Mucosal Melanoma

Despite treatment with pembrolizumab, the disease progressed rapidly both locally and distantly, necessitating palliative care. This case highlights the persistent challenges in diagnosing oral mucosal melanoma due to its atypical clinical and pathological features, emphasizes the critical role of immunohistochemistry in achieving an accurate diagnosis, and underscores the generally poor prognosis despite current therapeutic options. It also reinforces the importance of early detection and timely multidisciplinary management.

P2, N=25, Recruiting, Eye & ENT Hospital of Fudan University

Primary melanoma subtypes present significant differences in their immune and genomic landscapes, as well as their interactions. Distinct measures of pTMB carry added value compared to standard TMB for identification of tumour-immune associations across primary melanoma subtypes. Our findings indicate that pTMB is a relevant neoantigenicity marker in primary melanoma with the potential to modulate immune infiltration, leading to more aggressive disease.

Only tumor extension was independently associated with disease-free survival (HR: 7.325, 95%CI: 1.316-40.779) but a trend was seen for tumor size (p = 0.078). Our data shows that for primary anal canal melanoma, the anal cancer staging system in combination with the extent of tumor invasion is more adequate for patient stratification.

Patients with germline PVs were more likely to have two or more affected first-degree relatives (49.0% vs. 29.1%, p = 0.019). These findings highlight a meaningful germline contribution to MM risk and support the incorporation of genetic testing in this population.

Responders exhibited higher prevalence of persistent TCR clonotypes and tighter spatial proximity between activated CD4⁺ and CD8⁺ T cells. Although the pre-specified primary endpoint was not met, our findings identify activated CD4+/CD8+ T cell states and TCR persistence as key outcome-associated features, supporting immune-informed optimization of peri-operative therapy in mucosal melanoma.

P2, N=150, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial completion date: Aug 2026 --> Sep 2030 | Trial primary completion date: Aug 2026 --> Jan 2027

Strong agreement: it is recommended to perform systematic regional and remote extension assessment at diagnosis; PET-CT is the gold standard for remote assessment; isolated radiotherapy is not recommended for curative treatment; given the major risk of metastasis and the poor prognosis, alternatives to heavy destructive surgery should be considered in the rare cancer multidisciplinary tumor board; it is recommended to screen for NRAS, BRAF and KIT mutations, to identify possible treatment targets; reference imaging should be performed 3 months after end of treatment, using sinonasal and brain MRI and PET-CT; due to the risk of early recurrence, close follow-up is recommended during the first 2 years, then at least every 6 months up to 5 years postoperatively. Relative agreement: operable sinonasal mucosal melanoma should be treated by total macroscopic resection with negative margins followed by radiotherapy on the tumor bed; postoperative radiotherapy is recommended, to improve local control; neoadjuvant or adjuvant chemotherapy, other than immunotherapy or targeted therapy, is not recommended; for non-resectable and/or metastatic sinonasal mucosal melanoma, immunotherapy is the systematic first-line treatment; prophylactic lymph-node treatment is not recommended in N0 sinonasal mucosal melanoma; lymph-node surgery is recommended in N+ cases without remote metastasis, including cases of regional recurrence.

P2, N=50, Not yet recruiting, Fred Hutchinson Cancer Center

Integrated spatial proteomics and metabolomics reveal response-associated tumor-immune neighborhood architecture, stromal contexts linked to immune exclusion, and altered indole/tryptophan metabolism in the microenvironment. These spatial features nominate biomarkers and therapeutic hypotheses to improve immunotherapy for MuM.

However, the sample size is relatively small and needs to be increased for further research. https://clinicaltrials.gov/study/NCT03986515, identifier NCT03986515.

P1/2, N=67, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2026 --> Apr 2027 | Trial primary completion date: Apr 2026 --> Apr 2027