Answer: B - Myeloid/lymphoid neoplasm with PDGFRA fusion gene

Myeloid/lymphoid neoplasm with PDGFRA fusion gene results from from the formation of a PDGFRA fusion gene. The vast majority of cases result from a cytogenetically cryptic deletion of 4q12 resulting in FIP1L1-PDGFRA fusion, but PDGFRA fusion genes involving other partners are also included in this category. Bone marrow and peripheral blood blast counts are <20% in the majority of cases.

There is a strong male predominance with a male to female ratio of ~7:1. The median age at presentation is in the 5th decade of life.

The formation of PDGFRA fusion gene results in neoplastic transformation of a pluripotent hematopoietic stem cell that can give rise to eosinophils, neutrophils, monocytes, mast cells, B- cells and T-cells.

The bone marrow is hypercellular for age and typically shows markedly increased eosinophils and an increased number of mast cells .

Unlike the dense clusters of mast cells seen in the bone marrow of patients with systemic mastocytosis associated with the KIT D816V mutation, the mast cells associated with FIP1L1-PDGFRA fusion are typically scattered or form loose clusters.

The presence of marked eosinophilia should trigger a comprehensive work up including FISH for BCR::ABL1, CBFB rearrangement (to rule out AML with inv(16)), PDGFRA/B rearrangement (and other kinase fusion genes if the former studies are negative) and IHC work up for mastocytosis. Laboratory evaluation for patients presenting with unexplained eosinophilia must include evaluation for PDGFRA rearrangement. Routine karyotype is typically normal. The FISH probes that hybridize to the region between the FIP1L1 and PDGFRA genes are used to detect a cytogenetically cryptic 800-kb deletion including the region containing CHIC2, on the long arm of chromosome 4 (4q12) that results in formation of the FIP1L1-PDGFRA fusion gene. Imatinib has remarkable efficacy and is considered the definitive first-line therapy in patients with myeloid/lymphoid neoplasms with PDGFRA fusion gene.