Hypopigmented mycosis fungoides (HMF) is a form of cutaneous T-cell lymphoma (CTCL), a heterogeneous group of extranodal non-Hodgkin’s lymphomas. HMF has a unique set of defining features that include light colored to achromic lesions, a predilection for darker skin phototypes, an early onset of disease, and predominance of CD8+ T-cells, among others. In the current review, we detail the known pathways of molecular pathogenesis for this lymphoma and posit that an active Th1/cytotoxic antitumor immune response in part explains why this variant is primarily seen in children/adolescents and young adults, who do not exhibit signs of immunosenescence. As a result of this potent cytotoxic response, HMF patients experience mostly favorable overall prognosis, while hypopigmentation may in fact represent a useful surrogate marker of cytotoxic immunity targeting the malignant cells. Understanding the molecular processes behind the specific features that define HMF may lead to improved diagnostic accuracy, personalized prognosis by risk stratification, and improved management of HMF. Moreover, improving our knowledge of HMF may aid our further understanding of other cutaneous lymphomas.

Cancer testis (CT) antigens, under normal circumstances are uniquely expressed in testicular germ cells. Recent research has shown that meiosis-specific CT (meiCT) antigens are ectopically expressed in cutaneous T-cell lymphoma (CTCL) and may contribute to increased genomic instability. The aberrant activation of meiosis genes in a mitotic cell is now recognized as a distinctive process, “meiomitosis.” We have previously demonstrated the ectopic expression of several meiCT antigens in nine patient-derived CTCL cell lines and in expanded peripheral T lymphocytes isolated from Sézary Syndrome patients. In this study we analyzed the transcriptional expression of meiCT genes in Sézary Syndrome patients and healthy controls using publicly-available RNA sequencing (RNA-Seq) data. We corroborated our in silico analysis by examining the expression of 5 meiCT proteins in formalin-fixed, paraffin-embedded (FFPE) lesional samples from CTCL patients. Our results show significant differential gene expression of STAG3, SGO2, SYCP3 , and DMC1 in a cohort of Sézary Syndrome patients when compared to healthy controls. Additionally, our study demonstrates a heterogenous expression of meiCT genes involved in initiation ( STRA8 ), sister chromatin cohesion ( STAG3, SGO2 ), homologous chromosome synapsis ( SYCP3 ) and homologous recombination ( DMC1 ) in atypical lymphocytes in FFPE samples. Our results further confirm the ectopic expression of meiCT genes in CTCL which indicates that CTCL malignant cells likely undergo the process of cancer meiomitosis, as opposed to a typical mitotic division. The ectopic expression of meiCT genes together with investigations into the functional mechanisms of cancer meiomitosis will help provide a foundation to develop novel diagnostic tests to distinguish CTCL from benign inflammatory dermatoses and may enable us to develop additional targeted therapies for patients with this malignancy.

Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi’s sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.

Cancer meiomitosis is defined as the concurrent activation of both mitotic and meiotic machineries in neoplastic cells that confer a selective advantage together with increased genomic instability. MeiCT (meiosis-specific cancer/testis) genes that perform specialized functions in the germline events required for the first meiotic division are ectopically expressed in several cancers. Here we describe the expression profiles of meiCT genes and proteins across a number of cancers and review the proposed mechanisms that increase aneuploidy and elicit reduction division in polyploid cells. These mechanisms are centered on the overexpression and function of meiCT proteins in cancers under various conditions that includes a response to genotoxic stress. Since meiCT genes are transcriptionally repressed in somatic cells, their target offers a promising therapeutic approach with limited toxicity to healthy tissues. Throughout the review, we provide a detailed description of the roles for each gene in the context of meiosis and we discuss proposed functions and outcomes resulting from their ectopic reactivation in cancer.

Basal Cell Carcinoma (BCC) represents the most common form of all cancers. BCC is characteristically surrounded by a fibromyxoid stroma. Previous studies have suggested a shift towards a Th2 response, an increase in T regulatory lymphocytes and the presence of cancer-associated fibroblasts in the BCC tumor microenvironment. In this study, we aimed to further characterize the BCC tumor microenvironment in detail by analyzing BCC RNA-Sequencing data and correlating it with clinically-relevant features via in silico RNA deconvolution. Using immune cell type deconvolution by CIBERSORT, we have identified a brisk lymphocytic infiltration, and more abundant macrophages in BCC tumors compared to normal skin. Using cell type enrichment by xCell, we confirmed the observed immune infiltration in BCC tumors and compared them to normal skin. We observed a shift towards Th2 immunity in advanced and vismodegib-resistant tumors. Tumoral inflammation induced by macrophage activity was associated with advanced BCCs, while lymphocytic infiltration was most significant in nonadvanced tumors, likely related to an adaptive anti-tumoral response. In advanced and vismodegib-resistant BCCs, mesenchymal stem cell-like properties were observed. Particularly in vismodegib-resistant BCCs, fibroblasts and adipocytes were found at high number, which ultimately may contribute to the decreased drug delivery to the tumor. In conclusion, this study has revealed notable BCC tumor microenvironment findings associated with important clinical features. Microenvironment-altering agents may be used locally for "routine" BCCs and systematically for advanced or resistant BCCs.