Preliminary assessment of the diagnostic accuracy of cutaneous T-cell lymphoma through deep sequencing of T-cell receptor gamma gene

Background: The diagnostic challenges in early mycosis fungoides (MF) and other cutaneous T-cell lymphomas (CTCL) persist despite advancements in molecular methods.

Aim: The study aims to provide a preliminary assessment of next-generation sequencing in analyzing T-cell receptor gamma (TRG) sequences for distinguishing CTCL from benign inflammatory disorders.

Methods: Skin samples from CTCL and benign inflammatory skin disorders proven clinicopathologically were assessed for TRG by NGS.

Results: Our study analyzed skin samples from a total of 36 subjects, comprising 22 cases of CTCL, including 14 MF and 8 other CTCLs, alongside 14 cases of benign inflammatory skin disorders. According to the LymphoTrack criteria, monoclonality was detected in 75.0 % of the overall 24 CTCL patients. Specifically, in MF cases, 10 out of 14 were identified as monoclonality, with all four non-monoclonal cases being in the patch stage. For the other CTCL, 6 out of 8 cases displayed monoclonality. Among the overall 22 CTCL patients, 11 had multiple biopsies, with 9 displaying the same dominant clone across different sites. Among the 14 benign cases, only the case with erythrodermic psoriasis exhibited monoclonality. Our decision tree analysis suggests that a high frequency of the most abundant clone, its ratio to the third most abundant clone, and TRG V-I segment usage are effective markers aiding in diagnosing CTCL.

Conclusion: Combination of the clone frequencies, and TRG V segment usage may enhance diagnosis for MF and other CTCLs, aiding in differentiating them from benign conditions. However, molecular diagnosis for patch-stage MF remains challenging.