Metastatic Melanoma in a Retinoblastoma Survivor: Can Immunohistochemistry Save the Day?

Retinoblastoma (Rb) is a rare pediatric ocular malignancy, typically diagnosed before the age of five, with unilateral or bilateral presentation. We report the complex case of a 43-year-old female patient with an oncological family history suggestive of hereditary cancer predisposition syndrome that included multiple malignancies: Rb in her great-grandmother and sister, colonic adenocarcinoma in her grandfather, and pulmonary carcinoma in her father. She was diagnosed with bilateral Rb in childhood and achromic melanoma at the age of 40, with 1.9 mm Breslow thickness, ulceration, and brisk inflammatory infiltrate, staged as pT2b. Furthermore, an axillary lymph node tumor was excised and histologically displayed malignant proliferation of small- to medium-sized cells with high mitotic activity, necrosis, vascular invasion, and neurotropism. Immunohistochemistry was required to determine histogenesis and comprised diffuse p16, SOX10, pan melanoma positivity, mild preferentially expressed antigen in melanoma (PRAME) expression, and negativity for epithelial, neuroendocrine, hematopoietic, and other lineage markers, while Ki-67 was positive in 50% of tumor nuclei. The BRAF mutation testing was negative; therefore, the final diagnosis was cutaneous achromic melanoma with lymph node metastasis, the small-cell type. Retinoblastoma survivors face increased melanoma risk, especially of second cancers. This report highlights the necessity of regular dermatological surveillance and the diagnostic utility of immunohistochemistry in identifying metastases from melanomas occurring in this patient population.