Diffuse esophageal leiomyomatosis: Case report and review

Diffuse esophageal leiomyomatosis: Case report and review

C Calabrese, A Fabbri, P Fusaroli, et al. Diffuse esophageal leiomyomatosis: case report and review Carlo Calabrese, MD, Anna Fabbri, MD, Pietro Fusa...

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C Calabrese, A Fabbri, P Fusaroli, et al.

Diffuse esophageal leiomyomatosis: case report and review Carlo Calabrese, MD, Anna Fabbri, MD, Pietro Fusaroli, MD, Pasquale Di Gaetano, MD, Mario Miglioli, MD, Giulio Di Febo, MD

Diffuse esophageal leiomyomatosis

described. This is a report of a case of diffuse esophageal leiomyomatosis without involvement of other organs. Reported cases are analyzed with a particular focus on problems associated with correct diagnosis. CASE REPORT

Leiomyoma is the most frequent benign tumor of the esophagus,1 whereas diffuse esophageal leiomyomatosis is a rare pathologic entity. To date, only 60 cases of esophageal leiomyomatosis have been From the Department of Internal Medicine and Gastroenterology and the Department of Surgical and Anaesthesiological Sciences, University of Bologna, Bologna, Italy. Reprint requests: Carlo Calabrese, MD, Department of Internal Medicine and Gastroenterology, University of Bologna, Policlinico S. Orsola-Malpighi, Via Massarenti n°9, 40138, Bologna, Italy. Copyright © 2002 by the American Society for Gastrointestinal Endoscopy 0016-5107/2002/$35.00 + 0 37/4/122581 doi:10.1067/mge.2002.122581 590

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A 61-year-old man with progressive dysphagia for solid food and moderate weight loss over a period of 2 years presented with a food bolus impaction that spontaneously resolved with vomiting. Barium contrast radiography (Fig. 1) demonstrated irregular narrowing of the esophagus from 20 to 35 cm caused by multiple filling defects, one of which produced almost total occlusion of the lumen. Endoscopically, diffuse submucosal hemispheric firm lesions covered by normal-appearing esophageal mucosa were identified (Fig. 2). A hiatal hernia was present and the distal esophagus was noted to be lined by columnar type epithelium (Fig. 3). EUS revealed multiple masses throughout the entire length of esophagus, involving the longitudinal and circuVOLUME 55, NO. 4, 2002

Diffuse esophageal leiomyomatosis

C Calabrese, A Fabbri, P Fusaroli, et al.

lar smooth muscle layers and the muscularis mucosae. The echotexture of the lesions was heterogeneous with anechoic lacunae within an echogenic pattern. The third and fourth sonographic layers (submucosa and muscularis propria) were normal and clearly visible surrounding the tumors. The masses ranged in size from 1.8 to 4.5 cm (Fig. 4). Deep tissue samples were obtained with a guillotine needle under direct endoscopic vision, and a histologic diagnosis of leiomyoma was made. Laboratory tests including urinalysis, a fecal occult blood test, peripheral blood counts, standard biochemical studies, and tumor markers were all within normal limits. An electrocardiogram and chest radiograph did not disclose any significant abnormality. The patient refused esophagectomy. A semiliquid diet was prescribed. During a follow-up of 3 years no enlargement of the leiomyomas was apparent and the patient’s symptoms remained unchanged. He subsequently died of an acute myocardial infarction.

DISCUSSION Diffuse esophageal leiomyomatosis is a benign neoplastic lesion characterized by diffuse smooth muscle proliferation in the esophagus. Because there is confusion with regard to terminology, this entity should be distinguished from single and multiple leiomyomas. Histologically, esophageal leiomyomas are localized neoplastic lesions that involve the longitudinal or circular smooth muscle layers, whereas diffuse esophageal leiomyomatosis is characterized by circular and longitudinal layer smooth muscle proliferation within the wall of the entire esophagus. There is minimal cellular atypia, no detectable mitoses, and the overall cellularity is low.2 There is a patchy involvement of the muscularis mucosae. Smooth muscle proliferation is also present in the submucosa, and a myomatous pattern may occasionally be found in the muscle layer of blood vessels. There is no evidence of vascular invasion. Nerve plexuses are prominent in some areas and there is a mild inflammatory cell infiltrate consisting of lymphocytes, plasma cells, and eosinophils.3 Diffuse esophageal leiomyomatosis is 1.6 times more prevalent in women than men. The average age at diagnosis is 25.6 years (range 2-71 years). Only 13 cases (21.7%) have been reported in which localization was limited to the esophagus; in 21.7% gastric involvement was also present. Moreover, in 10% of cases there was smooth muscle hyperplasia of the trachea, bronchi, or female genitalia. Diffuse esophageal leiomyomatosis is frequently associated with Alport’s syndrome, a familial condition characterized by a hematuric nephropathy, sensorial deficiency, and ocular lesions.4 In 41 of the 60 reported cases (68.3%) of diffuse esophageal leiomyomatosis, Alport’s syndrome was also present. This latter condition is defined as an hereditary disease VOLUME 55, NO. 4, 2002

Figure 1. Barium esophagogram showing irregular narrowing of esophagus caused by multiple filling defects.

of type IV collagen transmitted as an X-linked dominant trait. Mutation of both the COL4A5 and COL4A6 genes, located head to head on Xq22 and encoding the alpha 5 and alpha 6 (IV) chains, are responsible for the abnormalities. Molecular studies have shown deletions of the 5’ end of both COL4A5 and COL4A6 including the intergenetic region. The GASTROINTESTINAL ENDOSCOPY

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C Calabrese, A Fabbri, P Fusaroli, et al.

Diffuse esophageal leiomyomatosis

Figure 2. Endoscopic view of hemispheric, firm lesion covered by normal-appearing esophageal mucosa. Figure 4. EUS image (sector scan, 7.5 MHz) of 2 × 4.5 cm echogenic mass arising from second sonographic layer (mucosa). The third and fourth layers are clearly displayed deep to the mass.

Figure 3. Endoscopy view of distal esophagus showing hiatal hernia, Barrett’s epithelium, and nodular lesions covered by normal mucosa.

breakpoint in COL4A6 is always located within intron 2. Immunohistochemistry has shown significant alterations of basement membranes in kidney and esophageal leiomyomas.4-6 Clinically, dysphagia is the most frequent symptom of diffuse esophageal leiomyomatosis (83.3% of cases); it is generally long-standing and progressive. Other symptoms include vomiting, retrosternal discomfort, dyspepsia, and respiratory symptoms, such as dyspnea and recurrent chest infections. In 3 reported cases, upper GI bleeding was the presenting manifestation.7-9 Three patients in other studies were asymptomatic.3,10,11 In many reported cases, the diagnosis of diffuse esophageal leiomyomatosis was evidently difficult. Chest radiograph may disclose abnormal findings with deviation of para592

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esophageal lines and tumoral opacity superimposed on the cardiac contour.11 Barium contrast radiography frequently suggested the diagnosis of achalasia (27 of 53 reported cases; 50.9%), often with a dilated esophagus and a relatively narrow gastroesophageal junction. Oblique anteroposterior views may reveal rounded lacunar images with a regular outline and no mucosal alteration. CT has been used to establish the diagnosis but in 66.7% of cases (14 of 21 patients) a misdiagnosis of achalasia was made. In fact, when the distal esophagus is not involved and thickened, CT cannot demonstrate evidence of leiomyomatosis, and thus suggests another benign cause of dysphagia such as primary achalasia. Nevertheless, in the majority of cases CT confirms the intramural nature of the lesions and quantifies the circumferential thickening of the esophagus. Esophageal manometry was performed in only 3 of the reported cases and demonstrated total absence of peristalsis in the esophageal body. In all cases there was a long, high-pressure zone in the distal 7 to 10 cm of the esophagus.12 At endoscopy, multiple hemispherical, firm lesions covered by normal mucosa are the features most suggestive of diffuse esophageal leiomyomatosis. This appearance was reported in only 16 of 29 cases (55.2%) in which endoscopy was performed. Nevertheless, this typical endoscopic feature was evident by barium contrast radiography. In the remaining cases the endoscopic appearance suggested achalasia. VOLUME 55, NO. 4, 2002

Diffuse esophageal leiomyomatosis

EUS is highly sensitive and relatively specific for the diagnosis of diffuse esophageal leiomyomatosis. To date, EUS has been used in only 3 patients with the correct diagnosis being made in each case. EUS can identify which component of the esophagus is thickened by virtue of its ability to distinguish mucosa, submucosa, muscularis propria, and adventitia. In particular, a mass arising in the submucosa, such as a lipoma, can be differentiated from one arising in the muscularis propria, such as a leiomyoma or leiomyomatosis. Extensive and uniform thickening of the longitudinal and circular smooth muscle layers differentiates leiomyomatosis from leiomyoma. EUS-guided fine-needle aspiration can be used to obtain a cytologic diagnosis for masses arising in submucosa as well as those extrinsic to the upper GI tract. However, the hypocellularity of many leiomyomatous lesions usually necessitates histologic rather than cytologic diagnosis.13,14 Management of patients with diffuse esophageal leiomyomatosis depends on clinical symptoms. For asymptomatic patients, who comprise only 5% of reported cases, clinical and endoscopic follow-up is satisfactory, but for those with severe and progressive dysphagia total esophagectomy is necessary and has been performed in 91.7% of reported cases. Partial gastrectomy must also be included for patients with involvement of the stomach. Myomectomy is usually not performed because the results are unsatisfactory. The diagnosis of diffuse esophageal leiomyomatosis should be considered in patients with longstanding dysphagia and multiple hemispherical submucosal lesions at endoscopy or radiography. When the predominant feature is smooth tapered narrowing of the distal esophagus, neither radiography or endoscopy will suggest the diagnosis, and achalasia is thus the most common misdiagnosis. In such cases, EUS must be always performed because it remains the only method for identification of the characteristic thickening of the esophageal wall and will thus indicate the correct diagnosis.

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C Calabrese, A Fabbri, P Fusaroli, et al.

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