{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:06:23Z","timestamp":1793048783793,"version":"4.5.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Systemic mastocytosis (SM) is a rare neoplasm resulting from extracutaneous infiltration of clonal mast cells (MC). The clinical features of SM are very heterogenous and treatment should be highly individualized. Up to 40% of all SM cases can be associated with another hematological neoplasm, most frequently myeloproliferative neoplasms. Here, we present a patient with indolent SM who subsequently developed a myeloid neoplasm with <jats:italic>PDGFRA<\/jats:italic> rearrangement with complete response to low-dose imatinib. The 63-year-old patient presented with eosinophilia and elevated serum tryptase level. Bone marrow analysis revealed aberrant MCs in aggregates co-expressing CD2\/CD25 and <jats:italic>KIT<\/jats:italic> D816V mutation (0.01%), and the <jats:italic>FIP1L1-PDGFRA<\/jats:italic> fusion gene was not identified. In the absence of \u2018B\u2019 and \u2018C\u2019 findings, we diagnosed an indolent form of SM. For 2 years after the diagnosis, the absolute eosinophil count progressively increased. Bone marrow evaluation showed myeloid hyperplasia and the <jats:italic>FIP1L1-PDGFRA<\/jats:italic> fusion gene was detected. Thus, the diagnosis of myeloid neoplasm with <jats:italic>PDGFRA<\/jats:italic> rearrangement was established. The patient was treated with imatinib 100 mg daily and rapidly obtained a complete molecular remission. The clinical, biological, and therapeutic aspects of SM might be challenging, especially when another associated hematological disease is diagnosed. Little is known about the underlying molecular and immunological mechanisms that can promote one entity prevailing over the other one. Currently, the preferred concept of SM pathogenesis is a multimutated neoplasm in which <jats:italic>KIT<\/jats:italic> mutations represent a \u201cphenotype modifier\u201d toward SM. Our patient showed an evolution from <jats:italic>KIT<\/jats:italic> mutated indolent SM to a myeloid neoplasm with <jats:italic>PDGFRA<\/jats:italic> rearrangement; when the eosinophilic component expanded, a regression of the MC counterpart was observed. In conclusion, extensive clinical monitoring associated with molecular testing is essential to better define these rare diseases and consequently their prognosis and treatment.<\/jats:p>","DOI":"10.3389\/fonc.2021.734025","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T14:56:57Z","timestamp":1638370617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: Evolution of KIT D816V-Positive Systemic Mastocytosis to Myeloid Neoplasm With PDGFRA Rearrangement Responsive to Imatinib"],"prefix":"10.3389","volume":"11","author":[{"given":"Mariarita","family":"Scium\u00e8","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy","family":"Ceparano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Eller-Vainicher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Fabris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Lonati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio Alberto","family":"Croci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Baldini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica Irene","family":"Grifoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 Revision to the World Health Organization Classification of Myeloid Neoplasms and Acute Leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26118","article-title":"Systemic Mastocytosis in Adults: 2021 Update on Diagnosis, Risk Stratification and Management","volume":"96","author":"Pardanani","year":"2021","journal-title":"Am J Hematol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21561","article-title":"Cytoreductive Therapy in 108 Adults With Systemic Mastocytosis: Outcome Analysis and Response Prediction During Treatment With Interferon-Alpha, Hydroxyurea, Imatinib Mesylate or 2-Chlorodeoxyadenosine","volume":"84","author":"Lim","year":"2009","journal-title":"Am J Hematol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4158567","article-title":"A 26-Year-Old Female With Systemic Mastocytosis With Associated Myeloid Neoplasm With Eosinophilia and Abnormalities of PDGFRB, T (4,5)(Q21;Q33)","volume":"2016","author":"Brown","year":"2016","journal-title":"Case Rep Hematol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25617","article-title":"World Health Organization-Defined Eosinophilic Disorders: 2019 Update on Diagnosis, Risk Stratification, and Management","volume":"94","author":"Shomali","year":"2019","journal-title":"Am J Hematol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1038\/leu.2008.287","article-title":"Five Years Since the Discovery of FIP1L1\u2013PDGFRA: What We Have Learned About the Fusion and Other Molecularly Defined Eosinophilias","volume":"22","author":"Gotlib","year":"2008","journal-title":"Leukemia"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-050054","article-title":"Low-Dose Imatinib Mesylate Leads to Rapid Induction of Major Molecular Responses and Achievement of Complete Molecular Remission in FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukemia","volume":"109","author":"Jovanovic","year":"2007","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11420","article-title":"The Efficacy of Imatinib Mesylate in Patients With FIP1L1-PDGFRalpha-Positive Hypereosinophilic Syndrome. 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