Subtypes of Systemic Mastocytosis Exhibit Distinct Immunomorphologic Features in Bone Marrow Biopsies
April Chiu, Magdalena B Czader, Rachel C Ochs, Dehua Wang, David C Park, Jungbluth A Achim, Denise Frosina, Aarti Goswami, Teruya-Feldstein Julie, Attilio Orazi. Memorial Sloan-Kettering Cancer Center, New York, NY; Indiana University School of Medicine, Indianapolis, IN; Weill Cornell Medical College, New York, NY
Background: Systemic mastocytosis (SM) is a clonal mast cell (MC) disorder marked by multifocal aggregates in bone marrow (BM) or other organs (major criterion). Minor criteria are atypical/spindle morphology, CD2/CD25 expression, elevated serum tryptase (ST), and KIT D816V mutation. There are 4 major SM subtypes: indolent (ISM), aggressive (ASM), with associated clonal hematological non-MC disease (AHNMD), MC leukemia (MCL). Recent European studies reported frequent CD30 expression in ASM and MCL but not ISM. Despite potential diagnostic utility of CD30, subtyping of SM remains largely based on clinical and laboratory findings. In this study, we aim to identify distinguishing BM histologic features in SM subtypes.
Design: Clinical and laboratory data of 43 SM pts from 2003-12 were reviewed. Paraffin sections from their BM biopsies were evaluated morphologically and by IHC (CD117,tryptase,CD2,CD25,CD30,P53,Ki-67).
Results: Pt characteristics: median age 56 (range 18-82); male:female 1.7:1. Subtypes: ISM-11, AHNMD-19, ASM-11, MCL-2. Almost all cases showed MCs that are predominately spindled, while both MCL cases showed predominantly round or bilobed MCs. CD2 (19/39) and CD25 (36/39) expression did not differ across the subtypes. CD30 expression was seen in 13/43 cases: ISM-0, AHNMD-6, ASM-6, MCL-1. P53 expression (≥5%) was seen in 11/42 cases: ISM-1, AHNMD-6, ASM-3, MCL-1. 38/43 cases showed <10% Ki-67. 15/41 cases showed ≥30% intertrabecular (IT) space involvement: ISM-1, AHNMD-7, ASM-5, MCL-2. 12/26 cases had KIT D816V mutation: ISM-1, AHNMD-7, ASM-4. 6/31 cases (AHNMD-5,ASM-1) had clonal abnormalities. ST was >100ng/ml in 14/34 cases: ISM-2, AHNMD-4, ASM-6, MCL-2. No significant difference in CBC was seen across SM subtypes.
Conclusions: Compared to other subtypes, ISM less frequently have CD30 expression (p=0.01), D816V mutation (p=0.05), markedly elevated ST (p=0.05), and ≥30% IT space involvement (p=0.02). Although P53 expression is less frequent in ISM, the difference is not significant (p=0.16). Both MCL cases showed striking round cell/bi-lobed morphology, suggesting derivation from a less differentiated progenitor, e.g. promastocyte. Our findings confirm that CD30 expression is more frequently observed in ASM and MCL, but is also seen in a significant portion of AHNMD cases, the latter has not been reported in European series. Routine CD30 evaluation in SM may have important therapeutic implications with advent of targeted anti-CD30 therapy.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 217, Wednesday Morning