OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
ELETREBI et al. (Sat,) studied this question.