S6412 From Indeterminate to Invasive: A Perisplenic Nodule Unveils Metastatic Melanoma of Unknown Primary Following Brain Metastases

Introduction: Melanoma of unknown primary (MUP) is a rare clinical entity. Visceral metastases as the initial finding are uncommon- and splenic involvement is particularly rare. We present a case of MUP in which a slowly enlarging perisplenic nodule, initially thought to be benign, preceded the development of hemorrhagic brain metastases. This case underscores the diagnostic challenges of indeterminate visceral lesions and highlights the need for early evaluation in high-risk anatomical sites. Case Description/Methods: A 75-year-old man with history of hepatocellular carcinoma (HCC) post resection and cirrhosis from hepatitis C (treated with ledipasvir/sofosbuvir) presented with stroke-like symptoms. Magnetic resonance imaging (MRI) of the brain confirmed findings of hemorrhagic metastatic disease. A concurrent computed tomography (CT) abdomen and pelvis was largely unremarkable, aside from a subtle increase in size of an indeterminate perisplenic nodule, now measuring 1.4 cm, described as likely containing hemorrhagic debris. This lesion had measured 1.1 cm on previous imaging studies done 11 and 6 months prior. The lesion had signal characteristics similar to the splenic parenchyma. MRI of the abdomen 3 weeks later showed growth to 2.4 cm with mild rim enhancement. Positron emission tompgraphy-CT demonstrated borderline FDG uptake in the lesion with no other suspicious findings. The patient subsequently underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the perisplenic lesion. Histopathology was positive for S100, HMB-45, MART-1, and SOX10, confirming the diagnosis of metastatic melanoma. Dermatologic and ophthalmologic evaluations revealed no primary lesions. He was referred to Radiation Oncology and began stereotactic brain radiotherapy. Discussion: This patient presented with intracranial hemorrhage and was found to have coincident progression of a hemorrhagic perisplenic lesion. While metastatic HCC was initially considered, recent imaging had shown no hepatic recurrence, and HCC rarely metastasizes to the brain. The final diagnosis of MUP was made following biopsy of the splenic lesion. This case underscores the diagnostic complexity of MUP and illustrates how a slowly enlarging, hemorrhagic perisplenic lesion—initially considered benign or indeterminate—can precede aggressive metastatic spread. It highlights the importance of early biopsy of indeterminate visceral lesions with increased size or metastases.