Aqueous humor cytology may provide a less invasive approach in diagnosing iris metastasis from lung adenocarcinoma without tissue biopsy in selected patients.
Researchers described a 56-year-old male patient with EGFR-mutated lung adenocarcinoma previously treated with osimertinib who was referred for decreased vision and elevated intraocular pressure (IOP) in the right eye. At presentation, IOP was 48 mmHg in the right eye vs. 15 mmHg in the left eye. Examination showed corneal edema, anterior chamber inflammation, fixed mydriasis, and multiple elevated white iris nodules, with no apparent retinal or choroidal involvement.
Aqueous humor obtained through anterior chamber paracentesis showed cohesive clusters and isolated atypical glandular epithelial cells with marked nuclear pleomorphism, prominent nucleoli, and evidence of glandular differentiation. The cytologic findings, classified as Class V, were consistent with metastatic adenocarcinoma. The researchers established the diagnosis of iris metastasis based on aqueous humor cytology without iris biopsy.
The ocular presentation occurred while the patient's systemic disease appeared clinically stable, with no new or progressive metastatic lesions evident at that time. Following the cytologic diagnosis, systemic restaging with contrast-enhanced computed tomography of the chest and abdomen and brain magnetic resonance imaging demonstrated multiple bone metastases involving the spine, sacrum, pelvis, bilateral humeri, bilateral femora, bilateral scapulae, and sternum.
The patient required treatment for tumor-associated secondary glaucoma. Initial therapy included topical antiglaucoma medications and oral acetazolamide. Phacoemulsification with intraocular lens implantation and microhook trabeculotomy performed 5 days postpresentation temporarily reduced IOP to 6 to 10 mmHg, but IOP subsequently increased to 50 mmHg despite maximal treatment. The patient underwent 3 sessions of transscleral cyclophotocoagulation. Following development of rubeosis iridis, he received 2 intravitreal injections of aflibercept for iris neovascularization.
During follow-up, the iris tumors progressed slowly while visual function and ocular comfort remained sufficiently stable that enucleation was not required. About 8 months following the initial visit, multiple white nodules developed on the left iris, consistent with contralateral metastatic involvement. The patient died from systemic progression of lung cancer 9 months following his initial ophthalmologic presentation.
Aqueous humor cytology can yield false-negative results depending on tumor burden, sampling volume, and the degree of tumor-cell exfoliation. Therefore, negative cytology does not exclude metastatic disease. When clinical suspicion remains high, particularly in patients with iris nodules, refractory inflammation, or secondary glaucoma, repeat sampling, iris tissue biopsy, and systemic restaging should be considered. Because the report involved a single patient, larger case series and prospective studies are needed to determine the sensitivity and specificity of aqueous humor cytology for epithelial malignancies.
“Cytologic analysis of the aqueous humor can serve as a valuable diagnostic alternative to biopsy and should be considered in appropriate clinical contexts,” wrote lead study author Atsushi Okubo, of the University of Tokyo and Japanese Red Cross Saitama Hospital, and colleagues.
The study authors reported no conflicts of interest.
