S5807 The Eye That Struck the Liver: A Rare Case of Uveal Melanoma Presenting as a Solitary Hepatic Mass

Introduction: Uveal melanoma is a rare but distinct subtype of melanoma with a marked predilection for hepatic metastasis. Unlike cutaneous melanoma, it follows a unique molecular and metastatic profile, often confounding the diagnosis when a primary lesion is not evident. Here we present a rare case of presumed uveal melanoma discovered incidentally as an isolated hepatic mass in a patient without prior melanoma history or detectable primary lesion. Case Description/Methods: A 58-year-old man with history of celiac disease was noted to have elevated aspartate aminotransferase/alanine aminotransferase and microcytic anemia (Hb 12.9 g/dL). Workup revealed an 8 cm hepatic mass on MRI. Core biopsy confirmed metastatic melanoma. The patient denied prior cutaneous or mucosal lesions. Colonoscopy and dermatologic total body skin exam were unremarkable. Ophthalmologic evaluation was initiated, though no classic GNAQ or GNA11 mutations were found on early molecular profiling. CT CAP and MRI brain showed no other significant disease. Given the liver-only pattern of metastasis and absence of cutaneous/mucosal primaries, the diagnosis of GNAQ/GNA11-wild-type uveal melanoma was favored. The patient was enrolled in an immunotherapy trial. Discussion: Over 90% of uveal melanomas metastasize to the liver, making it the principal site of distant disease. This hepatic tropism is so specific that isolated liver involvement in a melanoma of unknown primary often implicates a uveal origin—even without a detected ocular lesion. While GNAQ and GNA11 mutations are present in ∼83%–95% of uveal melanomas, a small but meaningful subset (∼5%–17%) is wild-type for both. These cases may harbor alternative mutations (CYSLTR2, PLCB4, EIF1AX, SF3B1) or none at all, underscoring the diagnostic difficulty. Importantly, absence of GNAQ/GNA11 does not exclude uveal origin, especially in patients lacking skin or mucosal findings. The absence of ocular findings may reflect a regressed or undetected primary tumor, a phenomenon seen in rare metastatic uveal melanoma cases. Primary hepatic melanoma remains a theoretical possibility but lacks convincing evidence and is considered vanishingly rare. This case highlights the diagnostic nuances of hepatic melanoma metastases in the absence of cutaneous or mucosal primaries, particularly in GNAQ/GNA11-negative disease. It emphasizes the need for high clinical suspicion, interdisciplinary collaboration, and consideration of uveal melanoma in solitary liver lesions, even when conventional genetic markers are absent.