# An Eye-Opening Approach: Cancer of Unknown Primary Source With Choroidal Metastasis Case Report

**Authors:** Erin Kaser, Vedin Barve, Alexander Blaschke, Constance Fry, Corey Waldman, Sarah Hackman, William Kelly

PMC · DOI: 10.2196/77895 · Interactive Journal of Medical Research · 2026-02-05

## TL;DR

A rare case of choroidal metastasis from an unknown primary cancer was managed with a combination of therapies, leading to long-term disease control.

## Contribution

This case highlights the effectiveness of multimodal treatment for choroidal metastasis in the immunotherapy era.

## Key findings

- Multimodal therapy including immunotherapy and radiation led to durable disease control in a patient with choroidal metastasis.
- Current guidelines lack direction for managing choroidal metastasis in the modern treatment era.
- A multidisciplinary approach can achieve unexpectedly prolonged survival in selected patients.

## Abstract

Choroidal metastases (CM) represent a rare but clinically significant manifestation of systemic malignancy, most frequently from lung cancer.

The choroid’s vascular anatomy allows hematogenous tumor seeding. Although CM may be the first clinical sign of an underlying malignancy, evidence guiding its management in the modern immunotherapy era remains limited, as most published cases predate the widespread use of immune checkpoint-inhibitors.

We describe a 33-year-old male patient presenting with ocular pain and visual disturbance, who was found to have an amelanotic choroidal lesion. Systemic workup revealed small pulmonary nodules and an iliac crest lesion. Sequential biopsies suggested that this was metastatic adenocarcinoma of unknown primary origin, but most likely of lung origin, without actionable mutations or PD-L1 (programmed death-ligand 1) expression. Management required multidisciplinary coordination and included carboplatin, paclitaxel, and pembrolizumab, followed by radiation to the orbit, iliac crest, and mediastinal sites of disease. Unfortunately, he experienced progression while on maintenance immunotherapy with new rib and brain lesions, for which he underwent treatment with platinum, pemetrexed, and bevacizumab with additional radiotherapy. Despite loss of vision in the affected eye, he achieved durable disease control and remains free of radiographic recurrent disease>4 years after diagnosis.

This case illustrates that multimodality salvage strategies—integrating systemic therapy with aggressive local radiation—can provide unexpectedly prolonged survival even after immunotherapy failure. Importantly, current guidelines offer minimal direction on managing CM in this context, and prior case reports do not reflect present-day treatment realities. The key message for clinicians is that CM should not automatically be approached with palliative intent; carefully selected patients may benefit from an oligometastatic strategy that actively targets limited metastatic sites to prolong survival. Our findings underscore the need for ophthalmology, radiation oncology, and medical oncology collaboration when vision-threatening or occult metastatic lesions arise.

For readers, the takeaway is that choroidal metastasis—particularly in the era of immunotherapy—warrants individualized, multidisciplinary evaluation rather than default palliation. Our case demonstrates that coordinated multimodality management can achieve long-term disease control, highlighting a treatment paradigm worth considering for selected patients and calling for updated guidelines that reflect modern therapeutic capabilities.

## Linked entities

- **Proteins:** CD274 (CD274 molecule)
- **Chemicals:** carboplatin (PubChem CID 426756), paclitaxel (PubChem CID 36314), platinum (PubChem CID 23939), pemetrexed (PubChem CID 135410875)
- **Diseases:** cancer (MONDO:0004992), adenocarcinoma (MONDO:0004970), lung cancer (MONDO:0005138)

## Full-text entities

- **Genes:** SLTM (SAFB like transcription modulator) [NCBI Gene 79811] {aka Met}, NKX2-1 (NK2 homeobox 1) [NCBI Gene 7080] {aka BCH, BHC, NK-2, NKX2.1, NKX2A, NMTC1}, ROS1 (ROS proto-oncogene 1, receptor tyrosine kinase) [NCBI Gene 6098] {aka MCF3, ROS, c-ros-1}, KRT7 (keratin 7) [NCBI Gene 3855] {aka CK7, K2C7, K7, SCL}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, RET (ret proto-oncogene) [NCBI Gene 5979] {aka CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, GATA3 (GATA binding protein 3) [NCBI Gene 2625] {aka HDR, HDRS}, TTF1 (transcription termination factor 1) [NCBI Gene 7270] {aka TTF-1, TTF-I}, MLANA (melan-A) [NCBI Gene 2315] {aka MART-1, MART1}, TG (thyroglobulin) [NCBI Gene 7038] {aka AITD3, TGN}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, SYP (synaptophysin) [NCBI Gene 6855] {aka MRX96, MRXSYP, XLID96}, Ttf1 (transcription termination factor, RNA polymerase I) [NCBI Gene 22130] {aka TTF-1, TTF-I}, PAX8 (paired box 8) [NCBI Gene 7849] {aka PAX-8}
- **Diseases:** RUL (MESH:C535682), rib (MESH:C537613), Cancer (MESH:D009369), sinus congestion (MESH:D012852), eye pain (MESH:D058447), lung cancer (MESH:D008175), adenocarcinoma (MESH:D000230), ocular disease (MESH:D005128), retinal pigment epithelium tumor (MESH:D019572), RML (MESH:D008878), blurry vision (MESH:D014786), pulmonary nodules (MESH:D055613), fibrosarcoma (MESH:D005354), NSCLC (MESH:D002289), cataract (MESH:D002386), lytic lesion (MESH:D009059), brain lesions (MESH:D001927), blindness (MESH:D001766), uveal lesion (MESH:D014603), pain (MESH:D010146), CUP (MESH:D009382), pulmonary, breast, and colorectal metastases (MESH:D001943), amelanotic choroidal lesion (MESH:D015862), Choroidal Metastasis (MESH:D009362), crest (MESH:D017675), lymph node (MESH:D000072717)
- **Chemicals:** DOTA-Tyr3-octreotate (-), Paclitaxel (MESH:D017239), capecitabine (MESH:D000069287), Pembrolizumab (MESH:C582435), Bevacizumab (MESH:D000068258), taxane (MESH:C080625), platinum (MESH:D010984), nivolumab (MESH:D000077594), erlotinib (MESH:D000069347), Pemetrexed (MESH:D000068437), carboplatin (MESH:D016190), ipilimumab (MESH:D000074324), gemcitabine (MESH:D000093542)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12875659/full.md

## References

16 references — full list in the complete paper: https://tomesphere.com/paper/PMC12875659/full.md

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Source: https://tomesphere.com/paper/PMC12875659