β-Catenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis

Although separating gastrointestinal stromal tumor (GIST) from mesenteric fibromatosis and sclerosing mesenteritis is clinically important, this distinction sometimes poses problems for practicing pathologists. In the STI571 (Gleevec, Imatinib) era, the problem may be further compounded when protocol-driven staining for CD117 (c-kit) is performed on spindle cell proliferations presenting in the bowel wall and mesentery using an antibody known to react with the majority of mesenteric fibromatoses when other antibodies are more specific. Because most mesenteric fibromatoses have mutations in the APC/β-catenin pathway and hence have abnormal nuclear accumulation of β-catenin protein, we studied β-catenin expression among a panel of other immunohistochemical stains to distinguish mesenteric fibromatosis, GIST, and sclerosing mesenteritis. Examples of gastrointestinal stromal tumors (GIST, 11), sclerosing mesenteritis (5), and mesenteric fibromatosis (10) were retrieved from the archives of our institutions. Cases were studied with an immunohistochemical panel consisting of CD117, β-catenin, CD34, smooth muscle actin, desmin, keratin, and S-100 protein. Cases were scored as "negative," "focally positive," or "diffusely positive." In evaluating β-catenin, nuclear accumulation was required. GIST all had CD117 (11 of 11, diffuse) and CD34 (11 of 11, diffuse) with variable actin (5 of 11, focal) and negative desmin, keratin, S-100 protein. All GIST lacked β-catenin (0 of 11). Mesenteric fibromatosis had CD117 (6 of 10, 3 focal, 3 diffuse), typically expressed more weakly than in GIST, actin (5 of 9, focal), and desmin (3 of 8, focal) in keeping with myofibroblastic differentiation but lacked CD34, S-100, and keratin. CD117 staining was not eliminated by use of a non-avidin-biotin technique. Nuclear β-catenin was detected in 9 of 10 fibromatoses, including one case associated with familial adenomatous polyposis. Two of five sclerosing mesenteritis cases focally expressed CD117. None of the sclerosing mesenteritis cases had nuclear β-catenin. Sclerosing mesenteritis cases were otherwise fibroblastic and myofibroblastic with focal actin in 5 of 5 and negative desmin, keratin, and S-100 protein but one had CD34 (1 of 5, focal). With increasing protocol-driven interest in evaluating bowel wall and mesenteric spindle cell lesions using CD117 (c-kit) antibodies, it is important for practicing pathologists to be aware that lesions other than GISTs are likely to express this antigen using certain antibodies. β-Catenin staining identifies lesions that are, instead, mesenteric fibromatoses.