Abstract
BackgroundSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a malignant primary T-cell lymphoma that is challenging to distinguish from autoimmune disorders and reactive panniculitides. Delay in diagnosis and a high misdiagnosis rate affect the prognosis and survival of patients. The difficulty of diagnosis is mainly due to an incomplete understanding of disease pathogenesis.MethodsWe performed single-cell RNA sequencing of matched subcutaneous lesion tissue, peripheral blood, and bone marrow from a patient with SPTCL, as well as peripheral blood, bone marrow, lymph node, and lung tissue samples from healthy donors as normal controls. We conducted cell clustering, gene expression program identification, gene differential expression analysis, and cell-cell interaction analysis to investigate the ecosystem of SPTCL.ResultsBased on gene expression profiles in a single-cell resolution, we identified and characterized the malignant cells and immune subsets from a patient with SPTCL. Our analysis showed that SPTCL malignant cells expressed a distinct gene signature, including chemokines families, cytotoxic proteins, T cell immune checkpoint molecules, and the immunoglobulin family. By comparing with normal T cells, we identified potential novel markers for SPTCL (e.g., CYTOR, CXCL13, VCAM1, and TIMD4) specifically differentially expressed in the malignant cells. We also found that macrophages and fibroblasts dominated the cell-cell communication landscape with the SPTCL malignant cells.ConclusionsThis work offers insight into the heterogeneity of subcutaneous panniculitis-like T-cell lymphoma, providing a better understanding of the transcription characteristics and immune microenvironment of this rare tumor.
Highlights
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma of mature cytotoxic T cells arising primarily in the skin without the evidence of extracutaneous involvement
The mononuclear cells were isolated from human lungs (LG), lymph nodes (LN), bone marrow (BM), and blood, and the untouched CD3+ T cells were enriched from single-cell suspensions of all tissues and blood using magnetic negative selection (MojoSort Human CD3+ T cell Isolation Kit; BioLegend) [12]
Multiple lymphadenopathies were proven by computerized tomography (CT) scans without hepatomegaly
Summary
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma of mature cytotoxic T cells arising primarily in the skin without the evidence of extracutaneous involvement. According to the 2016 World Health Organization (WHO) and 2018 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification, SPTCL is defined as subcutaneous lymphomas with an a/b T cell phenotype and neoplastic T cells expressing CD3, CD8, and cytotoxic proteins (GZMB, TIA-1, perforin) [1, 2]. Both children [3] and adults can be affected, with a median age at diagnosis of 36 years and female gender bias [4]. The difficulty of diagnosis is mainly due to an incomplete understanding of disease pathogenesis
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