Merkel cell carcinoma overlapping Bowen's disease: two cases report and literature review.

PURPOSE: Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin, which mainly occurs in the sun exposed sites of white patients over 65 years, with a higher recurrence and metastasis rate. Clinically, MCC overlapping Bowen's disease (BD) is a very rare subtype of MCC. Few cases in the literature have been described and the management is not well defined. We summarize and update the epidemiology, clinical and histopathological features, metastasis characteristics, local recurrence rate and management of it by presenting two cases of MCC overlapping BD and reviewing the literature over the last 11 years. DESIGN: We consulted databases from PubMed, ResearchGate and Google Scholar by MeSh "Merkel cell carcinoma" and "Bowen's disease", "Bowen disease" or "squamous cell carcinoma in situ", from January 2013 to December 2023 and reviewed the literatures. We reported two additional cases. RESULTS: Total 13 cases of MCC overlapping BD were retrospectively analyzed, in whom mainly in elderly women over 70 years, the skin lesions were primarily located on the faces, followed by the extremities and trunk. Most of them were asymptomatic, firm, dark red nodules arising on rapidly growing red or dark brown patches, or presenting as isolated nodules. Dermoscopy evaluation was rarely performed in the pre-operative diagnostic setting. All cases were confirmed by histopathology and immunohistochemistry. The most definitive treatment was extended local excision, but local recurrences were common. Of the 13 cases, 4 cases experienced local or distant metastasis. One suffered from an in-transit recurrence of MCC on the ipsilateral leg after local excision and lymph node dissection, whose metastasis completely subsided after avelumab treatment and without recurrence or metastasis during 6 months of follow-up. CONCLUSIONS: MCC overlapping BD is a very rare skin tumor mainly predisposed on the faces, with high misdiagnosis rate and recurrence rate. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. The acronym, AEIOUN, has been proposed to aid in clinical identification. Our reports and the literature review can provide a better awareness and management of it.

Characteristics influencing high-risk sexual behaviours in elderly men.

With the objective of investigating the characteristics influencing high-risk sexual behaviours in elderly men (60-74 years of age) in Chongqing, China, a total of 1433 healthy elderly men with sexual intercourse frequencies of one to six times/month who were willing to participate in the questionnaires were studied at four hospitals. We measured serum testosterone levels and performed follow-ups every six months, with a total of 1128 elderly men followed up after two years. We also investigated socio-economic and demographic characteristics (age, education, income, location, marital status and number of marriages), types of sexual partners, age differences with fixed sexual partners, frequency of sexual intercourse, combined basic age-related diseases, sexually transmitted infections (STIs) education, elderly self-care ability and high-risk sexual behaviours (frequency of sexual intercourse and number of sexual partners) using questionnaires. We analysed the influencing factors of high-risk sexual behaviours in elderly men using a univariate analysis, multivariate logistic regression analysis, BP neural network prediction and cluster analysis. Finally, we found that serum total testosterone, age, types of sexual partners, age differences with fixed partners and frequency of sexual intercourse are five factors that influence high-risk sexual behaviours in elderly men.

A novel P53/POMC/Gαs/SASH1 autoregulatory feedback loop activates mutated SASH1 to cause pathologic hyperpigmentation.

p53-Transcriptional-regulated proteins interact with a large number of other signal transduction pathways in the cell, and a number of positive and negative autoregulatory feedback loops act upon the p53 response. P53 directly controls the POMC/α-MSH productions induced by ultraviolet (UV) and is associated with UV-independent pathological pigmentation. When identifying the causative gene of dyschromatosis universalis hereditaria (DUH), we found three mutations encoding amino acid substitutions in the gene SAM and SH3 domain containing 1 (SASH1), and SASH1 was associated with guanine nucleotide-binding protein subunit-alpha isoforms short (Gαs). However, the pathological gene and pathological mechanism of DUH remain unknown for about 90 years. We demonstrate that SASH1 is physiologically induced by p53 upon UV stimulation and SASH and p53 is reciprocally induced at physiological and pathophysiological conditions. SASH1 is regulated by a novel p53/POMC/α-MSH/Gαs/SASH1 cascade to mediate melanogenesis. A novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype. Our study demonstrates that a novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype.