Spatial Clonal Discordance in Early Mycosis Fungoides Revealed by Compartment-specific TRBC1 Immunohistochemistry

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Abstract

Diagnosis of early mycosis fungoides (MF) is hindered by overlap with benign dermatoses and by the variable sensitivity of conventional polymerase chain reaction-based molecular clonality assays in paucicellular specimens. We demonstrate that T-cell receptor β-chain constant region 1 (TRBC1) immunohistochemistry (IHC) provides a spatially resolved assessment of T-cell clonality that may aid the evaluation of early MF. In early MF, we identified a characteristic "spatial clonal discordance," where monotypic TRBC1 expression is confined to intraepidermal T cells while dermal infiltrates remain polytypic. This compartment-specific pattern reflects neoplastic epidermotropism and may help explain discordant clonality results obtained by bulk molecular assays in paucicellular lesions. Conversely, tumor-stage MF and Sézary syndrome exhibited spatially concordant, pan-compartmental restriction. Digital image analysis showed high concordance between single-stain IHC and multiplex immunofluorescence, establishing TRBC1+ thresholds of ≤25% or ≥75% for defining clonality. Although this study is limited by its retrospective, single-center design and relatively small cohort, the findings establish TRBC1 IHC as a powerful, spatially informative tool. It effectively overcomes the "dilution effect" of reactive cells in early MF, serving as a high-sensitivity adjunct to conventional molecular testing for accurate, compartment-specific clonal evaluation.

Abstract as published, via PubMed.