Cowper Glands Identified in Prostate and Urethral Specimens: A Comprehensive Immunohistochemical Characterization and Potential Diagnostic Pitfall

Cowper glands recognition remains one of the key histoanatomic benign mimics of prostatic adenocarcinoma. In most instances, these can be identified based on the dimorphic population of lobulated acini and duct(s). However, in the prostate biopsy setting with incomplete/distorted cores, this may not be immediately apparent and may warrant use of immunohistochemistry to argue against prostatic adenocarcinoma. Although immunohistochemical pitfalls in Cowper glands have been described, to our knowledge a comprehensive evaluation of both traditional and purportedly prostate-specific novel markers in Cowper glands has not been previously performed. Herein, we studied the clinicopathological and immunohistochemical features of 21 male patients (age range 39-81 years; mean = 63 years), including 15 prostate biopsies (7 of which also had prostate cancer in the same specimen set and 2 of which had both prostate cancer and Cowper glands in the same biopsy core). Immunohistochemistry showed the following results in Cowper glands: 100% positive for NKX3.1, 100% positive (basal cells) for both high molecular weight keratin and p63, 57% positive for PSAP, 25% positive for PSMA, 5% positive for AMACR, and 0% positive for PSA. In conclusion, for specimens lacking appreciable dimorphic morphology, caution should be rendered when using prostate-specific markers (PSA, PSAP, PSMA, and NKX3.1) as these can show considerable staining in Cowper glands and be a pitfall. Instead, findings from this cohort indicate relying on basal markers (high molecular weight keratin/p63; either individually or in a "cocktail" approach) and PSA are most useful in distinguishing Cowper glands (retained basal cell markers staining) from prostatic adenocarcinoma.