Metastatic Melanoma with an Unknown Primary Origin Presenting with Postmenopausal Bleeding: A Case Report.

Background and Clinical Significance: Melanoma is predominantly a cutaneous malignancy, whereas metastatic involvement of the endometrium is exceptionally rare. Melanoma of unknown primary (MUP) accounts for a small portion of such cases. Patients typically present with abnormal uterine bleeding, and diagnosis can be challenging because metastatic melanoma can mimic other uterine malignancies. We report a rare case of MUP presenting with synchronous endometrial and subcutaneous metastases, a combination not previously reported in the literature. Case Presentation: A multiparous woman in her seventies presented with persistent postmenopausal bleeding. Transvaginal ultrasonography demonstrated endometrial thickening, and endometrial biopsy revealed metastatic melanoma confirmed by immunohistochemical positivity for S100, SOX10, HMB-45, and Melan-A. Positron emission tomography-computed tomography identified fluorodeoxyglucose uptake in the uterine corpus and a metabolically active subcutaneous lesion in the right anterolateral abdominal wall. Surgical excision of the abdominal lesion confirmed metastatic melanoma. Despite extensive investigations, including dermatological examination, ophthalmological assessment, and imaging studies, no primary tumor was identified. The patient underwent hysterectomy followed by adjuvant nivolumab. At 24-month follow-up, no evidence of disease recurrence was detected. Conclusions: Endometrial metastasis of melanoma may occur in the absence of an identifiable primary lesion and should be considered in patients presenting with abnormal uterine bleeding, particularly those with a history of melanoma or unexplained metastatic disease. Because these lesions frequently present as polypoid, nodular, or infiltrative endometrial masses, prompt hysteroscopy and endometrial sampling are essential for diagnosis. This case highlights the importance of comprehensive histopathological evaluation and multidisciplinary management in rare presentations of metastatic melanoma.