Clinical and pathological predictors of high risk histopathological features in retinoblastoma: Analysis of 236 eyes

Purpose To investigate the association between high-risk histopathological features (HRHFs) and clinical indicators in advanced retinoblastoma and to identify independent predictors of high-risk disease. Methods This single-center retrospective cohort study analyzed 236 enucleated eyes from patients with retinoblastoma treated at a tertiary referral center in Tehran, between 2001 and 2024. Clinical data and histopathological features were extracted. Eyes were classified into low-risk and high-risk groups based on HRHFs. Statistical analyses included univariate and multivariate logistic regression to identify factors independently associated with HRHFs. Results Of the 236 eyes, 58 (24.6%) demonstrated HRHFs. Patients with high-risk tumors were significantly older at diagnosis (31.9 ± 19.2 vs. 22.3 ± 18.9 months, p = 0.017) and enucleation (37.3 ± 24.8 vs. 26.6 ± 23.3 months, p = 0.009). In multivariate analysis, four variables remained independently associated with HRHFs: increasing age at enucleation (OR = 1.015; 95% CI: 1.001–1.029; p = 0.038), higher tumor height (OR = 1.171; 95% CI: 1.073–1.279; p < 0.001), iris neovascularization (OR = 60.12; 95% CI: 6.93–521; p < 0.001), and both exophytic endophytic growth pattern (OR = 11.92; 95% CI: 2.04–70.28; p = 0.006). Rosette subtype, growth pattern, and tumor necrosis were not independently predictive after adjustment. Conclusions Older age at enucleation, iris neovascularization, tumor height, and a combined exophytic endophytic tumor growth patterns are strong independent predictors of high-risk histopathologic features in retinoblastoma. Recognizing these indicators preoperatively may assist in risk stratification and guide treatment choices to enhance outcomes.