Gastrointestinal stromal tumors (GISTs) are a heterogeneous group of mesenchymal tumors with a wide spectrum of histologic features and consistent expression of c-Kit. We describe an 85-year-old woman who presented with left lower quadrant abdominal pain and was subsequently diagnosed as having a malignant GIST. The tumor was composed of short fascicles of spindle cells. In addition to the presence of tumor giant cells, the tumor also demonstrated many osteoclast-like giant cells, a feature that has not been previously described in the literature. These giant cells expressed histiocytic markers CD68 and alpha(1)-antitrypsin but not c-Kit, a marker for GISTs. Electron microscopy showed no features of smooth muscle differentiation in the giant cells. The possible origin of the osteoclast-like giant cells is discussed in the context of immunohistochemical and ultrastructural characteristics.

CONTEXT: One case of leiomyosarcoma and one case of gastrointestinal stromal tumor with prominent osteoclast-like giant cells have so far been reported in the digestive tract. OBJECTIVE: To ascertain the clinicopathologic features and biologic behavior of these tumors, we report 3 additional cases of leiomyosarcoma of the gastrointestinal tract and one malignant gastrointestinal stromal tumor. DESIGN: Histologic and immunohistochemical examinations were performed. Clinical and follow-up data were recorded, and the literature was reviewed. RESULTS: The age of the patients ranged from 50 to 68 years (mean, 62 years). One of the lesions arose in the stomach, one in the ileum, and 2 in the colon. Three tumors showed a strong positivity for muscle actin and desmin and were diagnosed as leiomyosarcomas, 2 of them showing spindle cells and 1 of them showing epithelioid cells. The fourth tumor reacted strongly positive for c-Kit (CD117) and vimentin, and it was diagnosed as an epithelioid malignant gastrointestinal stromal tumor. All tumors were characterized by numerous osteoclast-like giant cells that were unevenly distributed and that, using immunohistochemistry, reacted strongly with CD68. CONCLUSIONS: Malignant stromal tumors with osteoclast-like giant cells of the gastrointestinal tract are rare entities, are more commonly of a myogenic origin such as leiomyosarcoma, and seem to have an aggressive behavior.

Nine cases are presented of a distinctive morphologic variant of myogenic gastrointestinal stromal tumor characterized by an unusually prominent myxoid stromal background reminiscent of a neural neoplasm but lacking the immunohistochemical or ultrastructural features of peripheral nerve sheath or ganglionic differentiation. The patients included six women and three men aged 42 to 86 years (mean, 70). The lesions occurred in the stomach (seven cases) and small intestine (two cases) and ranged in size from 2.5 to 9.5 cm. They were described grossly as well circumscribed, unencapsulated, with a prominently myxoid and often cystic cut surface. Histologically, the lesions were composed of a proliferation of round, spindle, or stellate cells embedded in an abundant myxoid stroma. Histochemical stains showed strong positive reaction of the myxoid stromal background with alcian blue at pH 2.5; this staining reaction was abolished by treatment with hyaluronidase, indicating an abundance of connective tissue mucosubstances rich in hyaluronic acid. Immunohistochemical stains showed strong positivity of the tumor cells with vimentin antibodies in all cases and focal weak to moderate positive staining with muscle actin (HHF35) in eight cases and with desmin in two. Stains for keratin, S-100; epithelial membrane antigen, and collagen type IV were uniformly negative. Ultrastructural examination carried out in all cases showed features consistent with those previously described for myogenic gastrointestinal stromal tumors, namely, scattered mitochondria and prominent Golgi apparati, strands of rough endoplasmic reticulum, focal accumulation of intracytoplasmic microfilaments with occasional focal condensations, subplasmalemmal attachment plaques and immature cell junctions, focal extracellular basal lamina material, and surface-oriented micropinocytotic activity. The myxoid changes observed in these tumors may represent a secondary, nonspecific reaction pattern of the tumor cells to some noxious stimulus, or they may be a form of degenerative phenomenon such as that commonly observed in smooth-muscle tumors of the uterus and other sites. Myogenic gastrointestinal stromal tumors with prominent myxoid stroma should be distinguished from benign schwannoma of the stomach and gastrointestinal autonomic nerve tumors. Because of the differences in prognosis for these entities, immunohistochemical and ultrastructural examinations are recommended for the evaluation of gastrointestinal stromal neoplasms with prominent myxoid features.