Primary gastric EBV-positive cytotoxic-molecule-negative T-cell lymphoma with TET2 multihit mutations: a case report

Extranodal NK/T-cell lymphoma (ENKTL) is an Epstein-Barr virus (EBV)-positive lymphoma of the NK- or cytotoxic T-cell lineage. According to the World Health Organization Classification of Hematolymphoid Tumors, Fifth Edition (WHO-HAEM5), EBV-positive cases lacking cytotoxic molecules cannot be classified as ENKTL. To the best of our knowledge, this is the first documented case of primary gastric EBV-positive T-cell lymphoma lacking the expression of cytotoxic molecules. A 76-year-old woman initially presented with a disease confined to the stomach, with subsequent contiguous extension into the duodenum. Biopsies revealed small- to medium-sized atypical T cells with pale cytoplasm and irregularly folded nuclei, as well as intravascular infiltration. Tumor cells were positive for CD3, TCRβF1, and CD4 and negative for CD56, TIA-1, granzyme B, perforin, and PD-L1. EBV-encoded RNA in situ hybridization highlighted neoplastic T cells. These findings did not fulfill the criteria for any T/NK cell entity of WHO-HAEM5 including ENKTL and peripheral T-cell lymphoma not otherwise specified (PTCL, NOS). Targeted sequencing revealed TET2 multihit mutations, suggesting clonal hematopoiesis-linked pathogenesis. Given the patient's age and tumor location, we administered a reduced dose of DeVIC, followed by radiotherapy, achieving partial remission. This case expands the spectrum of EBV-associated T-cell lymphomas and highlights the need for additional cases to refine the classification and management.