Mucosal melanomas (MMs) are under-researched tumors with a poor prognosis that arise from melanocytes found in the mucous membranes at different anatomical locations throughout the body. MMs are an uncommon yet highly aggressive tumor that typically develops on mucosal surfaces, predominantly in the head and neck region. MM of the head and neck occurs in 8–10% of all head and neck melanomas. It most commonly affects the mucosa of the nasal cavity and paranasal sinuses (75%), followed by the oral cavity mucosa (25%). A family history and the presence of mucosal nevi are associated with the occurrence of MM. Inhaled and dietary carcinogens are also linked to the development of sinonasal melanoma, much like other malignancies of the nasal cavity. Overexpression of the C-KIT gene is found in more than 80% of all primary mucosal melanomas, with somatic mutations in 10–30% of cases. The presence of these genetic alterations is also reflected in recent clinical studies of specific gene inhibitors that have proven efficiency in the systemic therapy of melanoma. There are various treatment modalities for MM. Surgical therapy involves en bloc surgical resection with a macroscopically visible and palpable mucosal margin of 1.5–2 cm. Partial resection of the maxilla may be considered if it ensures adequate tumor-free margine. Because of its rarity, outcome data for locally advanced head and neck MM is limited and primarily derived from retrospective studies with small case numbers. This review aims to update and summarize findings from clinical trials, prospective observational studies, and retrospective studies, while also exploring future directions for multimodal treatment approaches in this area.

Background and Objectives: Squamous cell tumors arise from squamous epithelial cells. Polymorphisms in the FOXP3 gene may influence malignancy susceptibility. This study evaluated the potential association of FOXP3 rs3761548 (−3279 A/C) and rs2280883 (IVS9+459 T/C) polymorphisms with preinvasive and invasive squamous cell tumors of sun-exposed skin, sun-protected vulvar skin, and the ectocervix. Materials and Methods: This comparative observational study included 135 women aged >18 years surgically treated for squamous cell tumors of the skin (actinic keratosis, Bowen’s disease, squamous cell carcinoma), vulva (HSIL, differentiated VIN, squamous cell carcinoma), or ectocervix (LSIL, HSIL, squamous cell carcinoma). Sociodemographic, anthropometric, lifestyle, ultraviolet radiation exposure, reproductive, and sexual health data were collected. The FOXP3 rs3761548 and rs2280883 polymorphisms were genotyped; codominant, dominant, recessive, and overdominant genetic models were evaluated. Results: The three groups differed significantly in several sociodemographic, anthropometric, lifestyle, reproductive, and sexual health characteristics. No significant differences were observed for smoking, sun exposure, history of sunburns, contraceptive use, or history of abortions. The minor A allele frequency of rs3761548 was lower in the skin and vulvar tumor groups and slightly higher in the ectocervical tumor group than in reference populations; however, this difference was not significant (p = 0.066). None of the rs3761548 genetic models remained significant after LASSO regression. For rs2280883, the C allele frequency was lower in the skin and ectocervical groups but higher in the vulvar tumor group than the 46.0% reported in the reference population. The dominant model (CC + CT vs. TT) was associated with lower odds of skin tumors, whereas the recessive model (CC vs. TT + CT) was associated with higher odds (both p = 0.037). Conclusions: The distribution of the FOXP3 rs2280883 polymorphism differed according to tumor location. It was significantly associated with cutaneous squamous cell tumors under both dominant and recessive genetic models.

IGF2-H19 locus is important for normal development and growth, and its deregulation has been implicated in various cancers, with conflicting data in oral cancer. IGF2 and H19 expression was analyzed in oral cancer (SCC-25, SCC-15) and normal keratinocytes (HaCaT) cell lines, as well as in cancer tissue and adjacent non-cancerous tissues from 55 patients with oral cancer. The expression of IGF2 and H19 was increased in oral cancer cell lines compared with control cell line. In clinical samples, expression of the IGF2-H19 locus and its associated hsa-miR-675-5p was significantly lower in cancer tissue compared with adjacent non-cancerous tissue. IGF2, H19, and hsa-miR-675-5p demonstrated moderate ability to discriminate between oral cancer and non-cancerous tissues, while the combined analysis of all three molecules improved diagnostic performance. Our results suggest that IGF2-H19 and hsa-miR-675-5p may have potential as molecular biomarkers for discriminating between oral cancer and non-cancerous tissue, but do not appear to have prognostic value.