Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: a histopathological challenge

Abstract

Aims: Although systemic mastocytosis (SM) with an associated clonal haematological non-mast cell lineage disease (SM-AHNMD) is a major subtype of SM, little is known about its frequency among myelogenous neoplasms, and mastocytosis in particular, or about AHNMD subtype frequencies.Methods: Approximately 19 500 routine bone marrow biopsies were evaluated. Immunostaining with antibodies against tryptase, KIT, and CD25 and molecular analysis for detection of C-KIT point mutations were performed in approximately 550/4100 myelogenous malignancies including mastocytosis, almost all subtypes of myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative syndrome (MDS/ MPD), MPD, and acute myeloid leukaemia (AML). Results: SM was rare-it was diagnosed in only 64 bone marrows (0.3%) and made up 1.5% of myelogenous tumours. SM-AHNMD was the second most frequent subtype (20). SM-AHNMD was never included in the clinical differential diagnoses and was confirmed histologically in most cases only after appropriate immunostaining. The abnormal mast cell phenotype was confirmed by immunohistochemical demonstration of tryptase and CD25 coexpression. The following associated haematological neoplasms were found: MDS/MPS, AML, MPS, MDS, plasma cell myeloma, and unclassifiable myelogenous malignancy. C-KIT point mutations were detected in 16 of 20 cases. Conclusions: SM-AHNMD can be diagnosed histologically in bone marrow trephines only after immunostaining with antibodies against tryptase, KIT, and CD25. Eighteen of 20 AHNMDs were of myeloid origin. C-KIT point mutations were present in 16 of 20 cases. The prognostic relevance of detecting SM associated with another haematological neoplasm remains unclear, but mast cell resistance to most cytoreductive agents is of major importance for treatment planning.

Clinical presentation and management practice of systemic mastocytosis. A survey on 460 Italian patients

“…The retrospective nature of the study imposes, as obvious, caution in the generalization of information, that in any case constitute a valuable photography of the "real-life" settings for this disorder: the patients enrolled in this analysis, all strictly satisfying the WHO 2008 diagnostic criteria, were collected in ten Italian centers with dedicated programs, high diagnostic standards and extensive databases, thus vouching for accurateness of data. We interpret this high level of expertise as the most likely explanation for the lower relative frequency of aggressive forms, particularly SM-AHNMD, compared with other series [7,22,23] and conversely the more frequent representation of SM without skin lesions, an indolent course disease with intrinsic obstacles to an early diagnosis. We believe that in our series these variants were well represented as the results of a multidisciplinary network including dermatologists and allergists with high awareness who immediately referred patients with specific diagnostic suspicion.…”

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

“…These findings are similar to other reports. 3,10 All six cases of aggressive systemic mastocytosis were placed in this category because of the presence of anemia (hemoglobin o10 g/ 100 ml) according to the WHO classification. The most common associated clonal hematological disorder found in association with systemic mastocytosis was chronic myelomonocytic leukemia in four patients (Table 4).…”

Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group

“…In about 1 --3% of all patients with MDS, a co-existing systemic mastocytosis (SM) is found. 61 The diagnosis then changes to SM --MDS as per the WHO criteria. Aberrant mast cells in SM are CD117 bright and aberrantly express CD2 and/or CD25.…”