Vitreoretinal Lymphoma: From Pathobiology to Integrated Diagnosis

Vitreoretinal lymphoma (VRL) is a rare, high-grade intraocular malignancy able to mimic intermediate and/or posterior uveitis. Diagnosis is difficult because lymphomatous cells in ocular samples are scarce, fragile and rapidly degraded, particularly after corticosteroid exposure. This review examines how current knowledge of VRL pathobiology is reflected in its clinical, imaging and laboratory features and how these can inform diagnosis. Cytology remains the confirmatory test, while multimodal imaging helps localise vitreous, intraretinal and sub retinal pigmented epithelium (RPE) involvement and guides ocular sampling. Diagnostic yield depends on appropriate sample collection, handling and timely processing. Cytokine and molecular testing, including interleukin-10 (IL-10)/interleukin-6 (IL-6) assessment and detection of recurrent lymphoma-associated alterations such as MYD88 and CD79B, can provide diagnostic support when morphology is inconclusive. We also examine newer approaches designed to increase the information obtained from small-volume ocular samples through quantitative imaging and high-dimensional molecular profiling. The diagnostic value of each test depends on the anatomical distribution of disease and the characteristics of the specimen and is greatest when complementary findings are interpreted together.