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22 December 2023 - Case of the Month #534

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Thanks to Dr. Gulisa Turashvili, Emory University School of Medicine, Atlanta, Georgia, USA for contributing this case and discussion and to Dr. Stephanie Skala, University of Michigan, Ann Arbor, Michigan, USA for reviewing the discussion.





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Case of the Month #534

Clinical history:
A 46 year old woman underwent a total hysterectomy for uterine leiomyomas. A representative section of the grossly unremarkable cervix showed the following findings.

Microscopic images:



What is your diagnosis?

Click here for diagnosis, test question and discussion:


Diagnosis: Ectopic prostate tissue


Test question (answer at the end):
What is the most common clinical manifestation of ectopic prostate tissue involving the cervix?

  1. Abnormal bleeding
  2. Asymptomatic
  3. Exophytic mass
  4. Ulceration


Stains:
NKX3.1

NKX3.1



Discussion:
Ectopic prostate tissue is a benign glandular and squamous proliferation usually involving the ectocervix or transformation zone and characterized by morphologic and immunophenotypic features of prostate tissue. It is thought to represent a developmental abnormality due to misplaced Skene glands, androgen related metaplasia of endocervical glands due to association with longstanding testosterone therapy or possible derivation from mesonephric remnants (Am J Surg Pathol 2006;30:209, Int J Gynecol Pathol 2017;36:328). Most patients are premenopausal and the reported age ranges from 21 to 81 years (Int J Gynecol Pathol 2011;30:605). The majority of cases are incidental and diagnosed in hysterectomies or cervical excisions performed for other indications, although abnormal bleeding may rarely occur. Ectopic prostate tissue has an excellent prognosis and does not require treatment.

Macroscopically, the cervix is typically unremarkable. However, in rare cases ectopic prostate tissue may form a polypoid lesion or mass, mimicking other entities such as leiomyoma (Am J Surg Pathol 2000;24:1224). Polypoid forms of ectopic prostate tissue involving the vagina have been termed tubulosquamous polyp. Microscopically, ectopic prostate tissue is composed of ducts, glands and acini, sometimes cribriform structures, with squamous differentiation set in the cervical stroma and lacking continuity with surface epithelium. There is no stromal desmoplastic or inflammatory reaction and no myomatous stroma. The glandular component is comprised of a double cell layer with outer (basal) cells with scant cytoplasm and small bland nuclei and inner (luminal) cells with more abundant clear to eosinophilic, foamy to granular cytoplasm and small bland nuclei. Rarely, Paneth cell-like changes may be seen. The squamous cells exhibit variable degrees of maturation and glycogenation with eosinophilic to clear cytoplasm and small nuclei with smooth contours and dispersed chromatin. Rare findings include sebaceous glands, basaloid formations resembling hair follicles and microglandular proliferation resembling nephrogenic adenoma (Int J Gynecol Pathol 2011;30:605).

By immunohistochemistry, the luminal glandular cells are usually positive for prostate specific antigen (PSA) and prostate specific acid phosphatase (PSAP), which may be focal. Of note, 50% of cases may be positive for only one marker and 25% may be negative for both markers (Int J Gynecol Pathol 2011;30:605). NKX3.1 is typically positive and estrogen and progesterone receptors (ER, PR) are negative. CD10, androgen receptor (AR) and alpha-methylacyl-CoA racemase (AMACR) show variable positivity (Am J Surg Pathol 2006;30:209). The basal glandular cells are positive for 34betaE12 and p63 (Am J Surg Pathol 2000;24:1224, Am J Surg Pathol 2006;30:209). The squamous cells are negative for PSA and PSAP but may be positive for AR, ER and PR. p16 is negative to focally positive.

The differential diagnosis of ectopic prostate tissue includes in situ and invasive neoplasms. Human papillomavirus associated endocervical adenocarcinoma in situ can be ruled out based on the absence of stratified, irregular, hyperchromatic nuclei with mitotic figures and apoptotic bodies. Adenosquamous carcinoma usually shows infiltrative growth with stromal desmoplastic reaction and cytologic atypia. Adenoid basal carcinoma also demonstrates infiltrative growth with nests of atypical squamous epithelium close to epithelial surface and basaloid nests with bland cytology deeper into the cervical wall, often in association with high grade squamous intraepithelial lesion. All three entities show diffuse, block-like expression of p16 and no reactivity for PSA and PSAP in most cases; however, PSAP and NKX3.1 may be expressed in some adenoid basal carcinomas (Int J Gynecol Pathol 2021;40:400).

Test question answer:
B. Asymptomatic


Image 01 Image 02