Answer: Gastrointestinal stromal tumor (GIST) with epithelioid features

Histology: There has recently been a deluge of information about these which was nicely reviewed by Miettinen [1]. These tumors may be spindled to epithelioid. The term “leiomyoblastoma” is and old term which was later supplanted by “epithelioid smooth muscle tumor” and more recently by encompassing them under GIST since epithelioid morphology probably has little impact on outcome. They differ from smooth muscle tumors by having more tapered nuclei and more random orientation of their fascicles of spindle cells.

Discussion: The discovery that GISTs express CD117 (ckit) suggested that they are related to the interstitial cells of Cajal (intestinal pacemaker cells), but more recently, they have been shown to also express calponin, h-caldesmon, and embryonic smooth muscle myosin heavy chain, features which lead to the consideration of various forms of differentiation in a more primitive “stromal” cell. On a practical note, these tumors are reported all along the gastrointestinal tract from the esophagus to the anus and typically express both CD117 and CD34. Some have actin, but they do not express desmin. (Most mesenchymal tumors in the esophagus are leiomyomas but “stromal” examples have been recently described. All the esophageal GISTS were in the lower third of the esophagus and the patients with esophageal GISTS all died of disease.) Tumors indistinguishable from GISTS have also been reported in the abdomen and retroperitoneum unassociated with the GI tract. When these are encountered in daily practice, however, histogenesis becomes less relevant than anticipating outcome and a number of guidelines apply:

1. Behavior is site-specific. In a large AFIP series, the tumors of the esophagus did best (but this included true smooth muscle tumors in the AFIP series), followed by stomach, colorectum, and small bowel tumors behaved worst.
2. Some observers start with “low grade” in the small intestine, no matter what the appearance of the tumor.
3. Extra-intestinal lesions followed the small bowel survival curves, a finding confirmed more recently.

Because of all this, some suggest that a diagnosis of BENIGN should never appear in the small bowel, where you should start your diagnoses at “uncertain” or low grade no matter how bland the tumor looks. For the present, it is probably best to assess esophageal GIST and extra-GI GIST like small bowel. Lesions that are very small and have features of true smooth muscle differentiation in the esophagus can be diagnosed as leiomyoma (with bland cytology and low mitotic counts). Mucosal invasion in the colon and recto-anal area has recently been suggested as an adverse factor.

Differential Diagnosis
The differential diagnosis in this case is readily resolved with an immunohistochemical panel directed at excluding carcinoma and lymphoma and confirming GIST (keratin, lymphoid markers, CD34, CD117, and muscle markers). Inflammatory fibroid polyps most commonly occur in the stomach and consist of well-marginated fibrous-appearing lesions characterized by scattered eosinophils and a peculiar “onion-skin” pattern around vessels. In common with GIST, they express CD34 but are always benign and regarded as reactive lesions by many observers.