{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:06:25Z","timestamp":1793048785394,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Mast cell leukemia (MCL) is the leukemic form of SM with at least 20% mostly immature mast cells on bone marrow aspirate. MCL may develop de novo, in the absence of a prior SM, or it may represent a progression from a previous SM. MCL may be sub-divided into the more frequent, aggressive acute form with signs of organ damage (C-findings) and the chronic form lacking C-findings and presenting a more stable course, although over time, progression to acute MCL is common. The 2022 WHO subtype of MCL with an associated hematological neoplasm was renamed MCL with an associated myeloid neoplasm in the 2022 International Consensus Classification (ICC). The relevance of the distinction between the leukemic and aleukemic forms based on the percentage of circulating mast cells is a matter of debate. The current knowledge on MCL is restricted mainly to single reports or case series with a limited number of larger studies. Our aim is to provide a comprehensive overview of this rare disease in terms of clinical manifestations, morphology, phenotype, molecular characteristics, differential diagnosis, outcome and treatment. A general overview on mastocytosis is also included.<\/jats:p>","DOI":"10.3390\/cancers15061664","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T01:35:37Z","timestamp":1678325737000},"page":"1664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Mast Cell Leukemia: An Update with a Practical Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-9933","authenticated-orcid":false,"given":"Magda","family":"Zanelli","sequence":"first","affiliation":[{"name":"Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Quintini","sequence":"additional","affiliation":[{"name":"Hematology, Centro di Ricerca Emato-Oncologica\u2013C.R.E.O., University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Magnasco","sequence":"additional","affiliation":[{"name":"Pathology Unit, Ospedale SS Annunziata di Taranto, 74121 Taranto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Aprile","sequence":"additional","affiliation":[{"name":"Hematology Unit, Presidio Ospedaliero S.G. Moscati di Taranto, 74010 Taranto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2299-5160","authenticated-orcid":false,"given":"Andrea","family":"Palicelli","sequence":"additional","affiliation":[{"name":"Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9841-7856","authenticated-orcid":false,"given":"Maurizio","family":"Zizzo","sequence":"additional","affiliation":[{"name":"Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sanguedolce","sequence":"additional","affiliation":[{"name":"Pathology Unit, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4289-954X","authenticated-orcid":false,"given":"Stefano","family":"Ricci","sequence":"additional","affiliation":[{"name":"Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Pancetti","sequence":"additional","affiliation":[{"name":"Pathology Unit, Humanitas University, Pieve Emanuele, 20072 Milano, Italy"},{"name":"Pathology Unit, Humanitas Research Hospital-IRCCS, Rozzano, 20089 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Zuccal\u00e0","sequence":"additional","affiliation":[{"name":"Pathology Unit, Pugliese-Ciaccio Hospital Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Martino","sequence":"additional","affiliation":[{"name":"Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2576-6523","authenticated-orcid":false,"given":"Giuseppe","family":"Broggi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d Anatomic Pathology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8591-8010","authenticated-orcid":false,"given":"Rosario","family":"Caltabiano","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d Anatomic Pathology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Cavazza","sequence":"additional","affiliation":[{"name":"Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0591-6723","authenticated-orcid":false,"given":"Paola","family":"Parente","sequence":"additional","affiliation":[{"name":"Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mecucci","sequence":"additional","affiliation":[{"name":"Hematology, Centro di Ricerca Emato-Oncologica\u2013C.R.E.O., University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Martino","sequence":"additional","affiliation":[{"name":"Hematology, Centro di Ricerca Emato-Oncologica\u2013C.R.E.O., University of Perugia, 06129 Perugia, Italy"},{"name":"Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Ascani","sequence":"additional","affiliation":[{"name":"Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"ref_1","first-page":"437","article-title":"Uber Mastzellenleukamien","volume":"87","author":"Joachim","year":"1906","journal-title":"Dtsch. Arch. Fur Klin. Medizin."},{"key":"ref_2","unstructured":"WHO Classification of Tumours Editorial Board (2017). WHO Classification of Tumours Haematopoietic and Lymphoid Tissues."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1182\/blood-2012-07-442400","article-title":"Mast cell leukemia","volume":"121","author":"Lhermitte","year":"2013","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.3324\/haematol.2017.163964","article-title":"The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm","volume":"102","author":"Jawhar","year":"2017","journal-title":"Haematologica"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.leukres.2017.05.018","article-title":"Mast cell leukemia (MCL): Clinico-pathologic and molecular features and survival outcome","volume":"59","author":"Jain","year":"2017","journal-title":"Leuk. Res."},{"key":"ref_7","first-page":"100230","article-title":"Acute aleukemic mast cell leukemia: Report of a case and review of the literature","volume":"14","author":"Galura","year":"2020","journal-title":"Leuk. Res. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1159\/000504099","article-title":"The spectrum of aggressive mastocytosis: A workshop report and literature review","volume":"87","author":"Leguit","year":"2020","journal-title":"Pathobiology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kennedy, V.E., Perkins, C., Reiter, A., Jawhar, M., Lubke, J., Kluin-Nelemans, H.C., Shomali, W., Langford, C., Abuel, J., and Hermine, O. (2022). Mast cell leukemia: Clinical and molecular features and survival outcomes of patients in the ECNM Registry. Blood Adv.","DOI":"10.1182\/bloodadvances.2022008292"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating morphologic, clinical, and genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1093\/annonc\/mdu047","article-title":"Refined diagnostic classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): A consensus proposal","volume":"25","author":"Valent","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1182\/blood-2007-11-078097","article-title":"Mast cells and mastocytosis","volume":"112","author":"Metcalfe","year":"2008","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1159\/000328760","article-title":"Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: A consensus proposal","volume":"157","author":"Valent","year":"2012","journal-title":"Int. Arch. Allergy. Immunol."},{"key":"ref_14","first-page":"159","article-title":"Mastocytosis: A paradigmatic example of a rare disease with complex biology and pathology","volume":"3","author":"Valent","year":"2013","journal-title":"Am. J. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1182\/blood-2016-09-731893","article-title":"Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts","volume":"129","author":"Valent","year":"2017","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1177\/1066896919846648","article-title":"Gastrointestinal mastocytosis: A potential diagnostic pitfall to be aware","volume":"27","author":"Zanelli","year":"2019","journal-title":"Int. J. Surg. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zanelli, M., Pizzi, M., Sanguedolce, F., Zizzo, M., Palicelli, A., Soriano, A., Bisagni, A., Martino, G., Caprera, C., and Moretti, M. (2021). Gastrointestinal manifestations in systemic mastocytosis: The need of a multidisciplinary approach. Cancers, 13.","DOI":"10.3390\/cancers13133316"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/bjh.14967","article-title":"How we diagnose and treat systemic mastocytosis in adults","volume":"180","author":"Scherber","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/ajh.26118","article-title":"Systemic mastocytosis in adults: 2021 update on diagnosis, risk stratification and management","volume":"96","author":"Pardani","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"El Hussein, S., Chifotides, H.T., Khoury, J.D., Verstovsek, S., and Thakral, B. (2022). Systemic mastocytosis and other entities involving mast cells: A practical review and update. Cancers, 14.","DOI":"10.3390\/cancers14143474"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5727","DOI":"10.1182\/blood-2009-02-205237","article-title":"Systemic mastocytosis in 342 consecutive adults: Survival studies and prognostic factors","volume":"113","author":"Lim","year":"2009","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"66299","DOI":"10.18632\/oncotarget.11812","article-title":"Mast cell sarcoma: New cases and literature review","volume":"7","author":"Monnier","year":"2016","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1136\/jcp.2003.014860","article-title":"Systemic mastocytosis with associated clonal haematological non-mast cell lineage diseases: A histopathological challenge","volume":"57","author":"Horny","year":"2004","journal-title":"J. Clin. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zanelli, M., Ricci, S., Zizzo, M., Sanguedolce, F., De Giorgi, F., Palicelli, A., Martino, G., and Ascani, S. (2021). Systemic mastocytosis associated with \u201csmoldering\u201d multiple myeloma. Diagnostics, 11.","DOI":"10.3390\/diagnostics11010088"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.humpath.2017.03.014","article-title":"Acute mast cell leukemia associated with t(4;5)(q21;q33)","volume":"67","author":"Wang","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3343\/alm.2017.37.6.547","article-title":"Highly Aggressive de novo Aleukemic Variant of Mast Cell Leukemia without KIT D816V Mutation","volume":"37","author":"Suh","year":"2017","journal-title":"Ann. Lab. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/dc.23965","article-title":"Acute mast cell leukemia: A rare but highly aggressive hematopoietic neoplasm","volume":"6","author":"Costopoulos","year":"2018","journal-title":"Diagn. Cytopathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.leukres.2014.09.010","article-title":"Chronic mast cell leukemia: A novel leukemia-variant with distinct morphological and clinical features","volume":"39","author":"Valent","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00277-014-2207-9","article-title":"Chronic mast cell leukemia (MCL) with KIT S476I: A rare entity defined by leukemic expansion of mature mast cells and absence of organ damage","volume":"94","author":"Valent","year":"2015","journal-title":"Ann. Hematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jaci.2015.05.008","article-title":"Clinical, immunophenotypic and molecular characteristics of well-differentiated systemic mastocytosis","volume":"137","author":"Morgado","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0145-2126(01)00041-8","article-title":"Morphologic properties of neoplastic mast cells: Delineation of stages of maturation and implication for cytological grading of mastocytosis","volume":"25","author":"Sperr","year":"2001","journal-title":"Leuk. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00428-022-03423-3","article-title":"The international consensus classification of mastocytosis sand related entities","volume":"482","author":"Leguit","year":"2022","journal-title":"Virchows Arch."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"740","DOI":"10.3109\/10428194.2010.550072","article-title":"Aberrant expression of CD30 in aggressive systemic mastocytosis and mast cell leukemia: A differential diagnosis to consider in aggressive hematopoietic CD30-positive neoplasms","volume":"52","author":"Valent","year":"2011","journal-title":"Leuk. Lymphoma"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/leu.2015.284","article-title":"Additional mutations in SRSF2, ASXL1 and\/or RUNX1 identify a high-risk group of patients with KIT D816V (+) advanced systemic mastocytosis","volume":"30","author":"Jawhar","year":"2016","journal-title":"Leukemia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1159\/000048186","article-title":"Spectrum of associated clonal hematologic non-mast cell lineage disorders occurring in patients with systemic mastocytosis","volume":"127","author":"Sperr","year":"2002","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3109\/10428190009058500","article-title":"Clinical and biologic diversity of leukemias occurring in patients with mastocytosis","volume":"37","author":"Sperr","year":"2000","journal-title":"Leuk. Lymphoma"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1136\/jcp.2003.012864","article-title":"Acute myeloid leukaemia (AML) with t (8;21) associated with \u201coccult\u201d mastocytosis (SM-AHNMD). Report of an unusual case and review of the literature","volume":"57","author":"Bernd","year":"2004","journal-title":"J. Clin. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/ajh.10322","article-title":"Systemic mastocytosis with associated clonal hematological non-mast-cell lineage disease: Analysis of clinicopathologic features and activating c-kit mutations","volume":"73","author":"Pullarkat","year":"2003","journal-title":"Am. J. Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/sj.thj.6200164","article-title":"Myelomastocytic leukemia: Myeloid neoplasm characterized by partial differentiation of mast cell lineage cells","volume":"3","author":"Valent","year":"2002","journal-title":"Hematol. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1586\/17474086.2014.942280","article-title":"Myelomastocytic leukemia: Histopathological features, diagnostic criteria and differential diagnosis","volume":"7","author":"Horny","year":"2014","journal-title":"Expert Rev. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1080\/1042819021000039965","article-title":"Tryptase: A novel biochemical marker of acute myeloid leukemia","volume":"43","author":"Sperr","year":"2002","journal-title":"Leuk Lymphoma"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1200\/JCO.2014.55.2018","article-title":"Hematopoietic stem-cell transplantation for advanced systemic mastocytosis","volume":"32","author":"Ustun","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1038\/leu.2016.190","article-title":"Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2\/ASXL1\/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis","volume":"30","author":"Jawhar","year":"2016","journal-title":"Leukemia."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1038\/s41591-021-01539-8","article-title":"Efficacy and safety of avapritinib in advanced systemic mastocytosis: Interim analysis of the phase 2 PATHFINDER trial","volume":"27","author":"Gotlib","year":"2021","journal-title":"Nat Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1038\/s41591-021-01538-9","article-title":"Safety and efficacy of avapritinib in advanced systemic mastocytosis: The phase 1 EXPLORER trial","volume":"27","author":"DeAngelo","year":"2021","journal-title":"Nat Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/6\/1664\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:50:59Z","timestamp":1760122259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/6\/1664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,8]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["cancers15061664"],"URL":"https:\/\/doi.org\/10.3390\/cancers15061664","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,8]]}}}