Evaluating T-cell clonality in skin using a quantitative TRBC1 clonality score

Cutaneous T-cell lymphoma is a rare form of non-Hodgkin lymphoma, characterized by the clonal proliferation of neoplastic T cells in the skin. Its early diagnosis is often challenging owing to overlapping clinical features with inflammatory dermatoses. This study investigates TRBC1 as a marker for T-cell clonality in formalin-fixed, paraffin-embedded skin biopsies. We analyzed single-cell RNA-sequencing data from cutaneous T-cell lymphoma skin lesions to examine the expression of TRBC1 in T helper cells. To quantify the extent of TRBC1 polarization, we developed the TRBC1 clonality score (TRBC1-CS). Using patient-specific TRBV mRNA probes and TRBC1 antibodies, we demonstrated polarized TRBC1 expression in TRBV-defined clonal T helper cells in formalin-fixed, paraffin-embedded skin samples. Next, we established a simplified immunofluorescence panel consisting of T-cell markers and TRBC1 to differentiate between cutaneous T-cell lymphoma and benign dermatoses. The findings were validated in an independent cohort by comparing the TRBC1-CS with PCR-based T-cell clonality assays. The TRBC1-CS demonstrated high specificity for cutaneous T-cell lymphoma, enabling delineation from benign dermatoses. Validated in an independent cohort, TRBC1-CS exhibited specificity and positive predictive value superior to those of smaller panels and PCR-based methods. In conclusion, TRBC1 staining and TRBC1-CS provide practical and highly specific tools for assessing T-cell clonality in skin biopsies.