Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus - A clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases

Gastrointestinal stromal tumors (GISTs), the specific KIT-positive mesenchy mal tumors of the gastrointestinal tract, have been sporadically reported i n the rectum, but there are few clinicopathologic series. In this study we analyzed the clinicopathologic features of 133 anorectal GISTs, 3 intramura l leiomyomas (LMs), and 8 leiomyosarcomas (LMSs) from the files of the Arme d Forces Institute of Pathology and the Haartman Institute of the Universit y of Helsinki. Ninety-six GISTs were documented as KIT-positive and three a dditional ones as CD34-positive. Thirty-four tumors were included by their histologic similarity to KIT- or CD34-positive cases. GIST-specific c-kit g ene mutations, mostly in exon 11, were documented in 18 of 29 cases (62%). The GISTs occurred in adults with the age range of 17-90 years (median 60 y ears) with a significant male predominance (71 %). The tumors ranged from s mall asymptomatic intramural nodules to large masses that bulged into pelvi s causing pain, rectal bleeding, or obstruction. They were mostly highly ce llular spindle cell tumors; four tumors had an epithelioid morphology. The tumors coexpressed CD34 and KIT and were rarely positive for smooth muscle actin or desmin and never for S-100 protein. Seventy percent of patients wi th tumors >5 cm with more than 5 mitoses/50 high power fields (HPF) (n = 31 ) died of disease, whereas only one tumor <2 cm with <5 mitoses/50 HPF (n = 21) recurred and none caused death. Long latency was common between primar y operation and recurrences and metastases; either one occurred in 60 of 11 1 patients with follow-up (54%). Distant metastases were in the liver, bone s, and lungs. Three benign actin- and desmin-positive and KIT-negative intr amural LMs, similar to those seen in the esophagus, were identified. There were eight LMSs, six of which formed a polypoid intraluminal mass and were actin-positive and KIT-negative. Despite high mitotic counts, only one LMS patient died of disease. A great majority of rectal smooth muscle and strom al tumors are GISTs, which have a spectrum from minimal indolent tumors to overt sarcomas. Intramural LMs are exceptional, and true LMSs are rare, and similar to colonic ones, often present as intraluminal polypoid masses tha t appear to have a better prognosis than GISTs with similar mitotic rates.