Intraductal carcinoma of the prostate: A comprehensive literature review focused on grading challenges and controversies.

Intraductal carcinoma of the prostate (IDC-P) is characterized by neoplastic cell proliferation within pre-existing ducts or acini, exhibiting architectural and cytological atypia exceeding that of high-grade prostatic intraepithelial neoplasia. Its presence in needle biopsies and prostatectomies is associated with adverse clinical and pathological features, including large tumor volume, high grade, advanced stage, early biochemical recurrence, and intrinsic resistance to systemic therapy. Although rare, IDC-P can occasionally occur without concurrent invasive cancer or be associated with low-grade prostate cancer. Molecularly, IDC-P resembles its associated invasive carcinoma, sharing alterations typical of high-grade aggressive tumors. These findings support the hypothesis that IDC-P arises from the retrograde spread of invasive carcinoma, with ducts providing a protective niche against the tumor microenvironment. In contrast, isolated IDC-P and IDC-P associated with low-grade invasive carcinoma may represent precursor lesions. IDC-P must be distinguished from other intraductal lesions, both benign and malignant, particularly in needle biopsies, as its detection impacts therapeutic decisions. While grading does not apply to isolated IDC-P, there is an ongoing debate regarding IDC-P with synchronous invasive cancer. The International Society of Urological Pathology (2019) recommends incorporating IDC-P into Gleason score calculations, whereas the Genitourinary Pathology Society advises against grading it at all. Both approaches have merit, but further validation studies focusing on cases where IDC-P inclusion alters the final grade, though uncommon, are warranted.