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Recently, a distinct lymphonodal subtype, nodal gamma-delta T-cell lymphoma (NGDTCL), has been recognized, which is not well reflected in current lymphoma classifications.We here report a unique case of NGDTCL in a 61-year-old male presenting with cervical lymphadenopathy and refractory disease despite multiple lines of therapy. Histopathological analysis revealed diffuse infiltration of a CD4+\u2009gamma-delta T-cell lymphoma, with loss of CD7 and absence of cytotoxic marker expression. Notably, the lymphoma cells expressed two T follicular helper (TFH) cell markers, PD-1 and ICOS, initially leading to misclassification as a TFH lymphoma. Genomic profiling revealed pathogenic alterations of <jats:italic>TP53, CHEK2<\/jats:italic>, and loss of <jats:italic>CDKN2A<\/jats:italic> and <jats:italic>CDKN2B<\/jats:italic>. Additionally, a rearrangement of the <jats:italic>ITK<\/jats:italic>-gene, which is believed to play a role in \u03b3\u03b4 T-cell development, was identified. To our knowledge, this is the first report of a NGDTCL with co-expression of two TFH markers. This case broadens the phenotypic spectrum of NGDTCL and challenges current diagnostic concepts of T-cell lymphoma classification, particularly the notion that expression of CD4 and two TFH markers are sufficient for diagnosing nodal TFH lymphomas.<\/jats:p>","DOI":"10.1007\/s00428-025-04268-2","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T07:34:12Z","timestamp":1758872052000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nodal gamma-delta T-cell lymphoma: expression of TFH-markers causing diagnostic difficulties in a newly described entity"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3848-144X","authenticated-orcid":false,"given":"Viola 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The patient signed informed consent to allow material used for research purposes by investigators from the University Hospital Zurich, Switzerland.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}