Mycosis fungoides: differentiation from inflammation and detection of circulating tumour cells with the EuroClonality next-generation sequencing assay.

Abstract

Mycosis fungoides (MF) is a rare malignancy that is characterized by the presence of circulating tumour cells (CTCs) in a subgroup of patients. Reliably distinguishing MF from inflammatory skin conditions is challenging. To evaluate the potential benefits of next-generation sequencing (NGS)-based T-cell receptor rearrangement repertoire analysis in detecting clonal rearrangements in MF and inflammatory skin conditions. Skin biopsies and blood samples from 33 patients with MF and 10 patients with inflammatory skin conditions were analysed using TRB and TRG NGS. Twenty-seven patients had early-stage IA (n = 19) and IB (n = 8) MF, and six had advanced-stage disease (IIB, n = 5; IIIA, n = 1). Analysis applying standard abundance thresholds identified at least one clonal rearrangement in the skin DNA of 97% (n = 32/33) of patients with MF and in 90% (n = 9/10) of those with inflammatory skin conditions. To enhance specificity, an abundance and distribution-based approach was applied, which considered only rearrangements that significantly stood out from the physiological background as clonal (MF, n = 29/33; inflammatory skin conditions, n = 1/10), allowing for highly sensitive (88%) and specific (90%) discrimination between MF and other inflammatory skin conditions. CTCs were detected in 46% (n = 11/24) of patients with early-stage MF and in 60% (n = 3/5) of those with late-stage MF. NGS-based T-cell receptor repertoire analysis is a highly sensitive and specific method for the differential diagnosis of early-stage MF vs. inflammatory skin conditions, and for the sensitive molecular detection of CTCs.