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Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and comedones. In atypical presentations, histopathology is essential for the diagnosis. We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment. Histopathologically, both cases had classic MF features and shared a peculiar immunophenotype, with positivity for CD25 and FOXP3. Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T‐cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T‐cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF. [ABSTRACT FROM AUTHOR]

Background Merkel cell carcinoma (MCC) is an aggressive malignant neuroendocrine tumour. There are two subsets of MCC, one related to Merkel cell polyomavirus (MCPyV) and the other to ultraviolet radiation (UVR). MCPyV-positive and MCPyV-negative MCCs have been considered to be different tumours, as the former harbour few DNA mutations and are not related to UVR, and the latter usually arise in sun-exposed areas and may be found in conjunction with other keratinocytic tumours, mostly squamous cell carcinomas. Two viral oncoproteins, large T antigen (LT; coded by MCPyV_gp3) and small T antigen (sT; coded by MCPyV_gp4), promote different carcinogenic pathways. Objectives To determine which genes are differentially expressed in MCPyV-positive and MCPyV-negative MCC; to describe the mutational burden and the most frequently mutated genes in both MCC subtypes; and to identify the clinical and molecular factors that may be related to patient survival. Methods Ninety-two patients with a diagnosis of MCC were identified from the medical databases of participating centres. To study gene expression, a customized panel of 172 genes was developed. Gene expression profiling was performed with nCounter technology. For mutational studies, a customized panel of 26 genes was designed. Somatic single nucleotide variants (SNVs) were identified following the GATK Best Practices workflow for somatic mutations. Results The expression of LT enabled the series to be divided into two groups (LT positive, n = 55; LT negative, n = 37). Genes differentially expressed in LT- negative patients were related to epithelial differentiation, especially SOX9 , or proliferation and the cell cycle (MYC , CDK6), among others. Congruently, LT displayed lower expression in SOX9 -positive patients, and differentially expressed genes in SOX9 -positive patients were related to epithelial/squamous differentiation. In LT -positive patients, the mean SNV frequency was 4.3; in LT -negative patients it was 10 (P = 0.03). On multivariate survival analysis, the expression of SNAI1 [hazard ratio (HR) 1.046, 95% confidence interval (CI) 1.007–1.086; P = 0.02] and CDK6 (HR 1.049, 95% CI 1.020–1.080; P = 0.001) were identified as risk factors. Conclusions Tumours with weak LT expression tend to co-express genes related to squamous differentiation and the cell cycle, and to have a higher mutational burden. These findings are congruent with those of earlier studies. [ABSTRACT FROM AUTHOR]

HIV-associated neurocognitive disorders (HAND) affect 15–55% of HIV-positive patients and effective therapies are unavailable. HIV-infected monocyte-derived macrophages (MDM) invade the brain of these individuals, promoting neurotoxicity. We demonstrated an increased expression of cathepsin B (CATB), a lysosomal protease, in monocytes and post-mortem brain tissues of women with HAND. Increased CATB release from HIV-infected MDM leads to neurotoxicity, and their secretion is associated with NF-κB activation, oxidative stress, and lysosomal exocytosis. Cannabinoid receptor 2 (CB2R) agonist, JWH-133, decreases HIV-1 replication, CATB secretion, and neurotoxicity from HIV-infected MDM, but the mechanisms are not entirely understood. We hypothesized that HIV-1 infection upregulates the expression of proteins associated with oxidative stress and that a CB2R agonist could reverse these effects. MDM were isolated from healthy women donors (n = 3), infected with HIV-1ADA, and treated with JWH-133. After 13 days post-infection, cell lysates were labeled by Tandem Mass Tag (TMT) and analyzed by LC/MS/MS quantitative proteomics bioinformatics. While HIV-1 infection upregulated CATB, NF-κB signaling, Nrf2-mediated oxidative stress response, and lysosomal exocytosis, JWH-133 treatment downregulated the expression of the proteins involved in these pathways. Our results suggest that JWH-133 is a potential alternative therapy against HIV-induced neurotoxicity and warrant in vivo studies to test its potential against HAND. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 56-year-old woman with tumor-stage mycosis fungoides (MF) who responded well to a combination treatment of systemic gemcitabine and intralesional brentuximab vedotin (BV). The patient had previously undergone various treatments for MF, but they were ineffective or caused adverse events. Treatment with systemic BV resulted in significant clinical improvement, but the lesions recurred after 8 months. The patient was then treated with systemic gemcitabine and intralesional BV, which led to a marked improvement and resolution of all tumors. The article highlights the safety and efficacy of intralesional BV as a potential treatment option for CD30-positive cutaneous lymphoma with limited lesions. [Extracted from the article]

Simple Summary: Skin lesions in the context of MDS/MPN are frequent and poorly understood in the current literature. This paper thoroughly reviews the dermatoses reported so far in these patients based on their relationship with prognosis and its main clinical, histopathological and genetical features. Different histological patterns and mutations have been described in the literature. However, the true nature of the cells in these cutaneous infiltrates as well as their mutational background and the link with the underlying hematological neoplasm have to be further investigate in order to clarify their biological significance and the main therapeutic implications. A classification proposal is developed with the aim of helping dermatologists, hematologists and pathologists to recognize them when present in these complex patients. The figures and tables included in the text and in the supplemental material facilitate the understanding of each of the proposed categories. In addition, the main publications in which these dermatoses have been previously treated are indicated. Myeloid neoplasms and acute leukemias include different entities that have been recently re-classified taking into account molecular and clinicopathological features. The myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) category comprises a heterogeneous group of hybrid neoplastic myeloid diseases characterized by the co-occurrence of clinical and pathological features of both myelodysplastic and myeloproliferative neoplasms. The most frequent entity in this category is chronic myelomonocytic leukemia (CMML) which is, after acute myeloid leukemia (AML), the main myeloid disorder prone to develop cutaneous manifestations. Skin lesions associated with myelodysplastic and myeloproliferative neoplasms include a broad clinical, histopathological and molecular spectrum of lesions, poorly understood and without a clear-cut classification in the current medical literature. The aim of this review is to describe and classify the main clinical, histopathological and molecular patterns of cutaneous lesions in the setting of MDS/MPN in order to improve the diagnostic skills of the dermatologists, hematologists and pathologists who deal with these patients. [ABSTRACT FROM AUTHOR]