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Simple Summary: The skin is the outermost barrier of the human body and consists of different layers and cell types. Several environmental and genetic factors can induce skin aging and age-related diseases. One of the main problems in skin aging is that senescent cells are accumulated and secrete factors, which can induce senescence in other tissues. Many researchers are trying to identify treatment modalities (known as senotherapies) to eliminate the senescent cells and reverse the aging process for chronic age-related diseases. The aim of this study is to address the mechanisms that induce senescence and the molecules with potential HAFi effects that are currently investigated for skin aging. Further studies should be conducted to elucidate all the effects of current senotherapies on the skin and other organs. Current data suggest that ongoing research projects in the field may lead to the discovery of new effective anti-senescence strategies in the skin. The skin is the layer of tissue that covers the largest part of the body in vertebrates, and its main function is to act as a protective barrier against external environmental factors, such as microorganisms, ultraviolet light and mechanical damage. Due to its important function, investigating the factors that lead to skin aging and age-related diseases, as well as understanding the biology of this process, is of high importance. Indeed, it has been reported that several external and internal stressors contribute to skin aging, similar to the aging of other tissues. Moreover, during aging, senescent cells accumulate in the skin and express senescence-associated factors, which act in a paracrine manner on neighboring healthy cells and tissues. In this review, we will present the factors that lead to skin aging and cellular senescence, as well as ways to study senescence in vitro and in vivo. We will further discuss the adverse effects of the accumulation of chronic senescent cells and therapeutic agents and tools to selectively target and eliminate them. [ABSTRACT FROM AUTHOR]

A 31-year-old male presented with a firm, well-demarcated, erythematous, crateriform, and ulcerated nodule in the left lumbar region, which persisted for 3 months. Clinically, a keratoacanthoma was suspected. The histological analysis was consistent with perforating fibrous histiocytoma, a rare histopathologic variant of fibrous histiocytoma. To our knowledge, this is the third case reported in the literature. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Epidermal multinucleated keratinocytes, or epidermal grape cells, in the absence of any viral infection, are an important histological finding and a clue for the diagnosis of dermatoses induced by external irritation or aggression, dermatitis artefacta, and facticial dermatitis. Thermal damage such as cryogenic injury is part of the spectrum of causes to be evoked in case of their presence. [ABSTRACT FROM AUTHOR]

The spatial distribution of tumor‐infiltrating lymphocytes (TIL) predicts breast cancer outcome and response to systemic therapy, highlighting the importance of an intact tissue structure for characterizing tumors. Here, we present ST‐FFPE, a spatial transcriptomics method for the analysis of formalin‐fixed paraffin‐embedded samples, which opens the possibility of interrogating archival tissue. The method involves extraction, exome capture and sequencing of RNA from different tumor compartments microdissected by laser‐capture, and can be used to study the cellular composition of tumor microenvironment. Focusing on triple‐negative breast cancer (TNBC), we characterized T cells, B cells, dendritic cells, fibroblasts and endothelial cells in both stromal and intra‐epithelial compartments. We found a highly variable spatial distribution of immune cell subsets among tumors. This analysis revealed that the immune repertoires of intra‐epithelial T and B cells were consistently less diverse and more clonal than those of stromal T and B cells. T‐cell receptor (TCR) sequencing confirmed a reduced diversity and higher clonality of intra‐epithelial T cells relative to the corresponding stromal T cells. Analysis of the top 10 dominant clonotypes in the two compartments showed a majority of shared but also some unique clonotypes both in stromal and intra‐epithelial T cells. Hyperexpanded clonotypes were more abundant among intra‐epithelial than stromal T cells. These findings validate the ST‐FFPE method and suggest an accumulation of antigen‐specific T cells within tumor core. Because ST‐FFPE is applicable for analysis of previously collected tissue samples, it could be useful for rapid assessment of intratumoral cellular heterogeneity in multiple disease and treatment settings. [ABSTRACT FROM AUTHOR]

Cellular senescence is one of the important mechanisms of skin aging. In a recent study, we have shown that in patients with dermatoporosis, an extreme senescence condition of the skin, cells positive for p16Ink4a, a biomarker of senescence, were significantly increased in the epidermis. Senescent cells can develop a senescence-associated secretory phenotype (SASP) comprising pro-inflammatory cytokines, chemokines, and other soluble factors, leading to chronic inflammation and tissue dysfunction. These senescent cells and SASP pathways represent therapeutic targets for the development of senotherapeutics either by inducing selective cell death of senescent cells called senolytics, or suppressing markers of the SASP, called senomorphics. In this study where we conducted a retrospective immunohistochemical analysis of p16Ink4a expression in the skin samples of dermatoporosis patients included in a previous clinical study, we describe the senotherapeutic effect of retinaldehyde (RAL) and intermediate-size hyaluronate fragments (HAFi). Topical application of RAL and HAFi significantly reduced the number of p16Ink4a-positive cells in the epidermis and dermis in dermatoporosis patients which also showed a significant clinical improvement. [ABSTRACT FROM AUTHOR]

The Editor-in-Chief of Dermatopathology has announced a new article type called "Clinicopathological Challenge." This article format will present and discuss challenging clinical cases with clinical and histopathological photographs. The article will include sections such as "Case Presentation," "What Is the Diagnosis?," "Diagnosis," and "Discussion." The clinicopathological challenge articles will undergo the same peer review process as regular research articles. This new format aims to be instructive and beneficial for both novice and experienced dermatopathologists. The author invites potential authors to submit manuscripts in this new format. [Extracted from the article]