Abstract
Primary cutaneous γδ T cell lymphomas (PCGDTLs) represent a heterogeneous group of uncommon but aggressive cancers. Herein, we perform genome-wide DNA, RNA, and T cell receptor (TCR) sequencing on 29 cutaneous γδ lymphomas. We find that PCGDTLs are not uniformly derived from Vδ2 cells. Instead, the cell-of-origin depends on the tissue compartment from which the lymphomas are derived. Lymphomas arising from the outer layer of skin are derived from Vδ1 cells, the predominant γδ cell in the epidermis and dermis. In contrast, panniculitic lymphomas arise from Vδ2 cells, the predominant γδ T cell in the fat. We also show that TCR chain usage is non-random, suggesting common antigens for Vδ1 and Vδ2 lymphomas respectively. In addition, Vδ1 and Vδ2 PCGDTLs harbor similar genomic landscapes with potentially targetable oncogenic mutations in the JAK/STAT, MAPK, MYC, and chromatin modification pathways. Collectively, these findings suggest a paradigm for classifying, staging, and treating these diseases.
Highlights
Primary cutaneous γδ T cell lymphomas (PCGDTLs) represent a heterogeneous group of uncommon but aggressive cancers
For the second group (16 cases), the patients were originally diagnosed as mycosis fungoides because their clinical and histological features were highly similar to the cutaneous lymphomas of non-cytotoxic αβ T cells. 15/16 of these had patch/plaque stage disease and 1 presented with plaques and tumors
The remaining γδ mycosis fungoides (γδ MF) cases were identified by T cell receptor (TCR)-Seq or by immunohistochemistry (IHC) for γδ markers which have become routine at Northwestern
Summary
Primary cutaneous γδ T cell lymphomas (PCGDTLs) represent a heterogeneous group of uncommon but aggressive cancers. Vδ1 and Vδ2 PCGDTLs harbor similar genomic landscapes with potentially targetable oncogenic mutations in the JAK/STAT, MAPK, MYC, and chromatin modification pathways These findings suggest a paradigm for classifying, staging, and treating these diseases. For cutaneous γδ T cell lymphomas (CGDTLs), the cell of origin has long been presumed to be a Vδ2 cell based on Southern Blot analysis of four cases[12]. These findings have not been validated or correlated with clinical phenotype
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