Utility of the World Heath Organization classification criteria for the diagnosis of systemic mastocytosis in bone marrow

Abstract

In the World Health Organization classification, one major and four minor criteria are specified for the diagnosis of systemic mastocytosis. We report our experience using these criteria to diagnose systemic mastocytosis involving bone marrow. A total of 59 patients with clinically suspected systemic mastocytosis underwent comprehensive bone marrow examination, including immunophenotyping by immunohistochemistry and/or flow cytometry and molecular studies for KIT exon 17 mutations. Serum tryptase levels were also assessed. Of these 59, 53 (90%) patients met the diagnostic criteria for systemic mastocytosis. In these patients, multifocal dense infiltrates of mast cells, the major criterion, was observed in 36 (68%) patients. Atypical mast cell morphology was observed in 53 (100%), an aberrant immunophenotype was identified in 50 of 52 (96%), KIT mutation was present in 33 of 44 (75%), and an elevated serum tryptase (420 ng/ml) was detected in 44 of 52 (85%). In the six patients in which bone marrow examination could not confirm systemic mastocytosis, one had systemic mastocytosis involving spleen, one patient had chronic idiopathic myelofibrosis, and four had no specific diagnosis, but systemic mastocytosis was still considered most likely. Of these six patients, atypical mast cell morphology was identified in five, aberrant immunophenotype in five, KIT mutation in two, and elevated serum tryptase in two. None of these cases met the major criteria. We conclude that the World Health Organization criteria are useful for the diagnosis of systemic mastocytosis in bone marrow specimens. The results also show the relative values of traditional morphologic criteria (ie, major criterion) and the results of ancillary testing (ie, minor criteria). However, as illustrated by the case of splenic systemic mastocytosis as well as the patient with chronic idiopathic myelofibrosis, the current World Health Organization system is neither completely sensitive nor specific for systemic mastocytosis.

Evaluation of the WHO criteria for the classification of patients with mastocytosis

“…Undoubtedly, the WHO criteria represented a major step forward in both the diagnosis and classification of mastocytosis, contributing to the distinction between good-(eg cutaneous mastocytosis and indolent systemic mastocytosis) vs poor-prognosis subgroups (eg aggressive systemic mastocytosis, mast cell leukemia). However, since the initial proposal, only one study based on 59 patients 19 has prospectively evaluated the WHO criteria. Interestingly, preliminary data from this study indicate that based on the WHO criteria, some patients suffering from a true systemic mastocytosis cannot be classified as such.…”

“…The results showed the relative values of traditional morphologic criteria (ie major criterion) and the results of ancillary testing (ie minor criteria), suggesting that the WHO system is neither completely sensitive nor specific for systemic mastocytosis. 19 Here, we prospectively evaluate the utility of different clinical, biological, immunophenotypical, and molecular features of the disease (including all WHO major and minor diagnostic criteria), in a cohort of 133 patients uniformly diagnosed and followed at the Spanish Network on Mastocytosis (REMA). Based on our findings, a new algorithm is proposed, which may contribute to improve refined diagnosis and classification of mastocytosis.…”

“…19 A total of 59 patients with clinically suspected systemic mastocytosis, underwent comprehensive evaluation and 53 of them (90%) met the diagnostic criteria for systemic mastocytosis. In the six patients in which bone marrow examination could not confirm systemic mastocytosis, atypical mast cell morphology was identified in five, aberrant immunophenotype in five, KIT mutation in two, and elevated serum tryptase in two.…”

Flow Cytometric Immunophenotypic Analysis of Systemic Mastocytosis Involving Bone Marrow

“…Antibodies specific for tryptase and CD117 are most widely used and are useful for highlighting mast cells; however, neither antibody can distinguish benign from neoplastic mast cells. 2,3 Aberrant expression of CD2 or CD25 by mast cells in the bone marrow is more useful diagnostically because both antigens are often expressed by neoplastic mast cells but are not expressed in normal or reactive mast cells. 4,5 Therefore, assessment of CD2 and CD25 in the bone marrow is a potentially useful approach to establish the diagnosis of SM in the bone marrow.…”

“…In earlier studies, 2,5,8 flow cytometry immunophenotypic analysis has been used to assess cases of SM. In one study, authors concluded that flow cytometry immunophenotyping was more sensitive than histology combined with immunohistochemistical analysis for detecting bone marrow involvement.…”