesion in the superior navicular bone that extends to the joint margins. The lesional margins show subtle endosteal erosion with slight remodeled expansion. No lesional content is identified

Cartilage-Forming Tumors

3.5

Chondroblastoma

Fig. 3.42 Chondroblastoma. MR images of the lesion shown in Fig. 3.41. An axial T1-weighted image (left) shows a homogeneous intermediate signal, extending to all surfaces. Sagittal proton density (PD)weighted MRI with fat suppression (right) shows an inhomogeneous bright signal with multifocal endosteal erosions in the anterosuperior portion

Fig. 3.43 Chondroblastoma. A low-power view shows uniform mononuclear cells admixed with randomly distributed osteoclasttype multinucleated giant cells

123

124 Fig. 3.44 Chondroblastoma. At higher magnification, the tumor is composed of round, oval, and polygonal mononuclear cells with minimal to mild cytologic atypia and nonneoplastic multinucleated giant cells. Mitotic figures are present, but atypical forms are not seen. Necrosis, although rare, may be found but does not adversely affect prognosis

Fig. 3.45 Chondroblastoma. Variably sized, amorphous, bluish- to pink-stained islands (fibrochondroid) typically are present through the lesional tissue, which contain similarappearing mononuclear cells situated within lacunar spaces. Focal calcific deposits also may be seen

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Cartilage-Forming Tumors

3.5

Chondroblastoma

Fig. 3.46 Chondroblastoma. Cytologically, the chondroblasts are round, oval, or polygonal mononuclear cells and may, as in this case, appear epithelioid. The cells have well-defined cytoplasmic borders, abundant eosinophilic cytoplasm, and central or eccentric nuclei with frequent longitudinal grooves and occasional hyperlobulation, thus mimicking Langerhans cells

Fig. 3.47 Chondroblastoma. Sheets of chondroblasts with scattered giant cells. Calcification of the matrix helps distinguish a chondroblastoma from other giant cell–rich lesions, such as giant cell tumor of bone. When that occurs, it typically produces a characteristic “chicken-wire” pattern of pericellular mineralization

125

126 Fig. 3.48 Chondroblastoma. Mineralized matrix may become prominent, thus resulting in the radiographic appearance of spotty calcifications

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Cartilage-Forming Tumors

3.6

3.6

Chondromyxoid Fibroma

127

Chondromyxoid Fibroma

Fig. 3.49 Chondromyxoid fibroma. Note the eccentric, osteolytic lesion of the distal humerus, which focally destroys the lateral cortex. Chondromyxoid fibroma is the least common cartilage tumor. In its typical presentation, the tumor occurs in the intramedullary portion of the metaphysis of long bones, but it may affect any bone in the skeleton, including such rare sites as the cervical vertebrae. Imaging studies typically show a well-circumscribed lytic lesion with a sclerotic border and scalloping. Matrix calcification is rare, except when present in the juxtacortical location

Fig. 3.50 Chondromyxoid fibroma. This conventional radiograph shows a lesion in the midshaft of the right humerus with a slight eccentricity projecting anterolaterally. The lesional margins are well-defined and show a thin zone of sclerosis. There is considerable remodeled expansion of the lesion with buttressing, particularly in the proximal aspect. No lesional content is identified. Note that the diaphysis location is somewhat unusual for a chondromyxoid fibroma. The differential diagnosis also includes an aneurysmal bone cyst

128 Fig. 3.51 Chondromyxoid fibroma. At low magnification, chondromyxoid fibroma is characterized by a vaguely lobular growth pattern, with hypocellular centers and hypercellular peripheries. The tumor has a fibrous or chondromyxoid stroma. Well-formed hyaline cartilage is rarely seen

Fig. 3.52 Chondromyxoid fibroma. Cellular condensation at the periphery of the lobules. There may be a subtle microlobular pattern in the center of the lobules

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Cartilage-Forming Tumors

3.6

Chondromyxoid Fibroma

Fig. 3.53 Chondromyxoid fibroma. Dilated or congested blood vessels and scattered multinucleated giant cells also are seen frequently at the periphery of the lobules

Fig. 3.54 Chondromyxoid fibroma. The tumor cells usually are delicate spindle-shaped or stellate, with an indistinct to densely eosinophilic cytoplasm and bipolar or multipolar cytoplasmic extensions. Hyperchromasia and mild to moderate nuclear pleomorphism also may be seen. Mitotic figures are not present

129

130 Fig. 3.55 Chondromyxoid fibroma. A fatty component rarely is seen between the lobules. Calcifications typically are associated with an older age of onset and unusual anatomic locations, such as the skull, facial bones, and ribs

Fig. 3.56 Juxtacortical chondromyxoid fibroma. A sagittal T1weighted image reveals a lesion isointense with muscle surrounded by a low-signal rim. The periosteum is thickened but intact and is displaced anteriorly to the lesion (From Baker AC, Rezeanu L, O’Laughlin S, Unni K, Klein MJ, Siegal GP. Juxtacortical chondromyxoid fibroma of bone: a unique variant: a case study of 20 patients. Am J Surg Pathol. 2007;31:1662–8; with permission)

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Cartilage-Forming Tumors

3.6

Chondromyxoid Fibroma

Fig. 3.57 Juxtacortical chondromyxoid fibroma. Tumors arising from the periosteum or cortex are known to be associated with extensive calcifications, a feature not commonly seen in conventional chondromyxoid fibroma. This, along with the presence of multinucleated giant cells, may mimic the appearance of chondroblastoma. However, the latter occurs almost exclusively in the epiphysis and histologically does not have lobular configuration

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3.7

3

Synovial Chondromatosis

Fig. 3.58 Synovial chondromatosis. There is a large, lobulated soft tissue mass involving the anterior and posterior ankle joint seen in these images. The lesion demonstrates low signal intensity on T1 (left, sagittal), with heterogeneous enhancement on postcontrast imaging (right, axial). No bony involvement is identified. The radiologic differential diagnosis also includes tenosynovial giant cell tumor/pigmented vilonodular synovitis

Fig. 3.59 Synovial chondromatosis. The presence of variably cellular hyaline cartilage nodules covered by a thin fibrous layer or synovial lining is characteristic of the lesion. The chondrocytes typically are organized in clusters

Cartilage-Forming Tumors

3.7

Synovial Chondromatosis

Fig. 3.60 Synovial chondromatosis. Occasionally, a “diffuse” pattern also is present, as illustrated. Note the hypercellularity, plump nuclei with mild to moderate nuclear pleomorphism, and increased binucleated cells, features commonly associated with synovial chondromatosis. The overlying synovial cells are evident

Fig. 3.61 Synovial chondromatosis. Rarely, invasion of the cartilage nodules into adjacent bone may be seen. Such invasion is not indicative of malignant transformation

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3

Conventional Chondrosarcoma

Fig. 3.62 Chondrosarcoma. This conventional radiograph shows a 13.9-cm distal femoral diametaphyseal lesion in a 55-year-old woman. The lesion has a well-defined zone of transition, along with a ring and arc sclerotic matrix. Features suggesting a chondrosarcoma include a solid periosteal reaction, multiple areas of endosteal scalloping, and the large size of the lesion. Chondrosarcomas usually occur in patients aged 40 or older. They may be subclassified according to the site of origin as central (intramedullary) or peripheral (juxtacortical and periosteal), although others use these same terms to mean other things, such as whether it arises in an extremity (appendicular) or central core (axial), or whether it arises de novo or secondary to an exostosis

Cartilage-Forming Tumors

3.8

Conventional Chondrosarcoma

Fig. 3.63 Chondrosarcoma. Coronal (left) and sagittal (right) CT images demonstrate a lytic lesion in the subtrochanteric region of the left proximal femur containing amorphous internal calcifications and causing significant thinning of the posterior femoral cortex. In addition, there is thickening of the anteromedial cortex of the femur adjacent to the lesion

Fig. 3.64 Chondrosarcoma. Grossly, the tumor in the proximal femur has a characteristic glistening, tan-white to blue-gray appearance and grows in a lobular pattern. Note the apparent endosteal scalloping and cortical thickening adjacent to the tumor

135

136 Fig. 3.65 Chondrosarcoma. Specimen radiograph (left) and gross appearance (right) of another chondrosarcoma involving the distal femur. Note the soft tissue mass and pathologic fracture

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Cartilage-Forming Tumors

3.8

Conventional Chondrosarcoma

Fig. 3.66 Chondrosarcoma. The tumor is characterized by an invasive growth pattern, as depicted. Grading is the most useful factor to predict clinical outcomes, except for those chondrosarcomas arising in the bones of the fingers and toes. Although no universally accepted scoring system exists, chondrosarcoma generally is graded on a scale of 1–3, primarily based on cellularity, nuclear size and characteristics, and mitotic activity (see Table 3.1)

Fig. 3.67 Chondrosarcoma, grade 1. Like their benign counterparts, low-grade or grade 1 chondrosarcomas typically have a lobulated growth pattern with abundant cartilaginous matrix separated by narrow fibrovascular bands. At low power, grade 1 chondrosarcomas generally are more cellular than enchondromas at the same site

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Fig. 3.68 Chondrosarcoma, grade 1. This femoral lesion is mildly hypercellular with increased binucleated forms and occasional multinucleation but lacks notable nuclear pleomorphism. No evidence of tumor permeation is seen. Although the histologic features alone are not sufficient to support a diagnosis of chondrosarcoma, the combination of increased cellularity and its location in a non–small bone/nonperiosteal tissue are highly suggestive of a malignant process. In such

3

Cartilage-Forming Tumors

cases, radiologic–pathologic correlation is crucial in reaching a correct diagnosis. On the other hand, increased cellularity, binucleation, hyperchromasia, and myxoid change all may be present in enchondromas of the small bones of the hands and feet and in the cartilage cap of osteochondromas, as previously noted. Thus, the diagnosis of chondrosarcoma can be made only by unequivocal radiologic or histologic evidence of tumor permeation of cortical or medullary bone, or both

3.8

Conventional Chondrosarcoma

Fig. 3.69 Chondrosarcoma. Grades 1 and 2 chondrosarcomas commonly are associated with myxoid changes/chondroid matrix liquefaction

Fig. 3.70 Chondrosarcoma, grade 2. Note the significantly increased cellularity and cytologic atypia. Permeation of cortical and/or medullary bone is characteristic of chondrosarcoma and may be used to distinguish it from enchondroma

139

140 Fig. 3.71 Chondrosarcoma, grade 2. Permeation may extend through the haversian system of the cortex, a feature not present in enchondromas

Fig. 3.72 Chondrosarcoma, grade 2. Spindling of lesional cells is a feature of chondrosarcoma, commonly seen in higher-grade lesions

3

Cartilage-Forming Tumors

3.8

Conventional Chondrosarcoma

Fig. 3.73 Chondrosarcoma, high-grade. Cytologic atypia including enlarged nuclei, hyperchromasia, and visible nuclear details (“open chromatin”) typically are seen in high-grade lesions (grades 2 and 3) but are not a common feature of low-grade chondrosarcoma

Fig. 3.74 Chondrosarcoma, grade 3. Note the markedly increased cellularity and pleomorphic-appearing nuclei with prominent nucleoli and occasional macronucleoli. The presence of any atypical mitosis and/or necrosis should prompt the pathologist to consider a high-grade lesion. Pure grade 3 chondrosarcomas are rare. Highly malignant cartilage is seen more commonly as an element of chondroblastic osteosarcoma

141

142 Fig. 3.75 Chondrosarcoma. Chondrosarcoma varies in cellularity from field to field, and high- grade lesions often have lower-grade areas. The histologic features depicted in this image from a grade 2 chondrosarcoma are indistinguishable from those of a grade 1 lesion or even an enchondroma. In addition, the geographic relationship to the adjacent normal bone is not always preserved in curetted specimens. Once again, careful correlation with the radiologic findings is generally helpful, as is knowing the patient’s age, because chondrosarcoma essentially never occurs in children

Fig. 3.76 Chondrosarcoma. As in chondromas, endochondral ossification commonly is seen at the periphery of tumor lobules and should not be mistaken for chondroblastic osteosarcoma. In contrast, the identification of tumor osteoid or bone formation directly by tumor cells should point to the diagnosis of osteosarcoma

3

Cartilage-Forming Tumors

3.8

Conventional Chondrosarcoma

Table 3.1 Grading of chondrosarcomas

143 Grade 1

2

3

Cellularity/binucleation Mildly hypercellular, sparse binucleated cells

Nuclear features Plump vesicular nuclei with or without small nucleoli; occasional hyperchromasia Moderately cellular, frequent Notable cytologic atypia, binucleation or multinucleation including large nuclei, visible nuclear details, hyperchromasia, and prominent nucleoli Markedly hypercellular, Significant nuclear frequent binucleation or pleomorphism multinucleation

Mitotic activity Usually absent

May be present

Discernible to brisk

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3.9

3

Cartilage-Forming Tumors

Secondary Chondrosarcoma

Fig. 3.79 Secondary chondrosarcoma. A cross-section of the lesion seen in Fig. 3.78 shows a nodular tan-white cartilaginous mass with white chalky areas of calcifications diffusely embedded within the lobules of the mass

Fig. 3.77 Secondary chondrosarcoma. Resection of a proximal femoral “osteochondroma” from a 46-year-old man with a history of multiple hereditary osteochondromas demonstrates a poorly defined, 3.0-cm cartilage cap. Histologic examination revealed a grade 1 chondrosarcoma

Fig. 3.78 Secondary chondrosarcoma. This photograph exhibits a 21-cm cartilaginous mass arising at the site of a cartilage cap in a preexisting osteochondroma in the iliac crest in a 40-year-old man with multiple hereditary osteochondromas

Fig. 3.80 Secondary chondrosarcoma. This gross specimen, from a 36-year-old man with a history of Ollier disease, shows a firm, lobulated mass distorting the proximal aspect of the left humerus. This mass partially involves and destroys the humeral head. On cross-section, the mass is white-tan, glistening, and lobulated, with areas of necrosis and hemorrhage in the medial aspect. The lateral cortex is scalloped, whereas the medial cortex is expanded but grossly remains intact

3.9

Secondary Chondrosarcoma

Fig. 3.81 Secondary chondrosarcoma. The histologic features of secondary chondrosarcomas are those of conventional chondrosarcoma and should be graded as such. The tumors commonly are low-grade lesions. Invasion of the adjacent soft tissue (as illustrated) and permeation of cortical/medullary bone are helpful features in classifying the tumor as malignant

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3.10

3

Cartilage-Forming Tumors

Dedifferentiated Chondrosarcoma

Fig. 3.82 Dedifferentiated chondrosarcoma. This bulky mass from an 86-year-old woman replaces much of the femoral neck and is externalized to reside prominently within the posterior and medial surfaces of the femur. There are regions of cartilaginous matrix within the lesion as well as areas with bone-forming characteristics

Fig. 3.83 Dedifferentiated chondrosarcoma. This intramedullary lesion in the tibial diametaphysis demonstrates a fleshy mass with extensive hemorrhage and cystic degeneration, different from the usual hyaline and myxoid changes of chondrosarcoma

3.10

Dedifferentiated Chondrosarcoma

Fig. 3.84 Dedifferentiated chondrosarcoma. The histologic appearance of the lesion shown in Fig. 3.82. Dedifferentiated chondrosarcoma is characterized by a bimorphic lesion composed of two well-defined components: a well-differentiated cartilaginous tumor (enchondroma/low-grade chondrosarcoma) juxtaposed to a high-grade sarcoma. Malignant fibrous histiocytoma is the most frequent second component, although many other sarcomas also may arise, including osteosarcoma, fibrosarcoma, and rhabdomyosarcoma. The transition between the low-grade cartilage tumor and the noncartilaginous element typically is abrupt and without morphologic continuity, as illustrated in this image. However, the clear-cut separation may not always be appreciated, especially in the specimen obtained from curettings

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148

Fig. 3.85 Dedifferentiated chondrosarcoma. Rarely, the noncartilage portion may have a histologic appearance mimicking more than one tumor. Whereas sections of the lesion seen in Fig. 3.83 exhibit regions

3

Cartilage-Forming Tumors

characteristic of conventional osteosarcoma (not shown), other sections contain areas resembling a giant cell tumor of bone (left). The welldifferentiated cartilaginous portion is minimal (right)

3.10

Dedifferentiated Chondrosarcoma

149

Fig. 3.86 Dedifferentiated chondrosarcoma. Areas of dedifferentiation in the lesion seen in Fig. 3.83 exhibit features reminiscent of low-grade central osteosarcoma (left) and nonossifying fibroma or desmoid tumor of bone (right)

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3.11

3

Cartilage-Forming Tumors

Clear Cell Chondrosarcoma

Fig. 3.87 Clear cell chondrosarcoma. A conventional radiograph demonstrates a lytic lesion in the femoral head, with sharp margination and peripheral sclerosis. Clear cell chondrosarcoma is a rare, low-grade chondrosarcoma with a predilection for the epiphyseal location of long bones, especially the proximal femur or humerus

Fig. 3.88 Clear cell chondrosarcoma. An axial CT image showing a clear cell chondrosarcoma of the left iliac crest. The lesion contains radiodensities characteristic of cartilage

Fig. 3.89 Clear cell chondrosarcoma. The tumor contains soft but gritty materials with focal cystic degeneration. Gross features characteristic of cartilage are not present

3.11

Clear Cell Chondrosarcoma

Fig. 3.90 Clear cell chondrosarcoma. Histologically, the tumor consists primarily of lobulated groups of abundant clear cells. Although zones of conventional low-grade chondrosarcoma are present in many lesions, woven bone also may form directly in the stroma, thus resulting in the appearance of a chondroblastic osteosarcoma

Fig. 3.91 Clear cell chondrosarcoma. At higher magnification, the clear cells typically are round to polygonal and have a distinct cytoplasmic membrane and centrally or eccentrically located bland nuclei. Multinucleated giant cells also may be identified. Mitotic figures are rare

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3.12

3

Cartilage-Forming Tumors

Mesenchymal Chondrosarcoma

Fig. 3.92 Mesenchymal chondrosarcoma. A 47-year-old woman presented with a mass in the medial aspect of the distal left thigh. A conventional radiograph shows a well-circumscribed calcified mass projecting adjacent to the distal left medial femoral diametaphysis. Although the radiologic features may represent heterotopic ossification, there are atypical central densities that are poorly defined and have the appearance of cartilage (Photograph courtesy of Dr. Michael Pitt)

Fig. 3.93 Mesenchymal chondrosarcoma. An axial CT image of the lesion shown in Fig. 3.92 demonstrates cartilage-type matrix in the central portion of the lesion, which is well described by a thin rim of calcification (Photograph courtesy of Dr. Michael Pitt)

3.12

Mesenchymal Chondrosarcoma

Fig. 3.94 Mesenchymal chondrosarcoma. Sagittal MR images (left, T1-weighted; right, PD-weighted) of the lesion shown in Fig. 3.92 also suggest cartilage within the well-defined lesion. Mesenchymal chondrosarcoma is highly malignant, with a peak incidence in the second and third decades of life. The tumor shows a widespread skeletal distribution

153

but also may primarily affect extraskeletal sites, as in this case. Radiographically, these tumors typically are aggressive lesions and otherwise do not differ significantly from ordinary chondrosarcoma. Calcified matrix, poor margination, and cortical destruction/soft tissue mass frequently are seen (Photograph courtesy of Dr. Michael Pitt)

154 Fig. 3.95 Mesenchymal chondrosarcoma. Histologically, the tumor is characterized by a biphasic appearance composed of islands of well-differentiated hyaline cartilage embedded in sheets of small, round, blue cells. The cartilage nodules vary in size and may be calcified in the center or even ossified. The interface between the two components may be abrupt or gradual

Fig. 3.96 Mesenchymal chondrosarcoma. The cartilage may mimic normal chondrogenesis, as may be seen in the growth plate (thus benign-appearing) or may be indistinguishable from a well-differentiated chondrosarcoma. Therefore, a small biopsy specimen obtained from such areas may be mistaken for ordinary chondrosarcoma

3

Cartilage-Forming Tumors

3.12

Mesenchymal Chondrosarcoma

Fig. 3.97 Mesenchymal chondrosarcoma. A hemangiopericytoma pattern with staghorn-like vascular spaces is common in the hypercellular, small cell zones of this lesion

Fig. 3.98 Mesenchymal chondrosarcoma. Areas of a small cell component with an alveolar pattern. The small, round cells have uniform cytologic characteristics demonstrating hyperchromatic nuclei and minimal cytoplasm, simulating Ewing sarcoma or lymphoma. Subtle osteoid production also may be present, as illustrated

155

156 Fig. 3.99 Mesenchymal chondrosarcoma. Spindling of the small cells may be seen in the dense, hypercellular areas

Fig. 3.100 Mesenchymal chondrosarcoma. This image shows areas of mesenchymal chondrosarcoma in which the hyaline cartilage component predominates, whereas the small cell component remains only in the perivascular regions

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Cartilage-Forming Tumors

4

Fibrous and Fibrohistiocytic Lesions

Tumors composed solely of fibrous and fibrohistiocytic elements are diverse and cover the entire spectrum of clinical behaviors, ranging from benign, to locally aggressive, to malignant. These lesions generally produce unmineralized

collagen matrix, whereas high-grade tumors may not have any matrix. These lesions often have significant overlapping histologic features and require demographic information and radiologic correlation to reach the correct diagnosis.

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_4, © Springer Science+Business Media New York 2013

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4.1

4

Fibrous and Fibrohistiocytic Lesions

Nonossifying Fibroma (Metaphyseal Fibrous Defect, Fibrous Cortical Defect)

Fig. 4.1 Nonossifying fibroma. A conventional radiograph from a 17-year-old boy shows an eccentric, lobulated radiolucency in the cortex of his proximal tibial metaphysis. The lesion is sharply demarcated with a scalloped border and a narrow rim of marginal sclerosis. These features are characteristic of a nonossifying fibroma. The lesion is seen exclusively in young patients with an age range of 5–20 years. The vast majority of these fibromas occur eccentrically in the metaphysis of long bones, particularly in the distal femur and the proximal tibia. The radiographic appearance is almost always diagnostic, as in this case. These lesions are extremely common in young children, frequently multifocal and bilateral, and typically detected incidentally on radiography. Thus, some authorities believe they represent developmental defects rather than true neoplasms and prefer to use the term metaphyseal fibrous defect/fibrous cortical defect, although nonossifying fibromas sometimes is the preferred nomenclature for larger lesions detected in adolescence. The larger lesions may become symptomatic, especially in teenage patients

Fig. 4.2 Nonossifying fibroma. Anteroposterior view in a conventional radiograph of a 14-year-old girl demonstrating a well-marginated, nonaggressive, lytic lesion (biopsy-proven nonossifying fibroma) centered at the anterior proximal diaphysis of the left tibia. The lesion shows increased density in the more proximal portion, which is consistent with previous curettage and bone grafting. Note that there is a similar but smaller lesion at the lateral juxtacortical aspect of the left distal femoral metaphysis, which is characteristic of a nonossifying fibroma. The combination of multiple nonossifying fibromas and café-au-lait skin patches is known as the Jaffe-Campanacci syndrome

4.1

Nonossifying Fibroma (Metaphyseal Fibrous Defect, Fibrous Cortical Defect)

Fig. 4.3 Nonossifying fibroma. A large multiloculated lytic lesion in the distal tibial metaphysis is seen in a 13-year-old boy, with expansion of the cortex and sclerotic borders. The radiologic appearance is that of an aneurysmal bone cyst versus a nonossifying fibroma with an associated aneurysmal bone cyst. Histologic examination revealed a nonossifying fibroma with secondary aneurysmal bone cyst formation

Fig. 4.4 Nonossifying fibroma. Histologically, nonossifying fibromas typically are hypercellular lesions with variable growth patterns. The spindled cell regions are characteristically arranged in a whorled or storiform fashion

159

160 Fig. 4.5 Nonossifying fibroma. At higher magnification, the spindled fibroblasts are uniform, with regular nuclei without significant pleomorphism. Mitotic figures may be seen frequently, but atypical forms are absent. Scattered multinucleated giant cells are almost always dispersed throughout the lesion, as is hemosiderin deposition

Fig. 4.6 Nonossifying fibroma. Lipid-laden foamy histiocytes (lipophages, xanthoma cells) also commonly are seen, either in sheets or small clusters

4

Fibrous and Fibrohistiocytic Lesions

4.1

Nonossifying Fibroma (Metaphyseal Fibrous Defect, Fibrous Cortical Defect)

Fig. 4.7 Nonossifying fibroma. Multinucleated giant cells may be prominent in areas and thus may share many microscopic features with giant cell tumors of bone. However, the giant cells in nonossifying fibromas generally are nested and smaller and contain fewer nuclei than those in giant cell tumors

Fig. 4.8 Nonossifying fibroma. Despite their appearance as pure lytic processes radiographically, reactive new bone formation is not an uncommon finding in nonossifying fibromas, especially in older lesions, at the periphery of the lesion, or if a pathologic fracture is present

161

162 Fig. 4.9 Nonossifying fibroma. A histologic section of the lesion shown in Fig. 4.3. Superimposed secondary aneurysmal bone cyst formation may occur rarely (as in this case) and manifests clinically as a rapidly enlarging mass, thus presenting a diagnostic challenge

4

Fibrous and Fibrohistiocytic Lesions

4.2

4.2

Benign Fibrous Histiocytoma

163

Benign Fibrous Histiocytoma

Fig. 4.10 Benign fibrous histiocytoma. A 31-year-old woman presented with significant right leg pain. A lateral view by conventional radiography (left) and a sagittal view utilizing a CT scan (right) reveal a mixed lytic and sclerotic lesion in the proximal diaphysis of the right fibula with remodeled expansion and cortical thinning; however, no

cortical breakthrough, periosteal reaction, or soft tissue mass is seen. These radiologic findings may represent a fibro-osseous lesion, healing nonossifying fibroma, or bone cyst. The histologic examination of the resected specimen demonstrated a benign fibrous histiocytoma

164

Fig. 4.11 Benign fibrous histiocytoma. A lateral view of the left distal leg and posterior foot of a 64-year-old man reveals a lytic lesion that demonstrates a narrow zone of transition and extends to but does not involve the cortex. No significant lesional calcification or chondral matrix is seen, nor is a periosteal reaction noted. The radiologic differential diagnosis in this age group would include plasmacytoma, lymphoma, and metastatic disease. The histologic examination of the curetted specimen revealed a benign fibrous histiocytoma

4

Fibrous and Fibrohistiocytic Lesions

4.2

Benign Fibrous Histiocytoma

Fig. 4.12 Benign fibrous histiocytoma. Histologically, benign fibrous histiocytoma typically is composed of an admixture of spindled fibroblasts and multinucleated giant cells, thus making it indistinguishable from a nonossifying fibroma. The two entities therefore are separated on clinical and radiologic grounds rather than histomorphologic criteria. In any circumstance that is not typical of a nonossifying fibroma—for example, a location not in a long bone, a nonmetaphyseal

Fig. 4.13 Benign fibrous histiocytoma. A whorled, storiform pattern is evident, at least focally. Foamy histiocytes, chronic inflammatory cells, and hemosiderin deposits commonly are present

165

location if in a long bone, any anatomic site in a patient after skeletal maturation, the presence of pain in the absence of pathologic fracture, or a radiologic pattern lacking the well-demarcated sclerotic margins— a benign fibrous histiocytoma should be strongly considered. In the epiphysis, however, the histologic pattern also may represent involutional changes of a giant cell tumor of bone

166 Fig. 4.14 Benign fibrous histiocytoma. The spindle cell nuclei are variable, ranging from elongated to oval to round and from dark to pale to vesicular with a micronucleolus. No nuclear pleomorphism or atypical mitotic features are present

Fig. 4.15 Benign fibrous histiocytoma. A 13-year-old boy presented with a right distal femoral shaft fracture. A well-demarcated lytic lesion is seen in the region of the facture, which, on biopsy examination, showed features otherwise characteristic of a nonossifying fibroma. However, the factors of a slightly older age, along with the diaphyseal location of this lesion, ultimately rendered a diagnosis of a benign fibrous histiocytoma

4

Fibrous and Fibrohistiocytic Lesions

4.3

4.3

Desmoplastic Fibroma (Desmoid Tumor)

Desmoplastic Fibroma (Desmoid Tumor)

Fig. 4.16 Desmoplastic fibroma. At low magnification, proliferative bland spindled cells are arranged in ill-defined fascicles, set in a collagen-rich stroma. Regular distributed blood vessels also are evident. This lesion historically was considered the intraosseous counterpart of soft tissue fibromatosis. However, more recent molecular genetic studies throw this theory into dispute. Desmoplastic fibroma is rare and may involve any bone but reportedly is most frequently found in the mandible. Radiographically, it usually is a well-defined, radiolucent lesion. If it is large, the lesion may breach the periostium and extend into the soft tissue

Fig. 4.17 Desmoplastic fibroma. The cellularity varies from region to region. Highly cellular areas may show hyperchromasia and mild nuclear pleomorphism, even at this low power

167

168 Fig. 4.18 Desmoplastic fibroma. At higher magnification, the lesional cells typically are spindled or stellate in shape, with open chromatin and the absence of nuclear atypia. The background stroma is richly collagenous and variably hyalinized

Fig. 4.19 Desmoplastic fibroma. Accumulation of b-catenin in the nucleus, a feature commonly seen in soft tissue fibromatosis, can be visualized in a small subset of desmoplastic fibromas of bone

4

Fibrous and Fibrohistiocytic Lesions

4.4

4.4

Fibroma of Tendon Sheath

Fibroma of Tendon Sheath

Fig. 4.20 Fibroma of tendon sheath. A 53-year-old man presented with a subcutaneous nodule along the palmar aspect of his left hand, distal to the thenar eminence. The sonogram shows a solid homogeneous mass in the region, which measures 6 mm in maximum dimension and has a small amount of internal vascularity along the posterior peripheral margin. Fibroma of the tendon sheath is uncommon and typically appears as a small, nodular lesion near tendinous structures, mostly in the hands of adult males

Fig. 4.21 Fibroma of tendon sheath. Histologically, the tumor is composed of well-circumscribed nodules of spindled fibroblasts of variable cellularity. The hypercellular areas usually merge with paucicellular zones

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170 Fig. 4.22 Fibroma of tendon sheath. The lesional fibroblasts/ myofibroblasts have bland nuclear features and are embedded in collagenous stroma. Occasional typical mitotic figures may be seen

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Fibrous and Fibrohistiocytic Lesions

4.5

4.5

Fibrosarcoma

171

Fibrosarcoma

Fig. 4.23 Fibrosarcoma. This tumor presented as a subcutaneous mass

Fig. 4.24 Fibrosarcoma. A below-the-knee amputation of the patient shown in Fig. 4.23 demonstrates a large mass that occupies the medullary cavity of the mid-tibial shaft and raises the periosteum

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Fig. 4.25 Fibrosarcoma. A firm, creamy white mass involved the distal tibia of this 58-year-old man, with a soft tissue mass between the tibia and fibula. It remains undetermined whether the tumor arose in bone and expanded into the soft tissue, or vice versa

Fig. 4.26 Fibrosarcoma. A histologic section of the tumor shown in Fig. 4.25 demonstrates a hypercellular and hyperchromatic spindle-cell tumor with a characteristic “herringbone” pattern of growth. An extensive immunophenotypic workup failed to reveal any identifiable differentiation. Fibrosarcoma of bone (and soft tissue) is far less common than previously thought, with many of those so labeled reclassified as monomorphic synovial sarcoma on the basis of immunohistochemistry and molecular genetics

4

Fibrous and Fibrohistiocytic Lesions

4.5

Fibrosarcoma

Fig. 4.27 Fibrosarcoma. The tumor cells may be arranged in a haphazard fascicular fashion rather than in the more typical herringbone pattern. The stroma typically shows a variable amount of collagenous matrix

Fig. 4.28 Fibrosarcoma. A higher magnification shows the fairly uniform appearance of tumor cells. The distinction between a well-differentiated (low-grade) fibrosarcoma and a desmoplastic fibroma may be challenging when seen in small biopsy specimens. The important distinguishing features include hypercellularity, a herringbonelike and/or bundled growth pattern, and mild to moderate nuclear atypia with readily identifiable mitoses in fibrosarcoma

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174 Fig. 4.29 Fibrosarcoma. The histologic differentiation of a fibrosarcoma from a fibroblastic osteosarcoma is based solely on the absence or presence of tumor osteoid. However, dense collagen fibers dissected by tumor cells may closely resemble osteoid, as depicted in this image

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Fibrous and Fibrohistiocytic Lesions

4.6

4.6

Malignant Fibrous Histiocytoma

Malignant Fibrous Histiocytoma

Fig. 4.30 Malignant fibrous histiocytoma. Gross pathologic features of a biopsy-proven malignant fibrous histiocytoma in the proximal left tibia, post radiation therapy. There is a lobulated tan-pink to mottled tan-brown mass just beneath the articular surface of the tibial plateau. Malignant fibrous histiocytoma of bone is rare, with a broad age range, but mostly affects adults over 40 years of age. The tumor may occur de novo in bone or arise secondary to preexisting bone conditions, such as distant prior radiation, Paget disease of bone, bone infarct, or fibrous dysplasia, or as the dedifferentiated component of a formerly low-grade neoplasm, such as grade I chondrosarcoma. The tumor more often occurs in long bones, particularly the femur, and typically presents as a destructive lytic lesion, although mixed lytic/sclerotic lesions also are seen

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176 Fig. 4.31 Malignant fibrous histiocytoma. Like its more common soft tissue counterpart, malignant fibrous histiocytoma of bone is a high-grade sarcoma composed of spindled cells, histiocytic cells, or a combination of the two. The spindle cells typically are arranged in a storiform pattern, as shown in this photomicrograph. Multinucleated giant cells typically are scattered throughout the lesion

Fig. 4.32 Malignant fibrous histiocytoma. The histologic features are diverse and may vary from region to region. This image shows a prominent histiocytic appearance with highly pleomorphic nuclei

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Fibrous and Fibrohistiocytic Lesions

4.6

Malignant Fibrous Histiocytoma

Fig. 4.33 Malignant fibrous histiocytoma. Although the degree of cytologic atypia varies, more commonly significant cellular pleomorphism, bizarre nuclei, and brisk mitotic activity are present. Immunohistochemistry is useful to rule out other high-grade sarcomas (such as pleomorphic leiomyosarcoma or rhabdomyosarcoma) but has limited value in the diagnosis of malignant fibrous histiocytoma. The tumor may be focally positive for smooth muscle actin, desmin, CD68,

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cytokeratin, and epithelial membranous antigen; however, these are nonspecific and of no diagnostic significance. Most important is that the presence of any unequivocal tumor osteoid or bone, should lead to a diagnosis of malignant fibrous histiocytoma-like osteosarcoma, and the patient typically will receive neoadjuvant systemic chemotherapy prior to surgical resection

5

Fibro-osseous Lesions

Fibro-osseous lesion is a generic designation for a clinically diverse group of bone disorders in which the lesional tissue consists of large volumes of fibrous connective tissue, principally collagens type I and III, as well as an osseous component in the form of woven or lamellar bone or cementum with varying degrees of mineralization. These lesions exhibit nearly identical histomorphologic features, yet demonstrate widely ranging clinical behavior. The site-dependent morphology applies especially to fibro-osseous lesions, as some occur exclusively at a particular anatomic location (i.e., osteofibrous dysplasia and central ossifying fibroma).

A specific diagnosis is crucial because the management differs substantially from no treatment to complete excision. It should be noted as well that entities undergo name changes over time, especially among fibro-osseous lesions. Thus, ossifying fibroma is a synonym for osteofibrous dysplasia in long bones, whereas ossifying fibroma of maxillofacial bones is commonly referred to as central ossifying fibroma. Other synonyms (or perhaps variants) of this entity include cementifying fibroma, cemento-ossifying fibroma, juvenile (active/ aggressive) ossifying fibroma, and psammomatoid ossifying fibroma.

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_5, © Springer Science+Business Media New York 2013

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Fibrous Dysplasia

Fig. 5.1 Fibrous dysplasia. This conventional radiograph shows a mildly expansile, mixed lytic and sclerotic lesion in the intertrochanteric/subtrochanteric region of the proximal left femur of a 23-year-old woman. The lesion is centered in the medullary cavity and has a narrow zone of transition. Fibrous dysplasia traditionally was considered a noninherited developmental disorder. However, most recent studies have argued strongly that this entity is neoplastic because of its clonal nature (activating mutations in the GNAS1 gene and associated clonal chromosomal aberration). Fibrous dysplasia may occur in any bone of the human skeleton, with long bones (femur and tibia), craniofacial bones, and ribs being the most commonly affected sites. The typical radiographic appearance is a centrally located, expansile, lytic lesion with sharp margination in the metaphyseal or diaphyseal region (if in long bones). The radiologic terms used to describe the appearance of the internal architecture include ground glass, orange peel, cotton wool, and thumb whorl

Fibro-osseous Lesions

5.1

Fibrous Dysplasia

Fig. 5.2 Fibrous dysplasia. Anteroposterior (left) and lateral (right) views of the left distal femur of a 27-year-old man showing a mixed lytic/sclerotic, slightly expansile lesion in the medullary compartment of the distal femur extending into the metadiaphysis. There are well-defined margins without a surrounding periosteal reaction, suggesting a nonaggressive lesion. There is a diffuse ground-glass appearance of the lesion, which essentially involves the entire medullary compartment of the distal bone

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Fig. 5.3 Fibrous dysplasia. A lateral view of the left tibia and fibula of a 22-year-old man demonstrating a large intramedullary lesion within the tibial diaphysis with ill-defined patchy sclerosis. There is associated endosteal scalloping of the anterior cortex, coupled with a mild periosteal reaction along the posterior aspect of the tibia. Fibrous dysplasia is solely a proliferative intramedullary process, although an exophytic variant (fibrous dysplasia protuberans) does exist

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Fibro-osseous Lesions

Fig. 5.4 Fibrous dysplasia. This sagittal CT image from a 39-year-old man shows multiple well-demarcated intramedullary lytic lesions in the left humerus. The largest (7 cm) eccentrically involves the proximal humeral metadiaphysis with cortical breakthrough but no associated soft tissue mass or progressive periosteal reaction. Fibrous dysplasia may be a solitary (monostotic) lesion or may be polyostotic, involving multiple sites in one bone, multiple bones in a single limb, or multiple bones on one side of the body, or identified bilaterally in multiple bones. The last type accounts for 30 % of all cases and is intimately associated with McCune-Albright syndrome (fibrous dysplasia, endocrinopathy, and skin pigmentation) and Mazabraud syndrome (fibrous dysplasia and intramuscular myxomas). Although any age group may be affected, most patients at first presentation are younger than 30 years, whereas the polyostotic forms manifest mostly during the first decade of life

5.1

Fibrous Dysplasia

Fig. 5.5 Fibrous dysplasia. A conventional radiograph from a 9-yearold boy shows an expansile lytic lesion of the proximal right humerus involving the metaphysis and proximal diaphysis. There are multiple septations within the lesion. There is cortical thinning but no definite fracture. The radiologic impression favored a unicameral bone cyst and, less likely, an aneurysmal bone cyst. The pathologic examination of the curetted specimen revealed fibrous dysplasia with secondary cystification. Cystic degeneration is not an uncommon finding, especially in longstanding lesions. This may be accompanied by the presence of lipid-laden histiocytes on histologic examination

Fig. 5.6 Fibrous dysplasia. Coronal (left) and axial (right) CT images demonstrate an expansile lesion with groundglass density involving the entire left mandible and extending to the right mandible

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Fibro-osseous Lesions

Fig. 5.7 Fibrous dysplasia. Gross examination of the lesion involving a long bone (left, intact specimen; right, cross-section) reveals a large, expansile, intramedullary lesion with cortical scalloping but no breakthrough. Cystic degeneration is seen in this lesion

Fig. 5.8 Fibrous dysplasia involving the flat bone of the skull. A CT image demonstrates a well-demarcated lytic lesion in the skull (Photograph courtesy of Dr. Keith Harrison)

Fig. 5.9 Fibrous dysplasia involving the flat bone of the skull. The gross pathologic features of the lesion seen in Fig. 5.8. The lesional tissue is tan-white with a gritty consistency. Note the expanded contour and thin cortex as well as cystic degeneration in the center (Photograph courtesy of Dr. Keith Harrison)

5.1

Fibrous Dysplasia

Fig. 5.10 Fibrous dysplasia. At low magnification, fibrous dysplasia is characterized by the combination of variably mineralized trabecular bone and proliferating fibroblasts that produce a dense collagenous matrix. The bony trabeculae commonly are thin and arranged in a haphazard manner, with a curvilinear branching appearance that is often C-, S-, or Y-shaped

Fig. 5.11 Fibrous dysplasia. The fibrous stroma varies in cellularity and consists of bland spindled fibroblasts that may appear epithelioid in the cellular areas. The mitotic rate typically is low and no atypical mitoses are present. The osseous component is immature woven (or, rarely, lamellar) bone without osteoblastic rimming, a histologic feature distinguishable from that of osteofibrous dysplasia

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186 Fig. 5.12 Fibrous dysplasia. A relatively hypocellular area with dense fibrous stroma and characteristic C-shaped bony spicules

Fig. 5.13 Fibrous dysplasia. Polarization microscopy accentuates the woven nature of the lesional bone

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Fibro-osseous Lesions

5.1

Fibrous Dysplasia

Fig. 5.14 Fibrous dysplasia. The bony component may be rounded or ovoid, especially in areas with dense collagenized stroma. In rare cases, the entire bony component in long bones may have this configuration, mimicking cementicles

Fig. 5.15 Fibrous dysplasia. In longstanding lesions, the bony trabeculae may be thickened and form an inter-anastomosing network. They also may contain reversal cement lines, simulating the appearance of Paget disease

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188 Fig. 5.16 Fibrous dysplasia. The osteoid produced occasionally may take the form of rounded cementum-like bone or psammoma bodies. Such findings are seen more frequently in the craniofacial bone (photomicrograph of the lesion shown in Fig. 5.8)

Fig. 5.17 Fibrous dysplasia. Focal osteoblastic rimming of trabeculae is not an uncommon finding, especially in craniofacial locations. Note the active osteoclastic bone resorption, indicating active remodeling

5

Fibro-osseous Lesions

5.1

Fibrous Dysplasia

Fig. 5.18 Fibrous dysplasia. Osteoblastoma-like areas may occur in lesions of fibrous dysplasia, especially in the region of the head and jaw

Fig. 5.19 Fibrous dysplasia. Focal cartilage metaplasia may be seen and rarely may be extensive, thereby being mistaken for a cartilaginous tumor (Photograph courtesy of Dr. Michael Klein)

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190 Fig. 5.20 Fibrous dysplasia with secondary changes. Osteoclast-type multinucleated giant cells may be seen in fibrous dysplasia. This may result in an erroneous diagnosis of a giant cell tumor or other giant cell–rich lesions in a small biopsy specimen in which the giant cell component is prominent

Fig. 5.21 Fibrous dysplasia with secondary changes. The presence of foam cells (also termed lipophages or lipid-laden histiocytes) is not an infrequent finding and represents degenerative changes. Myxoid changes also may be seen

5

Fibro-osseous Lesions

5.1

Fibrous Dysplasia

Fig. 5.22 Fibrous dysplasia with secondary changes. Secondary cystification may be present, and if prominent, the dysplasia may be mistaken for a unicameral or aneurysmal bone cyst

Fig. 5.23 Fibrous dysplasia. Active bone remodeling may be seen at the periphery of the lesion

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192 Fig. 5.24 Fibrous dysplasia. A section of an expansile lesion demonstrating cortical breakthrough

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Fibro-osseous Lesions

5.2

5.2

Osteofibrous Dysplasia

193

Osteofibrous Dysplasia

Fig. 5.25 Osteofibrous dysplasia. Conventional radiographs showing an exclusively cortical-based lesion in the right distal tibial diaphysis (left) and status post internal fixation for a pathologic fracture (right). Osteofibrous dysplasia is a benign fibro-osseous lesion of childhood. It characteristically occurs in an intracortical location in the anterior

mid-shaft of the tibia, with or without involvement of the fibula. The differential diagnosis for such a location typically includes adamantinoma, although this tumor usually affects patients in their 20s and 30s. If the lesion involves the medullary cavity by extension, it also may resemble fibrous dysplasia radiographically

194 Fig. 5.26 Osteofibrous dysplasia. At low magnification, the lesional tissue is composed of irregularly shaped trabecular bone embedded in a variably cellular fibrous stroma. A zonal distribution may be seen, with the fibrous tissue dominating the center and larger and maturing bone prominent at the periphery. However, this zonal architecture may not be observed in extensively curetted specimens

Fig. 5.27 Osteofibrous dysplasia. The bony trabeculae are largely immature, woven in nature, and characteristically rimmed by plump osteoblasts, a histologically distinguishing feature from fibrous dysplasia. The fibrous stroma may have a storiform pattern

5

Fibro-osseous Lesions

5.2

Osteofibrous Dysplasia

Fig. 5.28 Osteofibrous dysplasia. Higher magnification of the tumor in Fig. 5.27 shows irregular bone spicules with prominent osteoblastic rimming. The spindled fibroblasts are bland, with low-grade nuclei. Mitoses are extremely rare, if any. In contrast to the composition of admantinoma, epithelial islands are not present. However, it is important to note that osteofibrous dysplasia often contains isolated, scattered cytokeratin-positive stromal cells, whereas the diagnosis of so-called osteofibrous dysplasialike adamantinoma requires groups (nests) of epithelial cells identifiable on hematoxylin and eosin–stained sections alone by most authorities. Thus, complete curettage of the lesion and complete sampling of the specimen are crucial for an accurate diagnosis

Fig. 5.29 Osteofibrous dysplasia. Osteoclasts may be present, indicating active bone remodeling. Other nonspecific findings include foamy histiocytes, hemorrhage, and cyst formation, probably representing degenerative changes identical to those seen in fibrous dysplasia

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5.3

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Fibro-osseous Lesions

Central Ossifying Fibroma

Fig. 5.30 Central ossifying fibroma. Coronal (left) and axial (right) CT images of a 45-year-old woman showing a well-defined expansile lesion involving the left mandible, which demonstrates heterogeneous matrix with areas of mineralization. These findings are characteristic of a central ossifying fibroma. Conventional central ossifying fibroma commonly occurs in the second to fourth decades of life, with a female predilection. Small lesions generally are asymptomatic and diagnosed incidentally. The tumor is seen more commonly in the mandible (posterior or molar region) than the maxilla. It typically is a well-circumscribed or

sharply demarcated lesion with smooth contours and may have radiolucent as well as radiodense areas, depending on the various contributions of the soft tissue and mineralized components. Although the classification remains controversial, so-called juvenile trabecular ossifying fibroma and juvenile psammomatoid ossifying fibroma are histologic variants characterized by rapid and destructive growth (thus also termed active or aggressive ossifying fibroma). They commonly affect younger individuals but also may occur in older patients

5.3

Central Ossifying Fibroma

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Fig. 5.31 Central ossifying fibroma. Coronal (left) and axial (right) CT images showing an expansile and demarcated lesion involving the left maxilla of a 17-year-old girl. The lesion is predominantly radiolucent, with focal areas of radiopacity

Fig. 5.32 Central ossifying fibroma. Coronal (left) and axial (right) sinus CT images demonstrating an expansile mass involving the roof of the left orbit and measuring approximately 2.0 cm, with no aggressive

features. No calcified matrix is seen within the lesion. Histologic examination revealed a psammomatoid ossifying fibroma

198 Fig. 5.33 Central ossifying fibroma. Histologically, the tumor is characteristically a fibro-osseous lesion closely simulating fibrous dysplasia. The mineralized component consists of irregular bone spicules. The fibrous tissue may vary significantly in cellularity, ranging from closely packed to nearly acellular. Distinction between these two fibro-osseous lesions solely on histologic grounds may be problematic in biopsy specimens

Fig. 5.34 Central ossifying fibroma. A representative section showing the sharply demarcated periphery of this lesion. When present, this appearance represents the most helpful distinguishing feature of central ossifying fibromas as opposed to the merging with its surroundings found in fibrous dysplasia. It is important to note that the presence of lamellar bone and osteoblastic rimming does not contradict the diagnosis of fibrous dysplasia in the maxillofacial bones as it would for lesions occurring in other locations. The most important discriminating feature is the radiologic presentation (CT scan on bone windows). For fibrous dysplasia, this would be an expansile lesion with homogeneously radiodense opacities and a ground-glass appearance that blends into the surrounding normal bone

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Fibro-osseous Lesions

5.3

Central Ossifying Fibroma

Fig. 5.35 Central ossifying fibroma. At a high magnification, the bony trabeculae may be seen to be woven and/or lamellar and typically rimmed by plump osteoblasts, but there also may be mixed bands of cellular osteoid without osteoblastic rimming. Increased osteoclast activity frequently may be seen as a result of rapid bone turnover. Mitotic figures may be seen in the proliferative fibroblasts, but atypical forms are not present

Fig. 5.36 Cementifying fibroma (cemento-ossifying fibroma). The mineralized tissue in central ossifying fibroma may present in the form of poorly cellular, basophilic, smoothly contoured spherules with a lamellated arrangement thought to be cementum (inset); therefore, the synonym cementifying fibroma or cemento-ossifying fibroma often is applied

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200 Fig. 5.37 Juvenile trabecular ossifying fibroma. A histologic section of the lesion shown in Fig. 5.31. The tumor consists of cell-rich fibrous tissue and cellular osteoid or bony trabeculae. The bony spicules may exhibit irregular mineralization and may form an anastomosing network. Juvenile trabecular ossifying fibroma has a low mean age range (8.5–12 years) and a predilection for occurrence in the maxilla

Fig. 5.38 Juvenile trabecular ossifying fibroma. At higher magnification, the bone spicules typically are lined by plump osteoblasts, a key but not exclusive feature distinguishing this tumor from fibrous dysplasia. Increased osteoclast activity also is seen

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Fibro-osseous Lesions

5.3

Central Ossifying Fibroma

Fig. 5.39 Psammomatoid ossifying fibroma. A histologic section of the lesion shown in Fig. 5.32. The tumor is characterized by variably sized ossicles resembling psammoma bodies admixed with a fibrous stroma typically seen in other types of ossifying fibroma. The ossicles may vary in number from a few to innumerable, and they may fuse to form larger aggregates. There also may be intermixed woven or lamellar bony trabeculae typically rimmed by osteoblasts (right lower corner). Psammomatoid ossifying fibroma more commonly occurs in the paranasal sinuses and supraorbital frontal region, with a peak incidence in the first and second decades, although it may occur in other locations and in older individuals

Fig. 5.40 Psammomatoid ossifying fibroma. A high magnification shows ossicles with irregular contours. Fusion of the ossicles may result in reversal (cement) lines

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202 Fig. 5.41 Psammomatoid ossifying fibroma. Section of an undecalcified specimen. The ossicles commonly show an irregular osteoid rim of varying thickness. These ossicles should not be confused with the cementum-like deposits seen in conventional central ossifying fibroma or cementifying fibroma. The particles in the latter typically have a smooth contour with a lamellated arrangement but no osteoid/collagenous rim. The ossicles in psammomatoid ossifying fibroma also must be distinguished from those in extracranial psammomatous meningiomas, the psammoma bodies of which demonstrate epithelial membrane antigen positivity

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Fibro-osseous Lesions

5.4

5.4

Liposclerosing Myxofibrous Tumor

Liposclerosing Myxofibrous Tumor

Fig. 5.42 Liposclerosing myxofibrous tumor. A lytic lesion is apparent within the right femoral neck with sclerotic margins but no periosteal reaction or endosteal scalloping. The radiologic appearance is that of a nonaggressive lesion. Liposclerosing myxofibrous tumor, also known as polymorphic fibro-osseous lesion of bone, is a benign fibro-osseous lesion composed of a complex mixture of histologic elements. The tumor has a relatively characteristic radiologic appearance and skeletal distribution despite its histologic complexity, with a striking predilection for the femur, particularly the intertrochanteric region. More importantly, it appears to be associated with an increased prevalence of malignant transformation compared with fibrous dysplasia and other benign fibro-osseous lesions. Interestingly, some of the cases show mutations identical to those seen in fibrous dysplasia, thus suggesting that the tumor may represent a histologic variant of the latter

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204 Fig. 5.43 Liposclerosing myxofibrous tumor. Histologically, the tumor is characterized by a benign fibro-osseous lesion with diverse histologic elements, including lipomatous, xanthomatous, myxomatous, and fibrous dysplasia-like features; it also may show cyst formation, “ischemic” ossification, and, rarely, cartilage. This image illustrates a fibrous dysplasia-like focus. The osseous component is woven in appearance and also may demonstrate cementum-like ossicles or Paget-type bone

Fig. 5.44 Liposclerosing myxofibrous tumor. A section showing fibrous tissue with intermixed hypertrophic fat, a constantly present lesional component. Fat necrosis also may be present. Also note the subtle myxoid changes

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Fibro-osseous Lesions

5.4

Liposclerosing Myxofibrous Tumor

Fig. 5.45 Liposclerosing myxofibrous tumor. An area with features of a fibroxanthoma

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6

Giant Cell–Rich Lesions

Although the vast majority of bone/joint tumors contain giant cells, this discussion of giant cell–rich lesions is limited to entities in which the giant cells are an essential lesional component: chief among these are giant cell tumors of bone, giant cell reparative granuloma, and aneurysmal bone cysts (Chap. 8). Giant cell reparative granuloma was first described as a nonneoplastic lesion of gnathic bones in children and young adults. Thereafter, the concept of giant cell reparative granuloma of extragnathic sites (also known as giant cell reaction) has been widely recognized. Given the significant histologic overlap, many practitioners have merged giant cell reparative granuloma of extragnathic sites with the solid variant of aneurysmal bone cyst, and the neoplastic nature of these interchangeably termed entities has been supported by the identification of various translocations. In addition, several other lesions may, on occasion, have prominent giant cell elements. Of these, the benign entities principally include tenosynovial giant cell tumor (pigmented villonodular synovitis, giant cell tumor of the tendon sheath); primary hyperparathyroidism (brown tumor, osteitis fibrosa cystica); and

cherubism. Most giant cell–rich sarcomas are either osteosarcomas (Chap. 2) or malignant fibrous histiocytomas (Chap. 4). The term malignant giant cell tumor refers to a high-grade sarcoma arising in a giant cell tumor of bone (primary) or occurring at the site of a previously documented giant cell tumor (secondary). Given the largely overlapping histomorphologic features of these lesions, correlation with the clinical and radiologic characteristics of the lesion is critical to reach the correct diagnosis. In particular, involvement of a particular anatomic site (i.e., the epiphysis for giant cell tumor of bone, the mandible for cherubism), the age at presentation (i.e., skeletally mature patients for giant cell tumor of bone, children for cherubism), and multifocality (primary hyperparathyroidism) are of significant diagnostic value. Additionally, recognition of lesional components other than giant cells is crucial to avoid erroneous interpretation. As emphasized throughout this book, other entities with giant cell populations include chondroblastoma, nonossifying fibroma, and malignant fibrous histiocytoma, to name but three.

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_6, © Springer Science+Business Media New York 2013

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6.1

6

Giant Cell–Rich Lesions

Giant Cell Tumor of Bone

Fig. 6.2 Giant cell tumor of bone. The lytic lesion is centered in the metaepiphysis of the right proximal humerus of a 43-year-old woman. It extends into the greater tuberosity and distally into the proximal diaphysis. There is a wide zone of transition with endosteal scalloping along the lateral margins. No periosteal new bone formation or soft tissue mass is identified Fig. 6.1 Giant cell tumor of bone. The conventional radiograph shows an expanded lytic lesion of the right distal radius in a 34-year-old man. The lesion extends to the subarticular cartilage with sharp nonsclerotic margins and no obvious cortical breakthrough or periosteal reaction. There are internal septations, but no matrix is seen. These findings likely represent a giant cell tumor with or without underlying aneurysmal bone cyst formation

6.1

Giant Cell Tumor of Bone

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Fig. 6.4 Giant cell tumor of bone. Gross appearance of a large giant cell tumor of the radius. The tumor is tan, meaty, and uniform in distribution, with extensive central necrosis. Foci of necrosis are more commonly seen in large lesions due to infarction

Fig. 6.3 Giant cell tumor of bone with secondary aneurysmal bone cyst formation. This CT scan of a 22-year-old woman shows a large lytic lesion in the proximal tibia abutting the articular surface laterally, which has scattered internal calcific septations and matrix. There is cortical thinning of the lateral margins and bony remodeled expansion without a soft tissue mass or periosteal reaction

210 Fig. 6.5 Giant cell tumor of bone. A coronal section of a giant cell tumor of the distal femur, which represents the most common location for this tumor. Note the secondary aneurysmal bone cyst formation, as well as cortical involvement and a pathologic fracture

6

Giant Cell–Rich Lesions

6.1

Giant Cell Tumor of Bone

Fig. 6.6 Giant cell tumor of bone. The mass in the distal femur is tan-brown and variegated in appearance, with extensive areas of hemorrhage and cystic changes. The tumor extends to the articular surface of the medial femoral condyle; the medial metaphyseal cortex is interrupted

Fig. 6.7 Giant cell tumor of bone. Confluent, osteoclast-like multinucleated giant cells lie uniformly with interspersed mononuclear cells. Cytologic atypia rarely may occur but is absent in the vast majority of cases

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212 Fig. 6.8 Giant cell tumor of bone. The presence of large multinucleated cells (often containing 50–100 nuclei) is a common finding. The interspersed oval to polygonal mononuclear stromal cells have cytologic characteristics reminiscent of histiocytes. The nuclei of the mononuclear cells and those of giant cells have a similar appearance, with open chromatin and small nucleoli. The cytoplasm typically is ill defined. Mitotic figures may be abundant, but atypical mitoses are not seen. It generally is accepted that these mononuclear cells represent the neoplastic component

Fig. 6.9 Giant cell tumor of bone. Vascular invasion is not an infrequent finding in giant cell tumors, and typically is seen in small-caliber vessels in the form of “plugs of tumor cells.” The presence of vascular invasion does not warrant a diagnosis of malignant giant cell tumor, nor does it appear to be of prognostic significance

6

Giant Cell–Rich Lesions

6.1

Giant Cell Tumor of Bone

Fig. 6.10 Giant cell tumor of bone. A prominent fibrohistiocytic component. This component, when dominating the histologic appearance, may closely simulate fibrohistiocytic lesions such as nonossifying fibroma or benign fibrous histiocytoma of bone, making radiologic correlation even more critical

Fig. 6.11 Giant cell tumor of bone. A spindle cell fibrohistiocytic component. The mononuclear cells may be spindle shaped and may even be arranged in a storiform pattern. Note that there are scattered foci of bone formation

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214 Fig. 6.12 Giant cell tumor of bone. An area with prominent foam cells. Collections of xanthomatous cells also are common findings because of intracytoplasmic cholesterol deposits. The cytomorphologic variations displayed here and in Figs. 6.10 and 6.11, when combined with sparse multinucleated giant cells in selected areas, may lead to a mistaken diagnosis of nonossifying fibroma or benign fibrous histiocytoma

Fig. 6.13 Giant cell tumor of bone. The section shows cortical destruction and new bone formation. Giant cell tumors typically lack prominent matrix production; however, small foci of osteoid and woven bone invariably are present, especially in lesions associated with pathologic fracture, at the periphery or the leading edges of a soft tissue recurrence, resulting in a characteristic “eggshell” appearance on radiographs. The newly formed bone has the appearance of a reactive process with prominent osteoblastic rimming, similar to that seen in aneurysmal bone cysts (see Chap. 8)

6

Giant Cell–Rich Lesions

6.1

Giant Cell Tumor of Bone

Fig. 6.14 Giant cell tumor with secondary aneurysmal bone cyst formation. Given that both are giant cell–rich lesions, identifying the underlying giant cell tumor may be challenging. Correlation with radiographic findings is essential in such cases

Fig. 6.15 Giant cell tumor of bone. Fine-needle aspirate stained with Diff-Quik. Although the presence of numerous multinucleated giant cells in fine-needle aspirations supports a diagnosis of a giant cell–rich lesion, it is not specific for a giant cell tumor of bone. Once again, radiologic and demographic correlation is crucial

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6

Giant Cell Reparative Granuloma of Gnathic Bones1

Fig. 6.16 Giant cell reparative granuloma of the jaw (also known as central giant cell reparative granuloma). This Panorex radiograph (S. S. White Co, Holmdel, NJ) of a 15-yearold girl revealed a large expansile radiolucent lesion in the right maxilla from the maxillary midline extending posteriorly to tooth #2. Note the loss of the base (roots) of all teeth on the patient’s right maxilla

Fig. 6.17 Giant cell reparative granuloma of the jaw. Similar to its extragnathic counterpart, giant cell reparative granuloma of the jaw typically consists of randomly distributed and often clustered multinucleated giant cells and abundant mononuclear round to oval cells in a background of variably collagenized stroma. Newly formed reactive osteoid or bone is an extremely common finding. Note that brown tumor of hyperparathyroidism may have an identical radiologic and microscopic appearance, thus is in the differential diagnosis, and must be excluded by appropriate laboratory studies

1

See Chap. 8 for giant cell reparative granuloma of extragnathic sites.

Giant Cell–Rich Lesions

6.2

Giant Cell Reparative Granuloma of Gnathic Bones

Fig. 6.18 Giant cell reparative granuloma. The tumor may contain spindle-shaped stromal cells arranged in a storiform pattern. Dispersed in the background are variably sized multinucleated giant cells identical to those seen in the fibrous wall (or solid variant) of an aneurysmal bone cyst. The spindled fibroblastic cells and giant cells lack cytologic atypia

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6

Giant Cell–Rich Lesions

Malignant Giant Cell Tumor

Fig. 6.19 Malignant giant cell tumor. The CT scan shows a large humeral head destructive mass with essentially no preserved cortex

Fig. 6.21 Malignant giant cell tumor. Fat-saturated coronal T1-weighted image of the tumor seen in Fig. 6.19

Fig. 6.20 Malignant giant cell tumor. T1-weighted axial MRI of the lesion shown in Fig. 6.19 shows the lesion is remarkable for significant cystic and necrotic changes

6.3

Malignant Giant Cell Tumor

Fig. 6.22 Malignant giant cell tumor. Specimen radiograph

Fig. 6.23 Malignant giant cell tumor. Corresponding gross appearance of the tumor shown in Fig. 6.22. A coronal section of the humerus reveals an aggressive lesion extending from the joint surface distally to the humeral metadiaphysis. The joint surface is partly collapsed as a result of undermining and infiltration by the tumor. Extensive cortical destruction and soft tissue masses are evident

Fig. 6.24 Malignant giant cell tumor. Microscopic appearance of the lesion shown in Fig. 6.23. The lesion is composed of abundant giant cells and extends to the articular surface

219

220 Fig. 6.25 Malignant giant cell tumor. In areas, the tumor resembles a giant cell tumor histologically, with numerous osteoclast-like multinucleated giant cells in a background of oval, polygonal, or spindled mononuclear cells devoid of significant cytologic atypia

Fig. 6.26 Malignant giant cell tumor. The same tumor shown in Fig. 6.25 reveals a diverse histologic morphology. A low-power view of other areas shows spindle-shaped and polyhedral cells arranged in sweeping fascicles and a “herringbone” pattern

6

Giant Cell–Rich Lesions

6.3

Malignant Giant Cell Tumor

Fig. 6.27 Malignant giant cell tumor. A higher-magnification view of Fig. 6.26 shows a frankly anaplastic tumor composed of spindled cells displaying cigar-shaped to pointed nuclei with varying degrees of hyperchromasia, cells with an increased nucleus-to-cytoplasmic ratio, and bizarre mitotic figures

Fig. 6.28 Malignant giant cell tumor. A more highly magnified view shows markedly atypical stromal cells and frequent atypical mitotic features

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6.4

6

Tenosynovial Giant Cell Tumor

Fig. 6.29 Diffuse-type tenosynovial giant cell tumor (pigmented villonodular synovitis [PVNS]). An arthroscopic view of PVNS, which typically involves the synovium of large weight-bearing joints. Note the diffuse thickening of the synovial membrane, with villous-like excrescences, which may appear golden yellow to dark brown depending on whether regions are rich in lipid-laden macrophages or hemosiderin deposits

Fig. 6.30 Diffuse-type tenosynovial giant cell tumor. The synovium is involved diffusely by sheets of mononuclear cells, with scattered multinucleated giant cells and hemosiderin granules. The overlying synovial lining remains intact in this case, with enlarged cuboidal synoviocytes. Previously regarded as a reactive process in response to repeated hemorrhage, tenosynovial giant cell tumors now are considered neoplastic, given that a significant proportion of these lesions bear a recurrent translocation t(1;2) (p13;q35), linking the CSF1 gene to the COL6A3 promoter and leading to overexpression of CSF1

Giant Cell–Rich Lesions

6.4

Tenosynovial Giant Cell Tumor

Fig. 6.31 Diffuse-type tenosynovial giant cell tumor. The tumor shows diffuse infiltration of the subsynovial connective tissue in a background of variably hyalinized stroma. It is interesting to note that the mononuclear neoplastic cells carrying the translocation form a minority population in the tumor, whereas the bulk of the cells within the lesion are nonneoplastic and are recruited by the local overexpression of CSF1

Fig. 6.32 Diffuse-type tenosynovial giant cell tumor. The section shows regions of lipid-laden histiocytes, which may be scattered throughout the lesion or grouped in small clusters

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224 Fig. 6.33 Diffuse-type tenosynovial giant cell tumor. This section shows PVNS with abundant hemosiderin-laden macrophages, resulting in a dark brown–appearing synovium

Fig. 6.34 Diffuse-type tenosynovial giant cell tumor. The multinucleated giant cells seen in PVNS are variably sized and typically are randomly distributed, unlike those in giant cell tumor of bone, which are uniformly distributed

6

Giant Cell–Rich Lesions

6.4

Tenosynovial Giant Cell Tumor

Fig. 6.35 Diffuse-type tenosynovial giant cell tumor. Note the proliferation of round to polygonal cells with small nucleoli, open chromatin, and variable amounts of eosinophilic cytoplasm. Nuclear grooves are identifiable. Mitotic figures may be present but usually are rare and lack atypical forms

Fig. 6.36 Localized tenosynovial giant cell tumor (giant cell tumor of tendon sheath). With a tendency to arise in extra-articular locations, these lesions typically grow as a well-circumscribed nodule without villous projections

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226 Fig. 6.37 Localized tenosynovial giant cell tumor. The lesion possesses the same cellular population as PVNS, but without villous projections and typically without the same degree of pigment deposition

Fig. 6.38 Localized tenosynovial giant cell tumor. Note that the mononuclear cells have nuclear characteristics identical to those of multinucleated giant cells. There often is a more collagenized stroma than PVNS

6

Giant Cell–Rich Lesions

6.4

Tenosynovial Giant Cell Tumor

Fig. 6.39 Localized tenosynovial giant cell tumor. Rarely, the lesion may have few or no giant cells. The diagnosis is based largely on the gross appearance, radiographic characteristics, and architectural/ cytologic features of the lesion histologically

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Giant Cell–Rich Lesions

Hyperparathyroidism (Brown Tumor)

Fig. 6.40 Hyperparathyroidism. A conventional radiograph of brown tumors of primary hyperparathyroidism involving the hand. Note the radiolucent, well-circumscribed lesions in the proximal phalanges of the ring and little fingers. The bony lesions may be seen in virtually any skeletal location, although the lesions usually occur in cortical bone. The earliest bone changes typically are visible in the hands, particularly in the phalanges and terminal tufts. Other common sites include the mandible, clavicle, ribs, pelvis, and femur

Fig. 6.41 Hyperparathyroidism. Conventional radiograph showing brown tumors involving the distal leg and foot. The effects of primary hyperparathyroidism largely depend on the duration of the disease and the serum level of parathyroid hormone. Multifocal subperiosteal resorption is an early sign and generally is considered pathognomonic of primary hyperparathyroidism

6.5

Hyperparathyroidism (Brown Tumor)

Fig. 6.42 Hyperparathyroidism. A lateral radiograph of the knee. Subperiosteal erosive lesions of the anterior patella and proximal tibial cortex are typical of hyperparathyroidism

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230 Fig. 6.43 Hyperparathyroidism. A conventional radiograph of the skull illustrating multiple lucent lesions in a patient with primary hyperparathyroidism. The differential diagnosis, which is heavily influenced by the patient’s age, largely includes metastasis and multiple myeloma in elderly individuals and Langerhans cell histiocytosis and fibrous dysplasia in children/ young adults. An infectious etiology also should be excluded

Fig. 6.44 Hyperparathyroidism. This Panorex scan of the mandible shows diffuse osteopenia with a focal osteolytic lesion within the body of the left mandible. Note the floating appearance of the posterior molars. In addition, there is loss of the normal lamina dura surrounding the teeth, a finding characteristic of hyperparathyroidism

6

Giant Cell–Rich Lesions

6.5

Hyperparathyroidism (Brown Tumor)

231

Fig. 6.46 Hyperparathyroidism. Axial CT scan of the sacroiliac joints. Note the radiolucent lesions of the bilateral ilia and erosions of the subchondral bone of the iliac aspect of the sacroiliac joints

Fig. 6.45 Hyperparathyroidism. The CT scan reveals an expansile lesion arising from the left maxilla, extending into the left nasal cavity and left maxillary sinus. There are heterogeneous lesional contents identified with multiple septations

232 Fig. 6.47 Hyperparathyroidism. Low-power magnification shows markedly irregular bony trabeculae that have been actively remodeled. The normal marrow spaces are replaced by tremendous fibrosis

Fig. 6.48 Hyperparathyroidism. Dissecting osteitis or “tunneling” resorption. This finding, along with peritrabecular fibrosis, represents the classic histologic appearance of longstanding hyperparathyroidism. One can appreciate the cyst walls seemingly on both sides of the bone (osteitis fibrosa cystic)

6

Giant Cell–Rich Lesions

6.5

Hyperparathyroidism (Brown Tumor)

Fig. 6.49 Hyperparathyroidism. Tunneling resorption and peritrabecular fibrosis. The fibrovascular connective tissue largely replaces the bony trabeculae and peritrabecular spaces

Fig. 6.50 Hyperparathyroidism. Higher magnification of a brown tumor shows active tunneling resorption

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234 Fig. 6.51 Hyperparathyroidism. Although osteoclast-type multinucleated giant cells invariably are present and may be the dominant feature in areas, these cells typically are unevenly distributed and vary in size, contrary to those in giant cell tumors of bone. Hemorrhage and hemorrhagic debris may be prominent, hence the term brown tumor

Fig. 6.52 Hyperparathyroidism. The preexisting bone is largely replaced by spindled fibroblasts. Reactive new bone frequently is present owing to active bone remodeling

6

Giant Cell–Rich Lesions

6.6

6.6

Cherubism

Cherubism

Fig. 6.53 Cherubism. This histologic appearance of cherubism is that of a benign fibro-osseous lesion histologically indistinguishable from giant cell reparative granuloma. The diagnosis is based largely on genetic counseling (childhood disease with an autosomal dominant hereditary pattern) and clinical characteristics (symmetric expansion of the jaws with a predilection for the mandible, resulting in a cherubic facial appearance)

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7

Small, Round Cell Lesions

Small, round cell lesions encompass a broad spectrum of entities, including reactive and inflammatory processes, benign neoplasms, and malignant tumors. Osteomyelitis is among the most common nonneoplastic conditions and denotes an inflammation of bone and bone marrow, commonly caused by bacteria (pyogenic osteomyelitis), although it may be produced by any type of organism. The incidence of small, round cell tumors of bone is tightly linked to the age at presentation, with Ewing sarcoma/primitive neuroectodermal tumor (PNET) and Langerhans cell histiocytosis (LCH) being the most common entities in young individuals. In contrast, hematologic neoplasms (myeloma and lymphoma)

constitute approximately 40 % of all bone tumors but occur almost exclusively in adults, especially elderly patients. Most entities included in this chapter are those of traditional small, blue, round cell tumors that produce minimal extracellular matrix, such as Ewing sarcoma/PNET and hematologic neoplasms, whereas others, such as LCH and Rosai-Dorfman disease, tend to be composed of mixed-cell populations. Several other tumors with small, round cell histomorphology, either those that occur primarily in bone (e.g., small cell osteosarcoma and mesenchymal chondrosarcoma) or metastases from other organs (e.g., neuroblastoma and most rhabdomyosarcomas), are discussed in other chapters.

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_7, © Springer Science+Business Media New York 2013

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7.1

Benign, Reactive, Inflammatory

7.1.1

Osteomyelitis

Fig. 7.1 Osteomyelitis. This conventional radiograph shows a cortically based lesion along the posterior aspect of the mid-tibial shaft, with a few small central areas of lucency that contain a small amount of amorphous calcification. Both the periosteal and endosteal surfaces are smooth, with no scalloping or aggressive periosteal changes. The radiographic appearance is typical of a Brodie abscess, a small intraosseous abscess frequently involving the cortex and walled off by reactive bone. Less likely differential diagnoses also include osteoid osteoma and a low-grade parosteal osteosarcoma

Small, Round Cell Lesions

Fig. 7.2 Osteomyelitis. Coronal magnetic resonance (MR) images of the lesion shown in Fig. 7.1. There is a focal area of abnormal low T1 (left)/high T2 (right) signal in the mid–right tibial diaphysis adjacent to an area of cortical thickening. Within this lesion, there is a multilobulated lesion that shows moderate enhancement. Adjacent soft tissues show minimal reactive edema. The findings are mostly consistent with a subacute osteomyelitis/Brodie abscess

7.1

Benign, Reactive, Inflammatory

Fig. 7.3 Osteomyelitis. A below-the-knee amputation showing longstanding chronic osteomyelitis in a patient with a posttraumatic fracture, a condition also known as infected nonunion (defined as a state of failure of union and persistence of infection at the fracture site for 6–8 months)

239

Fig. 7.4 Osteomyelitis. Chronic osteomyelitis involving the distal tibia and the tract of an intramedullary metallic rod, another example of an infected nonunion

240 Fig. 7.5 Osteomyelitis. The histologic findings of osteomyelitis depend on the stage (acute, subacute, and chronic). This image shows an example of acute pyogenic osteomyelitis involving the femur of a child. Note the bacterial colonies and abundant neutrophils forming the abscess. Pyogenic osteomyelitis is almost always caused by bacteria and usually affects long tubular bones of children. Hematogenous spread is the common route. The entrapped bone typically undergoes necrosis within the first 48 h, and the dead bone is known as a sequestrum. A draining sinus may be present when the periostium is ruptured, and a soft tissue abscess is formed. The subperiosteal new bone formed later around the devitalized infected bone is known as the involucrum

Fig. 7.6 Osteomyelitis. Less commonly, osteomyelitis may be caused by direct extension associated with trauma or iatrogenic implantation of infectious materials. This photomicrograph shows an example of osteomyelitis involving cortical bone through direct extension from a skin and deep soft tissue infection

7

Small, Round Cell Lesions

7.1

Benign, Reactive, Inflammatory

Fig. 7.7 Osteomyelitis. Acute osteomyelitis showing incapacitating bone destruction

Fig. 7.8 Osteomyelitis. Subacute osteomyelitis demonstrating mixed acute and chronic inflammatory infiltrates

241

242 Fig. 7.9 Osteomyelitis. After approximately 1 week, chronic inflammatory cells become predominant and release cytokines that stimulate osteoclast formation and bone resorption, subsequently inducing active bone remodeling. Fibrosis of marrow typically becomes apparent in the chronic stage. The disease has been called plasma cell osteomyelitis when plasma cells are particularly predominant and xanthogranulomatous osteomyelitis when foamy histiocytes are abundant

Fig. 7.10 Osteomyelitis. Active osteoclastic bone resorption and new bone formation in chronic osteomyelitis

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Small, Round Cell Lesions

7.1

Benign, Reactive, Inflammatory

Fig. 7.11 Osteomyelitis. Reactive new bone formation in chronic osteomyelitis

Fig. 7.12 Sclerosing osteomyelitis of Garré. Osteomyelitis may develop with extensive new bone formation that obscures the underlying osseous structure. This variant sometimes is referred to as sclerosing osteomyelitis of Garré (also known as periostitis ossificans) and is particularly common in gnathic bones

243

244 Fig. 7.13 Sclerosing osteomyelitis of Garré. Another example with extensive regenerative bone changes

Fig. 7.14 Fungal (mycotic) osteomyelitis. A section showing fungal osteomyelitis caused by Aspergillus species. Fungal osteomyelitis is uncommon and typically results from hematogenous spread, direct inoculation from trauma or a surgical procedure, or direct extension from an adjacent infection. Immunocompromised patients are predisposed to fungal osteomyelitis

7

Small, Round Cell Lesions

7.1

Benign, Reactive, Inflammatory

Fig. 7.15 Fungal (mycotic) osteomyelitis. Blastomycosis of bone. Note the yeast cells undergoing broad-based budding and granulomatous inflammation

Fig. 7.16 Syphilitic osteomyelitis. This condition may be seen in congenital syphilis and, less frequently, in acquired syphilis that involves bone in the tertiary phase. The histologic findings are nonspecific but typically show a granulomatous process, necrotic bone, and new bone formation

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7.1.2

7

Langerhans Cell Histiocytosis (Histiocytosis X, Eosinophilic Granuloma)

Fig. 7.17 Langerhans cell histiocytosis. A conventional radiograph showing a proximal femoral lesion in a 16-year-old boy. The lesion is lytic and expansile with well-defined margins. LCH of bone has a wide age distribution but occurs mostly in children, with a male predilection (2:1). This is in contrast to pulmonary LCH, in which female smokers predominate. Any bone may be involved, but craniofacial bones prevail followed by long bones. Most lesions are medullary and lytic, and have well-defined margins

Small, Round Cell Lesions

7.1

Benign, Reactive, Inflammatory

Fig. 7.18 Langerhans cell histiocytosis. Low-power magnification demonstrating a cellular lesion with loose aggregates of multinucleated giant cells in a mixed inflammatory background with prominent eosinophils

Fig. 7.19 Langerhans cell histiocytosis. The mononuclear cells (Langerhans cells) are histiocytic-appearing, with indistinct cell borders, clear to eosinophilic cytoplasm, and vesicular nuclei with occasional nuclear grooves. Multinucleated giant cells are seen frequently and may be prominent in areas

247

248 Fig. 7.20 Langerhans cell histiocytosis. A section showing collections of eosinophils (a so-called eosinophilic abscess). Note that the Langerhans cells may mimic Reed-Sternberg cells. This, along with the abundant eosinophils, may result in confusing the lesion with Hodgkin lymphoma

Fig. 7.21 Langerhans cell histiocytosis. At higher magnification, the Langerhans cells have ovoid, coffee bean, or reniform nuclei, with frequent longitudinal nuclear grooves and small inconspicuous nucleoli. Mitotic activity may be brisk, but atypical forms are not present

7

Small, Round Cell Lesions

7.1

Benign, Reactive, Inflammatory

Fig. 7.22 Langerhans cell histiocytosis. A touch preparation imprint shows a group of cells with characteristic nuclear grooves

Fig. 7.23 Langerhans cell histiocytosis. Langerhans cells are immunoreactive for S-100 protein in both nuclear and cytoplasmic patterns, a sensitive but not specific marker for the diagnosis

249

250 Fig. 7.24 Langerhans cell histiocytosis. CD1a immunoreactivity in a distinct membranous pattern (as illustrated) is more specific for Langerhans cells. Langerin (CD207) is another specific marker for this lesion. The ultrastructural finding of unique intracytoplasmic inclusions (known as Birbeck granules) is diagnostic but usually not necessary for the diagnosis

7

Small, Round Cell Lesions

7.1

Benign, Reactive, Inflammatory

7.1.3

251

Mastocytosis

Fig. 7.25 Mastocytosis. Mastocytosis is manifested by an abnormal growth and accumulation of mast cells in one or more organ systems. Although it most commonly manifests as a cutaneous disease in children, systemic mastocytosis generally is diagnosed after the third decade, with bone marrow being the site most commonly affected other than skin. The radiographic findings are variable and may show diffuse osteoporosis or focal osteolysis and osteosclerosis. Bone marrow biopsy

typically shows multifocal, sharply demarcated, paratrabecular or perivascular aggregates of mast cells resembling microgranulomas, as depicted in this photomicrograph. The marrow spaces may be focally or diffusely replaced by mast cells, which frequently are associated with significant fibrosis and thickening of the adjacent bone. The proliferative mast cells may become so spindled that they mimic fibroblasts

252 Fig. 7.26 Mastocytosis. At higher magnification, the histomorphologic appearance of mastocytosis is variable. The neoplastic cells may closely resemble normal mast cells. However, more frequently they are oval or spindled and have reniform or indented nuclei and clear to pale eosinophilic cytoplasm with sparse granules, thus mimicking histiocytes or the cells of hairy cell leukemia

Fig. 7.27 Mastocytosis. A Giemsa-stained sample showing cytoplasmic granules in the cells of mastocytosis. The most specific marker for identification of mast cells is mast cell tryptase. Other markers include napthol AS-D chloroacetate esterase and c-Kit (CD117), which also are characteristic of, but not specific for, mast cells

7

Small, Round Cell Lesions

7.1

Benign, Reactive, Inflammatory

7.1.4

253

Sinus Histiocytosis with Massive Lymphadenopathy (Rosai-Dorfman Disease)

Fig. 7.28 Rosai-Dorfman disease. A 44-year-old woman who had progressive pain in her right knee and right distal thigh over several months underwent radiologic evaluation. A conventional radiograph shows a multifocal lucent lesion of bone with a solidified lamellated periosteal reaction in the distal femoral diametaphysis, with posterior cortical invasion and a subtle soft tissue mass displacing the adjacent posterior fat plane. This condition primarily affects lymph nodes throughout the body, most commonly in the neck, with or without concurrent extranodal involvement. However, the extranodal manifestations may be the first or exclusive presentation of the disease, as in this case. Primary Rosai-Dorfman disease of bone has been reported in only a handful of patients

Fig. 7.29 Rosai-Dorfman disease. A sagittal MR image showing the distal femoral osseous lesion seen in Fig. 7.28, with soft tissue mass enhancement

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Small, Round Cell Lesions

Fig. 7.30 Rosai-Dorfman disease. Axial CT images of the lesion seen in Fig. 7.28 demonstrating an intramedullary lucent lesion with cortical disruption and a soft tissue component seen posteriorly

Fig. 7.31 Rosai-Dorfman disease. At lower magnification, the lesion is characterized by pale-appearing zones composed of large, foamy cells intermixed with small, blue round cells

7.1

Benign, Reactive, Inflammatory

Fig. 7.32 Rosai-Dorfman disease. At intermediate power, the lesion is remarkable for sheets of histiocytes with clear to pale eosinophilic cytoplasm with alternating aggregates of lymphocytes, plasma cells, and neutrophils. Emperipolesis (penetration by one cell into and through a larger cell), a constant feature of (but not specific for) Rosai-Dorfman disease, can be appreciated at this power. The histiocytes contain cytoplasmic fat and are immunoreactive for S-100 protein but negative for CD1a, a feature useful in distinguishing the diagnosis from LCH

Fig. 7.33 Rosai-Dorfman disease. A high magnification illustrating emperipolesis. The cells phagocytized by histiocytes commonly are lymphocytes (lymphocytophagocytosis). Other cell types, such as plasma cells, neutrophils, and red blood cells, also may be present within the cytoplasm of the histiocytes

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256 Fig. 7.34 Rosai-Dorfman disease. A Diff-Quik–stained fine-needle aspiration biopsy sample showing collections of histiocytes with emperipolesis

7

Small, Round Cell Lesions

7.1

Benign, Reactive, Inflammatory

7.1.5

Sarcoidosis

Fig. 7.35 Sarcoidosis. About 10 % of patients with systemic sarcoidosis develop musculoskeletal manifestations. Sarcoidosis of the bone is often difficult to diagnose radiologically, as these lesions may be small and have the appearance of other bone disorders. The characteristic histologic features are nonnecrotizing granulomas that contain epithelioid histiocytes, as illustrated in this image. However, the histologic diagnosis of sarcoidosis is one of exclusion, because a variety of other conditions, including infections and neoplasms, also are associated with granulomas

Fig. 7.36 Sarcoidosis. The histiocytes often fuse to form multinucleated giant cells. The granulomas in sarcoidosis may resolve spontaneously without complications or heal with residual fibrosis

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7.1.6

7

Xanthoma

Fig. 7.37 Xanthoma. Xanthomas of bone are rare and usually are well-defined, solitary, lytic lesions, often with sclerotic borders. Histologically, the lesion is composed of sheets of foam cells. Cholesterol clefts and multinucleated giant cells frequently are present. The differential diagnosis includes Rosai-Dorfman disease, LCH, nonossifying fibroma/benign fibrous histiocytoma, and, rarely, liposclerosing myxofibrous tumor. The findings also may represent changes secondary to other conditions. Thus, radiologic correlation is critical, especially in small biopsy specimens

Small, Round Cell Lesions

7.2

Malignant

7.2

Malignant

7.2.1

Lymphoma

259

Fig. 7.39 Lymphoma. An axial CT image from a 64-year-old woman showing a lytic and expansile lesion in the T6 vertebral body that subsequently was shown to be a B-cell lymphoma

Fig. 7.38 Lymphoma. A conventional radiograph demonstrates a comminuted fracture of the mid-left femoral diaphysis in a 67-year-old man, with the associated permeative destructive appearance of a malignant lymphoma. Lymphoma of bone may be either a primary process or a manifestation of a systemic disease. Primary lymphoma of bone accounts for approximately 7 % of malignant bone tumors, and 5 % of all extranodal lymphomas originate in bone. The femur is the most common site, followed by the spine and pelvic bones. Lymphoma of bone may occur at a single anatomic site or involve multiple bones. Radiologically, the tumors usually are poorly defined, lytic, sclerotic, or mixed lesions with a permeative growth pattern, but these features are nonspecific

260 Fig. 7.40 Lymphoma. MRI studies (left, Sagittal T1; right, Sagittal STIR) of the lesion seen in Fig. 7.39 demonstrating a T1-hypodense lesion with an associated pathologic compression fracture

7

Small, Round Cell Lesions

7.2

Malignant

Fig. 7.41 Lymphoma. Resected femoral specimen from a 73-year-old man with a history of chronic lymphocytic leukemia. A pathologic fracture in the distal femur is evident. It extends diagonally across the posterior surface and creates a large defect. Further examination showed a mass that completely filled the marrow and spilled out from the adjacent cortical bone, which, upon histologic examination, revealed a diffuse large B-cell lymphoma

261

262 Fig. 7.42 Lymphoma. Most lymphomas involving bone are diffuse large B-cell lymphomas. Histologically, the tumor typically infiltrates the marrow spaces and the haversian system in a permeative pattern. The normal structures typically remain intact

7

Small, Round Cell Lesions

7.2

Malignant

Fig. 7.43 Lymphoma. Rarely, the tumor may present as a destructive lesion, as in this case

Fig. 7.44 Lymphoma. At higher magnification, diffuse large B-cell lymphomas typically have large, round, noncleaved nuclei. Mitotic figures may be brisk

263

264 Fig. 7.45 Lymphoma. Crush artifact commonly is seen in biopsy specimens, which may obscure the cytologic features of the lymphoma cells. This, along with the presence of focal reactive new bone formation, may cause confusion with osteosarcoma

Fig. 7.46 Lymphoma. T-cell lymphomas of bone are rare but do occur. This photomicrograph illustrates an example of an anaplastic large cell lymphoma. Note the markedly large nuclei with significant pleomorphism. The tumor cells are immunoreactive with anaplastic lymphoma kinase antibodies (inset)

7

Small, Round Cell Lesions

7.2

Malignant

Fig. 7.47 Lymphoma. Extranodal Burkitt lymphomas commonly involve bone. In endemic Burkitt lymphoma, the jaws and other facial bones are the site of presentation in about 50 % of cases. In immunodeficiency-associated Burkitt lymphomas, bone marrow involvement is frequent. Note the abundant macrophages that have ingested apoptotic tumor cells, imparting a prominent starry sky pattern

Fig. 7.48 Leukemia. The diagnosis of leukemia typically is rendered by bone marrow aspirate and peripheral smears, along with flow cytometry and cytogenetic analysis. This image depicts an example of acute myeloid leukemia within the medullary cavity of a long bone

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7.2.2

7

Small, Round Cell Lesions

Plasmacytoma/Plasma Cell Myeloma

Fig. 7.50 Plasmacytoma/myeloma. A CT image showing an expansible, radiolucent lesion involving the right acetabulum and ischium of a 51-year-old man. There is minimal lesional matrix and no soft tissue mass. Again, the differential diagnosis includes metastasis and, less likely, fibrous dysplasia and a low- grade cartilage lesion

Fig. 7.49 Plasmacytoma/plasma cell myeloma. This conventional radiograph shows a well-defined lytic lesion in the proximal middle right femur of a 72-year-old man. No internal matrix is seen. The appearance is most consistent with a plasmacytoma/myeloma or metastasis. Plasmacytoma/myeloma typically manifests as one or more small osteolytic lesions causing bone pain. These two entities are cytologically and immunophenotypically identical. The term plasmacytoma is used when the lesion manifests as a localized, solitary osseous (or extraskeletal) lesion, whereas plasma cell myeloma (traditionally known as multiple myeloma) is diagnosed by the presence of M protein in serum or urine, bone marrow–derived clonal plasma cells or known plasmacytoma, and related end-organ damage (e.g., hypercalcemia, renal insufficiency, anemia, bone lesions), according to World Health Organization criteria

7.2

Malignant

267

Fig. 7.51 Plasmacytoma/myeloma. There are numerous round radiolucencies involving the calvarium, consistent with myelomatous osseous involvement. The tumor may involve any bone with active hematopoiesis

Fig. 7.53 Plasmacytoma/myeloma. There are diffuse osteoporosis and multifocal lytic lesions throughout the spine, resulting in vertebral body collapse (most severe at the T3 level) and multiple end-plate deformities. This constellation of findings is most consistent with myeloma, although diffuse metastatic disease may have a similar appearance

Fig. 7.52 Plasmacytoma/myeloma. A skeletal survey in a patient with a known history of plasma cell myeloma shows multiple small radiolucencies in both iliac and ischial bones of the pelvis. There also is diffuse osteopenia. Myelomas are characterized by multiple lytic bone lesions but also may present as “generalized osteoporosis” with no detectable foci of discrete bone destruction

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Small, Round Cell Lesions

Fig. 7.54 Plasmacytoma/myeloma. The lesion(s) may cause pathologic fractures that necessitate surgical resection. A coronal section of a femoral head shows multiple lesions in a patient with a known history of multiple myeloma

Fig. 7.55 Plasmacytoma/myeloma. A cross-section of the proximal femur demonstrates a hemorrhagic lesion replacing the cancellous bone

7.2

Malignant

Fig. 7.56 Plasmacytoma/ myeloma. Histologically, the tumor typically is a cellular lesion devoid of matrix production. The cells have small, round nuclei but generally contain abundant cytoplasm

Fig. 7.57 Plasmacytoma/ myeloma. At higher magnification, the tumor consists of a relatively uniform population of cells in contrast to most malignant lymphoma cases. The plasma cells commonly are well-differentiated, with eccentrically located nuclei, a characteristic clumped (clockface-like) chromatin pattern, and a perinuclear hof (large Golgi bodies)

269

270 Fig. 7.58 Plasmacytoma/ myeloma. A Diff-Quik–stained fine-needle aspiration specimen demonstrates plasma cells displaying eccentrically placed nuclei. A perinuclear clear zone (hof) exists in some cells. Note the binucleated plasma cell. Scattered in the background are naked plasma cell nuclei with the same clumped chromatin pattern. Nuclear pseudoinclusions (invaginations of cytoplasm into the nuclei) also may be seen

Fig. 7.59 Plasmacytoma/ myeloma. Poorly differentiated tumors may show significant cytologic atypia, and thus the plasma cell origin of the lesion cannot be recognized easily. In such cases, the plasma cell nature is best demonstrated by the strong and diffuse membranous staining pattern of CD138 (inset). Of importance, CD138 is highly sensitive but not specific to plasma cells unless a diagnosis of hematologic neoplasm has been established

7

Small, Round Cell Lesions

7.2

Malignant

Fig. 7.60 Plasmacytoma/myeloma. The clonal nature of the plasma cell neoplasms is best identified by immunostaining (left) or in situ hybridization analysis (right) for kappa and lambda light chains. This case represents a kappa-restrictive plasma cell myeloma. Historically,

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the monoclonal proliferation of plasma cells, whether they are malignant or benign (e.g., plasma cell myeloma, solitary plasmacytoma, or monoclonal gammopathy of undetermined significance), has been collectively termed plasma cell dyscrasia

272 Fig. 7.61 Plasmacytoma/ myeloma. In some case, amyloid may be formed as characteristic masses of amorphous eosinophilic aggregates, which may result in a foreign-body giant cell reaction, as depicted in the figure. Amyloid deposits may become so prominent that they overwhelm the plasma cell proliferation and appear as a mass lesion (so-called amyloid tumor or amyloidoma)

Fig. 7.62 Plasmacytoma/ myeloma. Congo red–stained amyloid deposits (AL; amyloid light chain) show characteristic apple-green birefringence in polarized light

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Small, Round Cell Lesions

7.2

Malignant

Fig. 7.63 Plasmacytoma/ myeloma. The amyloid deposits in a plasma cell dyscrasia may be distant from the plasma cell proliferation. Note there is an abnormal plasma cell proliferation in the marrow spaces in this bone marrow biopsy, whereas subtle amorphous eosinophilic materials are noted in the adjacent cortex

Fig. 7.64 Plasmacytoma/ myeloma. Congo red stain in the bone marrow biopsy sample shown in Fig. 7.63 highlights the amyloid deposits in the cortex, which demonstrates apple-green birefringence in polarized light (inset)

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7.2.3

7

Ewing Sarcoma/Primitive Neuroectodermal Tumor (PNET)

Fig. 7.65 Ewing sarcoma. A conventional radiograph (left) and coronal CT image (right) of the femur of a 12-year-old boy demonstrate an intramedullary lesion in the proximal left diaphysis extending to the physis of the greater trochanter. There is a solidifying lamellated periosteal reaction (onion-skinning) caused by successive layers of periosteal development. The Ewing sarcoma/ PNET family of tumors originally was thought to be two separate entities, with the latter demonstrating neuroectodermal differentiation as assessed by light microscopy, immunohistochemistry, or electron microscopy. It now is generally accepted that this family set of tumors are histologic variants of the same tumor spectrum because of the common genetic abnormalities, which are described later. Thus, it is relatively unimportant to designate a particular tumor as Ewing sarcoma or PNET

Small, Round Cell Lesions

7.2

Malignant

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Fig. 7.66 Ewing sarcoma. An axial CT image of the lesion seen in Fig. 7.65 demonstrates cortical erosion and significant cortical thickening. A soft tissue mass in the medial aspect is apparent. Ewing sarcoma may be seen at any age but occurs mostly in the first two decades of life and is the second most common pediatric bone malignancy after osteosarcoma. It also has a strong predilection for Caucasians. The classic location is the diaphysis or metaphysis of long, tubular bones, although it also may arise in the axial bones, such as the pelvis and ribs. Typically, the lesion presents as a permeative, intramedullary, osteolytic lesion and penetrates the cortex into the surrounding soft tissue as it progresses. Active periosteal reaction manifested as multilayered new bone formation, when present, is characteristic and gives rise to the onionskin appearance on conventional radiographs

Fig. 7.67 Ewing sarcoma. A below-the-knee amputation specimen from a patient after neoadjuvant chemotherapy for Ewing sarcoma. A sagittal transmural section shows a large mass in the distal tibia, most of which is in a subperiosteal location that erodes the underlying cortex (saucerization of bone)

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Fig. 7.68 Ewing sarcoma. A resected femoral specimen showing a complete response to neoadjuvant chemotherapy. Histologic examination revealed a necrotic tumor replaced by acellular fibrosis. Note the significant cortical thickening with a sinus tract

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Small, Round Cell Lesions

7.2

Malignant

Fig. 7.69 Ewing sarcoma. Histologically, the tumor typically appears to be solid sheets of uniform small, blue, round cells with a vascular-rich stroma. Extracellular matrix, if any, is minimal

Fig. 7.70 Ewing sarcoma. The tumor grows in a destructive fashion with prominent reactive new bone formation, resulting in an onion-skin appearance on radiography

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278 Fig. 7.71 Ewing sarcoma. At higher magnification, the neoplastic cells are slightly larger than normal lymphocytes and have fine chromatin with or without inconspicuous nucleoli, scant cytoplasm, and indistinct cell borders. Perivascular rosettes and Homer-Wright–type pseudorosettes (tumor cells surrounding a central core filled with eosinophilic extracellular material) may be seen in this image. The tumor cells frequently have cytoplasmic glycogen, which may be highlighted by periodic acid–Schiff staining

Fig. 7.72 Ewing sarcoma. A subpopulation of cells showing dense chromatin thought to represent degenerative changes or undergoing apoptosis. Geographic necrosis commonly is seen, frequently with a perivascular distribution of viable cells

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Small, Round Cell Lesions

7.2

Malignant

Fig. 7.73 Ewing sarcoma. A Diff-Quik–stained fine-needle aspiration specimen displaying characteristic coarse cytoplasmic vacuoles due to their glycogenrich cytoplasm. The presence of dimorphic, darker-stained (lymphocyte-like), and lighterstained (blastemic) cells is another classic feature that corresponds to the “light” and “dark” cells seen on ultramicroscopy

Fig. 7.74 Ewing sarcoma. Rare histologic variants include a sclerosing type (with hyalinized eosinophilic matrix as depicted), spindle cell sarcoma–like, large cell (atypical Ewing sarcoma), and adamantinoma-like

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280 Fig. 7.75 Ewing sarcoma. A large cell variant or atypical Ewing sarcoma. Note that the tumor cells are larger and more pleomorphic than the classic type. Mitotic figures may be discernible but are not abundant compared with the relatively dense cellularity

Fig. 7.76 Ewing sarcoma. Diffuse membranous expression of CD99 is characteristic of Ewing sarcoma/PNET but not specific

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Small, Round Cell Lesions

7.2

Malignant

Fig. 7.77 Ewing sarcoma. Most Ewing sarcomas (85–95 %) result from a recurrent t(11;22)(q24; q12) chromosomal translocation, which fuses the EWS gene on chromosome 22 and the FLI-1 gene on chromosome 11. Nuclear FLI-1 expression is seen in most Ewing sarcoma cases, as depicted in this image. Note that endothelial cells are strongly positive and serve as an internal control. Importantly, FLI-1 protein expression is not entirely specific for Ewing sarcoma, and it also is expressed in the great majority of lymphoblastic lymphomas, which also are CD99 positive.

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However, FLI-1 may be useful to distinguish Ewing sarcoma from smallcell osteosarcoma and mesenchymal chondrosarcoma, two other small, round, blue cell tumors of bone in children. The second most common translocation (5–10 %) is t(21;22)(q12;q12), which gives rise to the fusion of EWS to ERG. Other rare variant translocations (<1 %) are t(7;22) (p22;q12), t(17;22)(q12;q12), t(2;22)(q23;q12), and inv(22), resulting in the fusion of EWS to ETV1, E1AF, FEV, and ZSG genes, respectively. Thus, it is not surprising that some Ewing sarcomas are FLI-1 negative

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Fig. 7.78 Ewing sarcoma. Fluorescence in situ hybridization (FISH) analysis for chromosome rearrangements involving the EWS gene using a dual-color, break-apart probe is highly specific for Ewing sarcomas in the appropriate clinicopathologic setting, with variable sensitivities ranging from 50 to 90 %. In this technique, the red and green probes each bind to sequences upstream and downstream of the loci of interest. In normal interphase nuclei, only the secondary color (yellow) is observed. In a neoplastic cell carrying a reciprocal translocation, one of the yellow signals splits, resulting in separated primary color (red and

Fig. 7.79 Ewing sarcoma. Rarely, Ewing sarcomas may show cytokeratin expression as illustrated, a pitfall in the diagnosis. Again, clinical correlation, along with other ancillary modalities, is crucial in reaching the correct diagnosis

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Small, Round Cell Lesions

green) signals in addition to the yellow signal from the normal chromosome. Other sarcomas involving the EWS gene, including desmoplastic small round cell tumor [t(11;22)(p13;q12)], clear cell sarcoma [t(12;22) (q13;q13)], and extraskeletal myxoid chondrosarcoma [t(9;22) (q22;q12)], also may be detected by FISH analysis utilizing the same break-apart probe. However, these entities typically are not encountered in the differential diagnosis of Ewing sarcoma clinically and/or histologically

8

Cysts

The primary cystic lesions in bone include aneurysmal bone cysts, unicameral bone cysts, and, rarely, intraosseus ganglion cysts. Aneurysmal bone cyst is a rapidly growing, locally destructive lesion that affects all age groups and may affect any bone. It occurs more commonly during the first two decades of life. Most aneurysmal bone cysts occur in the metaphysis of long bones, followed by the posterior elements of vertebral bodies. Traditionally regarded as a reactive process, it now is generally accepted that primary aneurysmal bone cysts are neoplastic in nature, given that a significant proportion of cases demonstrate recurrent chro-

mosomal alterations resulting in rearrangements of the USP6 gene on the short arm of chromosome 17, whereas these cytogenetic abnormalities are absent in all secondary aneurysmal bone cysts, that is, those associated with another primary tumor, such as giant cell tumor of bone. Unicameral bone cyst, also known as simple bone cyst or solitary bone cyst, likewise commonly affects skeletally immature individuals, but is considered likely to be reactive or developmental in nature. An intraosseous ganglion cyst almost always occurs at the ends of long bones, and appears to be connected to the nearby joint.

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Aneurysmal Bone Cyst

Fig. 8.1 Aneurysmal bone cyst. Conventional radiograph showing a lytic lesion in the proximal right tibia of a 17-year-old boy. The lesion is located in the medial aspect and extends close to the articular surface of the tibia. No lesional content is identified. The physes are closed. Although the major radiologic consideration is that of a giant cell tumor, an aneurysmal bone cyst arising in the metaphysis rarely may extend to the epiphysis

Cysts

8.1

Aneurysmal Bone Cyst

Fig. 8.2 Aneurysmal bone cyst. A laterally eccentric lytic lesion in the distal tibial diametaphysis is identified that abuts the distal tibial physeal plate, with minimal surrounding sclerosis and remodeled expansion. The lesion appears to contain faint intrinsic/ internal septations. The radiographic differential diagnosis also includes a nonossifying fibroma and eccentric focal fibrous dysplasia, or, less likely, a giant cell tumor of bone

Fig. 8.3 Aneurysmal bone cyst. CT image of a large destructive lesion in the right acetabulum of a 15-year-old boy. Although aneurysmal bone cysts usually arise in the metaphysis of long bones (especially the femur, tibia, and humerus), they may affect any bone. This expansile, heterogenous, lytic lesion demonstrates multiple fluid levels. This appearance is mostly consistent with an aneurysmal bone cyst, although a telangiectatic osteosarcoma cannot entirely be excluded

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Fig. 8.4 Aneurysmal bone cyst. MRI reveals a 4.4-cm, mildly expansile lesion of the left proximal humerus in a 7-year-old boy. The lesion shows a low to intermediate signal on the axial T1-weighted image (similar to the muscle signal)

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Cysts

Fig. 8.6 Aneurysmal bone cyst. Conventional radiograph showing a primary aneurysmal bone cyst in the jaw of a 4-year-old boy. The lesion presents as an enlarging central mandibular mass. The inability of the pre-schooler to “hold-still” resulted in the multiple artifactual overlapping gnathic images

Fig. 8.7 Aneurysmal bone cyst. Gross appearance of an aneurysmal bone cyst of the mandible (see Fig. 8.6). Multiple blood-filled cystic areas are seen scattered around the perimeter of the mass lesion

Fig. 8.5 Aneurysmal bone cyst. A fat-saturated axial T2 image of the lesion shown in Fig. 8.4 reveals a bright fluid signal. Cystic lesions containing two types of fluids, such as edematous fluid and blood or proteinaceous fluid and fat, may create layering. This results in the socalled fluid–fluid layer characteristic of such lesions

8.1

Aneurysmal Bone Cyst

Fig. 8.8 Aneurysmal bone cyst. A low-power view shows blood-filled spaces surrounded by fibrous septa containing numerous multinucleated giant cells

Fig. 8.9 Aneurysmal bone cyst. The cyst spaces may collapse when thin-walled lesions are curetted. Often, the blood is washed off during tissue processing, resulting in thin fibrous membranes containing spindled fibroblastic cells and multinucleated giant cells. Amorphous collagen, osteoid, or partially mineralized bone also may be appreciated

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288 Fig. 8.10 Aneurysmal bone cyst. The fibrous septa consist of spindled fibroblasts without atypia and abundant osteoclasttype multinucleated giant cells, with intermixed inflammatory cells and reactive new bone. Hemosiderin deposition is a common finding. Note that the aneurysmal bone cyst is not a true cyst, owing to the absence of an epithelial or endothelial lining

Fig. 8.11 Aneurysmal bone cyst. Osteoid/reactive new bone formation is a common finding and almost invariably is seen in the fibrous septa, typically in the form of lace-like, thin strands separated by fibroconnective tissue, along the course of the cyst wall

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Cysts

8.1

Aneurysmal Bone Cyst

Fig. 8.12 Aneurysmal bone cyst. So-called blue bone in the wall of an aneurysmal bone cyst. The newly formed, basophilic woven bone rimmed by osteoblasts reportedly is seen in approximately one third of cases. However, its presence is not specific to aneurysmal bone cyst, as it may be seen in other entities, including Nora’s lesion and aggressive osteoblastoma

Fig. 8.13 Aneurysmal bone cyst. Note in this case, the new bone merges to form more mature-appearing, prominent, coarse, irregular trabeculae along the cyst wall, in a background of dense fibrous stroma and intermixed inflammatory cells

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290 Fig. 8.14 Aneurysmal bone cyst. Sections show the solid component of an aneurysmal bone cyst. Note the destruction of adjacent cortical bone, reflecting its aggressiveness

Fig. 8.15 Aneurysmal bone cyst. Higher magnification of the fibrous septa shows loosely arranged fibroblasts, capillary proliferation, inflammatory cells, multinucleated giant cells, and hemosiderin pigment. The spindle cells may show brisk mitotic activity but no cytologic atypia. Necrosis is rare, unless there has been a pathologic fracture

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Cysts

8.1

Aneurysmal Bone Cyst

Fig. 8.16 Aneurysmal bone cyst. Prominent bone production in the solid component of aneurysmal bone cyst. This bone production, along with the radiographic aggressive nature and brisk mitotic activity generally seen in such lesions, may lead to an erroneous diagnosis of osteosarcoma. However, the loose pattern of arrangement generally points to its benign, proliferative nature

Fig. 8.17 Solid variant of aneurysmal bone cyst. Although an aneurysmal bone cyst invariably possesses solid components, in some lesions the predominant lesional component is solid fibrogenic material, hence the term solid variant of aneurysmal bone cyst. The latter is histologically very similar, if not identical, to giant cell reparative granuloma. Although it has long been controversial whether these two lesions represent the same entity, the two largely overlapping entities have been merged by most authorities (see Chap. 6)

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Fig. 8.18 Solid aneurysmal bone cyst/giant cell reparative granuloma. Conventional radiographs show a lytic lesion in the mid-proximal phalanx of the left third finger. Although still debatable, traditionally it has

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Cysts

been thought that extragnathic giant cell reparative granuloma frequently involves the small bones of the hands and feet and rarely occurs in long tubular bones and vertebrae

8.1

Aneurysmal Bone Cyst

Fig. 8.19 Solid aneurysmal bone cyst/giant cell reparative granuloma. Gross appearance of the lesion shown in Fig. 8.18. Coexisting mixed solid and cystic components are common

Fig. 8.20 Solid aneurysmal bone cyst/giant cell reparative granuloma. Low-magnification image of the lesion shown in Fig. 8.19. Note the coexisting solid and cystic components

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294 Fig. 8.21 Solid aneurysmal bone cyst. The histologic differential diagnosis typically includes giant cell tumor of bone. The stromal component of the former generally is more collagenous than that of a giant cell tumor, with smaller giant cells randomly but not uniformly distributed

Fig. 8.22 Solid aneurysmal bone cyst. The mononuclear stromal component is composed of spindled fibroblasts, and the multinucleated giant cells are variably sized and randomly distributed. In contrast, the mononuclear cells in giant cell tumors are round to oval (monocyte/macrophage in origin), have more than 15–20 nuclei in the giant cells, and typically lie in a uniform manner. Prominent new bone formation frequently is seen in solid aneurysmal bone cyst/giant cell reparative granuloma and may be a dominant feature, but it typically is not identified in a giant cell tumor in the absence of microfractures

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Cysts

8.2

8.2

Unicameral Bone Cyst

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Unicameral Bone Cyst

Fig. 8.23 Unicameral bone cyst. Conventional radiograph showing a mixed lytic and sclerotic lesion within the proximal right humeral metadiaphyseal region. The margins are well-defined and sclerotic. There is little expansion of bone. No periosteal reaction, pathologic fracture, or definite soft tissue mass is identified. This radiologic appearance represents a unicameral bone cyst after curettage and partial methyl methacrylate cement packing, but it may just as easily represent a fibrous lesion without prior intervention

Fig. 8.24 Unicameral bone cyst. There is a radiolucency involving the proximal right femoral diaphysis that extends proximally into the intertrochanteric region. The radiolucency appears to have amorphous bone within the lesion. There is focal scalloping. No periosteal reaction, cortical irregularity, or fracture is seen. The radiologic differential diagnosis includes a nonaggressive cystic lesion versus a hematologic disorder such as lymphoma or plasmacytoma

296 Fig. 8.25 Unicameral bone cyst. Curetted fragments of tissue demonstrate fibrous septa similar to those seen in an aneurysmal bone cyst. In typical cases, the lining usually is inconspicuous or absent

Fig. 8.26 Unicameral bone cyst. Reactive bone may be seen adjacent to the cyst, as in this case

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Cysts

8.2

Unicameral Bone Cyst

Fig. 8.27 Unicameral bone cyst. Hemorrhage, hemosiderin pigment, and cholesterol clefts are common but nonspecific findings. Therefore, it is not uncommon for the diagnosis of a unicameral bone cyst to be one of exclusion and to depend on the presence of compatible radiologic findings and the absence of histologic characteristics that might otherwise suggest an alternative diagnosis

Fig. 8.28 Unicameral bone cyst. Higher magnification of the lesion shown in Fig. 8.27 reveals scattered multinucleated giant cells in fibroblastic stroma, resembling those of an aneurysmal bone cyst. Note the loose fibrous lining on the bone surface (upper left corner)

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8.3

8

Cysts

Ganglion Cyst

Fig. 8.30 Ganglion cyst. Sagittal proton-density MRI of the lesion shown in Fig. 8.29. An elongated homogeneous intermediate-signal juxtacortical mass demonstrates a low-intensity fibrous/bone wall contiguous with the adjacent cortex (Photo courtesy of Dr. Philip Lander)

Fig. 8.29 Ganglion cyst. This lateral radiograph of the left knee shows a sharply marginated thin periosteal bone density arising from the posterior metadiaphyseal cortex. Note the minimal bone spiculation and minimal adjacent cortical scalloping (Photo courtesy of Dr. Philip Lander)

Fig. 8.31 Ganglion cyst. Axial T2 image of the distal femoral diaphysis of the lesion shown in Fig. 8.29. A well-defined posterior juxtacortical mass demonstrates homogeneous fluid signal intensity. Note the minimal adjacent cortical irregularity (Photo courtesy of Dr. Philip Lander)

8.3

Ganglion Cyst

Fig. 8.32 Intraosseous ganglion cyst. Similar to their counterpart in soft tissue, intraosseous ganglion cysts may be unilobulated, but most often are multilobulated, with fibrous septa separating the cavities. Mucoid material (mucopolysaccharides), either in the lumen or dissecting the fibrous wall, is a common finding. Once again, because of the absence of epithelial lining of the cyst wall, a ganglion cyst is not a true cyst

Fig. 8.33 Ganglion cyst. Occasionally, the cyst may be lined by bland spindle cells, mimicking a true cyst. However, these “lining cells” are fibroblasts rather than endothelial or epithelial in nature

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9

Vascular Tumors

Primary vascular tumors of bone are rare, thus there is some controversy regarding their nomenclature; however, these tumors appear to include the entire spectrum of their soft tissue counterparts, ranging from highly benign hemangiomas to malignant angiosarcomas. Multifocality is common in both benign and malignant vascular lesions in bone. Hemangiomas typically are asymptomatic, and the radiologic features are almost always diagnostic. The classification of malignant vascular tumors has been more controversial,

with angiosarcoma being the most accepted entity for the cytohistologically high-grade lesions. Primary hemangioendotheliomas/epithelioid hemangioendotheliomas of bone occupy the transition zone between the biologic extremes, and controversies remain in classifying these lesions. Some authorities favor lumping them together with angiosarcomas as their low-grade cousins; however, they probably would be better recognized as borderline to intermediate-grade malignancies.

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Hemangioma

Fig. 9.1 Hemangioma. Coronal (left) and sagittal (right) CT images from a 35-year-old man show multiple lytic lesions throughout the left tibia and fibula. The radiologic findings are nonspecific and may represent granulomatous disease, lymphoma, or metastatic disease. Hemangiomas are relatively common lesions but are mostly asymptomatic. The tumor may occur at any age with a wide skeletal distribution, but most frequently involve the vertebral bodies and calvaria of adults

Fig. 9.2 Hemangioma. These tumors have variable histologic features, including capillary, cavernous, epithelioid, and histiocytic types. Their vasoformative nature typically is evident at low power. This image exhibits an intracortical cavernous hemangioma, which is composed of anastomosing ectatic engorged thin-walled blood vessels

Vascular Tumors

9.1

Hemangioma

Fig. 9.3 Hemangioma. This curetted specimen from an ischial lesion shows a collapsed hemangioma, in which the blood is mostly lost during processing. This lesion contains areas of fibrosis that entrap viable bony trabeculae

Fig. 9.4 Hemangioma. A higher-power view from an intracalvarial lesion shows endothelial cell–lined spaces. The lining cells of hemangiomas typically are flat, with darkstained nuclei devoid of cytologic atypia

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304 Fig. 9.5 Hemangioma. A histologic section from one of the lesions shown in Fig. 9.1 that reveals destruction of bone by a hemangioma. This appearance, along with the knowledge that there are multiple lesions, suggests the possibility of angiomatosis, which may be part of the spectrum of Gorham’s disease (also referred to as disappearing bone disease, vanishing bone disease, or massive osteolysis)

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Vascular Tumors

9.2

9.2

Hemangioendothelioma and Epithelioid Hemangioendothelioma

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Hemangioendothelioma and Epithelioid Hemangioendothelioma

Fig. 9.6 Hemangioendothelioma. Anteroposterior (left) and lateral (right) conventional radiographs from a 54-year-old woman with leg pain. There is a round lucent lesion in the mid-diaphysis of her left fibula. A periosteal reaction, as well as calcification, is seen at the

periphery of the lesion. Although such a lesion in this age group most likely represents metastatic disease, myeloma, or lymphoma, histologic examination revealed a hemangioendothelioma

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Fig. 9.7 Hemangioendothelioma. A 29-year-old man presented with pain, swelling, and discomfort involving his ankle region. A conventional radiograph shows an expansile lucent lesion most notable in the distal fibula, but also involving the talus. Multifocality is frequent for a vascular process such as hemangioendothelioma and multicentric intraosseous hemangioma

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Vascular Tumors

9.2

Hemangioendothelioma and Epithelioid Hemangioendothelioma

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Fig. 9.8 Hemangioendothelioma. CT images of the lesions seen in Fig. 9.7 showing cortically based, expansile radiolucent lesions involving the entire distal tibia (left) and calcaneus (right)

308 Fig. 9.9 Hemangioendothelioma. Histologically, these tumors may have varied appearances. The vasoformative nature generally is identifiable in most cases

Fig. 9.10 Hemangioendothelioma. A low-power view of a case with a solid growth pattern. The vascular nature may be subtle and is not easily recognizable in such cases because of the large amount of blood in both the vascular spaces and the extracellular space

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Vascular Tumors

9.2

Hemangioendothelioma and Epithelioid Hemangioendothelioma

Fig. 9.11 Hemangioendothelioma. Multinucleated giant cells may be seen in areas and occasionally may be prominent, thus causing confusion with other giant cell–rich lesions, such as aneurysmal bone cyst and giant cell tumor of bone

Fig. 9.12 Hemangioendothelioma. The cytologic atypia varies from region to region and from case to case. This image shows an obviously vasoformative spindle cell proliferation. Also note the presence of intermixed histiocytoid and epithelioid cells, which, when prominent, leads to a diagnosis of epithelioid hemangioendothelioma

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310 Fig. 9.13 Hemangioendothelioma. A high-power view demonstrating a spindle cell proliferation (upper right corner) and prominent osteoclast-type multinucleated giant cells, which represent reactive changes but may be mistaken for giant cell tumor of bone

Fig. 9.14 Hemangioendothelioma. This image represents a lesion composed predominantly of histiocytoid cells in a solid growth pattern. Mitotic activity frequently may be discernible. The lack of vasoformative features may result in a diagnostic challenge. A panel of immunohistochemical stains may be needed to recognize the vascular origin of the lesion

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Vascular Tumors

9.2

Hemangioendothelioma and Epithelioid Hemangioendothelioma

Fig. 9.15 Epithelioid hemangioendothelioma. The tumor may contain myxoid, chondroid, or hyalinized stroma. The lesional cells typically are arranged in strands, cords, or solid nests (Photograph courtesy of Dr. Brian Rubin)

Fig. 9.16 Epithelioid hemangioendothelioma. At high magnification, the cells typically have eosinophilic cytoplasm. The endothelial differentiation is best demonstrated by occasional cells containing intracytoplasmic lumina, in which erythrocytes may be visible (so-called blister cells). The signet ring–like appearance of these cells may be confused with that of metastatic adenocarcinoma (Photograph courtesy of Dr. Brian Rubin)

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Hemangiopericytoma/Solitary Fibrous Tumor

Fig. 9.17 Hemangiopericytoma. At low power, the tumor shows patternless growth with alternating hypercellular and hypocellular regions. Branching thin-walled blood vessels with a characteristic “staghorn” shape commonly are seen. Hemangiopericytoma is extremely rare in bone and has a nonspecific radiologic appearance. Most tumors are purely lytic lesions, thus the radiologic differential diagnosis essentially includes all lytic primary and metastatic tumors. Its more common soft tissue counterpart is indistinguishable histologically and immunophenotypically from solitary fibrous tumor, thus they have largely merged into a single entity outside the greater nasal cavity

Fig. 9.18 Hemangiopericytoma. At higher magnification, the tumor is composed of spindle, ovoid, and round cells with vesicular nuclei, devoid of cytologic atypia. The stroma ranges from loose/myxoid to dense/hyalinized. Thick collagen bands commonly are separated by tumor cells, thus imparting a keloidal appearance

Vascular Tumors

9.3

Hemangiopericytoma/Solitary Fibrous Tumor

Fig. 9.19 Hemangiopericytoma. Perivascular hyalinization is a common feature

Fig. 9.20 Hemangiopericytoma. The tumor is characteristically immunoreactive for CD34 (as depicted in this image) and, to a lesser extent, CD99. Endothelial markers are negative

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Vascular Tumors

Angiosarcoma

Fig. 9.21 Angiosarcoma. Gross examination of an above-the-knee amputation in a 75-year-old man is remarkable for a massively lytic, hemorrhagic, lobulated mass in the proximal femur, with associated pathologic fractures

Fig. 9.22 Angiosarcoma. A sagittal section of another above-the-knee amputation from a 78-year-old man. Two intraosseous hemorrhagic lesions are appreciated, one at the level of the proximal tibial metadiaphysis and the other in the tibial midshaft. The lesions have a dark brown and tan variegated appearance and ill-defined borders. The proximal lesion destroys both cortices extending posteriorly into the calf muscles, forming an extraosseous mass. The distal lesion destroys the anterior cortex. Although these findings undoubtedly represent aggressive lesions, multifocality in a single bone is highly suggestive of vascular neoplasms but not necessarily malignancy

9.4

Angiosarcoma

Fig. 9.23 Angiosarcoma. At low magnification, angiosarcoma may present as a vascular-rich, spindle cell lesion

Fig. 9.24 Angiosarcoma. The vasoformative growth pattern and extensive hemorrhage indicate a vascular origin

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316 Fig. 9.25 Angiosarcoma. High-grade angiosarcomas tend to be less vasoformative. However, the extensive extravasated red blood cells are highly suggestive of a vascular tumor. Further, a rudimentary vascular channel also is present (right side of the image). In addition, high-grade angiosarcomas generally have both epithelioid and spindle cell components, as depicted in this image. Mitotic figures including atypical forms are easily discernible

Fig. 9.26 Angiosarcoma. An angiosarcoma with an unusual, storiform growth pattern. Although the vasoformative nature is not obvious, abundant extravasated erythrocytes and small vascular channels are evident, even at this level of magnification

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Vascular Tumors

9.4

Angiosarcoma

Fig. 9.27 Epithelioid angiosarcoma. A high-grade epithelioid angiosarcoma showing marked cytologic atypia devoid of a vasoformative growth pattern. Epithelioid angiosarcomas typically are composed of large cells with abundant eosinophilic cytoplasm and large vesicular nuclei. CD31 (inset) is a relatively sensitive and specific marker for cells of endothelial origin, and is useful in the setting of a poorly differentiated tumor. Of important note, a significant proportion of angiosarcomas (particularly the epithelioid type) express cytokeratin, thus may potentially be confused with a metastatic carcinoma. CD31 immunoreactivity therefore becomes an essential distinguishing tool in this setting

Fig. 9.28 Angiosarcoma. A high-power view of the lesion seen in Fig. 9.26 (left). Note the atypical mitotic figure. CD34 (middle) and FLI-1 (right) are immunoreactive in most angiosarcomas, with variable sensitivities but less specificity than CD31. Although von Willebrand factor (VIII-related antigen), another commonly used marker, is the most specific vascular antigen, it is the least sensitive and shows only focal weak staining in most angiosarcomas

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318 Fig. 9.29 Epithelioid angiosarcoma. A lowmagnification view of the lesion seen in Fig. 9.22. Although the tumor cells are densely packed and vasoformative features are not apparent in areas, small vascular channels may be appreciated, even at this power

Fig. 9.30 Epithelioid angiosarcoma. The tumor may have a “pseudoglandular” growth pattern, closely resembling a metastatic carcinoma. A CD31 immunostain would demonstrate its vascular origin

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Vascular Tumors

9.4

Angiosarcoma

Fig. 9.31 Epithelioid angiosarcoma. This tumor is composed of dis-cohesive epithelioid cells in a solid growth pattern devoid of obvious vasoformative characteristics, closely mimicking metastatic lobular breast carcinoma. Once again, expression of cytokeratin along with endothelial markers is the typical immunophenotype of these lesions

Fig. 9.32 Epithelioid angiosarcoma. Metastatic epithelioid angiosarcoma (from the lesion seen in Fig. 9.22) in a popliteal lymph node. This tumor may easily be mistaken for metastatic carcinoma

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

This chapter is composed of rare primary mesenchymal tumors of bone that demonstrate various differentiation pathways, including those of myogenic, lipogenic, neural, and epithelial derivation. Metastatic carcinoma, by far the most

10

common malignancy in the skeleton, and metastatic sarcoma to bone, a rare event, should be excluded before accepting the diagnosis of a primary bone neoplasm.

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10

Leiomyoma of Bone

Fig. 10.1 Leiomyoma. Leiomyoma of bone is extremely rare and commonly affects facial bones. The tibia is the most common site among the extragnathic bones. The tumor typically is a radiolucent lesion that often is multilocular. Histologically, the tumors are identical to their soft tissue counterparts, showing bland spindle cells arranged in interlacing bundles. The lesional cells have abundant eosinophilic cytoplasm and cigar-shaped nuclei with vesicular chromatin. Mitotic figures are difficult to identify

Fig. 10.2 Leiomyoma. Zones of infarction may be present, especially in large lesions (as in tumors of extraskeletal sites), and should not be confused with tumor necrosis or portend a more ominous prognosis

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10.2

10.2

Leiomyosarcoma of Bone

323

Leiomyosarcoma of Bone

Fig. 10.4 Leiomyosarcoma. A 36-year-old woman presented with left knee swelling and pain. Imaging studies represented by this axial CT image demonstrated a large destructive lesion of the distal femur with cortical disruption and an accompanying soft tissue mass

Fig. 10.3 Leiomyosarcoma. Multifocal permeative lytic lesions with destruction of the medial cortex of the proximal humeral metadiaphyseal region are seen in this 33-year-old man with sickle cell disease. Leiomyosarcomas of bone are very rare and radiographically appear as aggressive radiolucent lesions with poorly defined margins; therefore, they commonly are mistaken for metastatic disease or infiltrative disease such as leukemia or lymphoma on radiographic imaging. Patients with sickle cell disease or anemia are not known to be at increased risk for bone neoplasms, and this dual occurrence in this patient is thought to be coincidental

324

Fig. 10.5 Leiomyosarcoma. Gross pathologic features of the lesion shown in Fig. 10.4. A firm, tan, and fleshy mass is noted in the distal femur. The mass replaces the cancellous bone of the metaepiphysis and destroys the medial cortex of the femur. The mass extends beyond the cortical surface and lifts the overlying periosteum, causing a Codman angle on the conventional radiologic image

Fig. 10.6 Leiomyosarcoma. Histologically, leiomyosarcomas of bone are identical to those in other locations. The lesional cells are plump, spindled, and arranged in bundles or fascicles. Areas of necrosis may be present

10

Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.2 Leiomyosarcoma of Bone Fig. 10.7 Leiomyosarcoma. At higher magnification, the tumor cells typically have cigar-shaped nuclei characteristic of smooth muscle origin, with a variable degree of cytologic atypia. Mitotic figures, including atypical forms, generally are discernible, as in this image

Fig. 10.8 Leiomyosarcoma. Smooth muscle differentiation may not always be readily identifiable by routine hematoxylin and eosin staining. The histologic section from the lesion seen in Fig. 10.3 demonstrates a poorly differentiated spindle cell neoplasm. A positive immunohistochemical (IHC) stain for smooth muscle actin confirmed the smooth muscle origin of the tumor (inset)

325

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10.3

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Rhabdomyosarcoma

Fig. 10.9 Rhabdomyosarcoma. A CT image shows a lytic lesion in the right L2 pedicle in a 15-year-old girl with a prior history of rhabdomyosarcoma in the paraspinal region at the level of L2

Fig. 10.10 Rhabdomyosarcoma. A biopsy from the lesion shown in Fig. 10.9 demonstrates a small, blue, round cell tumor. The confirmatory IHC stains revealed a residual/recurrent rhabdomyosarcoma (see Fig. 10.11). Most rhabdomyosarcomas of bone represent metastases, although they do infrequently arise de novo in bone

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10.3

Rhabdomyosarcoma

327

Fig. 10.11 Rhabdomyosarcoma. Rhabdomyosarcomas “stain” for desmin with cytoplasmic immunoreactivity (left), whereas MyoD1 expression shows a typical nuclear staining pattern (right)

328

Fig. 10.12 Rhabdomyosarcoma. A 4-year-old girl with a history of rhabdomyosarcoma of her right mandible presented with a pathologic fracture of the left femur at the junction of the neck and intertrochanteric region (between arrowheads)

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.3

Rhabdomyosarcoma

Fig. 10.13 Rhabdomyosarcoma. A biopsy from the lesion shown in Fig. 10.12 reveals a metastatic rhabdomyosarcoma. Note the abundant rhabdomyoblasts containing eccentric nuclei and deeply eosinophilic cytoplasm. It is interesting that although the primary lesion was classified as an embryonal rhabdomyosarcoma, the metastatic tumor shows prominent features of an alveolar rhabdomyosarcoma. Chemotherapy may induce embryonal rhabdomyosarcoma to differentiate sufficiently so as to confuse the histologic appearance. Cytogenetic confirmation for alveolar rhabdomyosarcoma [t(2;3) (q35;q14)] or [t(1;3)(p36;q14)] may be needed, given the prognostic significance of the differences between the two types

Fig. 10.14 Rhabdomyosarcoma. Spindle cell variant of embryonal rhabdomyosarcoma. The eosinophilic spindle cells are arranged in fascicles, resembling leiomyosarcoma. Here, immunohistochemistry or transmission electron microscopy may be needed for the diagnosis, especially in the absence of a previous documented history

329

330 Fig. 10.15 Rhabdomyosarcoma. Pleomorphic rhabdomyosarcoma composed of cells with bizarre nuclei and abundant cytoplasm, with frequent mitotic figures

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.4

10.4

Lipoma of Bone

Lipoma of Bone

Fig. 10.16 Lipoma. In the anterior calcaneus of this 50-year-old woman, there is a relatively lucent area without lesional content, fracture, or periosteal reaction. Lipoma of bone is exceedingly rare (<0.1 % of primary bone tumors). It may be in a cortical or parosteal location but most commonly arises in the medullary cavity

Fig. 10.17 Lipoma. An intramedullary lipoma showing sheets of mature adipocytes

331

332

10.5

10

Myxoma of Bone

Fig. 10.18 Myxoma. Gross pathologic features of a myxoma involving the jaw. Myxoma of bone is much less common than its soft tissue counterpart. The tumor typically involves gnathic bones and, rarely, long bones and presents as an expansile lesion radiographically

Fig. 10.19 Myxoma. Similar to its soft tissue counterpart, the tumor is composed of uniform and deceptively bland, short spindle and stellate-shaped cells with small nuclei. The cells are separated by abundant myxoid stroma containing sparse capillary-sized vessels. Tissue sampling is critical, with care taken to exclude other lesions that may contain prominent myxoid stroma such as chondrosarcoma, myxofibrosarcoma, chondromyxoid fibroma, and ganglia cyst

Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.6

10.6

Paraganglioma

Paraganglioma

Fig. 10.20 Paraganglioma. Although primary intraosseous paragangliomas do occur, they are exceedingly rare and tend to arise in the sacral bone. When the histologic diagnosis of a paraganglioma from a bone lesion is established, an extensive radiologic workup is necessary to rule out a metastasis. Histologically, the tumor cells typically grow in a distinctive organoid or Zellballen (“cell balls” in German) pattern surrounded by spindled sustentacular cells, and they are separated by a vascular-rich fibrous network. The lesional cells are polygonal to oval, with salt-and-pepper chromatin characteristic of neuroendocrine origin. Mitotic figures may be seen infrequently

Fig. 10.21 Paraganglioma. The cell balls may be separated by edematous or fibrotic stroma. Bizarre, hyperchromatic nuclei may be seen but have no diagnostic significance. In some reported cases S-100 protein immunoreactivity is said to be absent in the sustantacular cells, separating these lesions from paragangliomas in other regions

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Neurilemmoma/Schwannoma

Fig. 10.22 Schwannoma. An axial CT image of a 66-year-old man shows a 4.4-cm expansile mass arising from the medullary cavity of the mid-tibial diaphysis. The mass extends beyond the margins of the tibial diaphysis and appears to abut the interosseous membrane into the anterior compartment. Schwannomas may occur as primary lesions of bone, although a soft tissue origin is far more common. The mandible and sacrum are the most common sites of involvement. When the tumor arises in the midline (spine or sacrum), it is difficult to determine whether it is really of bone origin

Fig. 10.23 Schwannoma. Histologically, intraosseous schwannomas may or may not be encapsulated. The classic schwannomas have alternating hypercellular (Antoni A) and hypocellular (Antoni B) areas

Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.7

Neurilemmoma/Schwannoma

Fig. 10.24 Schwannoma. Well-defined Verocay bodies (nuclear palisading around cell processes) in Antoni A areas

Fig. 10.25 Schwannoma. Hypocellular, Antoni B areas typically have a myxoid stroma (a milieu similar to that of neurofibroma) and numerous thick-walled blood vessels with perivascular hyalinization

335

336 Fig. 10.26 Schwannoma. Cystic changes are common in hypocellular areas

Fig. 10.27 Schwannoma. A histologic section from the lesion shown in Fig 10.22. Although the biopsy sample may not be representative of the entire lesion, this tumor most likely represents a “cellular” schwannoma characterized by the presence of an exclusive Antoni A growth pattern, fascicular architecture, and the absence of Verocay bodies

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.7

Neurilemmoma/Schwannoma

Fig. 10.28 Schwannoma. A diffuse, strong immunoreactivity for S-100 protein performed on the subsequent level of the section shown in Fig. 10.27 confirmed the diagnosis of a schwannoma

337

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10.8

10

Malignant Peripheral Nerve Sheath Tumor

Fig. 10.29 Malignant peripheral nerve sheath tumor. Primary malignant peripheral nerve sheath tumors (MPNSTs) in bone are rare but tend to involve gnathic bones, although long bones also may be affected. Histologically, MPNST generally is a cellular spindle cell tumor with a fascicular growth pattern. The tumor may be negative or positive for S-100 protein, but the immunoreactivity typically is weak and focal in the latter (inset)

Fig. 10.30 Malignant peripheral nerve sheath tumor. At higher magnification, the lesional cells have wavy to buckled nuclei, eosinophilic cytoplasm, and indistinct cell borders. Mitotic activity may be brisk

Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.8

Malignant Peripheral Nerve Sheath Tumor

Fig. 10.31 Malignant peripheral nerve sheath tumor. MPNSTs may be found to exhibit bizarre nuclei mimicking malignant fibrous histiocytoma

Fig. 10.32 Epithelioid malignant peripheral nerve sheath tumor. Not infrequently, MPNSTs may be purely epithelioid, as illustrated. Rarely, the tumor also may show heterologous differentiation, including rhabdoid, osteoid, chondroid, and glandular features. This, along with the fact that most MPNSTs have weak/ focal or no S-100 protein expression, may result in diagnostic challenges. A history of neurofibroma/ neurofibromatosis is extremely helpful in that setting

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10.9

10

Ependymoma

Fig. 10.33 Ependymoma. A fat-suppressed T1-weighted MRI showing a solid mass lesion encasing the cauda equina and filling the spinal canal from the levels of L2 through L4 and S1 distally. Ependymoma usually is intracranial in pediatric cases, whereas it is spinal in adults. Rarely, ependymoma may occur in the pelvic cavity. Myxopapillary ependymomas are considered a biologically and morphologically distinct variant of ependymoma, occurring almost exclusively in the region of the cauda equina

Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.9

Ependymoma

Fig. 10.34 Ependymoma. Note the tapering fibrillary processes of the perivascular pseudorosettes. These structures usually are intensively immunoreactive with glial fibrillary acidic protein antibodies

Fig. 10.35 Myxopapillary ependymoma. An excisional biopsy of the lesion shown in Fig. 10.33 demonstrating a papillary arrangement around blood vessels. The mucinous material (containing neutral and acidic mucopolysaccharides) separates the tumor cells from a hyalinized vascular core and accumulates in microcysts

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.10 Adamantinoma

Fig. 10.36 Adamantinoma. Adamantinoma is a low-grade, malignant biphasic tumor of uncertain pathogenesis. The tumor has a strong predilection for the tibia (85–90 %), particularly the anterior midshaft, with or without involvement of the fibula. On radiography, the tumor typically is an expansile, lobulated, lytic lesion. The lesion commonly remains intracortical and extends longitudinally, but it also may invade the medullary cavity. Thus, the radiologic differential diagnosis always

Fig. 10.37 Adamantinoma. Another example showing small epithelial nests with a fibroosseous stroma. The latter typically contains woven bone spicules rimmed by osteoblasts, thus closely resembling osteofibrous dysplasia

includes osteofibrous dysplasia, fibrous dysplasia, and, less commonly, fibroma. Histologically, the tumor has a variety of morphologic patterns. The classic type is characterized by nests of epithelial cells with a fibrous stroma, as illustrated in this image. The main differentiation patterns are tubular, basaloid, squamous, spindle cell, and Ewing-like. These variants may be intermingled with one another in various proportions

10.10

Adamantinoma

Fig. 10.38 Adamantinoma. An IHC stain for pancytokeratin highlights the epithelial cell nests

Fig. 10.39 Adamantinoma. A high-power histomorphologic view showing basaloid epithelial islands, some of which demonstrate peripheral nuclear palisading

343

344 Fig. 10.40 Adamantinoma. A variable degree of squamous differentiation can be seen and, when prominent, may mimic the appearance of a squamous cell carcinoma

Fig. 10.41 Adamantinoma. A spindle cell variant showing a vague storiform pattern resembling a nonossifying fibroma

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.10

Adamantinoma

Fig. 10.42 Adamantinoma. Another spindle cell variant showing hypocellular and myxoid stroma. It would be easy to overlook the epithelial cells when they are present as isolated single cells in such cases

Fig. 10.43 Adamantinoma. An IHC stain for pancytokeratin on the section shown in Fig. 10.42 demonstrates abundant isolated epithelial cells

345

346 Fig. 10.44 Adamantinoma. The tumor is composed of uniform, solid sheets of small, round, blue cells, thus representing significant morphologic overlap with Ewing sarcoma. The lack of cytogenetic abnormalities characteristic of Ewing sarcoma [mainly t(11;22)] delineates a histologic variant of Ewing-like adamantinoma by some authorities. Conversely, those with the genotypic and phenotypic findings of Ewing sarcoma are classified as adamantinoma-like Ewing sarcoma

Fig. 10.45 Adamantinoma. This photomicrograph illustrates epithelial islands separated by fibrous stroma. Whereas the appearance of epithelial cells is predominantly that of a squamous cell carcinoma, a second element of basaloid cells also is evident

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.10

Adamantinoma

Fig. 10.46 Adamantinoma. The epithelial components contain a mixture of squamous and spindle cells

Fig. 10.47 Adamantinoma. Cortical breakthrough is seen in this section

347

348 Fig. 10.48 Adamantinoma. Although seen in this image, extracortical extension into soft tissue and skin rarely occurs

Fig. 10.49 Adamantinoma. A high-power view of the lesion shown in Fig. 10.48 demonstrates a poorly differentiated malignant neoplasm, thus closely mimicking a carcinoma or melanoma

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.11

Ameloblastoma

349

10.11 Ameloblastoma

Fig. 10.51 Ameloblastoma. A specimen radiograph of a resected portion of the mandible demonstrates a large multilocular lesion with welldefined corticated margins and resorption of the roots of the involved teeth, a characteristic feature of the aggressiveness of this tumor

Fig. 10.50 Ameloblastoma in an unusual location. This CT image shows an expansile lesion of the posterior maxilla filling the right maxillary sinus, with cortical rupture through the medial and lateral maxillary alveolar bone/inferior maxillary sinus walls. Ameloblastoma is the second most common epithelial odontogenic tumor, clinically characterized by an intraosseous, painless, slow-growing mass that is locally aggressive, with a high rate of recurrence and the potential to metastasize despite its benign nature. The tumor occurs exclusively in the gnathic bones, predominantly in the mandible, and rarely involves the sinonasal cavities

350 Fig. 10.52 Ameloblastoma. According to the World Health Organization (WHO) Histologic Classification of Odontogenic Tumors, ameloblastoma is a tumor of odontogenic epithelium with mature, fibrous stroma without odontogenic ectomesenchyme. It is subdivided into solid, multicystic, unicystic, and desmoplastic types. This image illustrates a low-power view of the solid type, showing its seemingly benign but highly infiltrative nature

Fig. 10.53 Ameloblastoma. Histopathologic patterns include follicular, plexiform, acanthomatous, and granular cell variants. A low-power view of the follicular pattern shows basophilic epithelial islands separated by bland fibrous tissue

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.11

Ameloblastoma

Fig. 10.54 Ameloblastoma. Various histopathologic patterns may be present within a single specimen. Follicular and acanthomatous (keratinizing) patterns are seen in this field

Fig. 10.55 Ameloblastoma. Epithelial nests showing columnar odontogenic epithelial cells with vacuolization of the cytoplasm and reverse polarization of the nuclei, characteristic features of ameloblastoma

351

352 Fig. 10.56 Ameloblastoma. The desmoplastic type is characterized by odontogenic epithelial cords compressed by mature, dense fibrous connective tissue, as viewed in this histologic image

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.12

Chordoma

353

10.12 Chordoma

Fig. 10.57 Chordoma. There is a large intraosseous mass involving the sacral body and bilateral ala extending into the adjacent bilateral neural foramen from the level of S3 to S5 at the sacrococcygeal junction

Fig. 10.58 Chordoma. A sagittal CT image of the lesion shown in Fig. 10.57 demonstrates that the destructive presacral mass closely abuts the posterior rectum. Classic chordomas/notochordal tumors arise from remnants of the notochord and thus occur exclusively along the midline. However, controversies exist as to the origin of chordomas because the tumors arise within the bone and not from intervertebral disks. Most of these tumors are located in the sacrococcygeal region and base of the skull. Furthermore, peripheral notochordal-like lesions frequently have been reported in the literature and have been shown to be immunophenotypically identical to classic lesions

seen in these magnetic resonance (MR) images. The mass is wellmarginated and extends into the presacral space, with heterogeneous low T1 (left) and increased T2 (right) signal characteristics

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

Fig. 10.59 Chordoma. A sagittal T1-weighted MR image (left) and an axial T2-weighted image (right) demonstrate a heterogeneous mass between the clivus and the pons

10.12

Chordoma

355

Fig. 10.60 Chordoma. Gross pathologic features of the lesion shown in Fig. 10.57. Bulging from the anterior surface of the sacrum is a large myxoid mass covered by a thin fascial plane. The lesion has a lobulated configuration and is stippled with areas of hemorrhage

Fig. 10.61 Chordoma. Another example revealing a soft, glistening mass that replaces the anterior cortices of the inferior sacrum and coccyx. The tumor is a mottled tan-gray color and has a soft gelatinous consistency and extensive areas of hemorrhage and necrosis

356 Fig. 10.62 Chordoma. At lower magnification, chordomas are characterized by a lobular growth pattern, with individual lobules separated by fibrous septa. The tumor cells may be arranged in strands (as depicted), cords, nests, or solid sheets in a background of abundant myxoid matrix

Fig. 10.63 Chordoma. Cording of the cells is a classic feature but may not be seen in all tumors. Soft tissue extension of the tumor can be appreciated in this photomicrograph

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.12

Chordoma

Fig. 10.64 Chordoma. An intermediate-power view showing tumor cells arranged in small nests and cords

Fig. 10.65 Chordoma. Some of the lesional cells demonstrate abundantly clear to pale eosinophilic cytoplasmic vacuoles (so-called physaliphorous cells), a constant feature of chordomas

357

358 Fig. 10.66 Chordoma. This image illustrates a solid growth pattern with prominent physaliphorous cells containing one or several intracytoplasmic vacuoles. The nuclei are variably sized but generally retain a low nuclear-to-cytoplasmic ratio. Small nucleoli often are visible

Fig. 10.67 Chordoma. A high-power view showing the nuclear features of physaliphorous cells. Mitotic activity may be discernible but is not frequent. The lesional cells may have a variable degree of nuclear enlargement, pleomorphism, and hyperchromasia, but these findings do not predict a worse prognosis. Rarely, the tumor may recur as a spindle cell sarcoma, also known as a dedifferentiated chordoma or sarcomatoid chordoma. However, some of these tumors may represent postradiation sarcomas

10

Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.12

Chordoma

Fig. 10.68 Chordoma. The physaliphorous cells may have an appearance of fat necrosis in the absence of prominent myxoid matrix. However, the cellular cohesion and lobulated growth pattern point to a chordoma

Fig. 10.69 Chordoma. A touch preparation imprint showing tumor cells with cytoplasmic vacuolization, some of which appear as nuclear pseudoinclusions

359

360 Fig. 10.70 Chondroid chordoma. A section from the lesion shown in Fig. 10.59 demonstrates prominent chondromyxoid matrix, thus mimicking a chondrosarcoma. Chondroid chordoma occurs exclusively in the base of the skull, particularly the sphenooccipital region

Fig. 10.71 Chondroid chordoma. The presence of abundant cytoplasmic vacuoles, along with the centrally located nuclei, may be mistaken for chondrosarcoma cells situated in the lacunar spaces, especially at lower magnification. Chordomas are immunoreactive for epithelial membrane antigen (EMA) and cytokeratin (CK) antibodies and are nonreactive with podoplanin (D2-40) antibody, whereas chondrosarcomas have exactly the opposite phenotype

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.12

Chordoma

361

Fig. 10.72 Chondroid chordoma. The cohesive nature and broad attachment of the cells can be appreciated at high magnification. In contrast, the cells of a chondrosarcoma typically exhibit discohesion and interact with one another through extended delicate cellular processes

Fig. 10.73 Chordoma. As noted previously, the lesional cells generally are immunoreactive with antibodies against pancytokeratin (left), EMA, and low molecular weight CKs, including CK19 (right), CK8,

and CK18. Brachyury is a newer, relatively specific and highly sensitive marker for chordoma

362 Fig. 10.74 Chordoma. The tumors characteristically express S-100 protein, a feature overlapping with chondrosarcomas. However, the latter almost never show immunoreactivity with epithelial markers

Fig. 10.75 Chordoma. The tumors also frequently express one or more cell adhesion molecules, including vascular cell adhesion molecule (CD106), CD44, E-cadherin, N-cadherin, and neural cell adhesion molecule (CD56, as depicted in this image)

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.12

Chordoma

Fig. 10.76 Chordoid meningioma. This biopsy sample from a T2 epidural soft tissue mass shows cords of epithelioid cells with abundant cytoplasmic vacuoles surrounded by myxoid stroma. Chordoid meningioma, an uncommon variant of WHO grade II meningioma, typically presents as a dural-based or paraspinal mass (as opposed to chordomas, which involve bone). Histologically, chordoid meningiomas closely resemble chordomas. However, coexisting areas of typical meningiomas frequently are present. The lesional cells characteristically express CK (inset) and EMA but are negative for S-100 protein and brachyury. Thus, recognition of this entity and its distinction from chordoma is essential

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.13 Synovial Sarcoma of Bone

Fig. 10.77 Synovial sarcoma. Coronal (left) and axial (right) CT images demonstrate a large, destructive, lytic lesion involving the entire right sacral ala extending into the sacral promontory. There also is marked

Fig. 10.78 Synovial sarcoma. An above-the-knee amputation of a 53-year-old man showing a large, tan, polypoid mass involving and destroying the entire knee

enlargement of the right S1 and S2 neural foramina, where multiple lytic lesions are seen scattered throughout both iliac wings. Primary synovial sarcoma of bone is extremely rare, with only scattered cases reported

Fig. 10.79 Synovial sarcoma. Another above-the-knee amputation shows a multilobulated, tan-white, solid mass involving the distal femur and femoral component of a total knee prosthesis. The mass was discovered to be a synovial sarcoma

10.13

Synovial Sarcoma of Bone

Fig. 10.80 Synovial sarcoma. Histologically, synovial sarcoma is a spindle cell tumor with a biphasic or monophasic growth pattern. Biphasic synovial sarcoma has both spindle and epithelial cell components in variable proportions. Note that this biphasic tumor is composed of predominantly spindle cells, with alternating hypercellular and hypocellular areas. Intermixed are scattered gland-forming epithelial elements

Fig. 10.81 Synovial sarcoma. Biphasic synovial sarcoma showing apparent gland-forming characteristics. Note the intraluminal necrotic debris, a frequent finding in the welldifferentiated glandular component

365

366 Fig. 10.82 Synovial sarcoma. Another biphasic synovial sarcoma of bone showing a poorly differentiated epithelial component with occult glandular differentiation. The epithelial element may form solid cords, nests, or rounded clusters. Squamous metaplasia may occur rarely

Fig. 10.83 Synovial sarcoma. A biphasic synovial sarcoma showing a loosely cellular spindle cell component with intermixed and poorly defined epithelial nests

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.13

Synovial Sarcoma of Bone

Fig. 10.84 Synovial sarcoma. The spindle cell component often occurs alone as the monophasic type, representing most synovial sarcomas of bone. The cells typically are arranged in solid sheets with long or short fascicles. Occasional nuclear palisading may be seen, as in this case. Solely glandular monophasic synovial sarcoma theoretically exists but is indistinguishable from an adenocarcinoma without the specific cytogenetic abnormality for synovial sarcoma [t(X;18)]

Fig. 10.85 Synovial sarcoma. A monophasic synovial sarcoma with a herringbone growth pattern mimicking a fibrosarcoma

367

368 Fig. 10.86 Synovial sarcoma. High-power view of the spindle cell component. The nuclei often are carrot shaped, with minimal to mild cytologic atypia. Increased mitotic activity may be seen but is not a predominant feature. Significant nuclear pleomorphism, abundant mitotic figures, and tumor necrosis typically are seen in the poorly differentiated synovial sarcoma

Fig. 10.87 Synovial sarcoma. A prominent hemangiopericytomalike growth pattern is seen frequently in synovial sarcomas

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.13

Synovial Sarcoma of Bone

Fig. 10.88 Synovial sarcoma. An area with myxoid stroma showing widely dispersed spindle cells

Fig. 10.89 Synovial sarcoma. Stromal calcification with or without ossification is reported in about one third of tumors, referred to as calcifying (ossifying) synovial sarcoma. This is particularly important for bone lesions because the osteoid may have a lacelike pattern and thus may be confused with osteosarcoma

369

370 Fig. 10.90 Synovial sarcoma. A primary synovial sarcoma of bone showing cortical breakthrough

Fig. 10.91 Synovial sarcoma. Biopsy of the lesion shown in Fig. 10.77 demonstrates a spindle cell lesion with a vague storiform pattern, thus mimicking a benign fibrous histiocytoma, an entity seen much more commonly as a primary tumor of bone. Synovial sarcomas express CKs and EMA with variable intensity. Several low molecular weight CKs, including CK7 (inset) and CK19, and high molecular weight CKs also may be expressed. The positivity of these epithelial markers commonly is focal. Some cases are immunoreactive only with certain CK subtype(s). Thus, multiple markers should be used

10

Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

10.13

Synovial Sarcoma of Bone

Fig. 10.92 Synovial sarcoma. Rarely, a monophasic synovial sarcoma may be composed of predominantly epithelioid, oval, or rounded cells devoid of gland formation (left). Although not specific, BCL2 protein is expressed diffusely in synovial sarcomas (right) and thus provides a relatively sensitive marker. Therefore, BCL2 positivity in a sarcoma, even in the absence of CK/EMA reactivity, should prompt the pathologist to search for other evidence of synovial sarcoma. The cytogenetic

371

hallmark (found in >90 % of cases) is t(X;18)(p11;q11), resulting in the fusion of the SYT gene on chromosome 18 and either of the three closely related genes SSX1, SSX2, and SSX4 on the X chromosome. The tumor also may be positive for CD99 and S-100 protein. The combination of these markers is useful to rule out other entities with an overlapping histomorphology, such as malignant peripheral nerve sheath tumor and Ewing sarcoma/primitive neuroectodermal tumor

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Myogenic, Lipogenic, Neural, and Other Mesenchymal Tumors

Fig. 10.93 Synovial sarcoma. A section of the lesion shown in Fig. 10.79 demonstrates epithelioid, oval, and rounded cell morphology (left). Note that the tumor is engaged in the production of a densely collagenous substance that resembles the lacelike osteoid characteristics of osteosarcoma. Although a small percentage of osteosarcomas demon-

strate CK positivity, the intense and strong expression of pancytokeratin (right), along with the presence of t(X;18)(p11;q11), leads to the best classification of the current case as synovial sarcoma, despite the apparent high degree of associated matrix production

Tumor-like Conditions

Many nonneoplastic conditions of bone may form mass lesions that clinically and/or radiologically mimic tumors. In

11

this chapter, selective conditions commonly encountered in clinical practice are discussed.

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_11, © Springer Science+Business Media New York 2013

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11.1

11

Avascular Necrosis

Fig. 11.1 Avascular necrosis. Bilateral avascular necrosis (also called osteonecrosis) viewed on conventional radiography shows flattening of the bilateral femoral heads, greater on the left, with subchondral lucency and sclerosis. There is associated mild degenerative disease, also more extensive on the left. Avascular necrosis is bone death caused by an interrupted or poor blood supply to the area. It is most common in the hip and shoulder but may affect other large joints. The risk factors include long-term corticosteroid use, alcohol abuse, sickle cell disease, Gaucher disease, radiation therapy, and trauma

Fig. 11.2 Avascular necrosis. Osteonecrosis of the right femur as again seen in a conventional radiograph; here, there is advanced degenerative disease showing collapse of the weight-bearing femoral head and near complete loss of the joint space

Tumor-like Conditions

11.1

Avascular Necrosis

Fig. 11.3 Avascular necrosis. Gross pathologic features of avascular necrosis. Note the wedge-shaped area of yellowish discoloration corresponding to the region of necrosis. The necrotic bone is separated from the overlying unremarkable articular cartilage. A slightly hyperemic border of bone is seen just beyond the necrosis

Fig. 11.4 Avascular necrosis. A cross-section of another femoral head showing a wedge-shaped area of osteonecrosis. Note that the overlying articular cartilage has been lifted, which often leads to destruction of the articular surface, a condition known as osteochondritis dissecans

375

376 Fig. 11.5 Avascular necrosis. Remote avascular necrosis with extensive secondary osteoarthritic changes

Fig. 11.6 Avascular necrosis. Histologically, osteonecrosis is characterized by dropout of the osteocytes from the lacunae (resulting in the appearance of empty spaces) and the absence of cells on the trabecular surface. Note also the necrotic debris in the marrow spaces secondary to death of the marrow elements

11

Tumor-like Conditions

11.1

Avascular Necrosis

Fig. 11.7 Avascular necrosis. The healing phase of avascular necrosis showing appositional new bone formation, a process called creeping substitution, similar to that seen in fracture repair

Fig. 11.8 Avascular necrosis. Subchondral revascularization is prominent in another example of the healing phase

377

378 Fig. 11.9 Osteochondritis dissecans. A typical osteocondrotic lesion showing active attempts of endochondral ossification. These latter changes sometimes are referred to as chondro-osseous metaplasia

Fig. 11.10 Osteoradionecrosis. This image illustrates osteonecrosis caused by radiotherapy for squamous cell carcinoma of the mandible, a condition also called osteoradionecrosis. A modest amount of appositional new bone formation also is present

11

Tumor-like Conditions

11.2

11.2

Bone Infarct

Bone Infarct

Fig. 11.11 Bone infarct. On this radiograph, an expansile lesion is seen within the distal left tibial metaphysis extending into the epiphysis. The lesion has a narrow zone of transition and demonstrates both sclerotic and lucent changes. No periosteal reaction or cortical breakthrough is identified. A bone infarct is often thought to be in the same spectrum of disease as osteonecrosis in that similar risk factors are seen in both conditions. In general, bone infarcts are lesions arising in the metaphysis and diaphysis of long bones, whereas those occurring in the epiphysis are labeled as secondary to avascular necrosis. Bone infarcts have no specific radiologic findings and can mimic a variety of conditions, including stress fractures, infectious or inflammatory processes, or neoplasms such as cartilaginous tumors

379

380 Fig. 11.12 Bone infarct. The histologic features of a bone infarct are similar to those seen in avascular necrosis

Fig. 11.13 Bone infarct. A longstanding bone infarct showing islands of dense fibrosis and prominent calcification

11

Tumor-like Conditions

11.3

11.3

Osteochondral Body

Osteochondral Body

Fig. 11.14 Osteochondral body. A conventional radiograph demonstrates moderate osteoarthritis of the right elbow. Note that numerous ossified bodies are present within the joint. Osteochondral bodies, also termed joint mice, are fragments of bone and cartilage lying free in the joint cavity. These bodies may arise from a variety of conditions

381

382 Fig. 11.15 Osteochondral body. Relatively circumscribed bony tissue covered by a thin layer of tan-white glistening hyaline cartilage describes this unusually large osteochondral lesion. Apparent cystic degeneration is present

Fig. 11.16 Osteochondral body. Histologically, osteochondral bodies may be composed of various portions of bone and cartilage but usually do not constitute a challenging diagnosis. This image illustrates a prominent cartilaginous surface mimicking the cartilage cap of an osteochondroma

11

Tumor-like Conditions

11.4

11.4

Gout

383

Gout

Fig. 11.18 Gout. A sagittal proton-density (PD) magnetic resonance (MR) image showing prepatellar bursa containing a gouty tophus. All tophaceous lesions show similar signal characteristics (low–intermediate T1 signals and heterogeneous T2 signals). They may appear as amorphous masses, linear crystalline-like deposits, or cystic lesions of the bursae

Fig. 11.17 Gout. The radiographic appearance of gout involving the metatarsocuneiform joints. Gout (also known as podagra in the big toe) is an inflammatory condition caused by uric acid crystals (tophi) that recurrently attack the joints; the metatarsal-phalangeal joint is most commonly affected. The radiographic findings may not appear on conventional radiographs even after a year of uncontrolled disease

Fig. 11.19 Gout. Tophaceous gout involving the knee joint exhibits a classic homogeneously chalky white cut surface

384 Fig. 11.20 Gout. The histologic appearance of urate crystals in tissue sections from an alcoholfixed specimen. Uric acid is water soluble; therefore, the crystals commonly are dissolved in tissue processing using water-based fixatives (i.e., buffered formalin). Note the prominent histiocytic and foreign body giant cell reaction

Fig. 11.21 Gout. The tissue section from a formalin-fixed specimen. Note that the dark-stained crystals are largely dissolved

11

Tumor-like Conditions

11.4

Gout

Fig. 11.22 Gout. A uric acid stain highlights the crystals but usually is unnecessary for the diagnosis

Fig. 11.23 Gout. Urate crystals are negatively birefringent under polarizing microscopy (from the tissue section shown in Fig. 11.20)

385

386 Fig. 11.24 Gout. A smear from a fresh specimen under polarized light demonstrates negatively birefringent needle-shaped crystals

11

Tumor-like Conditions

11.5

11.5

Calcium Pyrophosphate Dihydrate Disease

387

Calcium Pyrophosphate Dihydrate Disease

Fig. 11.25 Calcium pyrophosphate dihydrate disease. Conventional anteroposterior (left) and lateral (right) radiographs of the knee of a 66-year-old man demonstrate calcification in both menisci, articular cartilage, and posterior joint capsule, all characteristic of calcium pyrophosphate dihydrate disease (CPPD). Note that the outline of the posterior capsule is identified on the lateral view. This condition is a metabolic arthropathy caused by the deposition of calcium pyrophos-

phate dehydrate crystals in and around joints. The deposition of CPPD crystals in articular tissues is most common in older patients. Chondrocalcinosis is a generic term referring to the radiographic evidence of calcification in hyaline or fibrocartilage, or both. Multiple joints may be involved, with the knees most commonly affected. (Photograph courtesy of Dr. Michael Pitt)

388

Fig. 11.26 Calcium pyrophosphate dihydrate disease. CPPD may be asymptomatic or present as either acute or chronic arthritis. Pseudogout refers to gout-like episodes of an acute inflammatory reaction to CPPD crystals. Spontaneous onset of red, swollen, painful joint(s) is the typical presentation. This conventional radiograph shows soft tissue swelling surrounding the proximal and middle phalanx of the fourth toe with diffuse radiodensities (indicated by arrowheads). The radiographic differential diagnosis includes a calcified lipomatous lesion versus CPPD. The histologic examination of the resected lesion revealed CPPD

Fig. 11.27 Calcium pyrophosphate dihydrate disease. The deposits are chalky white grossly and appear as aggregates of amorphous and purple-blue crystals on low-power microscopy

11

Tumor-like Conditions

11.5

Calcium Pyrophosphate Dihydrate Disease

Fig. 11.28 Calcium pyrophosphate dihydrate disease. The surrounding tissue shows cartilage metaplasia typically associated with CPPD

Fig. 11.29 Calcium pyrophosphate dihydrate disease. A high-power view of calcium pyrophosphate dehydrate crystals

389

390 Fig. 11.30 Calcium pyrophosphate dihydrate disease. CPPD crystals are rhomboid and weakly positively birefringent when viewed in polarized light, as opposed to the needle-like morphologic appearance and strong negative birefringence of the uric crystals in gout. They are best detected in synovial fluid or un-decalcified tissue

Fig. 11.31 Calcium pyrophos phate dihydrate disease. The proliferative synovium shows cartilage metaplasia

11

Tumor-like Conditions

11.6

11.6

Bizarre Parosteal Osteochondromatous Proliferation

Bizarre Parosteal Osteochondromatous Proliferation

Fig. 11.32 Bizarre parosteal osteochondromatous proliferation (Nora’s lesion). This entity may present as a rapidly growing mass with aggressive features on imaging studies. Bizarre parosteal osteochondromatous proliferation (BPOP) usually affects the small tubular bones of the hands and, less commonly, the feet. This conventional radiograph from an 11-year-old girl shows a mature osseous excrescence extending from the dorsal medial aspect of the distal portion of the distal phalanx of the left toe. The lesion appears to be an “add-on” lesion, with no cortical or medullary continuity with the adjacent bone. Nora’s lesion originally was thought to be a reactive process. However, cytogenetic analysis has identified a unique nonrandom molecular signature [t(1:17) (q32;q21)], thus suggesting that this lesion is neoplastic in nature (Photograph courtesy of Dr. Michael Pitt)

391

392

Fig. 11.33 Bizarre parosteal osteochondromatous proliferation. Rarely, other skeletal sites may be affected. Coronal PD (left) and axial T2-weighted (right) MR images from a 15-year-old girl show a soft tissue lesion adjacent to the lateral aspect of the distal fibula, with mixed

Fig. 11.34 Bizarre parosteal osteochondromatous proliferation. The lesion typically is small (<2 cm) but has confusing findings histologically; at low-power magnification, it consists of a heterogeneous mixture of cellular cartilaginous tissue, bone, and proliferative fibroblasts

11

Tumor-like Conditions

bone and cartilage elements but no continuity with the fibula medulla, a feature that contrasts with osteochondroma. The histologic examination of the resected lesion demonstrated BPOP

11.6

Bizarre Parosteal Osteochondromatous Proliferation

Fig. 11.35 Bizarre parosteal osteochondromatous proliferation. The lesional components typically are arranged in a disorganized fashion

Fig. 11.36 Bizarre parosteal osteochondromatous proliferation. The periphery of the lesion typically is made up of wellcircumscribed lobulated cellular cartilage, and there may be an overlying fibrous pseudocapsule, as illustrated. In contrast to osteochondromas, the endochondral ossification in BPOP is less organized and irregular, with random and patchy areas of ossification

393

394 Fig. 11.37 Bizarre parosteal osteochondromatous proliferation. Intermixed with disorganized bone and cartilage is fibrovascular connective tissue with variable cellularity

Fig. 11.38 Bizarre parosteal osteochondromatous proliferation. The irregular calcified matrix has a distinct blue tint (referred to as “blue bone”), a characteristic feature of BPOP. A transition from one tissue type to another (chondro-osseous metaplasia) is evident in this image. The osteoblasts rimming the bony trabeculae do not exhibit cellular atypia

11

Tumor-like Conditions

11.6

Bizarre Parosteal Osteochondromatous Proliferation

Fig. 11.39 Bizarre parosteal osteochondromatous proliferation. Enlarged, bizarre chondrocytes with maturation into bone are seen in areas, whereas proliferative spindled fibroblasts show minimal cytologic atypia. Some mitotic activity in the spindle cell component may be present, but no atypical forms are discernible

Fig. 11.40 Bizarre parosteal osteochondromatous proliferation. A section showing nearly pure blue bone with loose fibrovascular stroma

395

396 Fig. 11.41 Bizarre parosteal osteochondromatous proliferation. Another example with relatively matured bone. Again, the characteristic blue bone still can be appreciated

11

Tumor-like Conditions

11.7

11.7

Subungual Exostosis

Subungual Exostosis

Fig. 11.42 Subungual exostosis. A conventional radiograph reveals a calcifying projection on the dorsal radial aspect of the left ring finger distal tuft, continuous with the underlying bone. Subungual exostoses are abnormal bony projections arising from the dorsal surface of the distal phalanx, beneath or adjacent to the nail. Predominantly seen in children and young adults, the lesions most commonly affect the great toe, but they also may occur under the smaller toenails or on the fingers. The exact pathogenesis of this condition is unclear, but it has been thought to reflect reactive changes resulting from microtrauma. However, like many similar lesions, cytogenetics have identified a nonrandom translocation arguing for a clonal population, i.e. neoplastic proliferation

397

398 Fig. 11.43 Subungual exostosis. Histologically, subungual exostoses typically show trabecular bone covered by a hyaline cartilage cap, as in osteochondromas. However, the resected specimen may not show a well-preserved architecture, as depicted in this photomicrograph (section of the lesion seen in Fig. 11.42). Thus, correlation with the radiographic findings is critical

11 Tumor-like Conditions

11.8 Myositis Ossificans

11.8

Myositis Ossificans

Fig. 11.44 Myositis ossificans. An axial pelvic CT image demonstrates a left acetabular fracture with multiple intraarticular loose fracture fragments. Irregular areas of intramuscular hyperdensity adjacent to the acetabular wall fracture are evident (arrowheads), most likely representing myositis ossificans, a reactive ossifying process. Myositis ossificans is thought to be related to trauma or other types of injury, and typically presents as rapidly growing, solitary, and wellcircumscribed masses of soft tissue, most commonly seen in the musculature

Fig. 11.45 Myositis ossificans. Histologically, myositis ossificans is characterized by a zonal proliferation of fibroblasts and bone-forming osteoblasts that progress through various stages of ossification. This low-power view shows a typical zonation pattern with mature bone formation at the periphery (left) and fasciitis-like areas in the center of the lesion (right)

399

400 Fig. 11.46 Myositis ossificans. A higher-power view showing the periphery of myositis ossificans with irregularly arranged well-formed bone trabeculae rimmed by plump osteoblasts

Fig. 11.47 Myositis ossificans. The intermediate portion of myositis ossificans showing the transition from trabeculae of immature osteoid to woven bone embedded in a stroma consisting of fibroblasts and inflammatory cells

11

Tumor-like Conditions

11.8 Myositis Ossificans Fig. 11.48 Myositis ossificans. The innermost portion of the lesion showing randomly arranged fibroblasts/ myofibroblasts intermingled with mixed inflammatory cells in a myxoid stroma, thus closely resembling nodular fasciitis. Mitotic figures invariably are present, especially in the early phase. Atypical mitotic forms are uniformly absent

Fig. 11.49 Myositis ossificans. Islands of immature or mature cartilage also may be seen and proceed to bone formation, simulating a fracture callus

401

402 Fig. 11.50 Myositis ossificans. Another example showing well-organized bony trabeculae with gradual transition of bone formation

Fig. 11.51 Myositis ossificans. A high-power view showing proliferation of spindled fibroblasts, plump osteoblasts, and degenerative skeletal muscle fibers

11

Tumor-like Conditions

11.8 Myositis Ossificans Fig. 11.52 Myositis ossificans. Over time, the lesion may become a shell of bone composed of only mature cortical or lamellar bone at the periphery, whereas the center becomes quiescent and consists of paucicellular fibroconnective tissue. Alternatively, the center also may be ossified and may contain fatty or hematopoietic marrow elements, thus making it indistinguishable from an osteoma

403

Reactive, Metabolic, and Developmental Conditions

This chapter covers several nonneoplastic, noninflammatory entities that are reactive, metabolic, or developmental in nature. Osteoarthritis almost exclusively affects weightbearing joints and remains mostly idiopathic in nature, although frequently it also is a consequence of other

12

conditions involving the joints and synovium. The metabolic and developmental conditions typically involve the skeleton systemically, although they may present as focal lesions (i.e., Paget disease and phosphaturic mesenchymal tumor).

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_12, © Springer Science+Business Media New York 2013

405

406

12.1

12

Reactive, Metabolic, and Developmental Conditions

Osteoarthritis

Fig. 12.1 Osteoarthritis. This conventional radiograph shows complete loss of the right superior hip joint space with large subchondral cyst formation at the acetabular and femoral aspects. Marginal osteophyte formation is seen, along with mild subchondral sclerosis. Mild chondrocalcinosis is suspected. The left side demonstrates joint space narrowing and mild osteophyte formation. Osteoarthritis, also known

Fig. 12.2 Osteoarthritis. This radiograph shows marked narrowing of the medial femorotibial compartment with marginal osteophyte formation and mild subchondral sclerosis. Milder degenerative changes also are identified within the lateral compartment

as degenerative joint disease or osteoarthrosis, may be idiopathic in origin or a common outcome to a variety of disorders involving synovial joints, including those of hereditary, developmental, metabolic, or mechanical etiology. The condition is characterized by damage to and loss of articular cartilage, subarticular bone sclerosis and cysts, osteophyte formation, synovial hyperplasia, and synoviocyte hypertrophy

12.1

Osteoarthritis

Fig. 12.3 Osteoarthritis. The weight-bearing surface of the femoral head shows eburnation of the underlying bone with minimal cartilage remaining. A coronal section reveals subarticular cysts underlying the surface with eburnation. Osteophyte formation is evident on the weight-bearing areas surrounding the ligamentum teres and the cortex approaching the femoral neck. (Bar scale same as Fig. 12.4)

Fig. 12.4 Osteoarthritis. The articular surface of the tibial plateau and the femoral condyle show extensive erosion of the articular cartilage and eburnation of the underlying bone. Prominent osteophytes are present at the edges of the articular surface

407

408

Fig. 12.5 Osteoarthritis. In contrast to normal articular cartilage (left), the osteoarthritic joints typically lose the smooth contour of articular surface as initial changes occur (right). Vertical clefting or fissuring is a

Fig. 12.6 Osteoarthritis. As the disease progresses, the articular cartilage continues to deteriorate until it is completely worn out, resulting in “polishing” of the bone due to bone-on-bone contact (eburnation). This underlying subchondral bone eventually becomes sclerotic and then necrotic owing to the lack of protection from the weight load as a result of the loss of the overlying cartilage

12

Reactive, Metabolic, and Developmental Conditions

common finding. These degenerative changes usually are focal and do not affect the entire articular cartilage uniformly

12.1

Osteoarthritis

Fig. 12.7 Osteoarthritis. Osteophyte formation. The new bone formation within the cartilage separates the cartilage into two layers: one lies on the surface of the osteophyte, whereas the other is buried deeply in the original line of articular surface. The inset illustrates a small, early osteophyte

Fig. 12.8 Osteoarthritis. Another example of an osteophyte protruding from the articular surface

409

410 Fig. 12.9 Osteoarthritis. A subchondral bone cyst, often referred to as a geode, beneath the area of eburnation. A geode is composed of fibrous connective tissue with or without fluid

Fig. 12.10 Osteoarthritis. Another geode, showing a well-formed cystic space devoid of epithelial lining. The cystic fluid typically is lost during tissue processing

12

Reactive, Metabolic, and Developmental Conditions

12.1

Osteoarthritis

Fig. 12.11 Osteoarthritis. Papillary synovial hyperplasia and synoviocyte hypertrophy are common findings in osteoarthritic synovium

411

412

12.2

12

Rheumatoid Arthritis

Fig. 12.12 Rheumatoid arthritis. A conventional radiograph of the right hand shows a dramatic abnormality of the right wrist with advanced pancarpal and secondary degenerative changes. There are subchondral erosions and cysts with a fusiform soft tissue swelling of the long finger proximal interphalangeal joint. There is less pronounced fusiform soft tissue swelling surrounding the index and long finger metacarpophalangeal joints. Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder, the hallmark feature of which is persistent symmetric polyarthritis of the synovial joints, principally affecting the hands and feet

Reactive, Metabolic, and Developmental Conditions

12.2

Rheumatoid Arthritis

Fig. 12.13 Rheumatoid arthritis. A low-power view of papillary synovial hyperplasia in RA. Note the extensive lymphoplasmacytic infiltrate with germinal center formation. The hyperplastic synovium and inflammatory exudate may form a mass lesion over the articular surface, a process known as pannus formation, which often leads to the destruction of articular cartilage and subchondral bone erosion

Fig. 12.14 Rheumatoid arthritis. Necrotizing granulomatous inflammation (rheumatoid nodule) is a frequent finding in RA that simulates infectious granulomata

413

414 Fig. 12.15 Rheumatoid arthritis. A higher-magnification image demonstrating a rheumatoid nodule with central necrosis, peripheral histiocytic palisading and multinucleated giant cells

Fig. 12.16 Rheumatoid arthritis. A large rheumatoid nodule undergoing cystic degeneration (from the lesion shown in Fig. 12.12)

12 Reactive, Metabolic, and Developmental Conditions

12.3

12.3

Detritic Synovitis

Detritic Synovitis

Fig. 12.17 Detritic synovitis. This image shows synovial tissue with an exuberant foreign body reaction to refractile polyethylene shards. Arthroplasty is one of the most common elective orthopedic surgical procedures for dysfunctional joints of various causes, including osteoarthritis, avascular necrosis, and RA. A common complication is aseptic loosening of the prostheses caused by mechanical failure of the materials employed (i.e., polyethylene, metal alloys, and methyl methacrylate) with excessive use. Detritic synovitis is a descriptive pathologic term for the constellation of changes associated with joint arthroplasties. Larger pieces of polyethylene are easily recognizable as amorphous refractile materials associated with extensive histiocytic and foreign body giant cell reactions, as illustrated

Fig. 12.18 Detritic synovitis. Photomicrograph of the same field shown in Fig. 12.17 on polarized microscopy confirming the presence of refractile polyethylene particulate debris

415

416

Fig. 12.19 Detritic synovitis. Small fragments of polyethylene commonly are needle shaped and may be overlooked (left), unless the slides are examined under polarized light (right). However, the presence of

12

Reactive, Metabolic, and Developmental Conditions

foreign body–type multinucleated giant cells and abundant histiocytes is an important clue

12.3

Detritic Synovitis

417

Fig. 12.20 Detritic synovitis. Especially with metal-on-metal prostheses, the metallic debris typically is seen within the histiocytes and, whether needle shaped or dot-like, it may be inconspicuous (left) or abundant (right). Well-formed granulomas also may be present

Fig. 12.21 Detritic synovitis. Papillary fibrocartilaginous metaplasia commonly is associated with detritic synovitis. Other nonspecific findings include hemosiderin-laden macrophages, coagulative necrosis in the absence of inflammation, and reactive myofibroblastic proliferation

418

12.4

12

Gaucher Disease

Fig. 12.22 Gaucher disease. In Gaucher disease, the marrow space is replaced by histiocytes with abundant cytoplasm. The disease, an autosomal recessive disorder, is the most common lysosomal storage disease caused by a defect in the housekeeping gene lysosomal gluco-cerebrosidase, which results in the accumulation of glucosylceramide, a cell membrane constituent of erythrocytes and leukocytes. The macrophages that phagocytose these cells cannot eliminate the waste product, which accumulates in fibrils with a tissue-paper appearance on light microscopy (i.e., Gaucher cells). Most of these patients develop visible bony abnormalities owing to the accumulated glucosylceramide

Fig. 12.23 Gaucher disease. A high-power view of lipidladen Gaucher cells with abundant eosinophilic cytoplasm

Reactive, Metabolic, and Developmental Conditions

12.4

Gaucher Disease

Fig. 12.24 Gaucher disease. Gaucher cells showing clear cytoplasm resembling crumpledup tissue paper. Other storage diseases may have a similar appearance

419

420

12.5

12

Reactive, Metabolic, and Developmental Conditions

Osteogenesis Imperfecta

Fig. 12.25 Osteogenesis imperfecta. Gross (left) and radiographic (right) appearance of a type II osteogenesis imperfecta (OI) from a 38-week-old fetus following intrauterine death. OI, a congenital disease resulting in extremely fragile bones, is caused by mutations in the genes encoding type I procollagen (i.e., COL1A1 and COL1A2). The severity of the disease varies greatly, with type I being the mild and commonest form and type II the most severe one. Patients typically develop a variable

degree of bone disorders, including osteopenia/osteoporosis, skeletal deformities, and multiple fractures. The classic extraskeletal symptoms include blue sclera and early hearing loss. Note that in this case, there is marked pneumothorax as a result of an attempt to ventilate the hypoplastic lungs. Note also the generalized osteopenia, multiple rib fractures, and ballotable brain due to the lack of ossification of the skull (Photograph courtesy of Dr. Ona Faye-Petersen)

12.5

Osteogenesis Imperfecta

Fig. 12.26 Osteogenesis imperfecta. Another example of type II OI, in a 22-week-old fetus. Note the skeletal deformities with disproportionately short upper and lower extremities (Photograph courtesy of Dr. Ona Faye-Petersen)

421

Fig. 12.27 Osteogenesis imperfecta. A full-body conventional radiograph demonstrates irregular, asymmetric bulky angulations of long bones throughout the entire skeletal system, numerous rib fractures (“beading”), and a poorly ossified skull (Photograph courtesy of Dr. Ona Faye-Petersen)

422 Fig. 12.28 Osteogenesis imperfecta. Gross pathologic features of long bones from type II OI showing normal articular cartilage and defective endochondral ossification (Photograph courtesy of Dr. Ona Faye-Petersen)

Fig. 12.29 Osteogenesis imperfecta. “Transparent skull” in OI caused by decreased mineralization of intramembranous ossification of calvarium (Photograph courtesy of Dr. Ona Faye-Petersen)

12

Reactive, Metabolic, and Developmental Conditions

12.5

Osteogenesis Imperfecta

Fig. 12.30 Osteogenesis imperfecta. In bone, the disease affects both endochondral and intramembranous ossification, and the degree of histologic change correlates well with the clinical severity of the disease. In contrast to the normal endochondral ossification of long bone in an

Fig. 12.31 Osteogenesis imperfecta. The defect in endochondral ossification of a rib is evident in this type II OI

423

age-matched fetus (left), this type II OI fetus demonstrates failure of endochondral ossification because of deficiency of the primary spongiosa of the metaphysis (right)

424 Fig. 12.32 Osteogenesis imperfecta. A fracture callus in OI. Note the exuberant chondrocyte proliferation without functional reparative bone formation

12

Reactive, Metabolic, and Developmental Conditions

12.6

12.6

Osteomalacia/Rickets

Osteomalacia/Rickets

Fig 12.33 Osteomalacia. Osteomalacia (meaning “softening of the bone” in Greek), known as rickets in children, is caused by defective bone mineralization. The causes of the disease are varied but ultimately result in a vitamin D deficiency. Different from osteoporosis, which is caused by a weakening of previously constructed bone, osteomalacia or rickets results from a defect in the bone-building process. Histologically, the disorder typically shows increased osteoblastic activity resulting in the production of enormous amounts of osteoid, with mineralization lagging behind the osteoid formation. A Goldner trichrome stain (mineralized bone is green and osteoid is orange) of a transiliac crest bone biopsy specimen from a patient diagnosed with osteomalacia shows a trabecula with a central region of mineralized bone covered by an excessive amount of unmineralized osteoid matrix

425

426

12.7

12

Reactive, Metabolic, and Developmental Conditions

Osteopenia/Osteoporosis

Fig. 12.34 Osteopenia/osteoporosis. A 20-year-old woman with severe regional enterocolitis resulting in malabsorption was treated with chronic oral steroids. Conventional spine radiographs (left, anteroposterior view; right, lateral view) show advanced osteopenia with decreased density and depression of sharply defined vertebral body end plates. Osteoporosis is defined by the World Health Organization as bone mineral density (BMD) 2.5 or more standard deviations below the mean peak bone mass of young, healthy adults (T-score £ −2.5).

Osteopenia refers to BMD that is lower than normal but not low enough to be classified as osteoporosis and, more specifically, is defined as a T-score between −1.0 and −2.5. Osteoporosis may be subclassified as primary type 1 (postmenopausal osteoporosis), primary type 2 (senile osteoporosis), or secondary. The last type results from many chronic predisposing conditions, such as lack of motion and prolonged used of glucocorticoids

12.7

Osteopenia/Osteoporosis

Fig. 12.35 Osteopenia/ osteoporosis. Histologically, osteopenia/osteoporosis typically shows smooth, significantly thinned trabeculae and markedly decreased connectivity, as illustrated. However, conventionally processed and stained slides are a notorious trap for either undercalling or overcalling osteopenia/ osteoporosis. When suspected clinically or identified on dual-energy x-ray absorptiometry scans, metabolic bone studies are required, with morphometric analysis to confirm the diagnosis

Fig. 12.36 Osteopenia/ osteoporosis. In osteoporosis, the trabeculae typically average between two and less than one mature adipocyte in thickness. Lamellated reversal lines, as evidence of bone remodeling, are visible

427

428

12.8

12

Osteopetrosis

Fig. 12.37 Osteopetrosis. Also known as marble bone disease or Albers-Schönberg disease, osteopetrosis is a rare congenital disorder with an autosomal recessive, autosomal dominant, or X-linked mode of inheritance caused by mutations in various genes and resulting in osteoclast dysfunction. The osteoclast differentiation is largely unaffected in osteopetrosis. Thus, the number of osteoclasts may be reduced, normal, or increased. Radiographically, the entire skeleton shows a marked increase in density. A “bone within bone” appearance also may be seen. Histologically, as depicted in this image, the medullary cavity is largely obliterated by persistent cartilage undergoing enchondral ossification (thus resembling the primary spongiosa), with minimal hematopoietic elements present

Fig. 12.38 Osteopetrosis. A section showing the growth plate. The bone trabeculae may be woven or lamellar in nature. Osteoclasts (arrowhead) often are large and may be abundant. They typically reside in a fibrovascular marrow but are not opposed to bone surfaces and thus the bone is devoid of resorption pits

Reactive, Metabolic, and Developmental Conditions

12.9

12.9

Paget Disease

Paget Disease

Fig. 12.39 Paget disease. A conventional radiograph of the skull demonstrates diffuse sclerotic changes with focal lucent lesions. Paget disease (osteitis deformans) is a localized disorder of bone remodeling of unknown etiology that may affect any skeleton. Both genetic and environmental factors have been implicated. Mutations in the SQSTM1 gene are found in a significant proportion of familial Paget disease and, to a much lesser extent, in sporadic cases. These mutations result in activated RANK signaling, which in turn leads to accelerated osteoclast formation and activity

429

430 Fig. 12.40 Paget disease. Sagittal (left) and axial (right) CT images demonstrate a mixed lytic/sclerotic, but predominantly sclerotic, lesion involving the T6 vertebral body and causing a compression fracture, with approximately a 50 % loss in height. The lesion also involves the pedicles and laminae. Paget disease may be divided into three phases: osteolytic, mixed osteoclastic-osteoblastic, and osteosclerotic. This reflects the initial osteoclastic activation followed by compensatory increased osteoblastic activity. At any one time, different stages of the disease may be demonstrated in an individual patient. The net effect is gain in bone mass. However, the newly formed bone is architecturally abnormal and becomes mechanically fragile and unstable

Fig. 12.41 Paget disease. A sagittal T1-weighted magnetic resonance image of the lesion seen in Fig. 12.40 (left) showing increased vascularity with intravenous contrast (right). Bone remodeling has expanded into the spinal canal, causing central spinal stenosis

12 Reactive, Metabolic, and Developmental Conditions

12.9

Paget Disease

Fig. 12.42 Paget disease. A low-power view of Paget disease showing markedly increased bone remodeling. The cancellous bone is replaced by haphazardly arranged thick bone trabeculae embedded in vascular-rich loose fibrous tissue

Fig. 12.43 Paget disease. A higher-magnification histopathologic image shows active osteoclastic bone resorption (left) and newly formed bone rimmed by plump osteoblasts (right). Note the prominent vascularity in pagetoid bone, which consists of patent capillaries, dilated arterioles, and large venous sinuses. This may lead to an incorrect diagnosis of a vascular tumor radiologically and pathologically if the biopsy sample is small

431

432 Fig. 12.44 Paget disease. The repeated bone resorption– formation common in Paget disease results in a mosaic pattern with accentuated reverse cement lines, the histologic hallmark of the disease

Fig. 12.45 Paget disease. When the osteoblastic phase predominates, the excessive bone formation results in more compact and coarse bone

12

Reactive, Metabolic, and Developmental Conditions

12.9

Paget Disease

Fig. 12.46 Paget disease. A trichrome stain of pagetoid bone demonstrating resorption lacunae (as evidence of active osteoclastic activity) and deposition of osteoid (highlighted by the red staining) by osteoblasts

433

434

12

Reactive, Metabolic, and Developmental Conditions

12.10 Phosphaturic Mesenchymal Tumor

Fig. 12.47 Phosphaturic mesenchymal tumor. The patient is a 32-yearold woman with a 2-year history of progressive weakness and pain, particularly in the groin region and lower extremities. A conventional radiograph shows bilateral, symmetric Looser zones (pseudofractures) in femoral necks. Laboratory studies revealed hypophosphatemia and hyperphosphaturia. Surgical removal of a dermatofibrosarcomous protuberance on her thigh resulted in improvement of her symptoms, and her serum and urine phosphate levels returned to the normal range. Also known as oncogenic osteomalacia, phosphaturic mesenchymal tumor is a heterogeneous group of rare mesenchymal tumors that often cause

rickets or osteomalacia as a paraneoplastic syndrome by the tumorproduced phosphatonin (fibroblast growth factor 23). Along with localized lesions, patients typically present with specific biochemical abnormalities, including hypophosphatemia, hyperphosphaturia, and decreased 1,25-dihydroxyvitamin D levels unresponsive to dietary supplementation owing to the phosphaturic activity of phosphatonin. The localized tumors may occur in bones and soft tissue with equal frequency and rarely involve the craniofacial regions (Photograph courtesy of Dr. Michael Pitt)

12.10

Phosphaturic Mesenchymal Tumor

Fig. 12.48 Phosphaturic mesenchymal tumor. Most tumors constitute a single histologic entity termed phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT). These tumors exhibit a broad histologic spectrum. Proliferation of small, bland, spindle cells with a prominent vascular element is common, as illustrated

Fig. 12.49 Phosphaturic mesenchymal tumor. The vascular component may dominate the lesion, thus simulating vascular tumors such as hemangiopericytoma and hemangioma

435

436 Fig. 12.50 Phosphaturic mesenchymal tumor. Smudged, osteoid-like extracellular matrix is common in PMTMCT

Fig. 12.51 Phosphaturic mesenchymal tumor. The matrix may calcify in a flocculent fashion, often described as “grungy calcifications”

12

Reactive, Metabolic, and Developmental Conditions

12.10

Phosphaturic Mesenchymal Tumor

Fig. 12.52 Phosphaturic mesenchymal tumor. Cartilagelike matrix in PMTMCT

Fig. 12.53 Phosphaturic mesenchymal tumor. Myxoid changes and microcyst formation are frequent findings in PMTMCT

437

438 Fig. 12.54 Phosphaturic mesenchymal tumor. Other common findings include abundant hemosiderin deposition, scattered or clustered osteoclast-like giant cells, and adipocytes

Fig. 12.55 Malignant phosphaturic mesenchymal tumor. Most tumors follow a benign clinical course, with complete resection resulting in normal serum phosphate levels and dramatic improvement of osteomalacia, whereas rare lesions behave in a malignant fashion, clinically resulting in recurrence and metastasis. Histologically, malignant PMTMCTs resemble an undifferentiated pleomorphic sarcoma or fibrosarcoma (as illustrated in this image) and exhibit hypercellularity, high nuclear grade, and increased mitotic activity

12

Reactive, Metabolic, and Developmental Conditions

12.10

Phosphaturic Mesenchymal Tumor

Fig. 12.56 Malignant phosphaturic mesenchymal tumor. An area of this malignant PMTMCT showing prominent osteoid-like matrix that is partly calcified

Fig. 12.57 Malignant phosphaturic mesenchymal tumor. A high-power view showing cellular pleomorphism and an atypical mitotic figure

439

440 Fig. 12.58 Malignant phosphaturic mesenchymal tumor. PMTMCT metastasized to a regional lymph node

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Reactive, Metabolic, and Developmental Conditions

Metastases to and from Bone

Bone, lymph nodes, lung, and liver represent the most common sites of tumor metastasis. Meanwhile, metastatic tumor within bone is the most common type of malignant tumor involving bone. Carcinomas are much more likely than sarcomas to metastasize to bone. Virtually all types of carcinomas can metastasize to bone. The most common origins include breast, lung, prostate, thyroid, and kidney. In fact, certain solid tumors have a particular propensity to seed within bone (e.g., prostate cancer), a theory known as the “seed and soil” hypothesis proposed by Stephen Paget more than a century ago. Radiographically, bone metastasis most commonly is osteolytic and, less frequently, osteoblastic or

13

mixed. Most lesions are mixed microscopically as a result of an active remodeling process. The use of immunohistochemistry has allowed pathologists to better identify the origins of many of these metastases, although a small proportion of cases remain “cancer of unknown primary origin” despite extensive radiologic and pathologic workup. Advances in molecular genetics are expected to narrow this category even further. The most common metastasis from bone is from osteosarcoma, and the most common site to which it spreads is the lungs. High-grade chondrosarcomas also may have distant metastases, which also usually occur, as do most sarcomas, in the lungs.

S. Wei, G.P. Siegal, Atlas of Bone Pathology, Atlas of Anatomic Pathology, DOI 10.1007/978-1-4614-6327-6_13, © Springer Science+Business Media New York 2013

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442

13.1

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Metastases to and from Bone

Metastases to Bone

Fig. 13.2 Metastatic breast carcinoma. A cross-section of the resected proximal femur shown in Fig. 13.1 demonstrates a tan-pink fleshyappearing tumor that replaces much of the cortex and central medulla

Fig. 13.1 Metastatic breast carcinoma. The lytic lesion involving the right greater trochanter, femoral neck, and proximal femoral diaphysis appears permeative with endosteal thinning in this conventional radiograph. No soft tissue mass is identified. The lesion most likely represents a metastatic carcinoma of the breast, given the patient’s history of breast cancer. The differential diagnosis radiologically also includes multiple myeloma or other small, blue, round cell tumors and, less likely, a primary bone tumor such as malignant fibrous histiocytoma

13.1

Metastases to Bone

Fig. 13.3 Metastatic breast carcinoma. The tumor exhibits well-formed glands. Note that the bone is almost completely replaced by tumor and surrounding desmoplastic response

Fig. 13.4 Metastatic breast carcinoma. This tumor is high grade and poorly differentiated. However, the gland-forming characteristics can still be appreciated in areas. An immunohistochemical (IHC) panel may be used to help define the cells as originating in the breast and, depending on the circumstances, might include estrogen receptor, progesterone receptor, gross cystic disease fluid protein 15, and mammaglobin among many others

443

444 Fig. 13.5 Metastatic breast carcinoma. This metastatic tumor is derived from lobular carcinoma of the breast and demonstrates predominantly plasmacytoid features

Fig. 13.6 Metastatic breast carcinoma. Mammaglobin is a relatively specific marker for the adult mammary gland but is less sensitive. This protein also may be expressed in tumors of other organs, such as the salivary gland and endometrium

13

Metastases to and from Bone

13.1

Metastases to Bone

Fig. 13.7 Metastatic breast carcinoma. Diff-Quik–stained fine-needle aspiration of metastatic breast carcinoma

Fig. 13.8 Metastatic renal cell carcinoma. Gross photograph of a distal femur with metastatic renal cell carcinoma showing a tan, fleshy, well-circumscribed mass lesion that destroyed the medial femoral cortex at the level of the metadiaphysis. The mass lifts the periosteum but does not penetrate it

445

446

Fig. 13.9 Metastatic renal cell carcinoma. A conventional radiograph of a patient with a known history of metastatic renal cell carcinoma to the right proximal femur demonstrates an intramedullary nail traversing a lytic destructive lesion involving the right femoral neck, lesser trochanter, and proximal femur

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Metastases to and from Bone

Fig. 13.10 Metastatic renal cell carcinoma. The gross specimen corresponding to the lesion shown in Fig. 13.9 demonstrates a hemorrhagic, necrotic mass that occupies the space between the inferior aspect of the head and the shaft of the femur. The eroded mass exposes the metallic prosthesis in the femoral neck

13.1

Metastases to Bone

Fig. 13.11 Metastatic renal cell carcinoma. Most metastatic renal cell carcinomas have a vascularrich, clear cell histomorphologic appearance and thus are easily recognizable. However, care must be taken to exclude clear cell metastases from other sites

Fig. 13.12 Metastatic renal cell carcinoma. Like other sarcomatoid carcinomas, sarcomatoid renal cell carcinoma may mimic a primary bone sarcoma. Therefore, a cytokeratin immunostain should be performed in all bone tumors of this type unless there is a clear-cut cytomorphologic finding

447

448 Fig. 13.13 Metastatic renal cell carcinoma. Diff-Quik–stained fine-needle aspiration shows a metastatic carcinoma with abundant vacuolated cytoplasm characteristic of clear cell renal cell carcinoma

Fig. 13.14 Metastatic lung cancer. Magnetic resonance images show a diffusely enhancing lesion with hypointense T1 (left) and hyperintense T2 (right) signal within the medial left femoral neck. No cortical disruption, endosteal scalloping, soft tissue mass, or periosteal reaction is seen. The findings are consistent with a metastasis and are strengthened given the patient’s history of lung cancer

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Metastases to and from Bone

13.1

Metastases to Bone

Fig. 13.15 Metastatic lung cancer. Gross appearance of the lesion shown in Fig. 13.14. The lesion is sclerotic, hemorrhagic, and cystic

Fig. 13.16 Metastatic adenocarcinoma of the lung. This image shows a poorly differentiated metastatic adenocarcinoma. Thyroid transcriptional factor 1 immunoreactivity (inset), along with a radiologic finding of a lung mass, supports the diagnosis of a metastatic lung carcinoma

449

450 Fig. 13.17 Metastatic small cell carcinoma of the lung. Because of crush artifact, there are few recognizable tumor cells. Immunoreactivity usually is retained in crushed specimens, although it may be affected by the decalcification process. Reactivity for neuroendocrine markers (chromogranin, synaptophysin, or CD56) and CD45 negativity would support the diagnosis of a neuroendocrine carcinoma and exclude most lymphomas or inflammatory processes. The findings are mostly consistent with a small cell carcinoma, as extensive crush artifact typically is not a feature of large cell neuroendocrine carcinoma

Fig. 13.18 Metastatic prostatic adenocarcinoma. A chest CT image shows numerous sclerotic lesions throughout the spine

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Metastases to and from Bone

13.1

Metastases to Bone

Fig. 13.19 Metastatic prostatic adenocarcinoma. The tumor cells demonstrate abundant cytoplasm and enlarged nuclei with prominent nucleoli, typical of prostatic adenocarcinoma

Fig. 13.20 Metastatic prostatic adenocarcinoma. The tumor cells are poorly differentiated and exhibit marked crush artifact, which may necessitate IHC examination for confirmation of prostatic origin

451

452 Fig. 13.21 Metastatic thyroid carcinoma. The tumor demonstrates well-formed follicles, some of which contain colloid. This, along with a history of thyroid carcinoma, is diagnostic of metastatic follicular carcinoma of the thyroid

Fig. 13.22 Metastatic squamous cell carcinoma. Gross photograph of a portion of the femoral diaphysis and metaphysis from a patient with a history of squamous cell carcinoma of the head and neck. There is a hemorrhagic, necrotic mass within the medullary cavity of the diaphysis

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Metastases to and from Bone

13.1

Metastases to Bone

Fig. 13.23 Metastatic squamous cell carcinoma. A histologic section of the tumor shown in Fig. 13.22 demonstrates a squamous cell carcinoma with nested and single cells that produces a prominent desmoplastic stromal reaction

453

454

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Metastases to and from Bone

Fig. 13.25 Metastatic medulloblastoma. A coronal pelvic CT image from the patient shown in Fig. 13.24 demonstrates an ill-defined peripheral sclerotic lesion in the left iliac bone

Fig. 13.24 Metastatic medulloblastoma. Radioisotope scintigraphy using technetium-99m in a 51-year-old woman with a history of medulloblastoma shows focally increased radiotracer uptake in the upper thoracic spine, within the anterior iliac bones bilaterally, and in the posterior left iliac bone near the sacroiliac joint, all consistent with metastases

13.1

Metastases to Bone

Fig. 13.26 Metastatic medulloblastoma. CT-guided biopsy of the lesion shown in Fig. 13.25 reveals a round, blue cell tumor consistent with metastatic medulloblastoma

Fig. 13.27 Metastatic gastric carcinoma. An example of signet-ring cell carcinoma consistent with the patient’s history of gastric carcinoma

455

456 Fig. 13.28 Metastatic hepatocellular carcinoma. The characteristic trabecular growth pattern and the presence of bile pigment suggest the site of origin

Fig. 13.29 Metastatic hepatocellular carcinoma. Although the tumor is poorly differentiated, the histologic features of large central nuclei with prominent nucleoli and abundant granular eosinophilic cytoplasm suggest a hepatocellular origin

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Metastases to and from Bone

13.1

Metastases to Bone

Fig. 13.30 Metastatic hepatocellular carcinoma. A canalicular pattern of staining with polyclonal carcinoembryonic antigen (left) is characteristic of hepatocellular carcinoma. Hep Par 1 (right) is another useful marker in the differential diagnosis but is nonspecific for hepatocellular

457

origin. Cautious use of these antibodies in a panel with other markers to rule out other possibilities is needed, especially in the absence of a history of malignancy

458 Fig. 13.31 Metastatic neuroblastoma. Compact lobules of small, blue, round cells are separated by vascular-rich fibrous septa in the humerus of this child. A history of neuroblastoma 18 months earlier solidifies the diagnosis

Fig. 13.32 Metastatic neuroblastoma. Abundant rosettes of the FlexnerWintersteiner type showing columnar cells forming in the central empty luminal spaces

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Metastases to and from Bone

13.1

Metastases to Bone

Fig. 13.33 Metastatic neuroblastoma. Homer-Wright pseudorosette formation exhibiting halo-like clusters of cells surrounding a central area of fibrillar matrix

Fig. 13.34 Metastatic neuroblastoma. Geographic necrosis is not uncommon. Mitotic activity may be brisk. In the absence of clear histomorphologic findings or disease history, an IHC panel may be critical in separating this lesion from others mimicking small, blue, round cell tumors of childhood, including Ewing sarcoma, leukemia and lymphoma, and rhabdomyosarcoma

459

460 Fig. 13.35 Metastatic urothelial carcinoma. Small clusters or nested epithelial cells showing highly pleomorphic nuclei. High-grade urothelial carcinomas often have foci of squamous differentiation or even keratinization and thus may be confused with poorly differentiated squamous cell carcinoma

Fig. 13.36 Metastatic germ cell tumor. A bone biopsy from a 25-year-old man with a remote history of testicular teratoma demonstrates gland-forming, mucin-containing cells in the pool of stromal mucin. Although the tumor cells were nonreactive for all germ cell markers tested, the lesion most likely represents a metastatic testicular teratocarcinoma with a mucinous adenocarcinoma arising out of teratomatous elements

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Metastases to and from Bone

13.1

Metastases to Bone

Fig. 13.37 Metastatic melanoma. Because it is referred to as one of the “great mimickers” in pathology, the possibility of metastatic melanoma should be considered in virtually any poorly differentiated neoplasm. The presence of abundant intranuclear pseudo-inclusions is an important clue

Fig. 13.38 Metastatic thymic carcinoma. This biopsy specimen from a pelvic bone lesion in a patient with a large anterior mediastinal mass demonstrates a poorly differentiated carcinoma. Further workup revealed that the tumor was strongly immunoreactive with CD5 and CD117 (c-Kit), thus confirming its thymic origin

461

462 Fig. 13.39 Metastatic cholangiocarcinoma. Bone metastasis from cholangiocarcinoma is extremely rare but does occur. Note the active osteoclastic bone resorption

Fig. 13.40 Metastatic colorectal carcinoma. Carcinomas of colorectal origin generally are recognizable without immunophenotyping. The well-formed glands and “dirty” necrosis are the most useful clues

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Metastases to and from Bone

13.2

13.2

Metastases from Bone

Metastases from Bone

Fig. 13.41 Metastatic osteosarcoma. A coronal CT image demonstrates a large mass in the left lung occupying almost the entire upper lobe with irregular low-density areas of necrosis, enhancement, and dystrophic calcification. Although a primary pulmonary sarcoma also might have this appearance, given the patient’s history of osteosarcoma, the mass likely represents metastatic disease

Fig. 13.42 Metastatic osteosarcoma. The histologic section of the lesion shown in Fig. 13.41 demonstrates a spindle cell sarcoma with abundant osteoid production, which is diagnostic for metastatic osteosarcoma

463

464 Fig. 13.43 Metastatic osteosarcoma. This tumor shows an abrupt transition from osteoblastic to chondroblastic types. The latter may be confused with chondrosarcoma if the osteoblastic component or tumor osteoid is minimal

Fig. 13.44 Metastatic osteosarcoma. Like its primary counterparts, metastatic osteosarcoma may have a variable histologic appearance. This image illustrates a metastatic osteosarcoma with predominantly epithelioid morphology

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Metastases to and from Bone

13.2

Metastases from Bone

Fig. 13.45 Metastatic chondrosarcoma. A coronal CT image shows multiple pulmonary- and pleural-based nodules bilaterally, characteristic of metastases

Fig. 13.46 Metastatic chondrosarcoma. A section from the lesions shown in Fig. 13.45 demonstrates metastatic chondrosarcoma. It should be noted that rarely chondrosarcoma may arise de novo in bronchial cartilage. Thus, a careful review of the patient’s medical history is essential

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Suggested Reading

Adler C-P. Bone diseases: macroscopic, histological, and radiological diagnosis of structural changes in the skeleton. New York: Springer; 2012. Bullough PG. Orthopaedic pathology. 5th ed. Maryland Heights: Mosby Elsevier; 2010. Bullough PG, Vigorita VJ. Orthopedic pathology. 3rd ed. Philadelphia: Mosby-Year Book; 1997. Campanacci M, Enneking WF. Bone and soft tissue tumors: clinical features, imaging, pathology and treatment. 2nd ed. New York: Springer; 1999. Dorfman HD, Czerniak B. Bone tumors. St. Louis: Mosby; 1998. Edeiken J, Dalinka M, Karaisick D. Edeiken’s roentgen diagnosis of diseases of bone. 4th ed. Baltimore: Williams & Wilkins; 1990. Fechner RE, Mills SE. Atlas of tumor pathology: tumors of bones and joints, Fascicle 8, vol. 3. Washington, DC: Armed Forces Institute of Pathology/American Registry of Pathology; 1993. Fletcher CDM, Unni KK, Mertens F. Pathology and genetics of tumours of soft tissue and bone (IARC WHO classification of tumours). Lyon: International Agency for Research on Cancer; 2006. Folpe AL, Inwards CY. Bone and soft tissue pathology: a volume in the foundations in diagnostic pathology series. Philadelphia: Saunders Elsevier; 2010. Greenspan A, Jundt G, Remagen W. Differential diagnosis in orthopedic oncology. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2007. Hameed O, Wei S, Siegal GP. Frozen section library: bone. New York: Springer; 2011. Horvai A, Link T. Bone and soft tissue pathology: a volume in the high yield pathology series. Philadelphia: Saunders Elsevier; 2012. Huvos AG. Bone tumors: diagnosis, treatment, and prognosis. 2nd ed. Philadelphia: Saunders; 1991. Khurana JS. Bone pathology. New York: Humana Press; 2009. Khurana JS, McCarthy EF, Zhang PJ. Essentials in bone and soft-tissue pathology. New York: Springer; 2010. Klein MJ, Bonar SF, Freemont T, Vinh TN, Lopez-Ben R, Siegal HJ, Siegal GP. Atlas of nontumor pathology: nonneoplastic diseases of

bones and joints, Fascicle 9, vol. 1. Washington, DC: American Registry of Pathology; 2011. Layfield LJ. Cytopathology of bone and soft tissue tumors. New York: Oxford University Press; 2002. Mazabraud A. Pathology of bone tumours: personal experience. Reprint of the 1st (1998) ed. New York: Springer; 2012. McCarthy EF. Bone and joint disorders (differential diagnosis in pathology). New York: Igaku-Shoin; 1996. McCarthy EF. Essentials in bone and soft-tissue pathology. New York: Springer; 2010. McCarthy EF, Frassica FJ. Pathology of bone and joint disorders with clinical and radiographic correlation. Philadelphia: Saunders; 1998. Milgram JW. Radiologic and histologic pathology of nontumorous diseases of bones and joints. Northbrook: Northbrook Press; 1990. Mirra JM. Bone tumors: clinical, radiologic, and pathologic correlations. Philadelphia: Lea & Febiger; 1989. Moser RP. AFIP atlas of radiologic-pathologic correlation: cartilaginous tumors of the skeleton, Fascicle 2, vol. 1. Philadelphia: Hanley & Belfus; 1990. Nielsen GP, Rosenberg AE. Diagnostic pathology: bone. Philadelphia: Amirsys Lippincott William & Wilkins; 2012. Schajowicz F, Sundaram M, Gitelis S, McDonald DJ. Tumors and tumorlike lesions of bone: pathology, radiology, and treatment. 2nd ed. New York: Springer; 1995. Schwamm HA, Millward CL. Histologic differential diagnosis of skeletal lesions. New York: Igaku-Shoin; 1995. Unni KK, Inwards CY. Dahlin’s bone tumors: general aspects and data on 10,165 cases. 6th ed. Philadelphia: Lippincott William & Wilkins; 2009. Unni KK, Inwards CY, Bridge JA, Kindblom L-G, Wold LE. AFIP atlas of tumor pathology: tumors of the bones and joints, Fascicle 2, vol. 4. Washington, DC: American Registry of Pathology; 2005. Vigorita VJ. Orthopaedic pathology. 2nd ed. Philadelphia: Wolters Kluwer; 2008. Wold LE, Unni KK, Sim FH, Sundaram M. Atlas of orthopedic pathology. 3rd ed. Philadelphia: Saunders Elsevier; 2008.

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Index

A Adamantinoma carcinoma/melanoma, 348 epithelial components, 347 Ewing sarcoma, 346 extracortical extension, 348 fibro-osseous stroma, 342 hypocellular and myxoid stroma, 345 pancytokeratin, 343 radiologic differential diagnosis, 342 spindle cell variant, 344 squamous cell carcinoma, 344 Adenocarcinoma prostatic adenocarcinoma, 451 sclerotic lesions, 450 teratomatous elements, 460 thyroid transcriptional factor 1, 449 Albers-Schönberg disease, 428 Ameloblastoma alveolar bone/inferior maxillary sinus walls, 349 desmoplastic type, 352 epithelial nests, 351 follicular and acanthomatous, 351 histopathologic patterns, 350 multilocular lesion, 349 odontogenic tumors, 350 Aneurysmal bone cyst basophilic woven bone, 289 bone production, 291 cystic components, 293 differential diagnosis, 285 fibrous septa, 290 formation, bone, 288 hemosiderin deposition, 288 lytic lesion, 284 mandibular mass, 286 mononuclear stromal component, 294 multinucleated giant cells, 287 proximal humerus, 286 solid variant, 291 stromal component, 294 tubular bones and vertebrae, 292 Angiosarcoma epithelioid (see Epithelioid angiosarcoma) intraosseous hemorrhagic lesions, 314 pathologic fractures, 314 red blood cells and rudimentary vascular channel, 316 spindle cell lesion, 315 vasoformative growth pattern, 315 Avascular necrosis bilateral, 374 chondro-osseous metaplasia, 378

creeping substitution, 377 femoral head, 375 necrotic debris, 376 osteonecrosis, 374 osteoradionecrosis, 378 pathologic features, 375 secondary osteoarthritic changes, 376 subchonral revascularization, 377

B Benign fibrous histiocytoma foamy histiocytes, 165 distal femoral shaft fracture, 166 giant cell tumor, bone, 165 lytic lesion, 164 periosteal reaction, 163 right distal femoral shaft fracture, 166 spindle cell nuclei, 166 Bizarre parosteal osteochondromatous proliferation (BPOP) cytologic atypia, 395 endochondral ossification, 393 fibrovascular connective tissue, 394 stroma, 395 lesional components, 393 matured bone, 396 osteoblasts, 394 osteochondromatous proliferation, 392 small tubular bones, 391 Bone cell tumor, 215 distal femur, 210 fibrohistiocytic component, 213 formation, 214 giant cell tumor, 208 gnathic (see Gnathic bones) infarct (see Bone infarct) lytic lesion, 208 medial femoral condyle, 211 multinucleated cells, 212 necrosis, 209 tumors (see Bone-forming tumors) vascular invasion, 212 xanthomatous cells, 214 Bone-forming tumors conventional osteosarcoma (see Conventional osteosarcoma) description, 23 high-grade surface osteosarcoma, 93–96 low-grade central osteosarcoma, 78–80 osteoblastoma (see Osteoblastoma) osteoid osteoma (see Osteoid osteoma)

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470 Bone-forming tumors (cont.) osteoma (see Osteoma) osteosarcoma, 23 parosteal osteosarcoma, 81–88 periosteal osteosarcoma, 89–92 secondary osteosarcoma, 97–99 small cell osteosarcoma, 71–77 telangietatic osteosarcoma, 67–70 Bone infarct fibrosis and calcification, 380 histologic features, 380 metaphysis and diaphysis, 379 BPOP. See Bizarre parosteal osteochondromatous proliferation (BPOP) Breast carcinoma, 442

C Calcium pyrophosphate dihydrate disease (CPDD) amorphous and purple-blue crystals, 388 cartilage metaplasia, 389 chondrocalcinosis, 387 dehydrate crystals, 389 rhomboid, 390 Callus bone, 13 fibrocartilage, 12 fracture site, 11 mineralization, 12 nonunion, 14–15 stroma, 13 Cartilage-forming tumors chondroblastoma, 122–126 chondroid matrix production, 101 chondroma (see Chondroma) chondromyxoid fibroma, 127–131 clear cell chondrosarcoma, 150–151 conventional chondrosarcoma (see Conventional chondrosarcoma) dedifferentiated chondrosarcoma, 146–149 enchondromatosis (see Enchondromatosis) mesenchymal chondrosarcoma (see Mesenchymal chondrosarcoma) osteochondroma (exostosis), 102–108 periosteal chondroma, 115–116 secondary chondrosarcoma, 144–145 synovial chondromatosis, 132–133 types, bone, 101 Central ossifying fibroma bony trabeculae, 199 epithelial membrane antigen positivity, 202 fibro-osseous lesion, 198 fibrous tissue, 198 focal areas, radiopacity, 197 fusion, ossicles, 201 Juvenile trabecular, 200 mineralized tissue, 199 psammomatoid ossifying, 201 small lesions, 196 Cherubism, 235 Chest wall hamartoma aneurysmal bone cyst, 18 chondroblastic osteosarcoma, 17 cyst wall, 18 lesions, 17 mediastinal shift, 16

Index proliferating cells, 19 solid and cystic component, 16 Cholangiocarcinoma bone metastasis, 462 osteoclastic bone, 462 Chondroblastoma cytologic atypia, 124 endosteal erosion, 122 eosinophilic cytoplasm, 125 lesional tissue, 124 mineralized matrix, 126 multinucleated giant cells, 123 necrosis, 123 Chondroid hamartoma cartilage, 21 solitary pulmonary nodule, 20 Chondroma benign neoplasms, hyaline cartilage, 109 binucleated forms, 111 bone formation, 110 cartilaginous tumor, 113 cellular pleomorphism, 112 expansile lytic lesion, 109 haversian system, 112 hyaline cartilage lesions, 110 lytic lesion, 109 mature cartilage, 111 periosteal histologic features, 116 hypercellularity and myxoid changes, 116 ring and arc type calcifications, 114 Chondromyxoid fibroma calcifications, 130 cellular condensation, 128 distal humerus, 127 hypercellular peripheries, 128 hyperchromasia, 129 juxtacortical, 130, 131 multinucleated giant cells, 129 sclerosis, 127 Chondrosarcoma clear cell (see Clear cell chondrosarcoma) conventional (see Conventional chondrosarcoma) osteoblastic component/tumor osteoid, 464 pulmonary-and pleural-based nodules, 465 secondary (see Secondary chondrosarcoma) Chordoma bilateral neural foramen, 353 cell adhesion molecules, 362 cellular cohesion and lobulated growth pattern, 359 chondromyxoid matrix, 360 chordomas/notochordal tumors, 353 cohesive nature, 361 cytoplasmic vacuolization, 359 dedifferentiated chordoma/sarcomatoid chordoma, 358 dural-based/paraspinal mass, 363 EMA and CK, 360 heterogeneous mass, 354 inferior sacrum and coccyx, 355 lobular growth pattern, 356 myxoid mass, 355 pancytokeratin, 361 physaliphorous cells, 357 small nests and cords, 357 soft tissue extension, 356

Index solid growth pattern, 358 S-100 protein, 362 CK. See Cytokeratin (CK) Clear cell chondrosarcoma chondroblastic osteosarcoma, 151 focal cystic degeneration, 150 multinucleated giant cells, 151 peripheral sclerosis, 150 Colorectal carcinoma, 462 Conventional chondrosarcoma cartilaginous matrix, 137 cellularity and cytologic atypia, 139 cytologic atypia, 141 enchondroma, 142 endochondral ossification, 142 endosteal scalloping, 134 femoral lesion, 138 grading, 143 malignant cartilage, 141 myxoid changes/chondroid matrix liquefaction, 139 permeation, 140 proximal femur, 135 radiologic–pathologic correlation, 138 soft tissue mass and pathologic fracture, 136 spindling, lesional cells, 140 Conventional osteosarcoma alveolar growth, 55 amputated specimen, 41 amyloid, 50 anaplastic tumor cells, 47 anteroposterior, 39 bone-forming, 53 chemotherapy, 64–65 chondroblastic, 41 chondroblastoma, 58 chondroid matrix, 51, 53 chondromyxoid, 60 core needle biopsy specimen, 45 description, 38 epithelioid variant, 56 fibroblastic and chondroblastic, 44 filigree osteoid, 50 giant cell–rich, 61 lacelike osteoid production, 46 leiomyosarcomatous dedifferentiation, 63 lytic and sclerotic lesion, 38 malignant tumor, 58 marrow enhancement, 40 MFH, 62 needle biopsy, 48 neoplastic cells, 59 osteoid network, 47 osteoid trabeculae, 46 pericellular, 52 periosteum, 40 plasmacytoid morphology, 49 pleomorphic tumor cells, 49 proximal tibia, 42 sclerosing type, 43 sclerosing variant, 56–57 spindle-cell malignancy, 55 tumor cells, 52 tumor osteoid, 60 vascular invasion, 54 CPDD. See Calcium pyrophosphate dihydrate disease (CPDD)

471 Cysts aneurysmal bone, 284–294 cystic lesions, 283 ganglion, 298–299 unicameral bone, 295–297 Cytokeratin (CK) antibodies and, 360 cellular processes, 361 lesional cells, 363

D Dedifferentiated chondrosarcoma bone-forming characteristics, 146 giant cell tumor, bone, 148 malignant fibrous histiocytoma, 147 tibia diametaphysis, 146 Desmoid tumor. See Desmoplastic fibroma Desmoplastic fibroma, 167–168 Detritic synovitis amorphous refractile, 415 fragments, polyethylene, 416 metal-on-metal prostheses, 417 papillary fibrocartilaginous metaplasia, 417 synovial tissue, 415

E EMA. See Epithelial membrane antigen (EMA) Enchondroma. See Chondroma Enchondromatosis arc-like calcifications, 118 binucleation and mild cytologic atypia, 121 cartilaginous tumors, 120 cellularity and myxoid change, 120 hemangioma, 121 innumerable expansile cartilaginous lesion, 118 multiple thrombosed hemangiomas, 119 sarcomatous transformation, 117 Ependymoma myxopapillary, 340 papillary arrangement, 341 perivascular pseudorosettes, 341 Epithelial membrane antigen (EMA) BCL2, 371 benign fibrous histiocytoma, 370 and CK, 360 pancytokeratin, 361 S-100 protein, 363 Epithelioid angiosarcoma cytologic atypia, 317 dis-cohesive cells, 319 popliteal lymph node, 319 pseudoglandular, 318 vascular channels, 318 hemangioendothelioma eosinophilic cytoplasm, 311 lesional cells, 311 Ewing sarcoma. See Primitive neuroectodermal tumor (PNET)

F Fibro-osseous lesions bone disorders, 179 central ossifying fibroma, 195–202

472 Fibro-osseous lesions (cont.) fibrous dysplasia (see Fibrous dysplasia) liposclerosing myxofibrous tumor, 203–205 osteofibrous dysplasia, 193–195 Fibrosarcoma desmoplastic fibroma, 173 haphazard fascicular fashion, 173 histologic differentiation, 174 hypercellular and hyperchromatic spindle-cell tumor, 172 periosteum, 171 soft tissue mass, 172 Fibrous and fibrohistiocytic lesions benign histiocytoma, 163–166 desmoplastic fibroma, 167–168 fibroma, tendon sheath hypercellular areas, 169 lesional fibroblasts/myofibroblasts, 170 subcutaneous nodule, 169 fibrosarcoma, 171–174 malignant histiocytoma, 175–177 nonossifying fibroma, 158–162 unmineralized collagen matrix, 157 Fibrous dysplasia active bone remodeling, 191 bony trabeculae, 185 collagenized stroma, 187 C-shaped bony spicules, 186 cystic degeneration, 184 expansile lesion, 192 fibrous stroma, 185 flat bone, skull, 184 focal cartilage metaplasia, 189 inter-anastomosing network, 187 intramedullary lytic lesion, 182 lipophages/lipid-laden histiocytes, 190 metadiaphysis, 181 mineralized trabecular bone, 185 noninherited developmental disorder, 180 osteoblastoma-like areas, 189 osteoclastic bone resorption, 188 osteoclast-type multinucleated giant cells, 190 osteoid, 188 pathologic features, lesion, 184 polarization microscopy, 186 secondary cystification, 191 tibial diaphysis, 182 unicameral bone cyst, 183 FISH. See Fluorescence in situ hybridization (FISH) Fluorescence in situ hybridization (FISH), 278

G Ganglion cyst distal femoral diaphysis, 298 intraosseous, 299 left knee, 298 “lining cells”, 299 Gastric carcinoma, 455 Gaucher disease autosomal recessive disorder, 418 lipid laden cells, 418 storage diseases, 419 Germ cell tumor, 460 Giant cell-rich lesions

Index bone, 208–215 cherubism, 235 description, 207 gnathic bones, 216–217 hyperparathyroidism, 228–234 malignant giant cell tumor, 218–221 tenosynovial giant cell tumor, 222–227 Gnathic bones osteoid, 216 spindle-shaped stromal cells, 217 teeth, 216 Gout birefringent needle shaped crystals, 386 chalky white cut surface, 383 formalin-fixed specimen, 384 metatarsocuneiform joints, 383 PD magnetic resonance, 383 polarizing microscopy, birefringent, 385 uric acid stain, 385 water-based fixatives, 384

H Hemangioendothelioma cytologic atypia, 309 epithelioid, 311 expansile radiolucent lesions, 307 multifocality, 306 multinucleated giant cells, 309 periosteal reaction, 305 spindle cell proliferation, 310 vascular spaces and extracellular space, 308 vasoformative nature, 308 Hemangioma bony trabeculae, 303 endothelial cell–lined spaces, 303 Gorham’s disease, 304 multiple lytic lesions, 302 vasoformative nature, 302 Hemangiopericytoma CD34, 313 collagen bands, 312 hypercellular and hypocellular regions, 312 perivascular hyalinization, 313 Hepatocellular carcinoma histologic features, 456 trabecular growth pattern, 456 High-grade surface osteosarcoma anaplastic change, 94 bone scan, 93 chondroid differentiation, 94 femoral metaphysis, 93 osteoblastic, 95 stroma, 96 Human skeletons, 1 Hyperparathyroidism anterior patella, 229 bony trabeculae, 232 hemorrhagic debris, 234 heterogeneous lesional, 231 lesions, 228 lucent lesions, 230 mandible, 230 parathyroid hormone, 228 reactive new bone, 234 sacroiliac joints, 231 tunneling resorption and peritrabecular fibrosis, 233

Index I IHC stains. See Immunohistochemical stains (IHC stains) Immunohistochemical stains (IHC stains) defined, 443 prostatic origin, 451

L Langerhans cell histiocytosis (LCH) bone, 246 CD1a immunoreactivity, 250 low-power magnification, 247 mitotic activity, 248 mononuclear cells, 247 nuclear grooves, 249 Reed-Sternberg cells, 248 S-100 protein, 249 LCH. See Langerhans cell histiocytosis (LCH) Leiomyoma radiolucent lesion, 322 tumor necrosis/ominous prognosis, 322 Leiomyosarcoma cigar-shaped nuclei, 325 destructive lesion, distal femur, 323 lesional cells, 324 multifocal permeative lytic lesions, 323 pathologic features, 324 smooth muscle differentiation, 325 Lipoma anterior calcaneus, 331 cortical/parosteal location, 331 intramedullary lipoma, 331 Liposclerosing myxofibrous tumor benign fibro-osseous lesion, 204 fat necrosis, 204 fibroxanthoma, 205 lytic lesion, 203 Lobular carcinoma, 444 Low-grade central osteosarcoma adjacent cortex, 79 bone formation, 79 epithelioid tumor cells, 80 femoral diaphysis, 78 spindle cells, 78 Lymphoma anaplastic kinase antibodies, 264 B-cell, 259 bone, 262 chronic lymphocytic leukemia, 261 cytologic features, 264 destructive lesion, 263 extranodal Burkitt lymphomas, 265 leukemia, 265 mid-left femoral diaphysis, 259 tumor cells, 264

M Maffucci syndrome. See Enchondromatosis Malignant fibrous histiocytoma (MFH) cytologic atypia, 176 histologic features, 175 osteosarcoma, 62 pathologic features, 175 post radiation therapy, 176

473 Malignant giant cell tumor anaplastic tumor, 221 humeral head destructive mass, 218 lesion, 218 mitotic features, 221 osteoclast-like multinucleated, 220 polyhedral cells, 220 Malignant peripheral nerve sheath tumor (MPNSTs) epithelioid malignant peripheral nerve sheath tumor, 339 fascicular growth pattern, 338 fibrous histiocytoma, 339 lesional cells, 338 Malignant tumors Ewing sarcoma, 274–282 lymphoma, 259–265 plasmacytoma/plasma cell myeloma, 266–273 PNET (see Primitive neuroectodermal tumor (PNET)) Mammaglobin adult mammary gland, 444 cystic disease fluid protein, 443 Mastocytosis bone marrow biopsy, 251 cytoplasmic granules, 252 histomorphologic appearance, 252 Mesenchymal chondrosarcoma cartilage-type matrix, 152 chondrogenesis, 154 cytologic characteristics, 155 hyaline cartilage, 154 skeletal distribution, 153 spindling, small cells, 156 Metastases from bone chondrosarcoma, 465 osteosarcoma, 463–464 Metastases to bone adenocarcinoma, 449 breast carcinoma, 442 cholangiocarcinoma, 462 colorectal carcinoma, 462 gastric carcinoma, 455 germ cell tumor, 460 hepatocellular carcinoma, 456–457 IHC, 443 lobular carcinoma, 444 lung cancer, 448–449 mammaglobin, 444 medulloblastoma, 454–455 melanoma, 461 metastatic breast carcinoma, 443 neuroblastoma, 458–459 prostatic adenocarcinoma, 450–451 renal cell carcinoma, 445–448 small cell carcinoma, lung, 450 squamous cell carcinoma, 452–453 thymic carcinoma, 461 thyroid carcinoma, 452 urothelial carcinoma, 460 MFH. See Malignant fibrous histiocytoma (MFH) MPNSTs. See Malignant peripheral nerve sheath tumor (MPNSTs) Myositis ossificans acetabular fracture, 399 bone formation, 402 cortical/lamellar bone, 403

474 Myositis ossificans (cont.) fibroblasts and inflammatory cells, 400 immature/mature cartilage, 401 myofibroblasts, 401 plump osteoblasts, 400 skeletal muscle fibers, 402 zonal proliferation, fibroblasts, 399 Myxoma capillary-sized vessels, 332 expansile lesion, 332

N Neurilemmoma biopsy sample, 336 hypercellular and hypocellular areas, 334 perivascular hyalinization, 335 S-100 protein, 337 tibial diaphysis, 334 verocay bodies, 335 Nonossifying fibroma bone grafting, 158 distal tibial metaphysis, 159 lipid-laden foamy histiocytes, 160 multinucleated giant cells, 161 pleomorphism, 160 proximal tibial metaphysis, 158 reactive new bone formation, 161 spindled cell regions, 159 superimposed secondary aneurysmal bone cyst formation, 162 Normal bone histology anatomy, 2 articular cartilage, 8 bone-forming osteoblasts, 7 fibrocartilage, 9 growth plate, 9 lamellar bone, 3–4 osteoclasts, 7 periosteum, 10 reversal line, 6 spongiosa, 10 woven bone, 5

O OI. See Osteogenesis imperfecta (OI) Ollier disease. See Enchondromatosis Osteoarthritis bone-on-bone contact, 408 cystic fluid, 410 femorotibial compartment, 406 osteophyte formation, 409 papillary synovial hyperplasia and synoviocyte hypertrophy, 411 protruding, osteophyte, 409 subchondral bone cyst, 410 tibial plateau and femoral condyle, 407 vertical clefting/fissuring, 408 weight-bearing surface, femoral head, 407 Osteoblastoma aneurysmal bone cyst, 33 epithelioid osteoblasts, 37 expansile lytic lesion, 34 lytic lesion, 29 ossification, 32

Index pleomorphism, 33 subchondral epiphyseal lesion, 30 technetium bone scan, 35 trabeculae, 32 vertebral column, 31 Osteochondral body cartilaginous surface, 382 joint mice, 381 tan-white glistening hyaline cartilage, 382 Osteochondroma benign tumor, 102 cancellous bone, 106 deformity, left humerus, 103 endochondral ossification, 107 focal myxoid change, 107 hereditary osteochondromatosis, 102 histologic features, 108 hyaline cartilage, 106 neurologic sequelae, 104 pathologic features, 105 sessile lesions, 104 Osteofibrous dysplasia bony trabeculae, 194 lesional tissue, 194 osteoblastic rimming, 195 right distal tibial diaphysis, 193 Osteogenesis imperfecta (OI) chondrocyte proliferation, 424 endochondral and intramembranous ossification, 423 pathologic features, 422 procollagen, 420 rib fractures and ossified skull, 421 skeletal deformities, 421 “transparent skull”, 422 type II, 423 Osteoid osteoma left tibia, 26 lesion, 26 nidus, 27 woven bone trabeculae, 28 Osteoma cancellous variant, 25 description, 24 osteoid (see Osteoid osteoma) Osteomalacia defective bone mineralization, 425 Goldner trichrome stain, 425 Osteomyelitis active osteoclastic bone resorption, 242 acute and chronic inflammatory infiltrates, 241 adjacent soft tissues, 238 bone destruction, 241 Brodie abscess, 238 chronic, 239 fungal (mycotic), 244, 245 histologic findings, 240 osteoclast formation, 242 periostitis ossificans, 243 reactive new bone formation, 243 regenerative bone, 244 syphilitic, 245 trauma/iatrogenic implantation, 240 Osteopenia/osteoporosis chronic oral steroids, 426 lamellated reversal lines, 427 metabolic bone studies, 427

Index Osteopetrosis bone trabeculae, 428 marble bone disease/Albers-Schönberg disease, 428 Osteosarcoma conventional (see Conventional osteosarcoma) high-grade surface osteosarcoma (see High-grade surface osteosarcoma) histologic appearance, 464 low-grade surface osteosarcoma (see Low-grade surface osteosarcoma) osteoblastic to chondroblastic types, 464 parosteal (see Parosteal osteosarcoma) periosteal (see Periosteal osteosarcoma) secondary (see Secondary osteosarcoma) small cell osteosarcoma (see Small cell osteosarcoma) telangietatic (see Telangietatic osteosarcoma)

P Paget disease accentuated reverse cement lines, 432 bone remodeling, 430 coarse bone, 432 compression fracture, 430 focal lucent lesions, 429 osteoclastic bone resorption, 431 pagetoid bone, 433 vascular-rich loose fibrous tissue, 431 Paraganglioma edematous/fibrotic stroma, 333 neuroendocrine origin, 333 Zellballen, 333 Parosteal osteosarcoma adjacent cortex and tumor extension, 82 bone spicules, 86 bony trabeculae, 85 cytologic atypia, 87 distal femur, 84 femoral shaft, 84 fibrous dysplasia, 85 misinterpretation, 87 pathologic features, 83 patient’s prognosis, 88 Periosteal osteosarcoma features, 90 lesion, 89 peripheral amorphous, 89 spindle cell proliferation, 90 spindle cells, 91–92 Phosphaturic mesenchymal tumor cellular pleomorphism, 439 hemosiderin deposition, 438 hypophosphatemia and hyperphosphaturia, 434 lymph node, 440 myxoid changes and microcyst formation, 437 osteoid-like extracellular matrix, 436 osteoid-like matrix, 439 PMTMCT, 435 serum phosphate levels, 438 vascular tumors, 435 Phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) cartilage, 437 malignant phosphaturic mesenchymal tumor, 439 myxoid changes and microcyst formation, 437

475 osteoid-like extracellular matrix, 436 pleomorphic sarcoma/fibrosarcoma, 438 Pigmented villonodular synovitis (PVNS), 222 Plasmacytoma/plasma cell myeloma cytologic atypia, 270 dyscrasia, 273 eosinophilic aggregates, 272 in situ hybridization analysis, 271 malignant lymphoma, 269 matrix production, 269 metastatic disease, 267 nuclear pseudoinclusions, 270 osteolytic lesions, 266 pathologic fracture, 268 radiolucencies, 267 PNET. See Primitive neuroectodermal tumor (PNET) Primitive neuroectodermal tumor (PNET) acellular fibrosis, 276 bone formation, 277 cytokeratin expression, 282 degenerative changes, 278 FISH, 282 geographic necrosis, 278 histologic variants, 279 lamellated periosteal reaction, 274 large cell variant, 280 neoadjuvant chemotherapy, 275 neoplastic cells, 278 soft tissue mass, 275 Prostatic adenocarcinoma sclerotic lesions, 450 tumor cells, 451 PVNS. See Pigmented villonodular synovitis (PVNS)

R RA. See Rheumatoid arthritis (RA) Reactive and inflammatory processes LCH, 246–250 mastocytosis, 251–252 osteomyelitis, 238–245 Rosai-Dorman disease (see Sinus histiocytosis, massive lymphadenopathy) sarcoidosis, 257 xanthoma, 258 Renal cell carcinoma histomorphologic appearance, 447 intramedullary nail, 446 metadiaphysis, 445 sarcomatoid carcinomas, 447 vacuolated cytoplasm, 448 Rhabdomyosarcoma bizarre nuclei, 330 cytogenetic confirmation, 329 cytoplasmic immunoreactivity, 327 eccentric nuclei and eosinophilic cytoplasm, 329 lytic lesion, 326 pathologic fracture, 328 spindle cell variant, 329 Rheumatoid arthritis (RA) cystic degeneration, 414 granulomatous inflammation, 413 lymphoplasmacytic infiltrate, 413 pancarpal and secondary degenerative changes, 412 rheumatoid nodule, 414 Rickets. See Osteomalacia

476 S Sarcoidosis histologic features, 257 multinucleated giant cells, 257 Secondary chondrosarcoma, 144–145 Secondary osteosarcoma distal humerus and proximal ulna, 97 fibrous dysplasia, 97 knee amputation, 98 medullary architecture, 97 metallic prosthesis, 99 Paget disease, skull, 99 Sinus histiocytosis, massive lymphadenopathy distal femoral osseous lesion, 253 emperipolesis, 256 eosinophilic cytoplasm, 255 intramedullary lucent lesion, 254 radiologic evaluation, 253 Small cell osteosarcoma cell type, 75 chemotherapy, 77 cytoplasm, 74 hypocellular areas, 76 lytic lesion, 72 osteoid/bone matrix, 73 pathologic features, 71 Solitary fibrous tumor. See Hemangiopericytoma Squamous cell carcinoma desmoplastic stromal reaction, 453 femoral diaphysis, 452 keratinization, 460 Subungual exostosis abnormal bony projections, 397 trabecular bone, 398 Synovial chondromatosis cellular hyaline cartilage nodules, 132 malignant transformation, 133 nuclear pleomorphism, 133 radiologic differential diagnosis, 132 Synovial sarcoma, bone adenocarcinoma, 367 BCL2 protein, 371 biphasic/monophasic growth pattern, 365 cellular spindle cell, 366 cytologic atypia, 368 hemangiopericytoma, 368 herringbone growth pattern, 367 intraluminal necrotic debris, 365 myxoid stroma, 369 occult glandular differentiation, 366 osteoid characteristics, 372 primary, 364 storiform pattern, 370 stromal calcification, 369

T Telangietatic osteosarcoma aneurysmal bone cyst, 69 cortical destruction, 69

Index endothelial lining, 68 lytic lesion, 67 multinucleated giant cells, 70 sclerosing variant, 70 Tenosynovial giant cell tumor cellular population, 226 diagnosis, 227 lesions, 225 lipid-laden histiocytes, 223 macrophages, 224 multinucleated giant cells, 224 neoplastic cells, 223 polygonal cells, 225 PVNS, 222 stroma, 226 synovium, 222 Thymic carcinoma, 461 Tumor-like conditions avascular necrosis (see Avascular necrosis) bone infarct (see Bone infarct) BPOP (see Bizarre parosteal osteochondromatous proliferation (BPOP)) CPDD (see Calcium pyrophosphate dihydrate disease (CPDD)) description, 373 gout (see Gout) myositis ossificans (see Myositis ossificans) nonneoplastic conditions, 373 osteochondral body (see Osteochondral body) subungual exostosis, 397–398

U Unicameral bone cyst femoral diaphysis, 295 fibrous septa, 296 hemorrhage and hemosiderin pigment, 297 lytic and sclerotic lesion, 295 reactive bone, 296 Urothelial carcinoma, 460

V Vascular tumors description, 301 hemangioendothelioma and epithelioid hemangioendothelioma (see Hemangioendothelioma) hemangioma, 302–304 hemangiopericytoma, 312–313 multifocality, 301

X Xanthoma, 258