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Summary: Melanoma is the deadliest form of skin cancer due to its propensity to metastasize. It arises from melanocytes, which are attached to keratinocytes within the basal epidermis. Here, we hypothesize that, in addition to melanocyte-intrinsic modifications, dysregulation of keratinocyte functions could initiate early-stage melanoma cell invasion. We identified the lysolipid sphingosine 1-phosphate (S1P) as a tumor paracrine signal from melanoma cells that modifies the keratinocyte transcriptome and reduces their adhesive properties, leading to tumor invasion. Mechanistically, tumor cell-derived S1P reduced E-cadherin expression in keratinocytes via S1P receptor dependent Snail and Slug activation. All of these effects were blocked by S1P2/3 antagonists. Importantly, we showed that epidermal E-cadherin expression was inversely correlated with the expression of the S1P-producing enzyme in neighboring tumors and the Breslow thickness in patients with early-stage melanoma. These findings support the notion that E-cadherin loss in the epidermis initiates the metastatic cascade in melanoma.

Abstract T-follicular helper (TFH) markers are expressed in the microenvironnement of marginal zone B-cell lymphoma (MZL), and in lymphomas arising from TFH-cells, sometimes making the differential diagnosis difficult. In the skin, the “TFH-spectrum” is poorly defined, going from primary cutaneous lymphoproliferative disorder with small/medium CD4+ T-cells (SMLPD) to cutaneous localizations of systemic angioimmunoblastic T-cell lymphoma (cAITL), and may pass through intermediate forms (primary cutaneous T-follicular helper derived lymphoma, not otherwise specified (PCTFHL,NOS)). We retrospectively analyzed 20 MZL, 13 SMLPD, 5 PCTFHL, and 11 cAITL clinically, histologically, and molecularly, to define tools to differentiate them. Characteristics that might favor the diagnosis of MZL over SMLPD are: multiple skin nodules (p

Abstract is missing (Short communication)

Introduction: The characteristics and the prognostic value of regression in primary melanomas are controversial. Objectives: To further characterize “hot” and “cold” tumor’s stromas and to investigate the association between dermoscopy, pathology, and the prognostic implications of regression. Methods: A 14-year-collection-based retrospective analysis was carried out on 40 patients with confirmed regressive melanomas. Results: The extent of regression in dermoscopy was associated with the stage of the regression (P = 0.05) and with the MelanA patterns in histology (P = 0.02). Blue-gray and gray-brown color of the peppering (P = 0.01), and the eccentric, multifocal character of the dermoscopic regression (P = 0.05) were associated with “hot” stromas (CD8+, Granzym B+). Focal histologic regression (regressing melanomas) was associated with a good outcome (P < 0.001), while a complete regression (regressed melanomas) was associated with melanoma-related death (P < 0.001). “Hot” stromas (CD8+ were significantly associated with survival at 10 years (P = 0.044), while “hot” stromas (Granzyme B+) were associated with the locoregional extension (P = 0.016), and the initial distant metastasis (P = 0.016). Conclusions: Dermoscopic features of regression in primary melanomas were associated with the stage of regression, its extent, and the “hot” or “cold” nature of the tumor stroma, with prognostic implications.

Abstract is missing (Short communication)