Intraductal Carcinoma of the Prostate: Extreme Nuclear Size Is Not a Diagnostic Parameter

High-grade prostatic adenocarcinoma involving duct/acinar structures is labeled intraductal carcinoma of the prostate (IDCP). As numerous studies have shown that IDCP is associated with high stage disease with a significant negative impact on cancer-specific survival, accurate diagnosis is crucial to ensure appropriate patient management. The definition of IDCP recommended by 2016 World Health Organization (WHO) classification suggests that cases of IDCP with micropapillary or loose cribriform architecture without comedonecrosis should have cells with ≥6× nuclear enlargement. It is unclear how this size criterion was derived and which of the parameters of nuclear size (nuclear diameter, nuclear surface area, or nuclear perimeter) it relates to. To evaluate the extent of nuclear enlargement in IDCP, we performed morphometric analyses relating to each of these parameters in 100 radical prostatectomy specimens. One hundred nuclei from foci of IDCP and 50 nuclei from foci of normal luminal epithelium were examined for each patient. Diagnosis of IDCP was based on cells with definite features of carcinoma present within duct/acinar structures. Comparing the means of each of the parameters between IDCP cells and benign luminal cells, there was a statistically significant enlargement in nuclear perimeter (P<0.0005), nuclear area (P<0.0005), and nuclear diameter (P<0.0005); however, the difference in mean nuclear size was limited to factors of 1.3×, 1.6×, and 1.3×, respectively. Three patients each had rare large nuclei (largest perimeter 45, 45, and 44 μm; maximum nuclear area 135, 136, and 136 μm2; and the largest diameter 18 µm in each). For these rare cells, the nuclear size difference, when compared with benign nuclei was; nuclear perimeter 2.0×, 2.1×, and 2.1×; nuclear area 3.6×, 3.8×, and 3.8×; and nuclear maximum diameter 3.0×, 2.5×, and 2.5×. The definition of nuclear enlargement of ≥6× was not reached in any of our cases, all of which clearly showed features of duct invasive carcinoma. In these cases, reliance on nuclear size criteria would have resulted in underdiagnosis of IDCP. This is of concern as failure to recognize IDCP, particularly in needle biopsies, could lead to delays in the timely treatment of aggressive high-grade prostate cancer, resulting in cancer progression and suboptimal patient oncological outcomes.