{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T05:08:49Z","timestamp":1778389729791,"version":"3.51.4"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Pathology at the University of Iowa Health Care"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Hypereosinophilia (HE), defined as an absolute eosinophil count (AEC)\u2009\u22651.5\u2009\u00d7\u2009109\/L, poses diagnostic challenges when distinguishing clonal myeloid neoplasms from idiopathic HE\/hypereosinophilic syndrome, particularly under WHO-HAEM5 criteria. We characterized patients with HE of persistent\/unknown cause (HEPU) undergoing bone marrow (BM) evaluation to refine diagnostic classification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified 307 BM biopsy specimens (2015-2023) mentioning \u201ceosinophilia.\u201d Patients with defined reactive or clonal etiologies were classified as group 2 (known etiology, n\u2009=\u2009269). The remaining patients constituted group 1 (HEPU, n\u2009=\u200938). We reviewed clinical data, morphology, cytogenetics\/fluorescence in situ hybridization (FISH), and myeloid next-generation sequencing (NGS), assigning final diagnoses via the fifth edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) criteria and the 2022 International Consensus Classification (ICC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to group 2, patients with HEPU were younger (median 48 vs 62\u2009years; P\u2009=\u2009.004) and exhibited higher initial AECs (2.8 vs 0.6\u2009\u00d7\u2009109\/L; P\u2009&amp;lt;\u2009.001). Comprehensive workup reclassified the HEPU cohort (n\u2009=\u200938) into the idiopathic spectrum (36.8%), reactive eosinophilia (28.9%), clonal disorders including myeloid and lymphoid neoplasms (28.9%), and mixed reactive vs idiopathic (5.3%) categories. While cytogenetics\/FISH were largely noncontributory (detecting FIP1L1::PDGFRA in 2 cases), myeloid NGS detected mutations in 47% (7\/15) of tested patients with HEPU, involving genes such as TP53, BCOR, SF3B1, and TET2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Integrated clinicopathologic and molecular assessment reclassified most HEPU cases as reactive or clonal, with only 39% remaining idiopathic. Myeloid NGS frequently identifies clonal variants critical for refining HE classification, although results require cautious interpretation within the WHO-HAEM5 and ICC 2022 context.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajcp\/aqag031","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T12:45:41Z","timestamp":1772887541000},"source":"Crossref","is-referenced-by-count":0,"title":["Hypereosinophilia of persistent\/unknown cause: a bone marrow\u2013based study integrating WHO-HAEM5 criteria and myeloid next-generation sequencing"],"prefix":"10.1093","volume":"165","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3663-3608","authenticated-orcid":false,"given":"Mohamed M","family":"Eletrebi","sequence":"first","affiliation":[{"name":"Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Sanchez-Ramirez","sequence":"additional","affiliation":[{"name":"Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdalla","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-9914","authenticated-orcid":false,"given":"Carol J","family":"Holman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"2026051000153555300_aqag031-B1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/ajh.26352","article-title":"World Health Organization-defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management","volume":"97","author":"Shomali","year":"2022","journal-title":"Am J Hematol"},{"key":"2026051000153555300_aqag031-B2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jaci.2012.02.019","article-title":"Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes","volume":"130","author":"Valent","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"2026051000153555300_aqag031-B3","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1182\/blood-2016-10-695973","article-title":"Myeloid neoplasms with eosinophilia","volume":"129","author":"Reiter","year":"2017","journal-title":"Blood"},{"key":"2026051000153555300_aqag031-B4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1159\/000489341","article-title":"The diagnostic work-up of hypereosinophilia","volume":"86","author":"Wang","year":"2019","journal-title":"Pathobiology"},{"key":"2026051000153555300_aqag031-B5","volume-title":"Haematolymphoid Tumours","author":"Cross","year":"2024","edition":"5th"},{"key":"2026051000153555300_aqag031-B6","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.3389\/fonc.2019.01374","article-title":"B-ALL with t(5; 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