Pathology of Cowper’s Gland of the Prostate 

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The Cowper’s glands are a pair of small exocrine glands of the male reproductive system, located in the urogenital diaphragm, deeply located at the level of the membranous (or bulbous) urethra, which empty their secretions into the penile urethra each via a small duct. They were initially identified in prostatic transurethral resection specimens as a potential mimic of prostate cancer. They have since been discovered also in prostatic transrectal ultrasound-guided core biopsy specimens, where their occasional occurrence amid skeletal muscle fibers further accentuate their mimicry of prostate cancer. Cowper’s glands are synonymous with bulbourethral glands. ^{[1, 2, 3]}

The Cowper’s gland (bulbourethral gland) is a normal anatomic structure that is rarely present within a transrectal prostatic biopsy. ^[1] An incidence of 0.006% in transrectal prostatic needle biopsies has been reported. ^[2]

The Cowper’s gland (bulbourethral gland) of the prostate is a normal anatomic structure.

The Cowper’s glands (bulbourethral glands) are located in the urogenital diaphragm, posterolateral to the membranous (or bulbous) portion of the penile urethra, below the apex of the prostate.

As these are normal anatomic structures, there are no specific clinicoradiologic features described for the Cowper’s glands (bulbourethral glands).

The Cowper’s glands (bulbourethral glands) are small yellowish glands, measuring up to 1 cm. However, they are usually not identified grossly, especially when encountered incidentally in prostatic specimens.

The Cowper’s glands (bulbourethral glands) can be recognized microscopically as a dimorphic population of mucinous acini and excretory ducts, arranged in a lobular pattern with interspersed fibrous tissue and variable amount of striated muscle bundles (see the image below).

The mucinous acini are lined by columnar cells filled with abundant pale, foamy cytoplasm to the extent of nearly occluding the acinar lumen and contain small basal nuclei without conspicuous nucleoli. Abundant intracytoplasmic mucin may be demonstrable on stains with mucicarmine or periodic acid-Schiff (PAS) with diastase. A layer of myoepithelial cells surrounds each acini, but they are frequently not discerned on hematoxylin & eosin (H&E) sections. Amidst the mucinous acini are excretory ducts lined by low cuboidal cells.

The lining cells are negative for prostatic-specific acid phosphatase (PSAP) and may be negative or focally positive for prostate-specific antigen (PSA). Studies from different centers have yielded different results with respect to the reactivity of the luminal secretory cells to PSA. In needle biopsy specimens studied by Cina et al, 4 of 7 cases of the Cowper’s glands (bulbourethral glands) showed focally heterogeneous clumped staining for PSA, ^[3] whereas 10 Cowper’s gland specimens obtained via autopsy by Saboorian et al were all negative for PSA. ^[4]

The myoepithelial cell layer may be highlighted by stains for high molecular weight keratin, such as 34bE12/p63, and smooth muscle actin.

Immunohistochemistry is useful in distinguishing the Cowper’s glands (bulbourethral glands) from the following:

Mucinous metaplasia of prostatic acini features cells that contain abundant mucin-filled cytoplasm that mimic Cowper’s glands (bulbourethral glands). However, they are usually closely associated with normal prostatic acinar epithelium within the same gland, and they also stain positive for PSA and PSAP. Additionally, mucinous metaplasia usually does not affect the entire lining of the prostatic gland or acinus, and there will be residual secretory prostatic epithelial cells devoid of mucinous changes.

Low-grade prostatic acinar adenocarcinoma can be interpreted erroneously due to the closely packed arrangement of the Cowper’s glands’ (bulbourethral glands) acini. The identification of a dimorphic population of acini and ducts as well as the bland nuclear features should raise the suspicion of a Cowper’s gland (bulbourethral gland). Additionally, Cowper’s glands (bulbourethral glands) are usually found in the vicinity of skeletal muscle fibers. Negative immunostaining for PSA and PSAP would exclude a prostatic origin of these glands.

Note: Foamy gland carcinoma of the prostate is characterized by relatively bland cytomorphologic features, with glands that are lined by cells with xanthomatous cytoplasm and basally located banal nuclei. These resemble the Cowper’s glands (bulbourethral glands) with their ample pale mucinous cytoplasm. It is important that the use of immunohistochemistry in the distinction of the Cowper’s glands (bulbourethral glands) from those of prostatic origin be based on a panel of antibodies rather than a single antibody.

Velazquez EF, Cold CJ, Barreto JE, Cubilla AL. Penis and distal urethra. Mills SE, ed. Histology for Pathologists. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2007. 977.

Epstein JI, Netto GJ. Mimickers of adenocarcinoma of the prostate. Biopsy Interpretation of the Prostate. 4th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008. 138-9.

Cina SJ, Silberman MA, Kahane H, Epstein JI. Diagnosis of Cowper’s glands on prostate needle biopsy. Am J Surg Pathol. 1997 May. 21(5):550-5. [Medline].

Saboorian MH, Huffman H, Ashfaq R, Ayala AG, Ro JY. Distinguishing Cowper’s glands from neoplastic and pseudoneoplastic lesions of prostate: immunohistochemical and ultrastructural studies. Am J Surg Pathol. 1997 Sep. 21(9):1069-74. [Medline].

Ronald Chin-Hong Goh, MBBS Associate Consultant, Department of Pathology, Singapore General Hospital

Disclosure: Nothing to disclose.

Puay-Hoon Tan, MD, MBBS, FRCPA, FRCPath Head, Department of Pathology, Singapore General Hospital

Puay-Hoon Tan, MD, MBBS, FRCPA, FRCPath is a member of the following medical societies: International Society of Urological Pathology

Disclosure: Nothing to disclose.

Liang Cheng, MD Professor of Pathology and Urology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine; Chief, Genitourinary Pathology Service, Indiana University Health

Liang Cheng, MD is a member of the following medical societies: American Association for Cancer Research, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Arthur Purdy Stout Society

Disclosure: Nothing to disclose.

Pathology of Cowper’s Gland of the Prostate 

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