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This narrative review synthesizes malignancy-related posterior segment findings and proposes a clinically oriented phenotype-to-confirmation framework for multimodal interpretation. A literature search was conducted in PubMed, Scopus, and Web of Science for publications from January 2000 to May 18, 2026. The review included choroidal metastasis, paraneoplastic retinopathies and choroidopathies, vitreoretinal lymphoma, hematologic infiltration, leukemic retinopathy, and anticancer therapy-related toxicity. Owing to heterogeneity in disease entities, imaging protocols, diagnostic confirmation, and study designs, the evidence was synthesized qualitatively. Findings were organized into five suspicion-triggering phenotypes: exudative choroidal mass, RPE-choroidal remodeling, vitreoretinal infiltrative, diffuse neuroretinal dysfunction, and treatment-imprint phenotypes. Each phenotype was linked to its principal mimickers and to appropriate additional investigations, including targeted multimodal imaging, electrophysiology, ocular-fluid analysis, molecular testing, or systemic oncologic reassessment. These phenotypes should not be regarded as validated diagnostic categories, but as clinical entry points for differential exclusion and diagnostic escalation. Artificial intelligence may eventually support image registration, lesion tracking, and longitudinal comparison; however, its role in these rare and heterogeneous disorders remains investigational.<\/jats:p>","DOI":"10.3389\/fopht.2026.1917738","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:22:06Z","timestamp":1790594526000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Posterior segment imaging clues to systemic malignancy: a phenotype-to-confirmation narrative review"],"prefix":"10.3389","volume":"6","author":[{"given":"Nikola","family":"Denda","sequence":"first","affiliation":[{"name":"Eye Clinic, University Clinical Center of Vojvodina","place":["Novi Sad, Serbia"]},{"name":"Faculty of Medicine, University of Novi Sad","place":["Novi Sad, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofija","family":"Davidovi\u0107 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