Atypical intraductal proliferation and intraductal carcinoma of the prostate on core needle biopsy: a comparative clinicopathological and molecular study with a proposal to expand the morphological spectrum of intraductal carcinoma

Aims: Atypical intraductal proliferation (AIP) of the prostate is histologically worse than high-grade prostate intraepithelial neoplasia, but lacks the diagnostic criteria of intraductal carcinoma of the prostate (IDC-P). The aim of this study was to compare the clinicopathological and molecular characteristics (ERG overexpression and PTEN loss) of AIP and IDC-P in core needle biopsies. Methods and results: One hundred and six [84 (5.6%) of 1480 consecutive and 22 retrospectively collected] cases met the criteria: AIP only (2.4%), IDC-P only (1.3%), and IDC-P coexisting with AIP (2%). Invasive adenocarcinoma [prostate adenocarcinoma (PCa)] was present in 96% and 97% cases of AIP and IDC-P, respectively. The mean number of glands/focus and the largest gland diameter for AIP and IDC-P were 7.6 (range, 2–27) and 11.7 (range, 1–51), and 0.59 mm (range, 0.2–1.1 mm) and 0.75 mm (range, 0.2–1.8 mm), respectively. For AIP, loose cribriform architecture was the most common (93%) morphology. IDC-P-associated PCa had more aggressive pathology, including the highest combined Gleason score (GS), high-grade GS ≥ 4 + 3, and largest percentage involvement of core by PCa and percentage positive cores, than AIP-associated PCa (P < 0.05). Within the AIP group, ERG status and PTEN status were similar to those of adjacent PCa in 97% and 88% of cases, respectively. Within the IDC-P group, ERG status and PTEN status were similar among IDC-P, AIP and PCa in 96% and 91% of cases, respectively. PTEN loss was frequently heterogeneous in PCa, and localized adjacent to AIP or IDC-P. Conclusions: AIP represents a lower-grade morphological spectrum of IDC-P, associated with intermediate-risk PCa. Patients with only AIP need an immediate repeat biopsy to rule out clinically significant PCa.