Diagnostic algorithm for HE incorporating 2016 WHO categories of eosinophilia-associated neoplasms

In patients presenting with HE, we recommend an initial work-up to rule out reactive (secondary) causes. If this work-up is negative, parallel or sequential testing for a primary (clonal) eosinophilia should be undertaken. Evaluation includes morphologic analysis of the peripheral blood and BM, immunohistochemistry (eg, CD117, tryptase, and CD25 in systemic mastocytosis), flow cytometric immunophenotyping to assess the presence of myeloid, B- and/or T-lymphocyte markers, and cytogenetic/molecular/ genetic testing. As shown in the algorithm, this combination of clinicopathologic and molecular testing can help identify a specific neoplasm and the WHO category within which it resides (shown in blue-colored boxes). Idiopathic HES is a diagnosis of exclusion and requires the presence of organ damage. HES is considered a provisional diagnosis until a cause of HE is discovered. Lymphocyte-variant hypereosinophilia is a clonal T-cell population producing cytokines that results in a reactive eosinophilia. *The provisional variants ETV6-JAK2 and BCR-JAK2 are also included in this category.

TK fusion genes in myeloid/lymphoid neoplasms with eosinophilia

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

• Rare myeloid as well as lymphoid neoplasms that share eosinophilia and recently recognized acquired genetic mutations within a specific group of genes resulting in an aberrant tyrosine kinase within a pluripotent hematopoietic stem cell.
• Eosinophilia may be absent in some cases.
• The genes involved are the platelet-derived growth factor receptor-α (PDGFRA) on chromosome 4q12, platelet-derived growth factor receptor-β (PDGFRB) at 5q32, fibroblast growth factor receptor 1 (FGFR1) at 8p11.2, and PCM1-JAK2 rearrangement.

FLIPI1-PDGFRA Translocation

• The most common PDGFRA rearrangement.
• Standard cytogenetics will not detect the FIP1L1-PDGFRA fusion gene; must be accomplished by either FISH or RT-PCR.
• The importance of the FIP1L1-PDGFRA translocation is underscored by its responsiveness to imatinib with rapid and complete hematologic remissions.

Morphology