Mastocytosis: State of the Art

Abstract

Mastocytosis is a neoplastic disease involving mast cells (MC) and their CD34+ progenitors. Symptoms in mastocytosis are caused by biological mediators released from MC and/or the infiltration of neoplastic MC in various organs, the skin and the bone marrow being predominantly involved. A WHO consensus classification for mastocytosis exists, which is widely accepted and includes three major categories: (1) Cutaneous mastocytosis (CM), a benign disease in which MC infiltration is confined to the skin, is preferentially seen in young children and exhibits a marked tendency to regress spontaneously. (2) Systemic mastocytosis (SM) which is commonly diagnosed in adults and includes four major subtypes: (i) indolent SM (ISM, the most common form involving mainly skin and bone marrow); (ii) a unique subcategory termed SM with an associated non-mast cell clonal hematological disease (SM-AHNMD); (iii) aggressive SM usually presenting without skin lesions, and (iv) MC leukemia, probably representing the rarest variant of human leukemias. (3) The extremely rare localized extracutaneous MC neoplasms, either presenting as malignancy (MC sarcoma) or as benign tumor termed extracutaneous mastocytoma. Diagnostic criteria for mastocytosis are available and are widely accepted. SM criteria include one major criterion (multifocal compact tissue infiltration by MC) and four minor criteria: (1) prominent spindling of MC; (2) atypical immunophenotype of MC with coexpression of CD2 and/or CD25 (antigens which have not been found to be expressed on normal/reactive MC); (3) activating (somatic) point mutations of the c-kit proto-oncogene usually involving exon 17, with the imatinib-resistant type D816V being most frequent, and (4) persistently elevated serum tryptase level (>20 ng/ml). To establish the diagnosis of SM, at least one major and one minor criterion, or at least three minor criteria, have to be fulfilled. The natural clinical course of mastocytosis is variable. Most patients, in particular those with CM and ISM, remain in an indolent stage over many years or even decades, while others, in particular those with aggressive SM, SM-AHNMD, or mast cell leukemia, show a progressive course, usually with a fatal outcome.

Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth

“…Systemic mastocytosis (SM) is a hematopoietic neoplasms defined by expansion and pathologic accumulation of mast cells (MC) in internal organs (1)(2)(3)(4)(5). In almost all patients, the bone marrow (BM) is affected (1)(2)(3)(4)(5).…”

“…In almost all patients, the bone marrow (BM) is affected (1)(2)(3)(4)(5). The transforming KIT mutation D816V is expressed in neoplastic cells in most patients (6)(7)(8)(9)(10).…”

“…Whereas clinically relevant organ damage is seen in aggressive SM (ASM) and MC leukemia (MCL) (1)(2)(3)(4)(5)11), mediator-related symptoms can develop in any category of SM (12)(13)(14). In patients in whom mediator-related symptoms are severe or even life-threatening, an IgE-mediated allergy may be detected (12)(13)(14)(15)(16)(17).…”

Chronic mast cell leukemia (MCL) with KIT S476I: a rare entity defined by leukemic expansion of mature mast cells and absence of organ damage

“…Systemic mastocytosis (SM) is a hematopoietic disease characterized by expansion of tissue mast cells (MCs) in various organ systems, including the bone marrow (BM), liver and spleen [1][2][3][4]. Despite recurrent mutations in codon 816 of the KIT protooncogene, SM is an extremely heterogeneous disease, ranging from a completely indolent course to lifethreatening disease-variants with short survival-times [1][2][3][4].…”

“…Despite recurrent mutations in codon 816 of the KIT protooncogene, SM is an extremely heterogeneous disease, ranging from a completely indolent course to lifethreatening disease-variants with short survival-times [1][2][3][4]. According to the proposed classification of the World Health Organization (WHO) and the EU-US consensus group, patients with advanced SM can be divided into aggressive SM (ASM), SM with an associated clonal hematologic non-MC-lineage disease (SM-AHNMD) and MC leukemia (MCL) [5][6][7].…”