CD27/CD70 pathway activation in primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder

Abstract

AbstractPrimary cutaneous CD4+ small or medium T‐cell lymphoproliferative disorder (PCSM‐LPD) is a clonal T‐cell proliferation disease confined to the skin. PCSM‐LPD shares expression of T follicular helper (Tfh) cell markers with various mature T‐cell lymphomas. However, the benign presentation of PCSM‐LPD contrasts the clinical behavior of other Tfh‐lymphomas. The aim of our study was to delineate the molecular similarities and differences between PCSM‐LPD and other Tfh‐derived lymphomas to explain the clinical behavior and unravel possible pathological mechanisms. We performed targeted next‐generation sequencing of 19 genes recurrently mutated in T‐cell neoplasms in n = 17 PCSM‐LPD with high and in n = 21 PCSM‐LPD with low tumor cell content. Furthermore, gene expression profiling was used to identify genes potentially expressed in the PD1‐positive (PD1+) neoplastic cells. Expression of some of these genes was confirmed in situ using multistain immunofluorescence. We found that PCSM‐LPD rarely harbored mutations recurrently detected in other T‐cell neoplasms. PCSM‐LPD is characterized by the invariable expression of the T‐cell‐receptor‐associated LCK protein. CD70 and its ligand CD27 are co‐expressed on PD1+ PCSM‐LPD cells, suggestive of autoactivation of the CD70 pathway. In conclusion, PCSM‐LPD differs from disseminated lymphomas of Tfh origin by their mutation profile. Activation of CD70 signaling also found in cutaneous T‐cell lymphoma represents a potential driver of neoplastic proliferation of this benign neoplasia of Tfh. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.