Renal Patho Lab 2 Part 1 Colored

OS 214: Excretory Module

Patholog y Dep t. Lectur er s

Pathology Lab 2 Part 1

OUTLINE Urology LCD module a. Chronic Pyelonephritis b. Clear Cell Renal Carcinoma c. Angiomyolipoma d. Wilm’s Tumor e. Prostate Adenocarcinoma f. Chronic Cystitis g. Invasive Urothelial Carcinoma II. Case Discussion a. Rapidly Progressive GN Type 1 b. IgA Nephropathy c. Focal Segmental GN d. Membranous GN e. Acute Tubular Necrosis f. Hyperplastic Arteriolitis III. Gross Specimen IV. Microscopy I.

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Exam 2

Can you delineate the cortex from the medulla (normal ratio of 1:3 or 1:4)? NO Light tan color of lesion - the lighter the color of the lesion, the more packed it is with cells Presence of ulceration? YES (encircled)

Light Microscope:

UROLOGY LCD MODULE Surgical Pathologist The one who studies specimens, usually from a surgeon, and makes a diagnosis depending on what they see from the specimen. They are also the ones who specify if the lesion is benign or malignant. • They rely on what they observe directly from the specimen itself and the clinical input coming from the clinician or surgeon • Specimen – may be a whole organ or a piece of tissue • Tissues are “fixed” by immersing them in formalin. This prepares the tissue for slide processing. Changes that may occur because of formalin include: o Areas of the tissue with increased number of cells per unit volume tend to become more white compared to less cellular areas of the tissues o Color of the tissues usually become lighter •

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Glomerulus: bowman’s space is enlarged (A) Tubules: normally found in spaces between the glomeruli. In this picture, you see a fibrous area which is almost devoid of tubules Blood Vessels – wall is thickened (B)

Renal Cell Carcinoma

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Kidney: Organ is 5-6 inches in length, and covered with fat

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When assessing the gross anatomy: o Calyx and Ureter: Is there anything blocking it? NO o Parenchyma

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ON High Power Inflammatory cells found on the slide (do you see the lymphocytes below the glomerolus?) Thyroidization is present (boxed) Casts (Tamm-Horsefall protein) inside tubules signify a long standing renal problem with decreased urine flow. When the tubules are dilated, they usually form broad casts and the kidney damage is irreversible.

ON Oil Immersion

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OS 214: Excretory Module

Patholog y Dep t. Lectur er s

Pathology Lab 2 Part 1

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Numerous lymphocytes and inflammatory cells

NtK from Robbins: Renal cell carcinomas represent about 1% to 3% of all visceral cancers and account for 85% of renal cancers in adults. The tumors occur most often in older individuals, usually in the sixth and seventh decades of life, showing a male preponderance in the ratio of 2 to 3 : 1. They usually have a gross yellow color and tumor cells resemble clear cells of the adrenal cortex but in truth, these tumors arise from the tubular epithelium and are therefore renal adenocarcinomas

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Clear Cell Renal Carcinoma

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Kidney: presence of hemorrhage (A) and necrosis (B). Normal kidney upper portion (circled) Most of the kidney is occupied with large mass (lower portion) (boxed)

Angiomyolipoma

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Light Microscope:

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Kidney: lower part is made of normal renal tissue Tumor is cleaner (less hemorrhage and necrosis compared to clear cell carcinoma) – a probable sign that the lesion is benign Light Microscope:

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Clear cell Renal Carcinoma with large nuclei (Fuhrman grade 4) Pathologists are responsible for the T part of grading Makes use of Fuhrman Grading system

The Fuhrman grade is based on nuclear size and shape and the prominence of nucleoli Grade 1: tumors have round, uniform nuclei with inconspicuous or absent nucleoli. Grade 2: Nuclear contours are more irregular than Grade 1; nuclei are about 15 microns in diameter. Nucleoli may be visible at high magnification. Grade 3: Nuclear contours are even more irregular. Nuclear diameters can approach 20 microns. Nucleoli are readily seen Grade 4: Looks quite different from normal kidney cells and has the worst prognosis.

Grade of the tumor is directly proportional to size of the nucleus and the aggression of the tumor.

NtK from Robbins: Renal cell carcinomas represent about 1% to 3% of all visceral cancers and account for 85% of renal cancers in adults. The tumors occur most often in older individuals, usually in the sixth and seventh decades of life, showing a male preponderance in the ratio of 2 to 3 : 1. They usually have a gross yellow color and tumor cells resemble clear cells of the adrenal cortex but in truth, these tumors arise from the tubular epithelium and are therefore renal adenocarcinomas Clear cell carcinoma. This is the most common type of renal cell ca, accounting for 70% to 80% of renal cell cancers. On histologic examination, the tumors are made up of cells with clear or granular cytoplasm and are nonpapillary. They can be familial, associated with VHL disease, or in most cases (95%) sporadic.

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Exam 2

Angiomyolipomas are made up of mature adipose, smooth muscle and blood vessels.

NtK from Robbins: Angiomyolipoma. This is a benign tumor consisting of vessels, smooth muscle, and fat. Angiomyolipomas are present in 25% to 50% of patients with tuberous sclerosis, a disease characterized by lesions of the cerebral cortex that produce epilepsy and mental retardation as well as a variety of skin abnormalities

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Wilms Tumor / Nephroblastoma

** visit http://webpathology.com/case.asp?case=66 for nice pictures of renal cell cancer 

March 11, 2009 | WEDNESDAY

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Patholog y Dep t. Lectur er s

Pathology Lab 2 Part 1

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Exam 2

Light Microscope:

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Highly cellular tissue with no tubules Notice the stroma (A), some gland like structures made by primitive cuboidal epithelial elements (B), and blastema (C dark staining cells)

CUT section o Multiple cysts on cut section o May be due to proliferation of stromal elements OR both stromal and glandular elements (when glandular elements proliferate, they manifest as cystic spaces)

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Light Microscope:

** check http://webpathology.com/case.asp?case=73 for more histological pictures of wilm’s tumor NtK from Robbins: Wilms tumor is the most common primary renal tumor of childhood and the fourth most common pediatric malignancy in the United States. Approximately 5% to 10% of Wilms tumors involve both kidneys, either simultaneously (synchronous) or one after the other (metachronous). Bilateral Wilms tumors have a median age of onset approximately 10 months earlier than tumors restricted to one kidney. It is usually found in 3 syndromes: WAGR syndrome (characterized by aniridia, genital anomalies, and mental retardation), DenysDrash syndrome (which is characterized by gonadal dysgenesis (male pseudohermaphroditism) and early-onset nephropathy leading to renal failure. The characteristic glomerular lesion in these patients is a diffuse mesangial sclerosis), and BeckwithWiedemann syndrome (characterized by enlargement of body organs (organomegaly), macroglossia, hemihypertrophy, omphalocele, and abnormal large cells in adrenal cortex (adrenal cytomegaly))

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Nodular Hyperplasia of the Prostate and Adenocarcinoma of the prostate

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Presence of Adenocarcinoma of the Prostate You see the tumor cells trying to form glands Gleason Grading system grades 1-3 = distinct glands grade 4 = fused glands grade 5 = no glands visible Gleason score = predominating grade + second most predominant grade

GLEASON GRADIG SYSTEM The pathologist assigns a grade to the most common tumor pattern, and a second grade to the next most common tumor pattern. The two grades are added together to get a Gleason score. For example, if the most common tumor pattern was grade 3, and the next most common tumor pattern was grade 4, the Gleason score would be 3+4 = 7. A lower Gleason indicates a well differentiated, or a lower potential to spread. A higher Gleason grade indicates a poorly differentiated cancer, or more likely to spread.

Prostate is normally symmetrical Prostate on this picture is not symmetrical. You can also notice multilobular structures

Gleason scores are associated with the following features: • Grade 1 - The cancerous prostate closely resembles normal prostate tissue. The glands are small, wellformed, and closely packed

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OS 214: Excretory Module

Patholog y Dep t. Lectur er s

Pathology Lab 2 Part 1

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Grade 2 - The tissue still has well-formed glands, but they are larger and have more tissue between them. Grade 3 - The tissue still has recognizable glands, but the cells are darker. At high magnification, some of these cells have left the glands and are beginning to invade the surrounding tissue. Grade 4 - The tissue has few recognizable glands. Many cells are invading the surrounding tissue Grade 5 - The tissue does not have recognizable glands. There are often just sheets of cells throughout the surrounding tissue.

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Light Microscope

ON High Power

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o There is some inflammation in the mucosa When evaluating the urothelium look for: number of cell layers (normal is 7 layers but if it is a tangential section there may be more than 7 layers), polarity, crowding of nuclei

Close up of merging glands The picture shows a grade 4 gleason grade due to the presence of fused glands

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Exam 2

The picture shows a grade 5 lesion since no glands are present in the field This picture shows pleomorphic hyperchromatic nuclei

Chronic Cystitis

Notice the ureter on the Right is dilated (probably because of the presence of a stone impacted on the outlet) Bladder also shows areas of hemorrhage

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Normally, there are 7 layers of urethelium Notice polarity of the nucleus and look for crowding of nuclei There is peculiar alignment – long axis of nuclei is perpendicular to the basement membrane

NtK from Robbins: Chronic Cystitis. The common etiologic agents of cystitis are the coliforms: Escherichia coli, followed by Proteus, Klebsiella, and Enterobacter. Women are more likely to develop cystitis as a result of their shorter urethras. Most cases of cystitis take the form of nonspecific acute or chronic inflammation of the bladder. In gross appearance, there is hyperemia of the mucosa, sometimes associated with exudate. Persistence of the infection leads to chronic cystitis, which differs from the acute form only in the character of the inflammatory infiltrate. There is more extreme heaping up of the epithelium with the formation of a red, friable, granular, sometimes ulcerated surface. Chronicity of the infection gives rise to fibrous thickening in the muscularis propria and consequent thickening and inelasticity of the bladder wall. Histologic variants include follicular cystitis, characterized by the aggregation of lymphocytes into lymphoid follicles within the bladder mucosa and underlying wall, and eosinophilic cystitis, manifested by infiltration with submucosal eosinophils together with fibrosis and occasionally giant cells. Most cases of eosinophilic cystitis represent nonspecific subacute inflammation, although, rarely, these lesions are manifestations of a systemic allergic disorder. All forms of clinical cystitis are characterized by a triad of symptoms: (1) frequency, which in acute cases may necessitate urination every 15 to 20 minutes; (2) lower abdominal pain localized over the bladder region or in the suprapubic region; and (3) dysuria-pain or burning on urination. Associated with these localized changes, there may be systemic signs of inflammation such as elevation of temperature, chills, and general malaise. In the usual case, the bladder infection does not give rise to such a constitutional reaction.

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OS 214: Excretory Module

Patholog y Dep t. Lectur er s

Pathology Lab 2 Part 1

VII.

Invasive Urothelial Carcinoma

Exam 2

Grading of Urothelial (Transitional Cell) Tumors WHO/ISUP Grades* Urothelial papilloma Urothelial neoplasm of low malignant potential Papillary urothelial carcinoma, low grade Papillary urothelial carcinoma, high grade WHO Grades†

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Urinary bladder cut in half. Notice that the lesion has occupied the whole bladder space This lesion is malignant Upper area is normal Urinary Bladder mucosa – has a smooth surface Lower portion is stiff and nodular with thick walls lesion Light Microscope:

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Presence of fibrovascular core. Since it is invasive, grading is not required because regardless of a low or high grade tumor, prognosis and management are still the same Treatment is via radial cystectomy When do you grade a tumor? When the tumor is not invading.

Urothelial papilloma Urothelial neoplasm of low malignant potential Papillary urothelial carcinoma, Grade 1 Papillary urothelial carcinoma, Grade 2 Papillary urothelial carcinoma, Grade 3

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CASE DISCUSSION by DR. TUAZON Case 1 – Rapidly Progressive Glomerulonephritis (RPGN) Type I / Crescentic Glomerulonephritis

NtK from Robbins: Urothelial carcinoma. gross patterns of urothelial cell tumors vary from purely papillary to nodular or flat. The tumors may also be invasive or noninvasive. Papillary lesions appear as red, elevated excrescences varying in size from less than 1 cm in diameter to large masses up to 5 cm in diameter. Multicentric origins may produce separate tumors. As was noted, the histologic changes encompass a spectrum from benign papilloma to highly aggressive anaplastic cancers. Overall, the majority of papillary tumors are low grade. Most arise from the lateral or posterior walls at the bladder base.

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Light microscopy: crescents from proliferation of parietal epithelial cells, infiltrating monocyte and macrophages, and fibrin (fibrin came from clotting mechanisms in the blood) Urinalysis: presence of macrophages

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OS 214: Excretory Module

Patholog y Dep t. Lectur er s

Pathology Lab 2 Part 1

Exam 2

Case 3 – Focal Segmental Glomerulosclerosis Six year old girl with idiopathic nephritic syndrome. Unresponsive to steroid and immunosuppressive therapy • Clue from the case in the diagnosis: unresponsive to steroid

• Immunofluorescence: linear deposit of IgG Case 2 – IgA Nephropathy Sixteen year old boy with isolated hematuria and renal insufficiency • Presents with hematuria (nephritic syndrome) • Source of hematuria may be upper or lower urinary tract • NOTE: hematuria from the upper urinary tract shows dysmorphic RBC and red cell cast

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Light microscopy: mesangial hypercellularity / proliferation

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Immunofluorescence: mesangial granular IgA

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Light microscope: o 3 glomeruli present in the field (encircled) o Inflammatory cells in the interstitium (lymphocytes) (A) o Segmental sclerosis – collapsed lumen with increased matrix (B) o Thickened basement membrane signaling Tubular atrophy © o Presence of hyaline cast inside some tubules. The basement membrane of these tubules are thinner because the cells have sloughed off due to cell death/necrosis (D) ** the term hyalinization is used for blood vessels and arterioles, while hyaline deposit is used for the glomerulus

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HPO o Segmental sclerosis showing increased matrix which signifies that this area are not functioning – in other words, DEAD.

Case 4 – Membranous Glomerulonephropathy / Glomerulonephritis / Glomerulopathy 50 year old man with idiopathic nephritic syndrome • Idiopathic / primary

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EM: mesangial electron dense deposits (A), nucleus of mesangial cell (B)

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OS 214: Excretory Module

Patholog y Dep t. Lectur er s

Pathology Lab 2 Part 1

Exam 2

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Light microscope: o Diffuse thickening of BM

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Light microscope: tubules have thin walls with loss of epithelial cells Case 6 – Acute Tubular Necrosis Sixty year old man who was poisoned by his wife. • Caused by a nephrotoxic substance

Silver staining BM spikes

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Light microscope: destroyed tubules with no cells (arrows)

Case 7 – Hyperplastic Arteriolitis Thirty year old woman with severe skin problems, severe hypertension, and acute renal failure • Skin lesion of the patient is scleroderma • Malignant hypertension - leads to ischemia by decreasing GFR and renal blood flow ** Most sensitive to ischemia: tubules since it is where active processes take place ** Most resistant to ischemia: glomerulus

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Immunofluorescence: finely granular diffuse capillary wall, presence of IgG

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EM: numerous subepithelial deposits (arrows)

Case 5 – Acute Tubular Necrosis Twenty five year old man who had been stabbed with a knife and shot with a gun • ATN may progress to acute renal failure

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Light microscope: o Thickening of the arterial wall (formation of onion skin walls) sometimes leading to obliteration of arterial lumen o Hyperplasia of the wall leads to onion skinning (feature of malignant HTN) o Fibrinoid necrosis of arteries causing fibrin clots  There is decrease of GFR

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Patholog y Dep t. Lectur er s

Pathology Lab 2 Part 1

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Leads to Ischemia (tubules are first affected while the glomerulus is resistant to ischemia)

Exam 2

bleed! Congrats sa lahat ng pumasa!  now I believe when they say renal is the hardest! Damn can’t wait for summer vacaction!!! 

--------------------------- END OF PART 1-------------------------Greetings: ADI: good luck sa exams next week! Lapit na bakasyon yehey!!! 

LEXI: groupmates! We shined kay dr. tuazon! Yay! Grabe ang renal magpaexam ano? Nose

March 11, 2009 | WEDNESDAY

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