Single-cell RNAseq profiling in a patient with discordant primary cutaneous B and T cell lymphoma reveals micromilieu-driven immune skewing

Background: Primary cutaneous lymphomas comprise a heterogeneous group of B and T cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed due to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages in comparison to the inflammatory infiltrate, an interplay that is currently only insufficiently understood. Objectives: To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma. Methods: Single-cell RNA sequencing (scRNA-seq) combined with T and B cell receptor sequencing. Results: We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle center lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumor cells and the tissue microenvironment revealed a type-2 immune skewing in MF, most likely guided by the expanded clone that also harbored upregulation of numerous pro-oncogenic genes. By contrast, PCFCL lesions exhibited a more type-1 immune phenotype, consistent with its indolent behavior. Conclusions: These data not only illustrate the diagnostic potential of scRNA-seq, but also allow the characterization of specific clonal populations shaping the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions. Comparison of skin cells from two histologically different tumors in a single patient >>> Raw data are unavailable due to patient privacy concerns. <<<