Contemporary Classification and Diagnostic Evaluation of Hypereosinophilia

To provide an in-depth review of the classification and diagnostic evaluation of hypereosinophilia (HE), with a focus on eosinophilic neoplasms.

A review of published literature was performed, and exemplary HE cases were identified.

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, "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2." 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.

A good knowledge of recent advances in HE is necessary to ensure prompt and accurate diagnosis, as well as to help optimize patient care.