Primary Anorectal Melanoma: Report of Two Cases of a Very Rare Disease

Primary anorectal melanoma (PAM) is a rare and aggressive malignancy accounting for less than 1% of anorectal cancers and 1–3% of all melanomas. It typically presents with non-specific symptoms such as rectal bleeding, anal pain, and weight loss, often leading to delayed diagnosis. We report two clinical cases of PAM: the first in a 52-year-old man with advanced disease and poor response to immunotherapy, and the second in a 73-year-old woman treated with chemoradiotherapy due to surgical ineligibility. Diagnosis in both cases was confirmed by histopathological and immunohistochemical analyses (S100 and HMB45 positivity). Imaging revealed locally advanced tumors without initial distant metastases. These cases highlight the diagnostic challenges and lack of standardized therapeutic protocols in PAM. While surgical excision remains the mainstay of treatment, the roles of chemotherapy, radiotherapy, and immunotherapy are evolving and not yet fully established. Prognosis remains poor, with high metastatic potential and low survival rates. This report underscores the need for heightened clinical awareness and further research to optimize the management of this rare malignancy.