The Clinical and Pathologic Features of Clonal Mast Cell Disorders That Fail To Meet the WHO Diagnostic Criteria for Systemic Mastocytosis
Adam J Wood, Dong Chen, Rong He, Curtis A Hanson. Mayo Clinic, Rochester, MN
Background: Mast cell (MC) diseases are a heterogeneous group of disorders characterized by clonal proliferation of MCs in skin (cutaneous mastocytosis, CM) or extracutaneous systems (systemic mastocytosis, SM). The WHO classification for SM requires 1 major and 1 minor criterion, or 3 minor criteria. The major criterion is dense infiltrates of MCs in bone marrow (BM) or other organs. The 4 minor criteria include: >25% cytologically atypical MCs, point mutation at codon 816 of KIT, aberrant MC expression of CD2 or CD25, and persistent serum tryptase elevation (>20 ng/mL). Rare mast cell disorders have been identified that only fulfill 1 or 2 minor criteria; these are referred to as monoclonal mast cell disorders (MMCD). Due to their rarity, their full clinical and pathologic spectra still remain to be characterized.
Design: We identified 20 cases that were restricted to having only 1 or 2 minor SM diagnostic criteria. Clinical findings, BM aspirate smears and biopsies, BM MC immunophenotypic studies by flow cytometry (FC) or immunohistochemistry (IHC), BM cytogenetic studies, and KIT D816V mutation studies on either BM or blood were reviewed.
Results: The median age was 47 years (range 25-81); M:F=7:13. 19/20 patients had allergic symptoms involving skin, gastrointestinal tracts and cardiovascular system. None met SM diagnostic criteria; 2 did have CM. 6/20 had either increased but singly distributed or minute clusters of atypical MCs. Aberrant MC coexpression of CD2 or CD25 detected by either FC or IHC were present in 14 cases. 7/14 patients were positive for the KIT D816V mutation. 7 had elevated serum tryptase levels; only 3 had tryptase levels >20ng/mL. Interestingly, 4 patients had concurrent myelodysplastic syndrome, chronic eosinophilic leukemia, chronic monomyelocytic leukemia, or myeloproliferative neoplasm. Only 1/13 tested cases had a clonal cytogenetic abnormality.
Conclusions: MMCDs can be observed in patients with CM, episodic allergic symptoms, and rarely in patients with non-MC myeloid neoplasms. These patients fail to meet the WHO criteria for diagnosis of SM. Since patients' tryptase levels are mostly normal or marginally elevated, thorough morphologic, immunophenotypic and molecular studies are required to determine whether these patients have a MC disorder. The basic diagnostic evaluation should always include: 1) tryptase IHC stains to evaluate the quantity and distribution of MCs in the BM and the degree of MC atypia and 2) KIT D816V mutation analysis. 3) IHC or FC studies to assess MC phenotypic aberrancy.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 216, Wednesday Morning