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Hypereosinophilia of persistent/unknown cause: a bone marrow-based study integrating WHO-HAEM5 criteria and myeloid next-generation sequencing
Journal article   Open access   Peer reviewed

Hypereosinophilia of persistent/unknown cause: a bone marrow-based study integrating WHO-HAEM5 criteria and myeloid next-generation sequencing

Mohamed M Eletrebi, Juan Sanchez-Ramirez, Abdalla Abdalla and Carol J Holman
American journal of clinical pathology, Vol.165(5), aqag031
05/05/2026
DOI: 10.1093/ajcp/aqag031
PMID: 42106910
Appears in  UI Libraries Support Open Access
url
https://doi.org/10.1093/ajcp/aqag031View
Published (Version of record) Open Access

Abstract

Hypereosinophilia (HE), defined as an absolute eosinophil count (AEC) ≥1.5 × 109/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. We identified 307 BM biopsy specimens (2015-2023) mentioning "eosinophilia." Patients with defined reactive or clonal etiologies were classified as group 2 (known etiology, n = 269). The remaining patients constituted group 1 (HEPU, n = 38). 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). Compared to group 2, patients with HEPU were younger (median 48 vs 62 years; P = .004) and exhibited higher initial AECs (2.8 vs 0.6 × 109/L; P < .001). Comprehensive workup reclassified the HEPU cohort (n = 38) 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. 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.
 Adolescent Adult Aged Aged, 80 and over Bone Marrow - pathology Eosinophilia - diagnosis Eosinophilia - pathology Female Hematologic Neoplasms - diagnosis High-Throughput Nucleotide Sequencing Humans Hypereosinophilic Syndrome - diagnosis Hypereosinophilic Syndrome - genetics Hypereosinophilic Syndrome - pathology In Situ Hybridization, Fluorescence Male Middle Aged Myeloproliferative Disorders - diagnosis World Health Organization Young Adult UIOWA OA Agreement

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