Special ArticleDifferential Diagnosis of Intraductal Lesions of the ProstateWobker, Sara E. MD, MPH; Epstein, Jonathan I. MDAuthor Information Departments of *Pathology †Urology ‡Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Jonathan I. Epstein, MD, 401 N. Broadway, Weinberg Building, Room 2242, Baltimore, MD 21231 (e-mail: email@example.com). The American Journal of Surgical Pathology: June 2016 - Volume 40 - Issue 6 - p e67-e82 doi: 10.1097/PAS.0000000000000609 Buy Metrics Abstract The category of intraductal lesions of the prostate includes a range of primary prostatic and nonprostatic processes with wide variation in prognosis and recommended follow-up. Studies have shown that pathologists are uncomfortable with the diagnosis of these lesions and that the diagnostic reproducibility is low in this category. Despite the diagnostic difficulty, their accurate and reproducible diagnosis is critical for patient management. This review aims to highlight the diagnostic criteria, prognosis, and treatment implications of common intraductal lesions of the prostate. It focuses on the recognition of intraductal carcinoma of the prostate (IDC-P) in prostate needle biopsies and how to distinguish it from its common mimickers, including high-grade prostatic intraepithelial neoplasia, invasive cribriform prostatic adenocarcinoma, urothelial carcinoma extending into prostatic ducts, and prostatic ductal adenocarcinoma. IDC-P is independently associated with higher risk disease, and its identification in a needle biopsy, even in the absence of invasive carcinoma, should compel definitive treatment. Conversely, high-grade prostatic intraepithelial neoplasia has a much better prognosis and in limited quantities does not even warrant a repeat biopsy. IDC-P must be distinguished from urothelial carcinoma involving prostatic ducts, as recommended treatment varies markedly. Ductal adenocarcinoma may confuse the pathologist and clinician by overlapping terminology, and morphology may also mimic IDC-P on occasion. The use of ancillary testing with immunohistochemistry and molecular markers has also been reviewed. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.