Prostatic gland ectopia in the uterine cervix: a diagnostic pitfall – case report

Abstract

Background

The occurrence of ectopic prostatic tissue in the female genital tract is an extremely rare condition, usually discovered incidentally. This anomaly has been reported in various parts of the genital tract, including the uterus, cervix and vagina, and is believed to be related to embryonic remnants or metaplastic alterations of normal tissues. The presence of ectopic prostatic tissue (EPT) in women without hormonal, gonadal or genetic disorders is an uncommon finding. Studies suggest that high levels of androgens may be associated with the development of EPT. Microscopic findings are poorly described, so this paper aims to describe the histopathological and immunohistochemical findings in a rare case of EPT diagnosed in a 39-year-old cisgender woman.

Case presentation

A 36-year-old cisgender female patient, with no comorbidities and no continuous medication use, sought medical care due to a complaint of a “ball sensation in the vagina.” Clinical examination revealed anterior genital prolapse and stage 3 uterine prolapse. The patient underwent a total laparoscopic hysterectomy and prolapse correction. During surgery, foci of endometriosis were found, and the lesions were excised at the same time. Histopathological examinations revealed a small leiomyoma associated with multifocal adenomyosis in the uterine body, a focus of endometriosis in the rectovaginal septum, ulcerated cervical mucosa with moderate chronic inflammation, Naboth cysts, and intraluminal squamous metaplasia in the cervical mucosa. An extensive complementary immunohistochemical study with nine antibodies was required, which was consistent with ectopia of prostatic glands in the cervix.Two months after the surgical intervention, the patient returned for a follow-up evaluation, showing good recovery and reporting no new complaints. Ovarian function was preserved.

Conclusion

This case highlights the importance of considering TPE in the differential diagnosis of cervical lesions. It also provides more detailed information on the pathogenesis and broadens the understanding of the histological alteration in question.

Context

The occurrence of prostatic tissue in the female genital tract is a rare condition, often discovered incidentally (Anderson 2020). It is usually diagnosed in premenopausal women, aged between 21 and 81 (Hawari 2020). This phenomenon has been described in various parts of the genital tract, including the uterus, cervix and vagina. Although the etiology is not completely elucidated, it is believed that ectopic prostatic tissue (EPT) in women without hormonal, gonadal or genetic disorders is an extremely rare finding, possibly related to embryonic remnants or metaplastic alterations of normal tissues (Kelly 2011).

Some studies suggest that the presence of prostatic tissue in the female genital tract may be associated with high levels of androgens (Kelly 2011; Long 2021). In addition, case reports show its occurrence in patients with disorders of sexual development (DSD) and in women who have received testosterone therapy to treat gender dysphoria. The prostate tissue found in these conditions has morphological and immunophenotypical characteristics similar to male prostate tissue, reacting positively to prostate tissue markers (Kelly 2011; Kim 2004).

In women, histopathological findings of cervical, vaginal and ovarian EPT have rarely been reported (McCluggage 2006).6 Although macroscopically the cervix doesn't show any alterations, microscopy shows ducts, glands and acini, and even cribriform structures with squamous differentiation (Hawari 2020).

Its rarity and the possibility of misdiagnosis make it important to report the cases found, so as to improve understanding of the disease and its histopathological characteristics (McCluggage 2006). Therefore, this case report aims to describe the diagnosis of TPE in a 39-year-old female patient and her anatomopathological investigation using macroscopy, microscopy and a broad immunohistochemical panel.

Case presentation

A 39-year-old cisgender female patient, with no previous comorbidities and no history of continuous medication use, presented to the clinic complaining of a “ball sensation in the vagina.” On clinical examination, she was found to have anterior genital prolapse (cystocele) and stage 3 uterine prolapse (when the most distal portion of the prolapse extends more than 1 cm beyond the hymen). She denied abnormal uterine bleeding or any other complaints. Given the advanced stage of the genital prolapse and the fact that she had already completed her desired childbearing, she opted for uterine removal and underwent a total laparoscopic hysterectomy on 02/07/2024, along with uterine prolapse correction using McCall’s culdoplasty. During surgery, endometriotic foci were identified in the rectovaginal septum, and the lesions were excised at the same time. The procedure was uneventful, and the surgical specimen was sent for pathological analysis.

On macroscopic assessment, the specimen weighed 136 g, with a uterus measuring 10.2 × 8.0 × 5.6 cm, with a pyriform shape, the dimensions of the cervix being 4.3 × 4.0 cm on the longest axes. The cervical mucosa showed a brownish, finely granular, ulcerated circular area measuring approximately 2.5 cm. The uterine body had a turbid appearance with congested and prominent vessels in the parametrium. The right fallopian tube was 6.6 cm long and 2.0 cm in diameter, with cystic formations in the serosa, the largest being 0.7 cm in diameter. The left fallopian tube was 6.3 cm long and was preserved for analysis. Extensive samples of the material were taken for histopathological examination.

Microscopic examination diagnosed the presence of a small leiomyoma associated with multifocal adenomyosis in the midst of a proliferative endometrium. The material sent from the recto-vaginal septum showed the presence of a focus of endometriosis in fibromuscular tissue. In addition, ulcerated cervical mucosa was observed, with moderate chronic inflammation in activity, with Naboth cysts and the presence of a cribiform cell group with intra-luminal squamous metaplasia (Fig. 1). The glandular aspect was not compatible with endocervical glands, and a complementary immunohistochemical study was recommended for better cell characterization.

Fig. 1

Ectopic Prostate Glands in the Cervix (Optical Microscopy, Hematoxylin and Eosin, Magnification 40x, 100x, 400x). A Squamous mucosa of the ectocervix showing sparse glandular proliferation in the stroma with a cribiform pattern. B Group of cribiform glands with intra-luminal squamous epithelium. C Highlighted is the double layer of outer (basal) cells with scarce cytoplasm and inner (luminal) cells with abundant clear to eosinophilic cytoplasm and the presence of central squamous metaplasia

An extensive immunohistochemical panel was carried out with nine antibodies: ki67, p16, vimentin, CD10, estrogen receptor (ER), cytokeratin 5/6 (CK 5/6), p63, NKX3.1 and PSMA (Fig. 2). The ki67 (proliferative index) was less than 1% in the cells of interest. The cribiform cell group, in its basal compartment, showed strong and diffuse positivity for NKX3.1 and PSMA, proving its prostatic origin, as well as partially reacting with CD10, Vimentin, p63 and CK 5/6. The p16 was completely negative, while the ER showed positivity in the luminal squamous component. Thus, the histological picture and immunohistochemical profile were consistent with prostate gland ectopia in the uterine cervix.

Fig. 2

Antibodies used to assess prostate gland ectopia in the uterine cervix (light microscopy, immunohistochemistry, 100 × magnification). P63: positivity in basal cells and squamous epithelium; P16: negativity for diffuse and en bloc evaluation; ER alpha EP1: positivity for estrogen receptor in cribiform glands; NKX3.1: strong and diffuse positivity for prostate marker in luminal cells

Two months after the surgical intervention, the patient returned for a follow-up evaluation, showing good recovery and reporting no new complaints. Ovarian function was preserved, and she did not develop early menopause; therefore, hormone replacement therapy was not initiated.

Discussion and conclusions

Ectopic prostatic tissue is a benign glandular and squamous proliferation that usually involves the ectocervix or transformation zone of the uterine cervix, characterized by morphological and immunophenotypical prostatic aspects. It is believed to represent a developmental abnormality due to poorly positioned Skene's glands, androgen-related endocervical gland metaplasia in association with long-standing testosterone use, or even possible derivation from mesone remnants (Nucci 2000; Sinha et al. 2024).

Macroscopically, the cervix usually has no detectable changes. However, in rare cases, it can form a polypoid lesion or mass, mimicking other entities such as leiomyoma (Anderson 2020). Microscopically, ectopic prostate tissue is made up of ducts, glands and acini, sometimes cribriform structures, with squamous differentiation inserted into the cervical stroma and without continuity with the epithelial surface. There is no desmoplastic or inflammatory reaction of the stroma and no myomatous stroma. The glandular component is made up of a double population with outer (basal) cells with scarce cytoplasm with small nuclei, as well as inner (luminal) cells with more abundant cytoplasm, clear to eosinophilic, foamy to granular. Rarely, changes similar to those of Paneth's cells can be observed. The squamous component shows varying 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 similar to hair follicles and microglandular proliferation similar to nephrogenic adenoma (Hawari 2020).

By immunohistochemistry, luminal gland cells are generally positive for prostate-specific antigen (PSA) and prostatic acid phosphatase specific antigen (PSAP)2. NKX3.1 is typically positive and estrogen and progesterone receptors (PR) are negative. CD10, androgen receptor (AR) and alpha-methylacyl-CoA racemase (AMACR) show variable positivity.9 Basal gland cells are positive for 34betaE12 and p63. Squamous cells are negative for PSA and PSAP, but can be positive for AR, ER and PR. p16 is negative (Nucci 2000; Kamaljeet et al. 2017).

The presence of ectopic prostate tissue has been observed in previous cases which suggested that prolonged androgen stimulation in the uterus can induce the development of prostate tissue in the cervix (Sitaraaman 2020). Prostate tissue originates from the periurethral glands, which are formed during the early stages of embryonic development in both sexes. In men, continuous stimulation by androgens causes these glands to proliferate, while in women, the absence of stimulation causes them to shrink. A frequent feature of the cases reported in the literature is the presence of high levels of androgens for prolonged periods, either due to an increase in endogenous production or the use of testosterone therapy (Long 2021). Another study provided evidence of the possible ability of the cervicovaginal epithelium to remain plastic during adulthood, as prostatic metaplasia was frequently observed in transgender male patients who started androgen therapy as adults (Kim 2004).

The differential diagnosis of this entity includes in situ and invasive neoplasms. Human papillomavirus associated with endocervical adenocarcinoma in situ can be ruled out based on the absence of stratified, irregular and hyperchromatic nuclei with the presence of mitotic activity and apoptotic bodies. Adenosquamous carcinoma usually shows infiltrative growth with desmoplastic stromal reaction and cytological atypia. Adenoid basal cell carcinoma also shows infiltrative growth with nests of atypical squamous epithelium close to the epithelial surface, often in association with a high-grade squamous intraepithelial lesion. All three entities show diffuse and block expression of p16 and no reactivity for PSA and PSAP in most cases; however, PSAP and NKX3.1 can be expressed in some basal adenoid carcinomas (Tschaidse 2022).

Given the rarity of the presence of ectopic prostate tissue in women, continuous documentation and analysis of individual cases are essential to better understand this cellular phenomenon, as well as to explore its microscopic characteristics, providing important information on its pathogenesis and alerting pathologists to this possibility in their routine work.