Summary Sézary syndrome (SS) is an aggressive cutaneous T‐cell lymphoma, characterized by erythroderma, lymphadenopathy and circulating malignant CD4 + T cells. Despite therapeutic advances, SS remains an incurable disease. Early diagnosis is therefore essential for timely therapeutic intervention; however, reliable biomarkers to identify circulating SS cells are still lacking. Recent studies highlighted dysregulation of the ectoenzymes CD39, CD73 and CD38 in SS, suggesting a potential role for these molecules in the disease. Thirty‐three patients were enrolled in this study, and CD39/CD73/CD38 expression was analysed on circulating CD4 + T cells by multiparametric flow cytometry, enabling discrimination between malignant and non‐malignant T‐cell subsets. SS cells exhibited marked CD39 or CD73 overexpression together with consistent CD38 downregulation, a pattern also confirmed in paired skin biopsy, whereas non‐malignant CD4 + T cells largely maintained expression profiles comparable to healthy controls. Genotyping further identified ENTPD1 single nucleotide polymorphism rs10748643 as a contributor to CD39 dysregulation, defining a CD39‐permissive subgroup characterized by CD39 + SS cells. In conclusion, the combined overexpression of CD39 or CD73 and loss of CD38 defines a distinct tumour‐restricted immunophenotypic signature in SS. Integrating these ectoenzymes into flow cytometry panels may improve detection of malignant CD4 + T cells across blood and skin, eventually strengthening diagnostic accuracy.
Marchisio et al. (Mon,) studied this question.