Highly sensitive assays are mandatory for the differential diagnosis of patients presenting with symptoms of mast cell activation: diagnostic work-up of 38 patients.

Mastocytosis is a heterogeneous disease caused by excessive mast cell (MC) proliferation. Diagnosis of systemic mastocytosis (SM) is based on the presence of major and minor criteria defined by the World Health Organization. Symptoms of MC activation can also occur in patients without SM or without allergic or inflammatory disease. These MC activation syndromes (MCAS) can be divided into primary (monoclonal) MCAS (MMAS) vs. secondary and idiopathic MCAS. In this single center study, the diagnostic work-up of 38 patients with a clinical suspicion of SM and/or with elevated basic tryptase levels is presented. Clinical symptoms, biochemical parameters, results of bone marrow investigation, flow cytometric immunophenotyping, and molecular analysis were retrospectively reviewed. Twenty-three patients were found to have a monoclonal MC disorder of which 19 were diagnosed with SM and 4 with MMAS. In 13/19 SM patients, multifocal MC infiltrates in the bone marrow were found (major criterion), while in 6 the diagnosis was based on the presence of ≥3 minor criteria. Flow cytometric analysis of bone marrow showed CD25 expression of MCs in all patients with SM and MMAS (range: 0.002-0.3% of cells). In bone marrow, the KIT D816V mutation was detected in all SM patients but in only 2 patients with MMAS (range: 0.007-9% mutated cells). Basic tryptase elevation was demonstrated in 16/19 patients with SM but also in 9/19 patients without SM. Our study reveals the heterogeneity of primary MC disorders and the importance of sensitive assays in patients suspected of having SM.