title: Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal.
abstract: Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of patients, circulating MCs are detectable. A major differential diagnosis to MCL is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have been published, several questions remain concerning terminologies and subvariants. To discuss open issues, the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) launched a series of meetings and workshops in 2011-2013. Resulting discussions and outcomes are provided in this article. The group recommends that MML be recognized as a distinct condition defined by mastocytic differentiation in advanced myeloid neoplasms without evidence of SM. The group also proposes that MCL be divided into acute MCL and chronic MCL, based on the presence or absence of C-Findings. In addition, a primary (de novo) form of MCL should be separated from secondary MCL that typically develops in the presence of a known antecedent MC neoplasm, usually aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also proposed. This prephase represents ASM with rapid progression and 5%-19% MCs in BM smears, which is generally accepted to be of prognostic significance. We recommend that this condition be termed ASM in transformation to MCL (ASM-t). The refined classification of MCL fits within and extends the current WHO classification; and should improve prognostication and patient selection in practice as well as in clinical trials.
authors.affiliation: Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. Electronic address: peter.valent@meduniwien.ac.at.
authors.forename: P
authors.initials: P
authors.lastname: Valent
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Sotlar
authors.affiliation: Division of Hematology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: W R
authors.initials: WR
authors.lastname: Sperr
authors.affiliation: Servicio Central de Citometria, Centro de Investigacion del Cancer (IBMCC; CSIC/USAL) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: L
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authors.lastname: Escribano
authors.affiliation: Division of Hematology, Department of Internal Medicine, University of Istanbul, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Yavuz
authors.affiliation: III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Reiter
authors.affiliation: Department of Pathology, University of New Mexico, Albuquerque, USA.
authors.forename: T I
authors.initials: TI
authors.lastname: George
authors.affiliation: Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: H C
authors.initials: HC
authors.lastname: Kluin-Nelemans
authors.affiliation: Imagine Institute Université Paris Descartes, Sorbonne, Paris Cité, Centre national de référence des mastocytoses, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Division of Allergic Diseases, Mayo Clinic, Rochester, USA.
authors.forename: J H
authors.initials: JH
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authors.affiliation: Hematology Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: H
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authors.lastname: Hägglund
authors.affiliation: Division of Hematology-Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis.
authors.forename: C
authors.initials: C
authors.lastname: Ustun
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Hornick
authors.affiliation: Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
authors.forename: M
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authors.lastname: Triggiani
authors.affiliation: Department of Haematology, Guys and St Thomas' NHS Foundation Trust, Guys Hospital, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Radia
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: C
authors.initials: C
authors.lastname: Akin
authors.affiliation: Department of Dermatology, University of Cologne, Cologne, Germany.
authors.forename: K
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authors.lastname: Hartmann
authors.affiliation: Stanford Cancer Center, Stanford University School of Medicine, Stanford.
authors.forename: J
authors.initials: J
authors.lastname: Gotlib
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Allergy & Immunology, Virginia Commonwealth University, Richmond.
authors.forename: L B
authors.initials: LB
authors.lastname: Schwartz
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: S
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Servicio Central de Citometria, Centro de Investigacion del Cancer (IBMCC; CSIC/USAL) and Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Laboratory of Allergic Diseases, NIAID, NIH, Bethesda, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Metcalfe
authors.affiliation: LBPA CNRS UMR8113, Ecole Normale Supérieure de Cachan, Cachan, France.
authors.forename: M
authors.initials: M
authors.lastname: Arock
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: H-P
authors.initials: HP
authors.lastname: Horny
mesh_terms: D001856:Bone Marrow Examination; D003937:Diagnosis, Differential; D018450:Disease Progression; D006801:Humans; D007946:Leukemia, Mast-Cell / Q000145:classification* / Q000175:diagnosis; D015479:Leukemia, Myelomonocytic, Acute / Q000145:classification* / Q000175:diagnosis; D015477:Leukemia, Myelomonocytic, Chronic / Q000145:classification* / Q000175:diagnosis; D008407:Mast Cells / Q000473:pathology; D008415:Mastocytosis / Q000473:pathology
keywords: KIT D816V; leukemia; mast cells; mastocytosis; prognostication; tryptase