{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:23:41Z","timestamp":1792599821221,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T00:00:00Z","timestamp":1591833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To provide an in-depth review of the classification and diagnostic evaluation of hypereosinophilia (HE), with a focus on eosinophilic neoplasms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A review of published literature was performed, and exemplary HE cases were identified.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Causes of HE are diverse and can be grouped under three categories: primary (neoplastic), secondary (reactive), and idiopathic. Advances in cytogenetics and molecular diagnostics have led to elucidation of the genetic basis for many neoplastic hypereosinophilic disorders. One common molecular feature is formation of a fusion gene, resulting in the expression of an aberrantly activated tyrosine kinase (TK). The World Health Organization endorsed a biologically oriented classification scheme and created a new major disease category, namely, \u201cmyeloid\/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2.\u201d Rearrangement of other TK genes and activating somatic mutation(s) in TK genes have also been reported in eosinophilic neoplasms. Diagnostic evaluation of HE involves a combination of clinical, histopathologic, and immunophenotypic analyses, as well as molecular genetic testing, including next-generation sequencing-based mutation panels. The management of primary HE is largely guided by the underlying molecular genetic abnormalities.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A good knowledge of recent advances in HE is necessary to ensure prompt and accurate diagnosis, as well as to help optimize patient care.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajcp\/aqaa056","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T03:29:08Z","timestamp":1585798148000},"page":"305-318","source":"Crossref","is-referenced-by-count":22,"title":["Contemporary Classification and Diagnostic Evaluation of Hypereosinophilia"],"prefix":"10.1093","volume":"154","author":[{"given":"Daiva M","family":"Mattis","sequence":"first","affiliation":[{"name":"Departments of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa A","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematopathology, MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanyi M","family":"Lu","sequence":"additional","affiliation":[{"name":"Departments of Pathology and Laboratory Medicine, University of California, San Francisco, San Francisco"},{"name":"San Francisco VA Healthcare System, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"2020080503204185500_CIT0001","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1586\/ehm.11.81","article-title":"Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field","volume":"5","author":"Valent","year":"2012","journal-title":"Expert Rev Hematol."},{"key":"2020080503204185500_CIT0002","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/ajh.25617","article-title":"World Health Organization\u2013defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management","volume":"94","author":"Shomali","year":"2019","journal-title":"Am J Hematol."},{"key":"2020080503204185500_CIT0003","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1136\/pgmj.70.826.536","article-title":"Eosinophils in the 1990s: new perspectives on their role in health and disease","volume":"70","author":"Wardlaw","year":"1994","journal-title":"Postgrad Med J."},{"key":"2020080503204185500_CIT0004","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":"2020080503204185500_CIT0005","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/ajh.23515","article-title":"Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death","volume":"88","author":"Anderson","year":"2013","journal-title":"Am J Hematol"},{"key":"2020080503204185500_CIT0006","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1086\/338026","article-title":"Diagnostic significance of blood eosinophilia in returning travelers","volume":"34","author":"Schulte","year":"2002","journal-title":"Clin Infect Dis"},{"key":"2020080503204185500_CIT0007","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Rev 4th ed","author":"Swerdlow","year":"2017"},{"key":"2020080503204185500_CIT0008","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":"2020080503204185500_CIT0009","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.iac.2007.07.002","article-title":"Lymphocytic variant hypereosinophilic syndromes","volume":"27","author":"Roufosse","year":"2007","journal-title":"Immunol Allergy Clin North Am"},{"key":"2020080503204185500_CIT0010","doi-asserted-by":"crossref","first-page":"151412","DOI":"10.1016\/j.anndiagpath.2019.151412","article-title":"Prevalence and spectrum of T-cell lymphoproliferative disorders in patients with hypereosinophilia: a reference laboratory experience","volume":"44","author":"Shi","year":"2020","journal-title":"Ann Diagn Pathol"},{"key":"2020080503204185500_CIT0011","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.jaci.2009.09.022","article-title":"Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy","volume":"124","author":"Ogbogu","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"2020080503204185500_CIT0012","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.amjms.2017.04.002","article-title":"Eosinophilic myocarditis","volume":"354","author":"Cheung","year":"2017","journal-title":"Am J Med Sci"},{"key":"2020080503204185500_CIT0013","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1182\/blood-2014-11-551614","article-title":"How I treat hypereosinophilic syndromes","volume":"126","author":"Klion","year":"2015","journal-title":"Blood"},{"key":"2020080503204185500_CIT0014","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00005792-197501000-00001","article-title":"The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature","volume":"54","author":"Chusid","year":"1975","journal-title":"Medicine (Baltimore)."},{"key":"2020080503204185500_CIT0015","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1055\/s-2006-939519","article-title":"Hypereosinophilic syndrome: lymphoproliferative and myeloproliferative variants","volume":"27","author":"Roufosse","year":"2006","journal-title":"Semin Respir Crit Care Med."},{"key":"2020080503204185500_CIT0016","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.jaci.2006.02.042","article-title":"Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report","volume":"117","author":"Klion","year":"2006","journal-title":"J Allergy Clin Immunol."},{"key":"2020080503204185500_CIT0017","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow","year":"2008"},{"key":"2020080503204185500_CIT0018","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jaci.2010.03.042","article-title":"Refining the definition of hypereosinophilic syndrome","volume":"126","author":"Simon","year":"2010","journal-title":"J Allergy Clin Immunol."},{"key":"2020080503204185500_CIT0019","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1365-2141.1987.tb02291.x","article-title":"Abnormalities of chromosome 12p13 and malignant proliferation of eosinophils: a nonrandom association","volume":"67","author":"Keene","year":"1987","journal-title":"Br J Haematol."},{"key":"2020080503204185500_CIT0020","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0092-8674(94)90322-0","article-title":"Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation","volume":"77","author":"Golub","year":"1994","journal-title":"Cell."},{"key":"2020080503204185500_CIT0021","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1056\/NEJM200104053441401","article-title":"Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia","volume":"344","author":"Druker","year":"2001","journal-title":"N Engl J Med."},{"key":"2020080503204185500_CIT0022","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1056\/NEJMoa022457","article-title":"Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia","volume":"348","author":"O\u2019Brien","year":"2003","journal-title":"N Engl J Med."},{"key":"2020080503204185500_CIT0023","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1056\/NEJMoa020150","article-title":"Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta","volume":"347","author":"Apperley","year":"2002","journal-title":"N Engl J Med."},{"key":"2020080503204185500_CIT0024","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1056\/NEJMoa025217","article-title":"A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome","volume":"348","author":"Cools","year":"2003","journal-title":"N Engl J Med."},{"key":"2020080503204185500_CIT0025","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1182\/blood-2010-05-286757","article-title":"Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease","volume":"117","author":"Elling","year":"2011","journal-title":"Blood."},{"key":"2020080503204185500_CIT0026","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.jaci.2007.05.024","article-title":"KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1\/PDGFRA-associated chronic eosinophilic leukemia are distinct entities","volume":"120","author":"Maric","year":"2007","journal-title":"J Allergy Clin Immunol."},{"key":"2020080503204185500_CIT0027","first-page":"1628","article-title":"A new myeloproliferative disorder associated with chromosomal translocations involving 8p11: a review","volume":"9","author":"Macdonald","year":"1995","journal-title":"Leukemia."},{"key":"2020080503204185500_CIT0028","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000046639","article-title":"The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1","volume":"107","author":"Macdonald","year":"2002","journal-title":"Acta Haematol."},{"key":"2020080503204185500_CIT0029","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.iac.2007.06.001","article-title":"Chronic eosinophilic leukemias and the myeloproliferative variant of the hypereosinophilic syndrome","volume":"27","author":"Bain","year":"2007","journal-title":"Immunol Allergy Clin North Am."},{"key":"2020080503204185500_CIT0030","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/bjh.12963","article-title":"Should myeloid and lymphoid neoplasms with PCM1-JAK2 and other rearrangements of JAK2 be recognized as specific entities?","volume":"166","author":"Bain","year":"2014","journal-title":"Br J Haematol."},{"key":"2020080503204185500_CIT0031","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/ajh.2830340113","article-title":"Neutrophilic myelofibrosis presenting as Philadelphia chromosome negative BCR non-rearranged chronic myeloid leukemia","volume":"34","author":"Stewart","year":"1990","journal-title":"Am J Hematol."},{"key":"2020080503204185500_CIT0032","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1158\/0008-5472.CAN-04-4263","article-title":"The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2","volume":"65","author":"Reiter","year":"2005","journal-title":"Cancer Res."},{"key":"2020080503204185500_CIT0033","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/s41379-018-0165-9","article-title":"Hematopoietic neoplasms with 9p24\/JAK2 rearrangement: a multicenter study","volume":"32","author":"Tang","year":"2019","journal-title":"Mod Pathol."},{"key":"2020080503204185500_CIT0034","doi-asserted-by":"crossref","first-page":"151405","DOI":"10.1016\/j.anndiagpath.2019.151405","article-title":"Myeloid neoplasm with eosinophilia and BCR-JAK2\/t(9;22)(p24;q11.2) morphologically mimicking chronic myeloid leukemia","volume":"44","author":"Thakral","year":"2020","journal-title":"Ann Diagn Pathol."},{"key":"2020080503204185500_CIT0035","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1056\/NEJMoa1403088","article-title":"Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia","volume":"371","author":"Roberts","year":"2014","journal-title":"N Engl J Med."},{"key":"2020080503204185500_CIT0036","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1038\/leu.2014.168","article-title":"ETV6-FLT3 fusion gene-positive, eosinophilia-associated myeloproliferative neoplasm successfully treated with sorafenib and allogeneic stem cell transplant","volume":"28","author":"Falchi","year":"2014","journal-title":"Leukemia."},{"key":"2020080503204185500_CIT0037","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00277-013-1843-9","article-title":"Successful allogeneic stem cell transplantation with long-term remission of ETV6\/FLT3-positive myeloid\/lymphoid neoplasm with eosinophilia","volume":"93","author":"Chonabayashi","year":"2014","journal-title":"Ann Hematol."},{"key":"2020080503204185500_CIT0038","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.3324\/haematol.2016.144345","article-title":"Characterization of leukemias with ETV6-ABL1 fusion","volume":"101","author":"Zaliova","year":"2016","journal-title":"Haematologica."},{"key":"2020080503204185500_CIT0039","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cancergen.2018.08.002","article-title":"Myeloproliferative neoplasm with ABL1\/ETV6 rearrangement mimics chronic myeloid leukemia and responds to tyrosine kinase inhibitors","volume":"228-229","author":"Xie","year":"2018","journal-title":"Cancer Genet."},{"key":"2020080503204185500_CIT0040","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.3324\/haematol.2017.165340","article-title":"Bone marrow morphology is a strong discriminator between chronic eosinophilic leukemia, not otherwise specified and reactive idiopathic hypereosinophilic syndrome","volume":"102","author":"Wang","year":"2017","journal-title":"Haematologica."},{"key":"2020080503204185500_CIT0041","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/modpathol.2016.75","article-title":"Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified","volume":"29","author":"Wang","year":"2016","journal-title":"Mod Pathol."},{"key":"2020080503204185500_CIT0042","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41375-018-0342-3","article-title":"Recurrent activating STAT5B N642H mutation in myeloid neoplasms with eosinophilia","volume":"33","author":"Cross","year":"2019","journal-title":"Leukemia."},{"key":"2020080503204185500_CIT0043","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/sj.leu.2404955","article-title":"Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms","volume":"22","author":"Tefferi","year":"2008","journal-title":"Leukemia."},{"key":"2020080503204185500_CIT0044","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1038\/leu.2017.240","article-title":"Cytogenetically cryptic ZMYM2-FLT3 and DIAPH1-PDGFRB gene fusions in myeloid neoplasms with eosinophilia","volume":"31","author":"Jawhar","year":"2017","journal-title":"Leukemia."},{"key":"2020080503204185500_CIT0045","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cancergen.2019.07.004","article-title":"Chronic myelomonocytic leukemia with ETV6-ABL1 rearrangement and SMC1A mutation","volume":"238","author":"Cessna","year":"2019","journal-title":"Cancer Genet."},{"key":"2020080503204185500_CIT0046","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/ajh.24075","article-title":"KIT D816V and JAK2 V617F mutations are seen recurrently in hypereosinophilia of unknown significance","volume":"90","author":"Schwaab","year":"2015","journal-title":"Am J Hematol."},{"key":"2020080503204185500_CIT0047","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1038\/leu.2016.73","article-title":"Predictors of survival in WHO-defined hypereosinophilic syndrome and idiopathic hypereosinophilia and the role of next-generation sequencing","volume":"30","author":"Pardanani","year":"2016","journal-title":"Leukemia."},{"key":"2020080503204185500_CIT0048","doi-asserted-by":"crossref","first-page":"e0185602","DOI":"10.1371\/journal.pone.0185602","article-title":"Idiopathic hypereosinophilia is clonal disorder? Clonality identified by targeted sequencing","volume":"12","author":"Lee","year":"2017","journal-title":"PLoS One."},{"key":"2020080503204185500_CIT0049","doi-asserted-by":"crossref","first-page":"e348","DOI":"10.3324\/haematol.2017.187302","article-title":"Molecular genetic characterization of myeloid\/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2","volume":"103","author":"Baer","year":"2018","journal-title":"Haematologica."},{"key":"2020080503204185500_CIT0050","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3343\/alm.2019.39.6.509","article-title":"Current aspects of clonal hematopoiesis: implications for clinical diagnosis","volume":"39","author":"Karner","year":"2019","journal-title":"Ann Lab Med."},{"key":"2020080503204185500_CIT0051","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/leu.2009.2","article-title":"FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib","volume":"23","author":"Lierman","year":"2009","journal-title":"Leukemia."},{"key":"2020080503204185500_CIT0052","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.jaci.2007.11.027","article-title":"Primary resistance to imatinib in Fip1-like 1-platelet-derived growth factor receptor alpha-positive eosinophilic leukemia","volume":"121","author":"Simon","year":"2008","journal-title":"J Allergy Clin Immunol."},{"key":"2020080503204185500_CIT0053","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2018-99-110388","article-title":"Interim results from fight-203, a phase 2, open-label, multicenter study evaluating the efficacy and safety of pemigatinib (INCB054828) in patients with myeloid\/lymphoid neoplasms with rearrangement of fibroblast growth factor receptor 1 (FGFR1)","author":"Verstovsek","year":"2018"},{"key":"2020080503204185500_CIT0054","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1080\/10428194.2017.1397663","article-title":"Myeloid\/lymphoid neoplasms with FGFR1 rearrangement","volume":"59","author":"Strati","year":"2018","journal-title":"Leuk Lymphoma."}],"container-title":["American Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/154\/3\/305\/33566475\/aqaa056.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/154\/3\/305\/33566475\/aqaa056.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T07:21:49Z","timestamp":1596612109000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajcp\/article\/154\/3\/305\/5856052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,11]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,6,11]]},"published-print":{"date-parts":[[2020,8,5]]}},"URL":"https:\/\/doi.org\/10.1093\/ajcp\/aqaa056","relation":{},"ISSN":["0002-9173","1943-7722"],"issn-type":[{"value":"0002-9173","type":"print"},{"value":"1943-7722","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9]]},"published":{"date-parts":[[2020,6,11]]}}}