Systemic Mastocytosis of the Gastrointestinal Tract: Clinicopathologic Analysis of 21 Cases
Leona A Doyle, Matthew J Hamilton, Cem Akin, Mariana C Castells, Jason L Hornick. Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Background: The major diagnostic criterion for systemic mastocytosis (SM) is the presence of mast cell aggregates in bone marrow or extracutaneous organs. The diagnosis of mastocytosis in gastrointestinal (GI) mucosal or liver biopsies therefore has significant therapeutic and prognostic implications, but the features of SM in GI biopsies are not well described. The aims of this study were 1) to determine the utility of GI biopsies for the diagnosis of SM and 2) to characterize the clinical, histologic and immunohistochemical features of SM in the GI tract.
Design: 21 patients with SM involving the GI tract were identified. Clinical, pathologic and immunohistochemical features were evaluated.
Results: 98 GI/liver biopsies (65 involved by SM; 62 mucosal, 3 liver) from 17 women and 4 men were evaluated (median age 55 yrs; range 18-77). The most commonly involved site was colon (17 patients, 81%) followed by duodenum (10), stomach (5), ileum (5), and liver (3). 15 patients had documented cutaneous mastocytosis. In 14 cases (67%) the first diagnosis of SM was made on GI biopsy. 17 patients had indolent disease and 4 aggressive (including 2 of 3 with liver involvement). 10 patients had documented D816V KIT mutation. Symptoms included diarrhea (15), abdominal pain (8), nausea (6), weight loss (3), and bloating, vomiting or reflux (2 each). Liver disease presented with hepatomegaly and ascites. Endoscopic abnormalities (in 58%) included erythema, granularity and nodules. Histologically, biopsies showed lamina propria infiltrates of ovoid to spindle-shaped mast cells in aggregates or sheets. 15 biopsies had only focal involvement (single aggregate). Mast cell density ranged from 42-278 per HPF (median 125). Prominent eosinophils were seen in 48% of involved colonic/ileal and 17% of gastric/duodenal biopsies; 2 patients were initially misdiagnosed as eosinophilic colitis. 16 (26%) positive biopsies showed other findings: architectural distortion (4), chronic duodenitis (3), villous blunting (4), chronic gastritis (3), and chronic active colitis (2; patient with co-existing ulcerative colitis). Mast cells were highlighted by diffuse staining for KIT and CD25 in all cases. Expression of tryptase was variable; 57% showed only scattered positive cells.
Conclusions: GI (especially colonic) biopsies can establish a diagnosis of SM in patients with GI symptoms. GI involvement is usually subtle and often associated with an eosinophilic infiltrate, which may obscure the mast cell infiltrate. KIT and CD25 are invaluable markers for the diagnosis. GI involvement does not correlate with aggressive disease.
Tuesday, March 5, 2013 8:15 AM
Proffered Papers: Section D, Tuesday Morning