20. FIP1L1::KIT fusion in a case of peripheral T-cell lymphoproliferative neoplasm responsive to tyrosine kinase inhibitor

Abstract

Myeloid/lymphoid neoplasms with eosinophilia and defining gene rearrangements commonly involve FIP1L1::PDGFRA. Eosinophilia is not an invariable feature. Neoplastic myeloid/lymphoid populations may be present at the same or different sites, with T-cell neoplasms being the conventional lymphoid component.

The case involves a 43-year-old male with chronic intractable disseminated skin rashes. Blood flow cytometry showed an aberrant T-cell population with no surface CD3 expression. Atypical T-cell infiltrates were present in the bone marrow, skin, and inguinal lymph node biopsy, and clonal TRG rearrangements were detected in blood, skin, and lymph node. However, there were no specific features to definitively classify the abnormal T-cell infiltrates. Bone marrow was fibrotic and hypercellular with only focal eosinophilia. Next-generation sequencing of blood and lymph node detected no significant mutations, and bone marrow cells demonstrated a normal karyotype. Fluorescence in situ hybridization demonstrated loss of both the CHIC2 and PDGFRA signals, with retention of the FIP1L1 signal. Whole-genome microarray analysis revealed an ∼1.3 Mb loss in the 4q12 region with breakpoints within the FIP1L1 and KIT genes. A novel FIP1L1::KIT fusion was confirmed by RNA-sequencing demonstrating in-frame retention of the KIT tyrosine kinase domain. The patient had a poor response to chemotherapy but superb response to the tyrosine kinase inhibitor, dasatinib.

FIP1L1::KIT fusion has not been described in systemic peripheral T-cell neoplasms without significant abnormality in myeloid lineage. This case indicates that KIT fusions are targetable genetic lesions and supports the inclusion of KIT fusions in the myeloid/lymphoid neoplasms with defining gene rearrangement.