Critical Evaluation of Diverse Clinical, Laboratory, Radiological and Histological Parameters Indicating Gastrointestinal Involvement for Diagnosis of Indolent and Aggressive Systemic Mastocytosis

Abstract 5159

In systemic mastocytosis (SM), involvement of the gastrointestinal (GI) tract through infiltration by mast cells and release of mast cell mediators is the third most common organ manifestation besides bone marrow and skin. GI-involvement contributes to several C-findings which are the basis for diagnosis of aggressive SM (ASM) including hepato-/splenomegaly with elevated transaminases and/or bilirubin, hypalbuminemia, portal hypertension, ascites, malabsorption and/or significant weight loss. Because systematic analyses on large series of patients have only rarely been reported, we sought to correlate histologically confirmed GI-infiltration of bowel and/or liver by mast cells with clinical symptoms, pathologic laboratory parameters and radiologic abnormalities in 58 SM patients (female, n=31; male, n=27; median age 43 years, range, 24–82). Fifty-four patients (93%) were KIT D816V positive. Primary inclusion criteria for this analysis were endoscopy with biopsies of the upper and lower GI tract and ultrasound. CT/MRI and liver biopsy (n=37) were performed if clinically indicated. All patients gave informed consent for participation in an IRB-approved registry for rare myeloproliferative neoplasms. Hematological C-findings (anemia <10g/dl and/or thrombocytopenia <100/nl) were present in 22/58 (38%) patients. Mast cell infiltration of the bowel (n=23), liver (n=10) or bowel and liver (n=8) was found in 41/58 (71%) patients. Significant weight loss, abdominal lymph nodes, ascites, hypalbuminemia and portal hypertension were observed in 56%, 54%, 49%, 27%, and 15%, respectively, of patients with GI-infiltration but not in any patient without GI-infiltration. In combination with hematological C-findings, ASM was diagnosed in 26/58 (45%) and indolent SM (ISM) in 32/58 (55%) patients. In ASM, GI-infiltration was found in 24/26 (92%) patients and at least one gastrointestinal C-finding in 23/26 (88%) patients. The contemporaneous presence of at least one hematological and at least one gastrointestinal C-finding was found in 20/26 (77%) of ASM patients. In contrast to the currently used WHO diagnostic criteria, ASM patients only rarely presented with elevated transaminases (5/26, 19%) or bilirubin (2/26, 8%) while alkaline phosphatase (AP, 21/26, 81%) and gamma glutamyltransferase (GGT, 15/26, 58%) were elevated in a significant higher proportion of patients. In 17 ISM patients with GI-infiltration, diarrhea (82%), food intolerance (47%) and splenomegaly (24%) were the most frequently observed symptoms while abdominal lymph nodes were not present at all. In summary, this analysis demonstrates that i) histologically confirmed GI-involvement is per se not sufficient for diagnosis of ASM, that ii) weight loss, hypalbuminemia, ascites and portal hypertension are indeed important gastrointestinal symptoms for disease classification which are frequently accompanied by hematological C-findings leading to diagnosis of ASM and that iii) abdominal lymphadenopathy and elevated AP/GGT are yet underestimated markers for diagnosis of ASM which may be superior to hepato-/splenomegaly with elevated transaminases and/or bilirubin.