Pathologic Quiz Case: An Unusual Cause of Exertional Dyspnea

A 52-year-old woman in good health presented to her family physician with a 6-month history of some difficulty swallowing solid foods and a 3-month history of dyspnea on severe exertion. These symptoms occurred in the absence of other respiratory, cardiac, or gastroesophageal reflux symptoms. She had never smoked. Alcohol consumption was rare. Physical examination was normal. A chest radiograph revealed a large opacity in the medial aspect of the left lower hemithorax. A contrast-enhanced computed tomographic (CT) scan of the chest showed a 9-cm heterogeneous mass abutting the left side of the distal esophagus extending from the infrahilar region to the left hemidiaphragm (Figure 1). The proximal esophagus was not dilated. Fiberoptic esophagoscopy revealed extrinsic compression of the lower esophagus and normal esophageal mucosa. Percutaneous fine-needle aspiration biopsy was nondiagnostic, but core biopsy revealed that the mass was a spindle cell tumor. At surgery, a large tumor mass was found in the inferior mediastinum. The tumor was intramural in the esophagus and was adherent to both the diaphragm at the hiatus and the left lower pulmonary lobe at the inferior pulmonary ligament. A complete resection required near-total esophagectomy with en bloc limited resection of the adherent diaphragm and lung parenchyma. Esophageal reconstruction was with a gastric conduit.The esophageal tumor measured 10.0 × 9.8 × 5.6 cm and weighed 235 g (Figure 2). The bosselated external surface contained numerous fibrous adhesions. Cross-section of the mass revealed a heterogeneous tumor with focal areas of hemorrhage and necrosis. Histologic examination revealed a dense cellular tumor composed of interlacing fascicles of spindle cells (Figure 3). Large foci of tumor necrosis were identified. The tumor cells had eosinophilic cytoplasm and enlarged, hyperchromatic, ovoid, vesicular nuclei with occasional nucleoli. Mild nuclear pleomorphism was present. Occasional tumor cells had abundant cytoplasm and were epithelioid in nature. Scattered mitotic figures were present with 5 mitotic figures per 50 high-power fields. Immunohistochemical stains directed against vimentin, desmin, muscle-specific actin, and smooth muscle actin (Figure 4) were all positive. Cytokeratins AE1 and AE3 and S100 protein were not detected. Examination of esophageal mucosa revealed no evidence of dysplasia or carcinoma. There was no tumor involvement of the adherent diaphragm or lung, and all surgical resection margins and paraesophageal lymph nodes were free of tumor.What is your diagnosis?Primary esophageal leiomyosarcomas are rare tumors that account for approximately 0.5% of all malignant esophageal neoplasms.1,2 Leiomyosarcomas constitute 90% of primary esophageal sarcomas,3 including fibrosarcoma, liposarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma, synovial sarcoma, chondrosarcoma, and osteosarcoma.3–5 Esophageal leiomyosarcomas, like other gastrointestinal leiomyosarcomas, are thought to arise primarily de novo from the muscularis mucosae or propria.2,6 These tumors are less commonly derived from the smooth muscle of blood vessel walls or from sarcomatous transformation of preexisting benign leiomyomas.6 Esophageal leiomyosarcomas can present grossly as polypoid intra-luminal, predominantly intramural or extraluminal tumor masses.2,3,6 All growth patterns of esophageal leiomyosarcoma can produce dysphagia, although extraluminal tumors may produce few and late esophageal symptoms, secondary to minimal lumen compression.6 Our patient's late clinical symptom of exertional dyspnea likely resulted from mechanical impairment of the diaphragm by a large extraluminal esophageal leiomyosarcoma. Dyspnea, secondary to tracheobronchial tree compression, is a rare clinical symptom of leiomyosarcomas and is observed in 5% of patients.7 Both intramural and extraluminal leiomyosarcomas can have normal overlying esophageal mucosa that may yield false-negative biopsy findings at esophagoscopy, especially if superficial biopsy specimens are taken.6,7 Leiomyosarcomas that ulcerate esophageal mucosa may clinically mimic the more common esophageal carcinomas.2 The majority of esophageal leiomyosarcomas behave clinically as low-grade malignancies with a tendency to metastasize late in their course.2,6,7 Ultimately, these neoplasms may directly extend to involve the lungs, pericardium, and pleura or may metastasize hematogenously.2,6Esophageal leiomyosarcomas are typically composed of spindle cells that organize in interlacing fascicles.3,7 These spindle cells exhibit varying degrees of both nuclear pleomorphism and mitotic activity. There are no malignant histologic features unique to esophageal leiomyosarcomas.3 Rather, tumor malignancy is based on criteria derived from both soft tissue and other gastrointestinal leiomyosarcomas.2,3,8 These criteria of malignancy include dense tumor cellularity, easily identifiable mitotic figures, infiltrative tumor borders, and metastatic dissemination. The relationship between tumor size and malignant behavior is well recognized in gastrointestinal stromal tumors of small bowel and stomach.9 The same is not true for esophageal smooth muscle tumors. A recent study by Emory et al9 could not confirm the prognostic importance of either tumor size or mitotic index for esophageal stromal tumors on account of inconclusive data. However, it has been suggested that esophageal smooth muscle tumors greater than 5.5 cm in diameter and with a mitotic index greater than 5 per 50 high-power field be considered malignant.10 A subpopulation of esophageal leiomyosarcomas is known to exist that exhibits few or no histologic features of malignancy.6,7 These tumors are extremely difficult to differentiate from benign leiomyomas and are ultimately identified by their aggressive clinical behavior. Cytologically benign, soft tissue, smooth muscle tumors may also exhibit malignant clinical behavior, like their esophageal counterparts.8 Esophageal leiomyosarcomas can be heterogeneous in composition secondary to multiple foci of hemorrhage and necrosis.3 Tumor heterogeneity is identified on CT scan as single central or multiple foci of low tumor density.2,6 Contrast material within tumors and extraluminal air are other radiologic features of esophageal leiomyosarcomas, particularly ones that have undergone cavitation.6In addition to benign leiomyomas, esophageal leiomyosarcomas must be differentiated from both pseudosarcomatous squamous cell carcinoma (SCC), otherwise known as carcinosarcoma, and the stromal proliferation of chronic ulcer beds.3 Pseudosarcomatous SCCs are typically polypoid, intraluminal esophageal tumors that are biphasic in nature.2,3 They are composed of SCC and pleomorphic spindle cells. The spindle cell component tends to predominate, and there can be little residual SCC, thus making differentiation from leiomyosarcoma difficult.3 Superficial fibroblasts and myofibroblasts of chronic esophageal ulcers may mimic leiomyosarcoma tumor cells by having hyperchromatic and pleomorphic nuclei, bizarre nuclear shapes, and occasional mitotic figures.3Standard therapy for esophageal leiomyosarcomas has not been established because of the rarity of these tumors.4 Traditional therapy has consisted of complete resection, including esophagectomy and partial gastrectomy if necessary.2,4,7 Long-term survival, however, has also been observed in patients treated with local excision alone.1 There has been little experience with radiotherapy of these tumors.4 Considering the infiltrative nature of esophageal leiomyosarcomas and the limited studies investigating their treatment, it would be prudent to continue with complete surgical resection as the mainstay of their management.

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