EBV-positive Hodgkin lymphoma with an immunosuppressive microenvironment during guselkumab (interleukin-23 inhibitor) therapy for chronic plaque psoriasis.

BACKGROUND

Psoriasis is an independent risk factor for classic Hodgkin lymphoma (cHL). Guselkumab has a favorable malignancy safety profile in clinical trials.

PURPOSE: To report the first documented Epstein-Barr virus (EBV)-positive cHL arising in a biologic-naive patient with psoriatic arthritis during guselkumab therapy for chronic plaque psoriasis, and to describe its tumor microenvironment.

METHODS

Excisional biopsy with immunohistochemistry, EBER in situ hybridization, and targeted sequencing, plus spatial single-cell proteomics (9-plex sequential immunofluorescence) of the diagnostic lymph node.

RESULTS

A man in his early 40s developed night sweats, syncope, and bulky right cervical lymphadenopathy 7 months after starting guselkumab. Biopsy showed mixed-cellularity EBV-positive cHL (latency IIa: EBER+, LMP1+, EBNA-2-). HRS cells were weak PAX5+, CD20 negative, CD15+, strong CD30+, OCT2 negative/weak, BOB1 negative/weak, and strong CD200+. The microenvironment contained CTLA4+ immunosuppressive T cells (10.15%), M2 macrophages (10.35%), modest Th2 cells (0.38%), a low Th1/Th2 ratio (~0.39), and Th17 cells (~13%). GATA3 and CCR4 immunohistochemistry confirmed modest Th2 skewing. After guselkumab was stopped, he achieved a complete metabolic response with ABVD and involved-site radiotherapy and remains in remission on apremilast.

CONCLUSIONS

The short latency and atypical Th2-skewed, myeloid-enriched microenvironment, in contrast to the typical Th1-dominant profile of EBV-positive cHL, raise the possibility of immune-milieu alteration under IL-23 inhibition. This case supports continued pharmacovigilance for rare lymphomas in patients receiving IL-23 inhibitors and the need for larger studies to clarify potential class effects.