Gastrointestinal stromal tumors and leiomyosarcomas in the colon - A clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases

Gastrointestinal stromal tumors (GISTs), mesenchymal tumors largely specifi c for the gastrointestinal tract, have been well defined in the stomach and small intestine, but have not been extensively documented or contrasted wi th true smooth muscle tumors in the colon. This study was undertaken to det ermine the clinicopathologic features of GISTs of the colon, excluding the rectum, and to compare them with leiomyosarcomas (LMSs) of the same locatio n. A total of 37 colonic GISTs and seven LMSs from the files of the Armed F orces Institute of Pathology and the Haartman Institute of the University o f Helsinki were analyzed. The GISTs occurred predominantly in adults older than 50 years of age (median, 67 yrs), and most were histologically maligna nt; four small benign tumors (less than or equal to 1 cm) were incidentally detected, and 10 others had minimal mitotic activity (five or fewer mitose s per 50 high-power fields). The colonic GISTs were typically transmural tu mors with frequent intraluminal and outward bulging components. Histologica lly, they usually showed a spindle cell pattern (92%), whereas 8% were epit helioid. Most tumors (19 of 25) were positive for CD117 (KIT) and for CD34 (16 of 27); six tumors coexpressed a-smooth muscle actin and CD117; none sh owed desmin or S-100 protein. C-kit mutations in exon 11 were seen in 5 (36 %) of 14 colonic GISTs. None of the patients with incidental small tumors h ad a recurrence, whereas 2 of 10 patients with tumors larger than 1 cm but minimal mitotic activity died of the disease with liver metastasis. Nearly all patients whose tumor was larger than 1 cm and showed more than five mit oses per 50 high-power fields died of disease; half had evidence of metasta sis. LMSs were typically intraluminally bulging, polypoid masses that showe d a histologic likeness to differentiated smooth muscle cells. They occurre d in five men and two women with a median age of 61 years. Most LMSs were h igh-grade histologically and showed smooth muscle actin, desmin, or both. A ll were negative for CD34 and CD117 and lacked c-kit mutations. Five of the seven patients died of disease, and two had a long-term survival, despite high mitotic activity. These results show that KIT-positive GISTs are more common than LMSs of the colon, and these tumor groups have clinicopathologi c differences that warrant their separation.