Atypical intraductal proliferation in prostate biopsy — a diagnostic grey zone with clinical implications

Atypical intraductal proliferation (AIP) is considered a borderline lesion, characterized by architectural complexity and cytological atypia greater than that seen in high-grade prostatic intraepithelial neoplasia, but insufficient to fulfil the diagnostic criteria for intraductal carcinoma (IDC). Consequently, AIP remains diagnostically challenging, and the clinical significance of this lesion is still uncertain. Emerging evidence suggests that AIP in prostate biopsy specimens is a strong predictor of unsampled IDC and other adverse pathological features, warranting reconsideration of the AIP role in prostate cancer risk stratification. Results from prospective and molecular studies indicate that AIP frequently coexists with intermediate-risk prostate cancer and shares molecular alterations with IDC, such as PTEN loss and ERG overexpression, reinforcing AIP potential as a marker of occult aggressive disease. Considering the growing emphasis on precision diagnostics and active surveillance in prostate cancer management, understanding the implications of AIP is particularly relevant.