{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:02:28Z","timestamp":1789650148157,"version":"4.0.0"},"reference-count":35,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Systemic mastocytosis (SM) with associated non-mast cell myeloid neoplasm is a rare condition, defined by the presence of both SM and a clonal non-mast cell neoplasm. Due to its rarity, the demographic and molecular characteristics are poorly understood. This study investigated seven patients diagnosed with this condition at our institution. Methods: Our institutional database was searched for \u201csystemic mastocytosis\u201d from 1 January 2020, to 31 December 2025. Each case was annotated to identify the primary cohort of this study, systemic mastocytosis with associated non-mast cell myeloid neoplasm (SM-AHN). Demographic characteristics, outcome, hematologic features at diagnosis, cytogenetics, and molecular characteristics were annotated. Eight cases of isolated SM diagnosed during the same period were also analyzed for comparison. All patients in the database were followed until their death or until 31 December 2025. All data were exported to SPSS v. 28 (IBM, Armonk, NY, USA\u00ae). Results: A total of seven patients were diagnosed with SM-AHN. Compared to isolated SM, SM-AHN patients showed older age at presentation, poorer hematologic values (increased anemia and thrombocytopenia), higher mutational burden, and poorer outcomes. KIT mutations were most common, predominantly D816V, with other variants like D816Y and L576F also observed. Additional frequent mutations included DNMT3A, TET2, ASXL1, SF3B1, EZH2, JAK2, NRAS, and SRSF2. Conclusions: Our findings, though limited by a small sample size, suggest that SM with associated myeloid neoplasm presents with distinct clinical and molecular features compared to isolated SM. This combined disorder is associated with older age, worse hematologic parameters, a higher mutational burden, and poorer prognosis. The frequent co-occurrence of mutations in other genes, in addition to KIT mutations, highlights the complex molecular landscape.<\/jats:p>","DOI":"10.3390\/jcm15187232","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:41:35Z","timestamp":1789645295000},"page":"7232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Clinical and Molecular Characteristics of Systemic Mastocytosis with Associated Non-Mast Cell Myeloid Neoplasm"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3299-4201","authenticated-orcid":false,"given":"Neha","family":"Seth","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Northwell Health, New Hyde Park, NY 11042, USA"},{"name":"Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell Health, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6680-7913","authenticated-orcid":false,"given":"Pratik Q.","family":"Deb","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Northwell Health, New Hyde Park, NY 11042, USA"},{"name":"Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell Health, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/978-3-030-78311-2_10","article-title":"Systemic Mastocytosis: Advances in Diagnosis and Current Management","volume":"181","author":"Pullarkat","year":"2021","journal-title":"Cancer Treat. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/ajcp\/aqaa183","article-title":"Mastocytosis","volume":"155","author":"Tzankov","year":"2021","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cilloni, D., Maffeo, B., Savi, A., Danzero, A.C., Bonuomo, V., and Fava, C. (2024). Detection of KIT Mutations in Systemic Mastocytosis: How, When, and Why. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202408.2240.v1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2021068","DOI":"10.4084\/MJHID.2021.068","article-title":"Systemic Mastocytosis: Multidisciplinary Approach","volume":"13","author":"Zanotti","year":"2021","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_5","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_6","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_7","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1182\/blood-2009-05-220145","article-title":"Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies","volume":"114","author":"Pardanani","year":"2009","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, J.Y., Ryder, C.B., Zhang, H., Cockey, S.G., Hyjek, E., Moscinski, L.C., Sagatys, E., and Song, J. (2023). Review and Updates on Systemic Mastocytosis and Related Entities. Cancers, 15.","DOI":"10.3390\/cancers15235626"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e923354","DOI":"10.12659\/AJCR.923354","article-title":"A Rare Case of Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) Involving Chronic Myeloid Leukemia: A Case Report and Literature Review","volume":"21","author":"Ibrahim","year":"2020","journal-title":"Am. J. Case Rep."},{"key":"ref_10","first-page":"448","article-title":"Systemic mastocytosis in association with chronic lymphocytic leukemia and plasma cell myeloma","volume":"3","author":"Du","year":"2010","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_11","first-page":"2048","article-title":"Systemic mastocytosis: Current status and challenges in 2024","volume":"9","author":"Ustun","year":"2025","journal-title":"Blood Adv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/s41375-024-02186-x","article-title":"Allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis: A retrospective analysis of the DRST and GREM registries","volume":"38","author":"Christen","year":"2024","journal-title":"Leukemia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e2021046","DOI":"10.4084\/MJHID.2021.046","article-title":"Systemic Mastocytosis: Molecular Landscape and Implications for Treatment","volume":"13","author":"Monaldi","year":"2021","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/leu.2017.234","article-title":"Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trial","volume":"32","author":"DeAngelo","year":"2018","journal-title":"Leukemia"},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.jaci.2021.06.030","article-title":"Developing a standardized approach for assessing mast cells and eosinophils on tissue biopsies: A Work Group Report of the AAAAI Allergic Skin Diseases Committee","volume":"148","author":"Zimmermann","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.iac.2014.01.005","article-title":"Mastocytosis: Immunophenotypical features of the transformed mast cells are unique among hematopoietic cells","volume":"34","author":"Horny","year":"2014","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1097\/01.pas.0000138181.89743.7b","article-title":"CD25 indicates the neoplastic phenotype of mast cells: A novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens","volume":"28","author":"Sotlar","year":"2004","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41375-024-02504-3","article-title":"Prognostic impact of expression of CD2, CD25, and\/or CD30 in\/on mast cells in systemic mastocytosis: A registry study of the European Competence Network on Mastocytosis","volume":"39","author":"Nilius","year":"2025","journal-title":"Leukemia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1182\/hematology.2022000366","article-title":"How to evaluate the patient with a suspected mast cell disorder and how\/when to manage symptoms","volume":"2022","author":"Akin","year":"2022","journal-title":"Hematology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.iac.2006.05.008","article-title":"Flow cytometric analysis of normal and neoplastic mast cells: Role in diagnosis and follow-up of mast cell disease","volume":"26","author":"Escribano","year":"2006","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0145-2126(01)00050-9","article-title":"Utility of flow cytometric analysis of mast cells in the diagnosis and classification of adult mastocytosis","volume":"25","author":"Escribano","year":"2001","journal-title":"Leuk. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/cyto.a.24950","article-title":"Critical pitfalls in the flow cytometric analysis of mast cells in patients with systemic mastocytosis","volume":"107","author":"Alheraky","year":"2025","journal-title":"Cytom. Part A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/cyto.b.21938","article-title":"Mast cell differentiation of leukemic blasts in diverse myeloid neoplasms: A potential pre-myelomastocytic leukemia condition","volume":"100","author":"Panda","year":"2021","journal-title":"Cytom. B Clin. Cytom."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s12308-022-00526-3","article-title":"Acute mast cell leukemia without KIT D816V mutation and lack of CD2 and CD25\u2014A case report of rare entity","volume":"16","author":"Patkowska","year":"2023","journal-title":"J. Hematop."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/ajh.23380","article-title":"Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease: Clinical significance and comparison of chromosomal abnormalities in SM and AHNMD components","volume":"88","author":"Wang","year":"2013","journal-title":"Am. J. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/ajcp\/aqaf042","article-title":"Systemic mastocytosis with an associated myeloid neoplasm: Report from the XVI European Bone Marrow Working Group Course and Workshop, Barcelona 2023","volume":"164","author":"Leguit","year":"2025","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2147\/JBM.S366367","article-title":"Management of Advanced Systemic Mastocytosis: Clinical Challenges","volume":"15","author":"Tremblay","year":"2024","journal-title":"J. Blood Med."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13045-026-01819-1","article-title":"Outcomes and prognostic factors in patients with systemic mastocytosis and an associated myeloid neoplasm: An international ECNM registry study","volume":"19","author":"Hermine","year":"2026","journal-title":"J. Hematol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5916","DOI":"10.1182\/bloodadvances.2025018389","article-title":"KIT mutation and AHN-associated oncogenic profiles in systemic mastocytosis with an associated hematological neoplasm","volume":"10","author":"Henriques","year":"2026","journal-title":"Blood Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1038\/leu.2015.4","article-title":"Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event","volume":"29","author":"Jawhar","year":"2015","journal-title":"Leukemia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1002\/ajh.24426","article-title":"Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival","volume":"91","author":"Pardanani","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41408-019-0189-5","article-title":"World Health Organization class-independent risk categorization in mastocytosis","volume":"9","author":"Pardanani","year":"2019","journal-title":"Blood Cancer J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1056\/NEJMoa1513098","article-title":"Efficacy and safety of midostaurin in advanced systemic mastocytosis","volume":"374","author":"Gotlib","year":"2016","journal-title":"N. Engl. J. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:09:50Z","timestamp":1789646990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/18\/7232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":35,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jcm15187232"],"URL":"https:\/\/doi.org\/10.3390\/jcm15187232","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}