Systemic mastocytosis: progressive evolution of an occult disease into fatal mast cell leukemia: unique findings on an unusual hematological neoplasm
- 236 Downloads
Systemic mastocytosis (SM) may be associated with a clonal hematopoietic non-mast cell-lineage disease (AHNMD). SM and AHNMD even may be clonally related. This report contributes to a better understanding of the different morphological aspects of SM by demonstrating that various AHNMDs can be detected in one patient during the course of disease. Routinely processed biopsy specimens of bone marrow and spleen removed from a 63-year-old man were investigated including a broad panel of immunohistochemical stainings. KIT codon 816 mutation analysis was carried out by melting point analysis of nested PCR products amplified from DNA of pooled microdissected mast cells. The histomorphological features of the initial bone marrow showed diffuse infiltration by hairy cell leukemia (HCL). Occult SM was only detected retrospectively by demonstration of a slight diffuse increase in loosely scattered, spindle-shaped mast cells carrying the activating point mutation KIT D816V . In the second bone marrow, core biopsy removed about two years later HCL had been completely eradicated, while a diagnosis of SM-AHNMD with multifocal compact mast cell infiltrates associated with a myeloproliferative neoplasm (MPN) and significant increase in eosinophilic granulocytes was established. The third and last bone marrow biopsy specimen lacked the features of both MPN and HCL but showed progression into a secondary mast cell leukemia (MCL) with a focal sarcomatous component. To the best of the authors’ knowledge, this is the first description of a case of SM-AHNMD with coexisting hematological neoplasms of lymphatic and myeloid origin initially presenting as occult disease and terminating as secondary MCL.
KeywordsMastocytosis SM-AHNMD Mast cell leukemia Eosinophilia c-Kit mutation Occult SM
This study was supported by grants from the Swedish Research Council; the Swedish Cancer Society; the Center for Allergy Research, Karolinska Institute and through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institutet.
Conflict of interest
The authors report no conflict of interest.
- 5.Horny HP, Akin C, Metcalfe DD, Bennett JM, et al. Mastocytosis. In:Swerdlow SH, Campo E, Harris NL, et al., (eds.). World Health Organization (WHO) Classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research and Cancer (IARC); 2008. pp 54–63.Google Scholar
- 10.Morgado JM, Sánchez-Muñoz L, Teodósio CG, Jara-Acevedo M, et al. Immunophenotyping in systemic mastocytosis diagnosis: ‘CD25 positive’ alone is more informative than the ‘CD25 and/or CD2’ WHO criterion. Mod Pathol. 2012 Jan 6. doi: 10.1038/modpathol.2011.192. [Epub ahead of print].
- 13.Nagata H, Worobec AS, Oh CK, et al. Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci USA. 1995;92:10560–4.PubMedCrossRefGoogle Scholar
- 17.Sotlar K, Bache A, Stellmacher F, et al. Systemic mastocytosis associated with chronic idiopathic myelofibrosis: a distinct subtype of systemic mastocytosis associated with a [corrected] clonal hematological non-mast [corrected] cell lineage disorder carrying the activating point mutations KITD816 V and JAK2V617F. J Mol Diagn. 2008;10(1):58–66.PubMedCrossRefGoogle Scholar
- 26.Bain B, Pierre R, Imbert M, et al. Chronic eosinophilic leukemia and hypereosinophilic syndrome. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors, World Health Organization (WHO) classification of tumours. Pathology & genetics. Tumours of haematopoietic and lymphoid tissues vol. 1; 2001. pp. 29–31.Google Scholar