Multimodal Management of Isolated Pulmonary Metastasis From Choroidal Melanoma: A Case Report

Choroidal melanoma (CM) is the most common type of uveal melanoma (UM), which represents the most common primary intraocular malignancy in adults, and it is characterized by a high risk of distant metastasis despite adequate local treatment.While the liver is the predominant site of relapse, isolated pulmonary involvement can occur, which represents an uncommon clinical phenotype.We report the case of a 47-year-old woman with late isolated lung metastasis from previously treated CM, diagnosed eight years after primary treatment with episcleral brachytherapy.Comprehensive genomic profiling revealed a high tumor mutational burden (TMB) of 16.5 mutations/Mb and a somatic nonsense neurofibromin 1 (NF1) variant (p.R2637*), in the absence of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation or neuroblastoma RAS viral oncogene homolog (NRAS) mutation, findings atypical for UM.The patient was human leukocyte antigen A02:01 (HLA-A02:01) negative, precluding tebentafusp therapy.She received dual immune checkpoint blockade (nivolumab 1 mg/kg plus ipilimumab 3 mg/kg), experiencing manageable cutaneous and endocrine toxicities.However, she subsequently experienced disease progression.Subsequent management included stereotactic body radiotherapy (SBRT) (45 Gy in five fractions) and cytotoxic chemotherapy with carboplatin area under the curve 5 (AUC 5) and paclitaxel (175 mg/m 2 ), with dose reduction due to toxicity.At 18-month follow-up, the patient remains in surveillance with stable disease.This case underscores the utility of expanded molecular profiling in metastatic choroidal melanoma (mCM) to identify predictive biomarkers and emerging therapeutic targets in a disease with limited standard-ofcare options.