Rice2003.pdf

Benign Esophageal Tumors: Esophagoscopy and Endoscopic Esophageal Ultrasound Thomas W. Rice Benign esophageal tumors are uncommon. Flexible fiberoptic esophagoscopy (esophagoscopy) has improved detection but is ineffective in classification of extramucosal tumors. Endoscopic esophageal ultrasound (EUS) is vital in diagnosis. Small lesions that have either a homogeneous anechoic, intermediate, or hyperechoic pattern are almost exclusively benign. These findings, plus the determination of the layer of origin within the esophageal wall, permit precise and accurate noninvasive diagnosis. The diagnosis of a benign esophageal tumor by esophagoscopy and EUS in an asymptomatic patient requires, at most, surveillance but no therapy. © 2003 Elsevier Inc. All rights reserved.

A

comprehensive knowledge of the esophageal wall along with the ability to evaluate it and paraesophageal tissues are necessary for diagnosis and to determine therapy of benign esophageal tumors. Flexible fiberoptic esophagoscopy (esophagoscopy) and endoscopic esophageal ultrasound (EUS) are essential tools in the evaluation of esophageal tumors.

The Esophageal Wall, Esophagoscopy, and EUS The esophageal wall is composed of three distinct layers: mucosa, submucosa, and muscularis propria (Fig 1). The mucosa has three elements: epithelium, lamina propria, and muscularis mucosa. The inner most layer is stratified, nonkeratinizing squamous epithelium. It is separated and isolated from the remainder of the esophageal wall by a basement membrane. Immediately beneath is the lamina propria. This loose matrix of collagen and elastic fibers forms a superficial undulating layer, the invaginations into the epithelium produce epithelial papillae. Lymphatics in the lamina propria are an anatomic feature unique to the esophagus. The muscularis mucosae surrounds the lamina propria. This smooth muscle layer pleats the two inner layers of the From the Division of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, OH . Address reprint requests to Thomas W. Rice, MD, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. © 2003 Elsevier Inc. All rights reserved. 1043-0679/03/1501-00035-2$30.00/0 doi:10.1016/S1043-0679(03)00035-2

20

mucosa into folds that disappear with distension of the lumen. The submucosa is composed of connective tissue that contains a rich network of blood vessels and lymphatics. The dense submucosal lymphatic plexus facilitates early dissemination of esophageal malignancies. Elastic fibers and collagen combine to make this the strongest esophageal layer. Submucosal glands of mixed type are characteristic to the esophagus. The muscularis propria is the muscular sleeve that provides the propulsive force necessary for swallowing. There are two layers of muscle: an inner circular layer and an outer longitudinal layer. The upper cervical esophagus is composed entirely of striated muscle. There is a gradual transition from striated to smooth muscle within muscle bundles until the esophagus is entirely smooth muscle at the upper and mid-third junction. Lymphatic channels pierce the muscularis propria draining into the regional lymphatics and/or directly into the thoracic duct. The esophagus has no investing adventitia. Paraesophageal tissue is composed of fibro-fatty tissue that lies directly against the outer fibers of the muscularis propria. Esophagoscopy provides unsurpassed visual inspection of the epithelium. At esophagoscopy, an intramural or paraesophageal tumor appears as an extramucosal mass bulging into the esophageal lumen (Fig 2). Intramural tumors are usually mobile and the esophagoscope can generally pass without any evidence of obstruction. It is difficult, if not impossible, to distinguish these uncommon tumors at esophagoscopy. There are few features or locations that are pathognomonic

Seminars in Thoracic and Cardiovascular Surgery, Vol 15, No 1 ( January), 2003: pp 20-26

Benign Esophageal Tumors

21

Figure 1. The esophageal wall is composed of mucosa, submucosa, and muscularis propria. The mucosa is composed of epithelium, lamina propria, and muscularis mucosa.

for any tumor. Biopsy allows histopathologic assessment of the mucosa, but is limited to the epithelium and lamina propria.1,2 Occasionally, biopsy specimens include the muscularis mucosa. Deeper specimens may be obtained by rebiopsy of the previous biopsy site. However, if the overlying mucosa is normal, biopsy should be avoided for it is likely to be nondiagnostic and may complicate enucleation. The esophageal wall and paraesophageal tissues are viewed as five discrete layers by EUS (Fig 3). These layers are seen as alternating hyperechoic (white) and hypoechoic (black) rings. They represent superficial mucosa (inner layer, hyperechoic), deep mucosa (second layer, hypoechoic), submucosa (third layer, hyperechoic), and muscularis propria (fourth layer, hypoechoic). The paraesophageal tissue is the fifth ultrasound layer. EUS characterization of paraesophageal masses and lymph nodes and EUSdirected fine needle aspiration (EUS FNA) of suspicious intramural and paraesophageal masses and regional lymph nodes are part of EUS examination.3

Benign Esophageal Tumors Benign esophageal tumors occur much less frequently than malignant tumors. Because most

patients are asypmtomatic, these tumors are probably more common than previously reported. Benign esophageal tumors were reported in only 0.5% of autopsies.4 Although they represented almost 20% of tumors identified at autopsy, less than 1% of clinically detected esophageal neoplasms are benign. Esophagoscopy has increased detection of these tumors. Because the majority of benign tumors are asymptomatic, slow growing, discovered incidentally, and have a low malignant potential, most require nothing more than diagnosis and, occasionally, surveillance.5 However, large and/or strategically located tumors are more likely to become symptomatic and require removal. If symptomatic, patients with benign esophageal tumors typically present with dysphagia; however, odynophagia, reflux, regurgitation, chest pain, hiccups, anorexia, or respiratory complaints including cough, dyspnea, or pneumonia may be present. Esophagoscopy is limited to partial mucosal evaluation. EUS is essential in the diagnosis of benign esophageal tumors; therefore, classification by layer of origin in the esophageal wall is the most useful means of categorizing benign esophageal tumors (Table 1). EUS identification of intramural masses also relies on the ultra-

22

Thomas W. Rice

Figure 2. A, Barium esophagram demonstrates a broad-based extramucosal mass that lies at an oblique angle to the esophageal lumen. B, Computed tomography (CT) shows a polypoid-filling defect in the esophagus. CT is unable to differentiate luminal from mural or periesophageal origin. C, Esophagoscopy reveals a mass that projects into the esophageal lumen but does not disrupt the mucosa. D, Biopsy of the overlying mucosa illustrates normal squamous epithelium overlying a fragment of normal lamina propria. E, These examinations are suggestive of leiomyoma but fail to confirm the diagnosis (see Fig 4). This symptomatic mass was excised. Histopathology review reveals a hypocellular proliferation of cytologically bland spindle cells with eosinophilic cytoplasm and no mitotic activity or necrosis, a leiomyoma.

Benign Esophageal Tumors

23

Figure 3. The esophageal wall is visualized as five alternating layers of differing echogenicity by EUS. The first (inner) layer is hyperechoic (white) and represents the superficial mucosa (epithelium and lamina propria). The second layer is hypoechoic (black) and represents the deep mucosa (muscularis mucosae). The third layer is hyperechoic and represents the submucosa. The fourth layer is hypoechoic and represents the musculais propria. The fifth layer is hyperechoic and represents the paraesophageal tissue. The thickness of ultrasound layers does not equal the actual thickness of the anatomic layers.

sound characteristics of the tumor. Homogeneous lesions that are anechoic, of intermediate echogenicity, or hyperechoic are almost exclusively benign.6 A heterogeneous echo pattern may be seen in benign tumors, but this endosonographic finding, particularly in lesions greater than 3 to 4 cm in largest diameter, is suspicious for malignancy. Interobserver agreement is good for characterizing benign esophageal tumors; however, operator experience is a major factor in accurate EUS diagnosis.7

Tumors of the Mucosa Squamous epithelium of the esophagus is subject to the same dermatologic conditions and tumors as the skin. Biopsy is indispensable in diagnosing these conditions. Squamous papillomas are small (⬍1 cm), solitary, sessile projections in the distal

esophagus. Usually an incidental finding, endoscopic biopsy is necessary to differentiate squamous papillomas from small superficial squamous cell carcinomas. EUS may confirm the noninvasive nature of this lesion. Because progression to malignancy is rare, asymptomatic lesions are not followed. Symptomatic papillomas or those with atypical histologic features require endoscopic or surgical excision. Papillomas are associated with human papilloma virus and chronic irritation such as gastroesophageal relux disease (GERD). Fibrovascular polyps are collections of fibrous, vascular, and adipose tissue lined by normal squamous epithelium. Microscopically, fibrovascular polyps are expansions of the lamina propria.8 These polyps usually arise in the cervical esophagus, extend into the esophageal lumen,

Thomas W. Rice

24

Table 1. Endosonographic Classification of Benign Esophageal Tumors EUS Layer

Esophageal Tumor

First/second (mucosa/ deep mucosa)

Squamous papilloma Fibrovascular polyp Granular cell tumor Retention cyst Lipoma Fibroma Neurofibroma Granular cell tumor Leiomyoma* Cysts Cysts

Third (submucosa)

Fourth (muscularis propria) Fifth

*Leiomyomas may theoretically arise from the second ultrasound layer (muscularis mucosa), but these tumors most commonly arise from the fourth ultrasound layer.

and may reach into the stomach. Most patients eventually complain of dysphagia and/or respiratory symptoms. Spectacular presentations include regurgitation into the hypopharynx and mouth with subsequent aspiration and, occasionally, sudden death by asphyxiation. Barium esophagram and computed tomography best detect these lesions. Because fibrovascular polyps fill the esophageal lumen and have a composition similar to the mucosa, definition by esophagoscopy or EUS may be difficult or impossible.9 Granular cell tumors are the third most common benign esophageal tumor, and the esophagus is the most common gastrointestinal site of these tumors. Most are located in the distal esophagus. Their origin is neural from the schwann cell. The majority of patients with granular cell tumors are asymptomatic and rarely require surgery. At endoscopy, these lesions are yellow, firm nodules. Endoscopic biopsy is diagnostic in only 50% of patients.10 EUS evaluation typically demonstrates a tumor less than 2 cm in diameter, with an intermediate or hypoechoic, mildly inhomogeneous solid pattern with smooth borders and rising from the inner two EUS layers.10,11 Less than 5% originate from the submucosa. Malignant variants are rare and distinguished by size (⬎4 cm), nuclear pleomorphism, and mitotic activity.12 Atypical EUS findings may predict the rare malignant granular cell tumors.

Tumors of the Submucosa Esophageal stromal tumors are rare and include lipomas, fibromas, and hemangiomas. Lipomas

are indirectly detected at esophagoscopy as a bulging of the overlying esophageal mucosa. They have a pale yellow appearance and soft texture when probed with an esophagoscope. Endoscopic biopsies usually produce normal overlying squamous epithelium because these samplings rarely penetrate the submucosa. EUS demonstrates a hyperechoic homogeneous lesion that originates in and is confined to the submucosal layer. Usually asymptomatic and most often found incidentally, lipomas require no follow-up. Fibromas and neurofibromas are very uncommon. At endoscopy, they are firm “to the touch.” These lesions are less hyperechoic than lipomas. Symptomatic submucosal tumors are uncommon and most symptoms unrelated. These tumors are typically incidental findings of a shotgun investigation of atypical symptoms such as chest pain, cough, etc. If excision is required, enucleated by endoscopic or minimally invasive techniques should be considered. Hemangiomas may present with dysphagia and bleeding. Most are in the lower esophagus and they may be mistaken for esophageal varices. EUS examination reveals a hypoechoic mass with sharp margins arising from the second or third EUS layer.13,14 Treatment may include observation, simple excision, fulgarization, or radiotherapy depending on size and complications.

Tumors of the Muscularis Propria Leiomyomas are benign smooth muscle tumors of the muscularis propria. Origin from the muscularis mucosa is rare.15 Leiomyomas are the most common benign esophageal tumors and account for more than 70% of all benign tumors. The majority arises from the inner circular muscle layer in the distal and mid-thoracic esophagus. There is no gender preponderance and they typically occur in patients 20 to 50 years old, significantly younger than those with esophageal carcinomas. Although frequently asymptomatic and discovered incidentally, leiomyomas can cause dysphagia, pain, or bleeding. Distal esophageal leiomyomas are often associated with GERD symptoms. Barium esophagram demonstrates smooth filling defects; esophagoscopy, a normal overlying mucosa; and EUS, a hypoechoic, sharply bordered tumor arising in the fourth ultrasound layer (Figs 2 and 4). Diagnosis of small leiomyomas (⬍1 cm in diameter) may be en-

Benign Esophageal Tumors

25

Esophageal Cysts Esophageal cysts are the second most common benign esophageal tumor accounting for 20% of these lesions. The minority are acquired epithelial cysts arising in the lamina propria. Submucosal glandular inflammation is the suspected cause. The majority of esophageal cysts are congenital foregut cysts. They are lined with squamous, respiratory, or columnar epithelium and may contain smooth muscle, cartilage, or fat. Esophageal duplication is a subtype of foregut cyst; it is lined with squamous epithelium and its submucosal and muscularis elements interdigitate with the muscularis propria of the esophagus. They may be associated with vertebral and spinal cord abnormalities. Many foregut cysts present in the first year of life with life-threaten-

Figure 4. An esophageal leiomyoma. Upper panel, EUS of this most common benign tumor demonstrates a hypoechoic, homogeneous, well-demarcated tumor with no associated lymphadenopathy. EUS balloon overdistension blends the first three ultrasound layers into one hyperechoic layer. The tumor arises from and is confined to the fourth ultrasound layer (arrow). Lower panel, A benign leiomyoma arises from and is confined to the muscularis propria.

hanced with the use of miniature ultrasound probes.16 Atypical EUS findings are a tumor ⬎4 cm in diameter, irregular margins, mixed internal echo characteristics, and associated regional lymphadenopathy. Endoscopic biopsies do not reach the muscularis propria, and EUS FNA is unlikely to provide the cellular architectural characteristics necessary to differentiate leiomyomas from leiomyosarcomas, which are exceedingly rare. Malignant transformation of benign leiomyomas has been infrequently reported. Surgical resection, by minimally invasive techniques if possible, is indicated for symptomatic leiomyomas. In asymptomatic tumors with typical EUS features, expectant therapy and EUS observation is indicated.

Figure 5. A foregut cyst. Upper panel, EUS demonstrates a mass (arrows) adjacent to the trachea and esophagus. The cyst has two components, one hyperehoic (white) representing proteinaceous material and one hypoechoic (black) representing fluid. Lower panel, A foregut cyst in close proximity to the esophagus and trachea.

26

Thomas W. Rice

ing respiratory compression. However, removal of all cysts has been suggested because most become symptomatic in the adult. EUS can clearly define the intramural or extraesophageal nature of these tumors and further determine their anechoic, cystic nature (Fig 5).17-20 Transesophageal drainage of a foregut cyst has been reported, but drainage of the cyst without destruction of its lining may result in recurrence.21

Conclusions Benign esophageal tumors are uncommon and often asymptomatic. Frequent use of esophagoscopy has increased detection of these tumors. Endoscopic biopsy, limited to the superficial mucosa, is of nominal use in defining these tumors. EUS is essential in the diagnosis of benign esophageal tumors. EUS determines both the layer of origin in the esophageal wall and the ultrasound characteristics of the tumor. Asymptomatic tumors characterized as benign by EUS can be confidently followed.

References 1. Woods KL, Anand BS, Cole RA, et al: Influence of endoscopic biopsy forceps characteristics on tissue specimens: results of a prospective randomized study. Gastrointest Endosc 49:177-183, 1999 2. Schafer TW, Hollis-Perry KM, Mondragon RM, et al: An observer-blinded, prospective, randomized comparison of forceps for endoscopic esophageal biopsy. Gastrointest Endosc 55:192-196, 2002 3. Larsen SS, Krasnik M, Vilmann P, et al: Endoscopic ultrasound guided biopsy of mediastinal lesions has a major impact on patient management. Thorax 57:98-103, 2002 4. Plachta A: Benign tumors of the esophagus. Am J Gastroenterol 38:639-652, 1962 5. Melzer E, Fidder H: The natural course of upper gastrointestinal submucosal tumors: an endoscopic ultrasound survey. Isr Med Assoc J 2:430-432, 2000 6. Kawamoto K, Yamada Y, Utsunomiya T, et al: Gastrointestinal submucosal tumors: evaluation with endoscopic US. Radiology 205:733-740, 1997

7. Gress F, Schmitt C, Savides T, et al: Interobserver agreement for EUS in the evaluation and diagnosis of submucosal masses. Gastrointest Endosc 53:71-76, 2001 8. Lewin K, Appelman, HD. Mesenchymal tumors and tumor-like proliferations of the esophagus. In: Atlas of Tumor Pathology: Tumors of the Esophagus and Stomach. Washington, DC: Armed Forces Institute of Pathology; 1996:45-61. 9. Schuhmacher C, Becker K, Dittler HJ, et al: Fibrovascular esophageal polyp as a diagnostic challenge. Dis Esophagus 13:324-327, 2000 10. Palazzo L, Landi B, Cellier C, et al: Endosonographic features of esophageal granular cell tumors. Endoscopy 29:850-853, 1997 11. Love MH, Glaser M, Edmunds SE, et al: Granular cell tumour of the oesophagus: endoscopic ultrasound appearances. Australas Radiol 43:253-255, 1999 12. Goldblum JR, Rice TW, Zuccaro G, et al: Granular cell tumors of the esophagus: a clinical and pathologic study of 13 cases. Ann Thorac Surg 62:860-865, 1996 13. Araki K, Ohno S, Egashira A, et al: Esophageal hemangioma: a case report and review of the literature. Hepatogastroenterology 46:3148-3154, 1999 14. Maluf-Filho F, Sakai P, Amico EC, et al: Giant cavernous hemangioma of the esophagus: endoscopic and echo-endoscopic appearance. Endoscopy 31:S32, 1999 15. Takada N, Higashino M, Osugi H, et al: Utility of endoscopic ultrasonography in assessing the indications for endoscopic surgery of submucosal esophageal tumors. Surg Endosc 13:228-230, 1999 16. Xu GM, Niu YL, Zou XP, et al: The diagnostic value of transendoscopic miniature ultrasonic probe for esophageal diseases. Endoscopy 30(suppl 1):A28-32, 1998 17. Bhutani MS, Hoffman BJ, Reed C: Endosonographic diagnosis of an esophageal duplication cyst. Endoscopy 28: 396-397, 1996 18. Faigel DO, Burke A, Ginsberg GG, et al: The role of endoscopic ultrasound in the evaluation and management of foregut duplications. Gastrointest Endosc 45:99-103, 1997 19. Massari M, De Simone M, Cioffi U, et al: Endoscopic ultrasonography in the evaluation of leiomyoma and extramucosal cysts of the esophagus. Hepatogastroenterology 45:938-943, 1998 20. Lim LL, Ho KY, Goh PM: Preoperative diagnosis of a paraesophageal bronchogenic cyst using endosonography. Ann Thorac Surg 73:633-635, 2002 21. Van Dam J, Rice TW, Sivak MV, Jr: Endoscopic ultrasonography and endoscopically guided needle aspiration for the diagnosis of upper gastrointestinal tract foregut cysts. Am J Gastroenterol 87:762-765, 1992