Although rare elsewhere in the gastrointestinal tract, leiomyomas (LMs) are the most common esophageal mesenchymal neoplasms. In contrast, gastrointestinal stromal tumors (GISTs) predominate in the stomach and intestines but have not been documented in the esophagus. This study was undertaken to determine the clinicopathologic features and frequency of esophageal GISTs compared with LMs and leiomyosarcomas (LMSs) of the esophagus. A total of 68 stromal/smooth muscle tumors from the Armed Forces Institute of Pathology and the Haartman Institute of University of Helsinki were reclassified by current histologic and immunohistochemical criteria. There were 17 GISTs, 48 LMs, and three LMSs. The esophageal GISTs occurred in 12 men and five women with a median age of 63 years (range, 49-75 years). All tumors were from the lowest third of the esophagus, and the most common complaint was dysphagia, whereas two tumors were detected incidentally. Histologically the tumors had an overall basophilic appearance and showed combinations of solid, myxoid, and perivascular collarlike patterns with a spindle cell histology in 13 patients and epithelioid histology in four patients. All tumors were positive for CD117 and for CD34, whereas two patients were also positive for α-smooth muscle actin (SMA) and three patients were positive for desmin. One patient showed a unique immunophenotype with coexpression of CD117, CD34, SMA, and desmin. Nine patients died of disease, including all who had a tumor larger than 10 cm, and also one patient whose tumor showed five mitoses per 50 high-power fields. In comparison, esophageal LMs (n = 48) occurred in a younger population (median age, 35 years) but, similar to the GIST group, men predominated (67%). All LMs were clinically indolent tumors with no tumor-related mortality. The LMs showed eosinophilic cytoplasm, and were positive for desmin and SMA, and negative for CD117 and CD34. All three LMSs were large high-grade tumors that showed muscle cell markers but no CD117. All patients died of disease. Esophageal GISTs showed mutations in exon 11 of c-kit as described previously in gastric and intestinal GISTs. The separation of GISTs from esophageal LMs is important diagnostically because the former group has a high risk of malignant behavior.
Leiomyomas (LMs), tumors that show histologic resemblance to normal smooth muscle cells, are the most common mesenchymal tumors of the esophagus. However, they are rare elsewhere in the gastrointestinal (GI) tract. 1,19,36 By contrast, most GI mesenchymal tumors belong to the group of specific gastrointestinal stromal tumors (GISTs). These are cellular spindle or epithelioid tumors that show rudimentary if any smooth muscle differentiation, 18,19 and correspond largely to the previous designations of cellular LM, 2 leiomyoblastoma, and leiomyosarcoma (LMS). 3
Although the typical LMs are positive for actin and desmin, and negative for CD34, the stromal tumors are usually positive for CD34, almost uniformly negative for desmin, and are negative for smooth muscle actin (SMA) in the majority of patients. 21,22,24,37 By electron microscopy, the stromal tumors are heterogeneous and may show smooth muscle or autonomous nerve system-like differentiation or both, or no differentiation at all in some patients. 6 Perhaps the best defining feature for the stromal tumors is their expression of KIT-protein (CD117), which is not present in LMs. 9,11,31,34 Also, activating mutations have been found in the juxtamembrane domain of the c-kit gene in a subset of GISTs. 9,12,14,25-27 Additional differences between esophageal LMs and GISTs have been shown in deoxyribonucleic acid (DNA) copy number changes. 30
The current Armed Forces Institute of Pathology (AFIP) fascicle of tumors of esophagus and stomach states that it is not clear whether there is a group of unique malignant stromal tumors of the esophagus as there is in the stomach.16,p.151 During recent years we have encountered several examples of esophageal stromal tumors that corresponded histologically to GISTs seen in the stomach and small intestine. Such esophageal stromal tumors have not been generally recognized and have not been separated from smooth muscle tumors, and their pathologic features and clinical behavior have therefore remained uncharacterized.
In this study, we describe CD117-and CD34-positive esophageal stromal tumors as a minority of esophageal mesenchymal neoplasms, and compare them with typical LMs and LMSs. We also demonstrate that the esophageal stromal tumors show c-kit gene mutations as documented previously in gastric and intestinal GISTs, thereby being fully comparable with the GISTs in their main locations. 8,14