title: Diagnostic criteria and classification of mastocytosis: a consensus proposal.
abstract: The term 'mastocytosis' denotes a heterogeneous group of disorders characterized by abnormal growth and accumulation of mast cells (MC) in one or more organ systems. Over the last 20 years, there has been an evolution in accepted classification systems for this disease. In light of such developments and novel useful markers, it seems appropriate now to re-evaluate and update the classification of mastocytosis. Here, we propose criteria to delineate categories of mastocytosis together with an updated consensus classification system. In this proposal, the diagnosis cutaneous mastocytosis (CM) is based on typical clinical and histological skin lesions and absence of definitive signs (criteria) of systemic involvement. Most patients with CM are children and present with maculopapular cutaneous mastocytosis (=urticaria pigmentosa, UP). Other less frequent forms of CM are diffuse cutaneous mastocytosis (DCM) and mastocytoma of skin. Systemic mastocytosis (SM) is commonly seen in adults and defined by multifocal histological lesions in the bone marrow (affected almost invariably) or other extracutaneous organs (major criteria) together with cytological and biochemical signs (minor criteria) of systemic disease (SM-criteria). SM is further divided into the following categories: indolent systemic mastocytosis (ISM), SM with an associated clonal hematologic non-mast cell lineage disease (AHNMD), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL). Patients with ISM usually have maculopapular skin lesions and a good prognosis. In the group with associated hematologic disease, the AHNMD should be classified according to FAB/WHO criteria. ASM is characterized by impaired organ-function due to infiltration of the bone marrow, liver, spleen, GI-tract, or skeletal system, by pathologic MC. MCL is a 'high-grade' leukemic disease defined by increased numbers of MC in bone marrow smears (>or=20%) and peripheral blood, absence of skin lesions, multiorgan failure, and a short survival. In typical cases, circulating MC amount to >or=10% of leukocytes (classical form of MCL). Mast cell sarcoma is a unifocal tumor that consists of atypical MC and shows a destructive growth without (primary) systemic involvement. This high-grade malignant MC disease has to be distinguished from a localized benign mastocytoma in either extracutaneous organs (=extracutaneous mastocytoma) or skin. Depending on the clinical course of mastocytosis and development of an AHNMD, patients can shift from one category of MC disease into another. In all categories, mediator-related symptoms may occur and may represent a serious clinical problem. All categories of mastocytosis should be distinctively separated from reactive MC hyperplasia, MC activation syndromes, and a more or less pronounced increase in MC in myelogenous malignancies other than mastocytosis. Criteria proposed in this article should be helpful in this regard.
authors.affiliation: Department of Internal Medicine I, Division of Hematology, University of Vienna, Währinger Gürtel 18-20 Vienna, Austria. peter.valent@akh-wien.ac.at
authors.forename: P
authors.initials: P
authors.lastname: Valent
authors.forename: H P
authors.initials: HP
authors.lastname: Horny
authors.forename: L
authors.initials: L
authors.lastname: Escribano
authors.forename: B J
authors.initials: BJ
authors.lastname: Longley
authors.forename: C Y
authors.initials: CY
authors.lastname: Li
authors.forename: L B
authors.initials: LB
authors.lastname: Schwartz
authors.forename: G
authors.initials: G
authors.lastname: Marone
authors.forename: R
authors.initials: R
authors.lastname: Nuñez
authors.forename: C
authors.initials: C
authors.lastname: Akin
authors.forename: K
authors.initials: K
authors.lastname: Sotlar
authors.forename: W R
authors.initials: WR
authors.lastname: Sperr
authors.forename: K
authors.initials: K
authors.lastname: Wolff
authors.forename: R D
authors.initials: RD
authors.lastname: Brunning
authors.forename: R M
authors.initials: RM
authors.lastname: Parwaresch
authors.forename: K F
authors.initials: KF
authors.lastname: Austen
authors.forename: K
authors.initials: K
authors.lastname: Lennert
authors.forename: D D
authors.initials: DD
authors.lastname: Metcalfe
authors.forename: J W
authors.initials: JW
authors.lastname: Vardiman
authors.forename: J M
authors.initials: JM
authors.lastname: Bennett
mesh_terms: D000328:Adult; D017668:Age of Onset; D000465:Algorithms; D015415:Biomarkers; D001856:Bone Marrow Examination / Q000379:methods; D018801:CD2 Antigens / Q000032:analysis; D019070:Cell Lineage; D002648:Child; D004796:Clinical Enzyme Tests; D002999:Clone Cells / Q000473:pathology; D018450:Disease Progression; D005060:Europe / Q000453:epidemiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D007527:Isoenzymes / Q000097:blood; D007946:Leukemia, Mast-Cell / Q000145:classification / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D008407:Mast Cells / Q000737:chemistry / Q000473:pathology; D012515:Mast-Cell Sarcoma / Q000145:classification / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D008415:Mastocytosis / Q000145:classification / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology; D009154:Mutation; D009656:North America / Q000453:epidemiology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000097:blood; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013194:Staining and Labeling / Q000379:methods; D053802:Tryptases; D014781:Viscera / Q000473:pathology
chemical_list: D015415:Biomarkers; D018801:CD2 Antigens; D018836:Inflammation Mediators; D007527:Isoenzymes; D015375:Receptors, Interleukin-2; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; D053802:Tryptases