Gastrointestinal stromal tumors of the vermiform appendix: clinicopathologic, immunohistochemical, and molecular study of 2 cases with literature review

Gastrointestinal stromal tumors (GIST) are rare in the vermiform appendix. Only 5 cases have been reported so far, all being 14 mm or less, and they have yet not been investigated at the molecular level. Here, we report 2 appendiceal gastrointestinal stromal tumors in a 78-year-old woman and a 72-year-old man with a history of endometrial adenocarcinoma and urinary bladder carcinoma, respectively. The first patient had a history of pelvic irradiation. Both gastrointestinal stromal tumors were incidental findings at surgery for appendicitis-like symptoms and on follow-up for bladder carcinoma, respectively. Tumors were 5 and 25 mm and were located in the mid portion and the tip, respectively. The larger gastrointestinal stromal tumor was pedunculated. Both revealed a spindle cell histology with variable stromal hyalinization and occasional skeinoid fibers in 1 case. Immunohistochemistry showed reactivity for CD117 and CD34 and loss of p16 in both. Case 2 overexpressed the catalytic subunit of the human telomerase reverse transcriptase immunohistochemically. Molecular analysis of KIT revealed a missense mutation K558R in case 1 and an in-frame deletion I571_R588 in case 2, both in the juxtamembrane domain (exon 11). Comparative genomic hybridization was successful in case 2 (larger lesion) and revealed no chromosomal imbalance. We suggest that the molecular pathogenesis of appendiceal gastrointestinal stromal tumors beyond initiating KIT mutations might be different from their gastric and intestinal counterparts. The coincidence of loss of p16 and overexpression of human telomerase reverse transcriptase seems to be in contradiction to the small size, the benign nature, and the limited growth potential of appendiceal gastrointestinal stromal tumors.