Melanoma of Unknown Primary Origin: A Case Report and Literature Review

Aim: Melanoma of unknown primary origin (MUP) is a rare clinical entity, accounting for approximately 3-4% of all cases of melanoma. It is defined as histologically confirmed metastases of melanoma occurring in the absence of any identifiable primary lesion. Due to its rarity, diagnostic and therapeutic guidelines remain poorly defined. The aim of this literature review of published case reports is to investigate the most commonly affected anatomical sites, the most frequent presenting symptoms, the diagnostic approaches, and the available therapeutic strategies. Case presentation: 81-year-old woman was admitted with a right inguinal mass of unknown origin. Biopsy revealed metastatic melanoma involving the inguinal lymph nodes, with no clinically or radiologically detectable primary lesion. The patient underwent right inguinal-iliac-obturator lymphadenectomy. The postoperative course was uneventful, with no significant medical or surgical complications. Considering the patient's advanced age and overall condition, no adjuvant therapy was administered, and a strategy of active surveillance was adopted. At present, no evidence of disease recurrence has been observed. Results: A total of 94 case reports were included in our review. MUP appears to be more frequent in males than in females. The axillary lymph nodes were the most commonly involved site, followed by the cervical and inguinal lymph nodes. Among extranodal sites, the gastrointestinal tract, particularly the stomach and small bowel, was most frequently affected. Patients with MUP should be managed similarly to those with melanoma of known primary origin (MKP), based on corresponding stage and anatomical involvement. Conclusions: MUP is an uncommon and challenging presentation of metastatic melanoma. Its pathogenesis remains unclear, although several theories, including immune-mediated regression of the primary lesion, have been proposed. MUP should be staged as stage IV disease and treated with the same systemic therapies used for stage IV MKP, including immune checkpoint inhibitors and targeted agents. Prompt recognition and standardized management are crucial to optimizing outcomes in this subset of patients.