Pathology of Cowper's Gland (Bulbourethral Gland) of the Prostate

The Cowper's glands, also known as bulbourethral glands, ^{[1, 2, 3]}  are a pair of small exocrine glands of the male reproductive system, located in the urogenital diaphragm, deeply located posterolateral to the membranous (or bulbous) portion of the urethra, and below the apex of the prostate. The glands 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.

The Cowper's glands (bulbourethral glands) are normal anatomic structures that are rarely present within a transrectal prostatic biopsy. ^[1]  An incidence of less than 0.01% in transrectal prostatic needle biopsies has been reported. ^{[2, 4]}

As these are normal anatomic structures, there are no specific clinicoradiologic features described for the Cowper's glands (bulbourethral glands). ^[4] Pathologic changes rarely arise, although Cowper's glands (bulbourethral glands) may mimic prostatic carcinoma. ^[4]

On occasion, syringoceles (cystic dilatations) of the Cowper's gland duct occur in young boys to adult men. ^{[5, 6, 7]}  Lower urinary tract symptoms (eg, urinary obstruction, urinary tract infection) may ensure or there may be associated complications requiring surgical intervention. ^{[5, 6, 7]} Giant multicystic cystadenoma of Cowper's gland, ^[8]  and a case of adenoid cystic carcinoma of the urethra/Cowper's gland with concurrent high-grade prostatic adenocarcinoma ^[9] have also been reported.

Gross findings

The Cowper's glands (bulbourethral glands) are small yellowish glands, measuring up to 1 cm. ^[4] However, they are usually not identified grossly, especially when encountered incidentally in prostatic specimens.

Microscopic findings

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). ^[4]

Pathology of Cowper's gland of the prostate. This histolgic image depicts Cowper's glands observed in a transrectal ultrasound-guided core biopsy of the prostate. The Cowper's glands comprise mucinous glands with small to absent central lumina, seen just deep to prostatic urethral mucosa. Note the presence of skeletal muscle fibers in the immediate vicinity.

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 of the Cowper's glands (bulbourethral glands) 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. ^[10]

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: This condition 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: This disease 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 to base the use of immunohistochemistry on a panel of antibodies rather than a single antibody in the distinction of the Cowper's glands (bulbourethral glands) from those of prostatic origin.