title: Aleukemic mast cell leukemia with abnormal immunophenotype and c-kit mutation D816V.
abstract: Mastocytosis comprises a heterogeneous group of disorders characterized by proliferation and accumulation of mast cells in 1 or more organ systems. Mast cell leukemia (MCL) is an extremely rare subtype of mastocytosis in which a leukemic spread of mast cells and a rapid progression of disease is seen. In typical cases, mast cells are found in the peripheral blood. However, an aleukemic variant of MCL (formerly termed malignant mastocytosis) has also been described. We here report a case of aleukemic MCL with abnormal immunophenotype of mast cells and the classical c-kit point mutation Asp-816-Val (=D816V). The 75-year-old male patient had a short history of weight loss and lymphadenopathy. There were no urticaria pigmentosa-like skin lesions. The bone marrow was diffusely infiltrated with atypical mast cells that comprised more than 80% of all nucleated cells on a bone marrow smears. As assessed by immunohistochemistry, neoplastic mast cells expressed tryptase, chymase, CD2, CD25, CD68, and the KIT protein (CD117). Mutation analysis revealed the c-kit mutation D816V. Since circulating mast cells could not be detected in the peripheral blood, the diagnosis of aleukemic MCL was established in accordance to the updated WHO consensus classification. This case further supports the notion that the pathogenesis (c-kit mutation D816V) in MCL is closely related to that found in indolent mast cell disorders. However, additional (but yet unknown) molecular (genetic) defects have to be considered to explain the extremely heterogenous clinical course in these patients.
authors.affiliation: Department of Pathology, University of Luebeck, Luebeck, Germany. noack@patho.mu-luebeck.de
authors.forename: Frank
authors.initials: F
authors.lastname: Noack
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
authors.forename: Martin
authors.initials: M
authors.lastname: Notter
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Horny
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001853:Bone Marrow / Q000378:metabolism; D018801:CD2 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation; D004247:DNA / Q000737:chemistry; D004252:DNA Mutational Analysis; D018450:Disease Progression; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007621:Karyotyping; D007938:Leukemia / Q000235:genetics* / Q000276:immunology*; D007946:Leukemia, Mast-Cell / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000166:cytology; D008415:Mastocytosis; D009154:Mutation; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013696:Temperature; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018801:CD2 Antigens; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit; D015375:Receptors, Interleukin-2; C067980:CD68 antigen, human; D000097382:CD68 Molecule