Abstract
BackgroundSubcutaneous panniculitis-like T cell lymphomas represent a rare and difficult to diagnose entity of cutaneous T cell lymphomas. SPTL affects predominantly young adults and presents with multifocal subcutaneous nodules and frequently associated autoimmune features. The pathogenesis of SPTL is not completely understood.MethodsThe aim of this study was to unravel molecular pathways critical to the SPTL pathogenesis. Therefore, we analyzed 23 skin samples from 20 newly diagnosed SPTL patients and relevant control samples of adipose and non-malignant panniculitis tissue by using gene expression microarray, quantitative PCR, and two-colour immunohistochemistry.ResultsInterestingly, indoleamine 2,3-dioxygenase (IDO-1), an immunotolerance-inducing enzyme, was among the most highly overexpressed genes in all comparisons. The expression of Th1-specific cytokines, known to be associated with autoimmune inflammation (i.e. IFNG, CXCR3, CXCL9, CXCL10, CXCL11, and CCL5), were also significantly increased. Confirmed using immunohistochemistry, the morphologically malignant lymphocytes expressed CXCR3 and CXCL9. IDO-1 expression was found both in some morphologically malignant lymphocytes rimming the adipocytes and in surrounding CD11c− CD68− cells but not in CD11c+ dendritic cells in the microenvironment. The proportion of FoxP3+ cells in SPTL exceeded that in the benign panniculitis samples.ConclusionsOur results indicate that the up regulation of the tolerogenic IDO-1 together with the up regulation of IFNG, CXCR3 ligands, and CCL5 are features of SPTL lesions. We anticipate that the IFNG-inducible IDO-1 expression contributes to the formation of an immunosuppressive microenvironment, favorable for the malignant T cells. This study provides a relevant molecular basis for further studies exploring novel therapeutic means for subcutaneous T cell lymphoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0160-2) contains supplementary material, which is available to authorized users.
Highlights
Subcutaneous panniculitis-like T cell lymphomas represent a rare and difficult to diagnose entity of cutaneous T cell lymphomas
Autoimmune diseases are common among Subcutaneous panniculitis-like T cell lymphoma (SPTL) patients [2,3], as 20% of the patients in the European cohort had an associated autoimmune disorder, most commonly systemic lupus erythematosus (SLE) and some cases were first misdiagnosed as lupus panniculitis [1]
SPTL skin samples demonstrate up regulation of IDO-1 and Th1 type cytokines We first compared SPTL skin samples to normal subcutaneous fat tissue to exclude the effect of normal fat gene expression
Summary
Subcutaneous panniculitis-like T cell lymphomas represent a rare and difficult to diagnose entity of cutaneous T cell lymphomas. Subcutaneous panniculitis–like T-cell lymphoma (SPTL, ORPHA86884) represents a rare entity of T-cell lymphomas. The most recent WHO-EORTC classification, together with the EORTC Cutaneous Lymphoma Group Report, confine SPTL to subcutaneous lymphomas with an α/β T-cell phenotype and neoplastic T-cells expressing CD3, CD8 and cytotoxic proteins (GZMB, TIA-1, perforin) [1]. In a recent joint study by the EORTC Cutaneous Lymphoma Group [1], the main clinical, histopathological, and prognostic features of SPTL were defined in a longterm collection of 83 European SPTL cases. Autoimmune diseases are common among SPTL patients [2,3], as 20% of the patients in the European cohort had an associated autoimmune disorder, most commonly systemic lupus erythematosus (SLE) and some cases were first misdiagnosed as lupus panniculitis (lupus profundus) [1]. The prognosis of SPTL is favourable, with a 5-year survival of 91% (82% if hemophagocytic syndrome is present)
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