A 31-year-old man presented to an ophthalmologist with a 2-week history of intermittent flashes in both eyes.
The source of the flashes turned out to be a partial retinal detachment secondary to choroidal metastases from a non–small cell lung cancer with an unusual genetic profile, Dr. Rajesh Rao and colleagues reported online in the April issue of the Journal of Clinical Oncology.
Retinal exams of both eyes had revealed yellow, subretinal masses; in the right eye, these showed blocked choroidal fluorescence in the laminar venous plane, consistent with exudative retinal detachment, reported Dr. Rao, an ophthalmologist at the University of Michigan, Ann Arbor, and his coauthors (J. Clin. Oncol. 2014 April 14 [doi:10.1200/JCO.2013.50.2740]).
Two years earlier, the nonsmoking patient had been diagnosed with a stage IV non–small cell lung tumor with regional nodal and rib metastasis. Platinum-based therapy and bevicizumab were ineffective. A genetic evaluation revealed a fusion gene that encodes for the oncogenic EML4-ALK tyrosine kinase.
Dr. Rajesh Rao
The patient immediately started the then-investigational crizotinib, a newly developed small-molecule ALK kinase inhibitor. Although the patient’s lung lesions improved, he developed choroidal and brain metastases within 6 months. The eye lesions were treated with proton beam therapy with partial response. He subsequently died of a pulmonary embolism 1 year after the crizotinib treatment began.
Choroidal metastases are the most common intraocular tumor and often arise from a lung cancer. In this case, fluorescein angiography of the right eye showed early, blocked choroidal fluorescence corresponding to the locations of the subretinal masses. It is tempting to speculate that the vascular characteristics of the metastases found are characteristic of the non–small cell lung cancer EML4-ALK translocation, but larger studies are needed, the investigators said.
The EML4-ALK fusion mutation found in the patient’s lung tumor occurs in 5% of non–small cell lung cancer patients, but is detected six times more often in white nonsmokers or light smokers than in regular smokers. Therefore, any nonsmoking patient who presents with choroidal metastases – with or without a known primary lung tumor – should be tested for the translocation. However, future studies will be needed to demonstrate whether crizotinib represents a new tool to treat ophthalmic complications of ALK-positive cancers, such as neuroblastoma or lung-related orbital and intraocular metastases, exudative retinal detachment, and other pathologic effects, the investigators wrote.
The authors reported no financial conflicts of interest.
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