Evaluating T-Cell Clonality In Skin Using a Quantitative TRBC1-Clonality Score

Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma, characterised by the clonal proliferation of neoplastic T-cells in the skin. Its early diagnosis is often challenging due to overlapping clinical features with inflammatory dermatoses. This study investigates T-cell receptor beta constant 1 (TRBC1) as marker for T-cell clonality in FFPE skin biopsies. We analysed single-cell RNA sequencing data from CTCL skin lesions to examine the expression of TRBC1 in Th-cells. To quantify the extent of TRBC1 polarisation, we developed the TRBC1 Clonality-Score (TRBC1-CS). Using patient-specific TRBV mRNA-probes and TRBC1 antibodies, we demonstrated polarised TRBC1 expression in TRBV-defined clonal Th-cells in FFPE skin samples. Next, we established a simplified immunofluorescence panel consisting of T-cell markers and TRBC1 to differentiate between CTCL and benign dermatoses. The findings were validated in an independent cohort by comparing the TRBC1-CS to PCR-based T-cell clonality assays. The TRBC1-CS demonstrated high specificity for CTCL, enabling delineation from benign dermatoses. Validated in an independent cohort, TRBC1-CS exhibited superior specificity and positive predictive value compared to 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.