Clinical and Pathologic Features of Mast Cell Diseases in Patients with Unexplained Episodic Allergic Symptoms
Adam J Wood, Dong Chen, Rong He, Curtis A Hanson. Mayo Clinic, Rochester, MN
Background: Unexplained episodic allergic symptoms involving various organ systems can be seen in patients with mast cell (MC) diseases including cutaneous mastocytosis (CM), systemic mastocytosis (SM) and monoclonal mast cell activation syndrome (MMAS; defined as 1-2 minor SM diagnostic criteria). The prevalence of MC diseases in this patient population is unknown. Our goal was to determine the clinical and pathologic features of MC diseases in such a patient population.
Design: We identified 121 patients evaluated in the Allergy Clinic at Mayo Clinic who had bone marrows (BM) performed. We reviewed clinical data, blood and BM aspirate smears, BM biopsyies, and laboratory results. The laboratory results included serum tryptase, BM MC immunophenotyping (by flow cytometry or immunohistochemistry), chromosome and FISH studies (PDFRA, PDGFRB, ARG, ABL), and mutation analysis of KIT D816V and JAK2 V617F.
Results: 21/121 patients had indolent SM (M:F=4:17); median age was 54 yrs (range 29-64 yrs); 6 also had CM. 18 had elevated serum tryptase levels (≥11.5 ng/mL); 15 had tryptase levels > 20 ng/mL. 20/21 fulfilled the major SM criterion; all had >25% cytologically atypical MCs. Immunophenotypically aberrant MCs were present in 17/17 cases. 13/14 were positive for KIT D816V mutation. 4/121 patients (median age 46 yrs [M:F=1:3]) were consistent with a MMAS. There were singly distributed, spindle-shaped MCs that aberrantly coexpressed CD2 and CD25 in 3 cases; a positive KIT D816V mutation in 1. 3/4 had mildly elevated tryptase levels (4.3-14.7 ng/mL). The remaining 97 patients had normal MCs; however, 24 had elevated tryptase levels (12.5-120 ng/mL) with 10 cases >20ng/mL; no KIT D816V mutation was found in the 55 patients evaluated. No JAK2 V617F mutation was seen in 20 tested patients; only 2/81 patients had karyotypic abnormalities, related to an underlying myeloma and MDS.
Conclusions: The results of our study show that patients with SM may present to an allergy clinic for evaluation. ∼20% of patients in our study, who presented in that fashion and warranted subsequent BM evaluation, had MC diseases, mostly indolent SM and, rarely, MMAS. The basic diagnostic evaluation of these patients should include a tryptase IHC stain to evaluate the quantity, distribution, cytologic atypia of MCs in the BM biopsy and a KIT D816V mutation analysis. When suspicion for a myeloid neoplasm is absent, cytogenetic and JAK2 mutation studies are unnecessary. Elevation of serum tryptase level has limited predictive and diagnostic value for MC disease in an allergy clinic patient population.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 242, Monday Morning