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

ESDR437 - Single-cell RNA sequencing reveals specific T cell and fibroblast populations that can distinguish early mycosis fungoides from parapsoriasis and atopic dermatitis lesions

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.