Pre-Biopsy Diagnostic Accuracy for Orbital Lymphoma versus Inflammatory Orbital Disease: A 10-Year Retrospective Study at a UK Tertiary Centre

Purpose: To determine the diagnostic accuracy of pre-biopsy clinical and radiological assessment in differentiating orbital lymphoma from inflammatory orbital disease, and to identify clinical, anatomical, and pathological predictors of diagnostic failure. Methods: A single-center retrospective diagnostic accuracy study (STARD 2015-compliant) of 88 consecutive orbital biopsies was performed at Leeds Teaching Hospitals NHS Trust between January 2014 and December 2024. Cases were classified as lymphoma (n = 36) or inflammatory disease (n = 52) based on histopathology. Index tests were pre-biopsy clinical and radiological impressions. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios were calculated with 95% confidence intervals. Age was evaluated as a continuous discriminator using receiver operating characteristic (ROC) analysis. Presenting features, anatomical compartment, and symptom duration were compared between groups. Results: Clinical assessment achieved sensitivity of 55.6% (95% CI 39.6% - 70.5%) and specificity of 90.4% (95% CI 79.4% - 95.8%). Radiological assessment achieved a sensitivity of 61.1% (95% CI 44.9% - 75.2%) and a specificity of 88.5% (95% CI 77.0% - 94.6%). Age was a strong discriminator (area under the ROC curve 0.874, 95% CI 0.793 - 0.954; p < 0.001); an optimal threshold of ≥55 years yielded sensitivity of 94.4% and NPV of 95.0%. Twelve lymphoma cases (33.3%) were missed by both assessors (false negative [FN]-Both). Extraconal lymphoma had the highest FN-Both rate (44.4%). Proptosis was significantly more prevalent in lymphoma (41.7% vs 17.3%; p = 0.015). Lymphoma cases had a shorter median symptom duration (5 vs 6 months; Mann-Whitney p = 0.008), reflecting the chronic relapsing course of IgG4-related disease and sarcoidosis in the inflammatory group. Four systematic failure patterns were identified. Conclusions: Pre-biopsy assessment reliably raises suspicion of orbital lymphoma when positive but cannot safely exclude it when negative. Age over 55, extraconal location, and proptosis are key risk factors. Orbital biopsy remains indispensable regardless of pre-test impression.