Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted.

Background: Prognostic factors for initial response of advanced cutaneous squamous cell carcinoma to cemiplimab treatment are lacking. Il-6 has been found to affect immune cell populations which impact tumor development. The aim was to investigate the prognostic significance of IL-6 serum levels before and during treatment. Methods: Serum levels of IL-6 were correlated with clinical outcomes in a retrospective study. Results: Overall, 39 patients were enrolled. High serum levels of IL-6 (> 5.6 pg/ml) were associated with poorer survival (45.1% vs 0 deaths; OS: 16.1 ± 1.5 vs 20.8 ± 0 months, 95% CI 13,046 to 19,184) and shorter PFS (10.3 ± 1.9 vs 18.9 ± 1.5 months; 95% CI 3433 to 10,133) in patients with advanced CSCC treated with cemiplimab. In addition, patients whose IL-6 level increased after treatment with cemiplimab, independently of the basal level, had a poorer response to treatment than patients whose level was reduced or stable after immunotherapy. Conclusions: Serum levels of IL-6 at baseline and changes after cemiplimab immunotherapy may have a prognostic significance in patients with advanced cutaneous squamous cell carcinoma.

Checkpoint inhibitors can cause an imbalance in immune tolerance that may clinically manifest as immune-related adverse events (irAEs). These events may involve many organs and tissues, including t...

Purpose of Review: The treatment strategy for BRAF-mutated melanoma remains unsatisfactory, although the advent of immune checkpoint inhibition has improved the prognosis of advanced melanoma. This article reports current evidence on the efficacy and safety of sequential immunotherapy with targeted therapy in patients with BRAF-mutated melanoma. It discusses criteria for the use of available options in clinical practice. Recent Findings: Targeted therapy provides rapid disease control in a relatively high proportion of patients, although the development of secondary resistance limits the duration of responses; in contrast, immunotherapy may induce slow but more durable responses in a subset of patients. Summary: Therefore, the identification of a combination strategy for the use of these therapies seems a promising perspective. Currently, inconsistent data have been obtained, but most studies indicate that the administration of BRAFi/MEKi prior to immune checkpoint inhibitors appears to reduce the efficacy of immunotherapy. On the contrary, several clinical and real-life studies suggest that frontline immunotherapy with subsequent targeted therapy may be associated with better tumor control than immunotherapy alone. Larger clinical studies are ongoing to confirm the efficacy and safety of this sequencing strategy for treating BRAF-mutated melanoma with immunotherapy followed by targeted therapy.

Renal cell carcinoma (RCC) may metastasize to almost any organ, but bowel metastases are highly unusual. A 75-year-old man presented with symptoms and signs of severe anaemia due to bowel bleeding and abdominal pain due to recurrent bowel intussusception. The patient underwent surgery and was identified to have intraluminal metastases from metastatic RCC. To the best of our knowledge, few cases of metastases from RCC manifesting as synchronous intraluminal polypoid tumours have been described in the literature. The present report focused on the importance of two aspects that must be considered: The role of accurate diagnosis and of surgery treating intestinal metastases that may lead to symptom control and prolonged survival.