Primary malignant melanoma of the parotid gland (PMMPG) is an exceptionally rare neoplasm, comprising less than 0.7% of all parotid malignancies and often mistaken for metastatic melanoma. This case presents a 66-year-old man with a painless, slowly enlarging right parotid mass. Imaging revealed a lesion localized to the superficial parotid lobe with FDG (fluorodeoxyglucose)-avid level II lymph nodes. Fine-needle aspiration suggested melanoma, confirmed by immunohistochemistry. The patient underwent total parotidectomy, neck dissection, adjuvant radiotherapy and immunotherapy with pembrolizumab under ongoing oncologic surveillance. Histopathology confirmed melanoma with nodal metastasis and negative margins, with no evidence of local recurrence at 6-month follow-up. Diagnosis of PMMPG demands exclusion of other primary sites and prior excision history, making immunohistochemistry essential. Treatment typically involves surgical resection and radiotherapy; however, prognosis remains poor due to high recurrence and metastasis rates. PMMPG requires a coordinated, multidisciplinary approach. Although aggressive intervention offers the best outcomes, the long-term prognosis is limited. Continued research is essential, particularly focusing on molecular differentiation from clear cell sarcoma and the identification of specific molecular markers that can guide targeted therapy.

Background: Endometrial carcinoma (EC) is classified into four distinct molecular subgroups including ultramutated DNA polymerase epsilon (POLE). POLE-mutated tumors have the best prognosis and are a promising target for immunotherapy. This meta-analysis consolidated the reported variation of POLE-mutant frequency and assessed prognostic value in EC. Methods: Internet searches explored scientific data bases: EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials databases. Data was extracted from eligible studies including: sample size, number of positive POLE-mutant cases, sequencing information, clinicopathologic data, and survival data. Meta-analysis and a random-effects model produced pooled estimates of POLE frequency and prognostic parameters using 95% confidence intervals (CI), hazard ratios (HR), and odd ratios (OR). Results: Six thousand three hundred and forty-six EC patient cases were pooled from 25 studies. The pooled proportion of POLE gene mutation in EC was 8.59% (95% CI, 7.01 to 10.32), of which 8.22% (95% CI, 6.27 to 10.42) were type I and 0.93% (95% CI, 0.34 to 1.81) type 2. Clinicopathologic data showed that POLE-mutated tumors are mostly endometrioid. They present at higher levels in earlier stages (I–II) of EC (89.51%; 95% CI, 81.11 to 95.66) at the highest grade III (51.53%; 95% CI, 36.08 to 66.84) with reduced myometrial invasion (OR, 1.48, 95% CI, 0.99 to 2.20). Survival analysis indicated favorable overall survival (HR, 0.90), disease-specific survival (HR, 0.41), and progression-free survival (HR, 0.23) for POLE mutant EC. Conclusions Almost one-tenth of EC patients have POLE-mutated tumors. Given their improved prognostic potential, identifying the POLE mutation status is key for the management of EC patients.