437 Single-cell RNA sequencing reveals specific T cell and fibroblast populations that can distinguish early mycosis fungoides from parapsoriasis and atopic dermatitis lesions

The diagnosis of early mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, is often delayed due to clinical and histopathological similarities with benign inflammatory dermatoses. Moreover, its clear delineation from spectrum so-called “parapsoriasis” still controversial. For further insight on a molecular level, we performed single-cell RNA sequencing profile skin biopsies patients presenting clinically small- or large-patch dermatitis compared them atopic (AD) lesions healthy control (HC) individuals. Respective histological diagnoses MF, parapsoriasis/fingerprint AD were assigned by dermatopathologist in blinded fashion. We found 6 out 7 harbor either an expanded alpha/beta gamma/delta clone, constituting 17.3-53.6% all TCR+ cells, consistent MF. By contrast, small-patch contained highly polyclonal pattern, indistinguishable HC skin. However, only harbored “Th2A” CD3+CD4+IL17RB+CRTH2+ IL13-expressing cell type, previously associated allergic sensitization tissue-resident disease memory formation Expanded MF clones deficient for CD7 expression, line lymphomatous phenotype, overexpressed LGALS3, PGK1, IL26, OSTF1, LDHA comparison T cells. On stromal uniquely COL6A5+CCL19+COL18A1+ fibroblasts, while showed elevated frequencies CD36+IL6+ fibroblast population, that was largely absent HC, parapsoriasis samples. In sum, Th2A cells specific subpopulations distinguish parapsoriasis, presence noticeable clonal expansion