Evaluation of Ancillary Test Utilization for Mast Cell Diseases
Rong He, Adam J Wood, Dong Chen, Curtis A Hanson. Mayo Clinic, Rochester, MN
Background: Mast cell (MC) diseases involves skin or other organs including bone marrow (systemic mastocytosis, SM). The WHO criteria for SM requires 1 major and 1 minor criteria, or 3 minor criteria. The major criterion is multifocal dense MC infiltrates in bone marrow (BM)/other extracutaneous organs. The 4 minor criteria are:>25% atypical MCs, KIT D816V mutation, aberrant MC expression of CD25/CD2, and persistent serum tryptase elevation. The aim of this study was to compare various MC tests and establish effective pathology guidelines of evaluating SM.
Design: We retrospectively reviewed the findings from patients who had clinical suspicion of MC disorders and underwent comprehensive work-ups (2004-2011), including BM morphology, MC immunophenotyping by flow cytometry (FC) and immunohistochemistry (IHC), BM or blood KIT D816V mutation, and serum tryptase levels.
Results: 137 patients met the inclusion criteria were identified. 46 were diagnosed with SM. 39/46 SM cases met the major and ≥ 1 minor criteria; the remaining 7 fulfilled ≥ 3 minor criteria. All patients who met the major criterion showed abnormal, spindled MC morphology. In this group, aberrant expression of CD25 and CD2 was detected by FC in 36 (92.3%) and 26 (66.7%) cases, respectively; FC failed to detect any MCs in 3 cases. KIT D816V mutational analysis was done on 15 BM and 8 bloods, with a detection rate of 86.7% and 75%, respectively. In the 7 SM patients who did not meet the major criterion, the most frequent findings were aberrant CD25 expression by FC (100%), a positive KIT D816V mutation (100%), and atypical MC morphology (85.7%). Only 2 demonstrated CD2 expression by FC (28.6%). IHC studies in 42 SM cases showed a 100% tryptase and CD117 concordance rate for detecting MC. CD25 by IHC was positive in all 17 tested BM. CD2 by IHC was positive in only 2/12 BM (16.7%). 10/12 cases were CD25+CD2- by IHC and the other 2 were CD25+CD2+. 15/17 were positive for CD25 by both FC and IHC. In the other 2, IHC on biopsies detected aberrant CD25 expression while FC failed to detect any MC. 4 cases had both blood and BM KIT D816V analyses; 3 were positive in both and 1 was positive only in BM.
Conclusions: BM studies that meet the major SM criterion almost always demonstrate abnormal MC morphology. Tryptase IHC on BM biopsy is sufficient to establish the SM diagnosis. Cases that do not meet the major SM criterion require additional studies including KIT D816V mutational analysis, preferably on BM. Although both FC and IHC can detect CD25, IHC may be more sensitive than FC. Lastly, CD2 by IHC or FC lacks sensitivity for detecting clonal MCs in BM.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 215, Wednesday Morning