Management and sequelae of a local skene's gland adenocarcinoma recurrence

Abstract

Background

Primary adenocarcinoma of the Skene's gland is exceedingly rare, with only about two dozen well-documented cases in medical literature. Its immunophenotypic similarities to colorectal and prostatic adenocarcinoma create diagnostic challenges, and optimal management remains undefined. Treatment of recurrent disease is individualized and relies on little data to guide management.

Case

A 62-year-old woman presented in 2017 with a periurethral mass diagnosed as moderately differentiated Skene's gland adenocarcinoma, demonstrating a gastrointestinal-type immunophenotype (CK20+, CDX2+, p53+, PSA focal+, partially CK7 and p16+, ER/PR–, PAX8–). She achieved complete clinical response after definitive chemoradiation with cisplatin in 2018. Biopsy-confirmed local recurrence was identified in 2020 with exam suggestive of fixation to the pubic bone, prompting interstitial high-dose-rate brachytherapy. Clinical presentation and subsequent imaging revealed progressive destructive changes of the pubic symphysis, a large pelvic abscess, and septic osteomyelitis. After treatment with antibiotics, subsequent MRI and PET findings suggested chronic osteomyelitis and radiation-induced necrosis. The patient underwent anterior pelvic exenteration with cystectomy, resection of the pubic symphysis, neovagina creation and ileal conduit urinary diversion. Her postoperative course was complicated by small-bowel obstruction, C. difficile colitis, hydronephrosis, nephrolithiasis, chronic kidney disease, and a right lower extremity DVT. At five-year follow-up, she remains alive with no evidence of disease.

Conclusion

This case demonstrates the diagnostic complexity of locally recurrent Skene's gland adenocarcinoma in the context of prior radiation and the curative potential of re-irradiation which ultimately necessitated an anterior exenteration in this case. Multidisciplinary evaluation is essential when managing periurethral malignancies in a previously irradiated pelvis.

Highlights

• •Skene's gland adenocarcinoma is a rare periurethral malignancy with histologic overlap with colorectal and prostate cancer.
• •Curative intent re-irradiation can be considered if resection is not feasible in recurrent Skene’'s gland adenocarcinoma.
• •Re-irradiation with curative intent can lead to significant adverse events that may require surgical resection.

1. Introduction

Primary adenocarcinoma of the Skene's gland is exceedingly rare with only a small number of well documented cases in the literature. The Skene's glands, also known as the female periurethral glands, are homologous to the male prostate and may express prostate related markers such as prostate specific antigen (PSA) or prostatic acid phosphatase (PAP) in both normal and neoplastic tissue (Roberts et al., 2000). Because of their periurethral location and small size, neoplasms arising in these glands often present late and may be misdiagnosed initially as urethral diverticula, vaginal wall masses, or benign periurethral cysts (Zuo and Napoe, 2023).

Histologically, Skene's gland adenocarcinomas demonstrate a markedly heterogeneous immunophenotype. Some tumors resemble prostatic acinar adenocarcinoma (PSA+, NKX3.1+, AMACR+), whereas others show enteric (colorectal type) differentiation (CK20+, CDX2+, MUC2+, CK7−), or mixed features including mucinous or signet ring cell components (Sugawara et al., 2023). This overlapping immuno-profile often creates diagnostic confusion with primary colorectal, prostatic, or Müllerian adenocarcinomas, making careful histopathologic analysis essential for accurate diagnosis (Giri, 2009).

Due to its rarity, there are no standardized treatment guidelines for Skene's gland carcinoma. Management strategies have historically been extrapolated from urethral, vaginal, and periurethral cancers and include local excision, partial urethrectomy, anterior exenteration, radiation therapy (external beam or brachytherapy), and systemic chemotherapy (Gakis et al., 2020). A case series published in 2018 described four patients treated with limited resections, with variable follow up, while a 2022 systematic review identified 15 published cases, noting that local excision remains the most common initial therapy, although radical resection and radiation have also been employed (Ferris et al., 2018).

Recurrent disease presents unique challenges. Because recurrent tumor may arise in a previously irradiated field, distinguishing between recurrence, radiation-induced fibrosis or necrosis, or chronic infection (such as osteomyelitis) becomes difficult both clinically and radiographically. (Elgendy et al., 2024) To our knowledge, this is the first case report to comment on the management and outcome of a locally recurrent skene's gland adenocarcinoma.

2. Case presentation

A 62-year-old woman presented in December 2017 with several months of periurethral pressure and was found to have a left-sided periurethral lesion. An examination under anesthesia identified a firm, irregular mass with biopsy demonstrating a moderately differentiated adenocarcinoma positive for CK20, CDX2, and p53, with partial CK7 and p16 expression, and negative for ER, PR, and PAX8. This immunohistochemical pattern, suggestive of gastrointestinal adenocarcinoma, was considered consistent with a Skene's gland primary based on anatomic location and tumor morphology. Imaging showed no evidence of metastatic disease.

Through shared decision-making with the patient and multidisciplinary care team, concurrent chemoradiation was chosen as a bladder-sparing approach to treatment. It was thought that surgical management carried a substantial risk of post-operative urinary incontinence due to the size and location of the tumor. The patient underwent definitive chemoradiation beginning in April 2018 and received 45 GY in 25 fractions of external beam radiation therapy to the pelvis and boost to the Skene's gland tumor of 14 GY in 7 fractions (total 59 Gy in 32 fractions), administered with weekly cisplatin 40 mg/m². She tolerated treatment well and achieved a complete clinical and radiographic response.

In February 2020, she developed urinary hesitancy and vaginal spotting. Pelvic examination identified a recurrent lesion involving the anterior vaginal wall beneath the mid-urethra, thought to be fixed to the anterior pubic ramus. Core biopsy demonstrated moderately differentiated adenocarcinoma consistent with recurrence of her original disease. PET/CT showed no distant disease but confirmed a hypermetabolic periurethral lesion.

Due to the fixed nature of the lesion and perceived inoperability, she was referred for salvage high dose-rate interstitial brachytherapy at a tertiary cancer center. The applicator insertion was performed in an intraoperative MRI-guided suite. While under general anesthesia, a 6 cm tandem was inserted into a uterus. A split-obturator was then placed around the tandem within the vagina. A template was placed over the obturator and secured to the perineum. Following this, 18 interstitial catheters were placed around the obturator and the peri-urethral region. An MRI scan was obtained, and catheter adjustments were made to ensure complete coverage of the mass. Once the final MRI scan was obtained, a CT scan was obtained. The patient was then extubated. Over the next 4 days, she received a prescription dose of 42 Gy in seven fractions to the vaginal tumor. The high-risk clinical target volume (CTV) D90 (minimum dose received by 90% of the tumor) was 107% of the prescription dose. The rectum D2cc (maximum received by 2 cc of the rectum) and bladder D2cc were 30% and 73% of the prescription dose, respectively. The urethra D0.1 cc was 125.0%. MRI treatment-planning images are shown in the Fig. 1. As shown in Fig. 1b, the pubic bone contacted the most inferior portion of the high-risk CTV.

Fig. 1.

Axial (a) and sagittal (b) MRI T2-treatment planning images of the interstitial implant. The target volume is highlighted as a blue shade. Interstitial needles are placed within the target volume. The 100% isodose line (6 Gy) is represented by the thick yellow line. Other isodose lines include 150% (red), 125% (green), 115% (light blue), 90% (orange), 75% (purple), and 50% (green). In (a), the Foley catheter and vaginal obturator are highlighted by the orange and green arrows, respectively. In (b), the pubic bone is highlighted by the blue arrow.

Follow-up MRI in August 2020 demonstrated interval reduction in the mass, with decreased enhancement and restricted diffusion consistent with treatment response. In November 2020, the patient developed new, severe pubic and pelvic pain, difficulty ambulating, and subjective fevers. MRI revealed septic arthritis of the pubic symphysis with emphysematous joint effusion, extensive surrounding myositis, and a 7.0 × 2.8 × 5.7 cm rim-enhancing pelvic abscess extending from the pubic symphysis to the anterior vaginal introitus, concerning for osteomyelitis. She was admitted to the hospital and showed improvement after 3 days of IV Levofloxacin and Metronidazole and was ultimately discharged home to complete a 6-week course of antibiotics. PET/CT and MRI in March 2021 favored chronic osteomyelitis with radiation-associated necrosis rather than definite tumor recurrence. She was seen by Orthopedic Oncology. Given persistent pain, ongoing infection, a non-resolving abscess, and destructive bony changes, multidisciplinary consensus favored surgical management via anterior exenteration. Her last documented ECOG performance status was 0 in January of 2021.

In May 2021 at the age of 66 she underwent an anterior pelvic exenteration with total abdominal hysterectomy, bilateral salpingo-oophorectomy, cystectomy, resection of the anterior vaginal wall, creation of an omental J-flap for pelvic floor reconstruction and neovagina formation, resection of the pubic symphysis, and urinary diversion with an ileal conduit. Final pathology revealed no residual malignancy. Her postoperative course was significant for Clostridioides difficile colitis and adynamic ileus. She was ultimately discharged home on postoperative day 10. Late post-operative complications included an acute kidney injury in the setting of right hydronephrosis which ultimately resolved spontaneously, a right lower extremity deep vein thrombosis, and ongoing stage IIIa chronic kidney disease.

At her most recent visit, five years after her pelvic exenteration, the patient remains clinically well and has no radiographic, clinical, or laboratory evidence of recurrent disease. She continues routine follow up with Gynecologic Oncology, Nephrology, and Urology.

3. Discussion

Primary adenocarcinoma of the Skene's gland remains an exceptionally uncommon malignancy, with limited published case reports to shape our understanding of its presentation, diagnostic features, and management challenges. Because these tumors arise from periurethral glands homologous to the prostate, they often display immunophenotypic patterns not typically encountered in female lower genitourinary cancers. This includes expression of markers more characteristic of prostatic or intestinal epithelium, creating a diagnostic interface between urologic, gynecologic, and gastrointestinal pathology. This patient's tumor exhibited intestinal type differentiation, a pattern described in several clinicopathologic series of urethral and Skene's gland adenocarcinomas. (Tian et al., 2023)

Despite emerging case reports and small studies, no standardized treatment algorithm exists for Skene's gland adenocarcinoma. Management generally mirrors strategies used for female urethral carcinoma and is highly individualized. Multimodal treatments including chemotherapy, radiation, or surgical resection are employed to achieve durable control. (Feddock et al., 2017) For this patient, concurrent chemoradiation was chosen as a bladder-preserving strategy and produced an initial complete response, consistent with prior reports indicating that periurethral adenocarcinoma responds well to radiation-based therapy.

Recurrent disease in a previously irradiated field introduces management complexity. Though repeat re-irradiation can be delivered with curative intent, there is also a higher risk of toxicity. In a series of 42 patients with recurrent pelvic malignancies treated with interstitial brachytherapy, the success rate was 73%, and the risk of grade 3+ toxicity was 16.7% (Song et al., 2024). Despite the challenges with this patient's recurrence, curative intent treatment was pursued given her localized recurrence. This patient may have been at greater risk of osteomyelitis, given the close contact of the pubic bone with the target volume. To the best of our knowledge, there are no commonly accepted available dose constraints for bone adjacent to a target volume treated with HDR brachytherapy.

Surveillance after re-irradiation also remains challenging. Within irradiated tissues, structural distortion, fibrosis, edema, and inflammation can obscure tumor margins or simulate recurrent malignancy on imaging. PET and MRI, while central to evaluating pelvic recurrence, may show increased uptake or signal abnormalities related to infection, osteoradionecrosis, or chronic inflammatory change rather than cancer (Elgendy et al., 2024). In the present case, destructive changes of the pubic symphysis and significant FDG avidity raised strong suspicion for recurrent tumor, yet ultimately reflected a severe radiation-associated process rather than recurrent malignancy.

Late pelvic complications such as osteomyelitis, septic arthritis of the pubic symphysis, and periurethral abscess are increasingly recognized among survivors of pelvic malignancies, particularly when prior radiation is combined with local infection, urinary leakage, or instrumentation (Yang et al., 2021). These conditions often present with pain, difficulty ambulating, or urinary symptoms, and can be challenging to diagnose definitively without surgical exploration, especially when imaging findings parallel those seen in tumor invasion. The current case aligns with published experience showing that radiation-associated osteomyelitis tends to be persistent and difficult to eradicate with antibiotics alone, often requiring surgically based source control. (Ugurluer et al., 2014)

When medical management of chronic radiation toxicities fails, surgical management is often required. In this case, anterior pelvic exenteration in an appropriately selected patient with an excellent performance status offered both a definitive therapeutic and diagnostic treatment that has led to long term clinical stability. Although traditionally performed for locally recurrent gynecologic cancers, exenteration has also been used in select cases to manage complex radiation associated complications. (Moolenaar et al., 2023) Resection of necrotic bone, drainage of chronic pelvic collections, and reconstruction with well vascularized tissue can provide long term resolution of symptoms and prevent further morbidity.

Long-term follow up in rare diseases such as Skene's gland adenocarcinoma is valuable. Few published cases provide more than two to three years of outcome data, and even fewer describe outcomes following recurrence, reirradiation, or salvage exenteration (Blick et al., 2015). The patient's sustained five-year disease-free interval following anterior pelvic exenteration contributes meaningful insight into the curative potential of re-irradiation for a local recurrence when surgical treatment is not thought to be feasible.

4. Conclusion

This case highlights the diagnostic and therapeutic complexities associated with primary adenocarcinoma of the Skene's gland, an exceedingly rare malignancy with no established management guidelines. This patient's course illustrates several important considerations, including the potential for late local recurrence after definitive chemoradiation, the challenges of distinguishing recurrent tumor from post-radiation changes on imaging, and the risk of severe radiation associated complications such as osteomyelitis and pelvic abscess. These conditions may closely mimic malignant progression and require a high index of suspicion and multidisciplinary evaluation. Salvage anterior pelvic exenteration provided both definitive diagnosis and durable disease control in this patient, who remains free of recurrence five years after surgery. This favorable long-term outcome demonstrates that curative treatment is achievable even in the setting of non-operable locally recurrent periurethral adenocarcinoma.

CRediT authorship contribution statement

Naziba Nuha: Writing – original draft, Data curation, Conceptualization. Katherine Trymbulak: Writing – review & editing, Writing – original draft, Data curation. Martin King: Writing – review & editing, Data curation. Benjamin Margolis: Writing – review & editing, Supervision, Methodology, Conceptualization.

Patient consent statement

Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.