1 Introduction

Globally, about 0.02% of all female cancers and fewer than 1% of female genitourinary tract tumors are female urethral carcinomas. The histological variation of this rare disease includes 70% of cases of squamous cell carcinoma, 20% of transitional cell carcinomas, and 8%–10% of adenocarcinomas. Primary urethral adenocarcinoma is more common in females than in males and is thought to arise from the skene's glad [1]. In Kenya, where this case was managed, data on female urethral adenocarcinoma is limited. Most studies done and cited were on other genitourinary tumors. WHO urethral cancer classification Urethral adenocarcinoma in females is further subcategorized into two histological variants, which are mucinous/columnar and clear cell types [2]. Neuroendocrine tumors, lymphoma, urethral diverticular, vulvar or vaginal melanoma, urethral polyps, caruncle, and leiomyoma are among the common differentials of urethral adenocarcinoma [3, 4].

Urinary frequency, localized tenderness, urethrorrhagia, urethral obstruction, dysuria, urinary tract infection, concomitant hematuria or urethrocutaneous fistula, and dyspareunia are examples of clinical symptoms that are neither pathognomonic nor diagnostic for this disorder. Our patient presented with some of these symptoms which include increased urinary frequency, dysuria, recurrent urinary tract infections, sensation of incomplete bladder emptying, which was associated with feeling of a vaginal mass and foul-smelling vaginal discharge. These nonspecific symptoms cause delay in diagnosis and lead to more advanced diseases. The clear cell histological subtype has been linked to congenital associations with recurrent urinary tract infections and urethral diverticula as risk factors.

A complete history, physical examination, and diagnostic tests like urethrocystoscopy and abdominal CT or MRI are all part of the diagnosis process. The diagnosis is confirmed by a urethral biopsy. The prognosis is dependent on the disease's location, histological grade, clinical stage, and treatment options, which include monotherapy or multimodal therapy [5, 6].

In this paper, we discuss the case of a 53-year-old female who was received at Africa Inland Church (AIC) Kijabe Hospital in Kenya from the gynecology clinic of the same hospital. She was diagnosed with urethral adenocarcinoma with mucin production confirmed by histopathology and managed accordingly. The aim of writing this case is to highlight the importance of thorough assessment of female patients presenting with a urethral mass, involving other concerned specialties early when in doubt and the role of early multidisciplinary team (MDT) management in patients presenting with urethral adenocarcinoma. It is also to highlight the importance of lower-level service provision centers to refer patients presenting with recurrent urinary tract infections rather than managing them repeatedly for the same diagnosis.

2 Case Management

2.2 Examination

Examination was done by a consultant Urologist; general examination was unremarkable. Focal examination revealed a protruding 6 cm × 5 cm fungating mass at the urethral orifice that was fixed, tender, with associated contact bleeding at the inferior aspect, and palpable bilateral inguinal lymph nodes (Figure 1).

Examination under anesthesia and urethrocystoscopy with urethral biopsy was done by the consultant Urologist at AIC Kijabe Hospital. Intraoperative findings were a fungating urethral orifice mass and a panurethral mass extending close to the bladder neck. The bladder mucosa was normal. Several biopsy specimens were taken from the urethra by the Urologist and sent for histopathology.

2.3 Investigations

The specimen was processed and analyzed by the consultant pathologist at AIC Kijabe hospital and reported as a well-differentiated urethral adenocarcinoma with mucin production; a gland with cells arranged in an irregular pattern on (Figure 2A,B) showing finger-like projections of the urothelial lining, blood vessels, and an area of mucin production.

After a thorough history was taken, examination was done and biopsy of the lesion taken, a Pelvic magnetic resonance imaging (MRI) was requested by the consultant urologist as the gold standard imaging. The aim was to establish the local extent of the tumor, presence of metastasis as well as pelvic lymph node involvement. The MRI was reported by the consultant radiologist at AIC Kijabe Hospital and reported a cauliflower-like mass (Figure 3A) involving the entire retropubic urethra measuring 63.9 × 35.4 × 45.0 mm, invading the endopelvic fascia, lower urinary bladder neck, pubourethral, periurethral, paraurethral ligaments bilaterally, perineal membrane, and clitoral hood with a TNM staging of T4N2Mx (Figure 3B).

3 Discussion

Female urethral adenocarcinoma is a rare urological malignancy; in this paper, we discuss the case of a 53-year-old female who was managed with chemoradiation in which we noted the importance of early diagnosis and a multidisciplinary approach to be beneficial. Although the exact cause of female urethral adenocarcinoma is unknown, literature revealed associations of the tumor with the paraurethral skene's gland, which is similar to the prostate gland; consequently, PSA staining may be present in these tumors; however, this may not be the case in most cases. Different studies on histological subtype prevalence showed varying results; it is found that the higher incidence of this condition is in those above 50 years [6, 7].

The most common etiological risk factors reported are recurrent urinary tract infections and urethral diverticula; however, different studies have mentioned other factors such as leukoplakia, chronic irritation, human papilloma virus infection or other viral infections, polyps, caruncles, chronic irritation due to indwelling catheters, and sexually transmitted diseases. Some reported the congenital association in the case of the clear cell subtype [8, 9]. Carvalho Neto and colleagues in 2016 [1] hypothesized an association between smoking and urethral adenocarcinoma. In addition to being treated for recurrent urinary tract infections, our patient also smoked as a secondary smoker; her spouse was a chain smoker.

Clinical symptoms may vary depending on the timing of presentation but can be either obstructive lower urinary tract symptoms (straining and feeling of incomplete bladder emptying) or irritative (increased urinary frequency and dysuria) or both, hematuria or bloody urethral discharge, and a protruding urethral mass. There may be associated dyspareunia, abscess, or urethrocutaneous fistula in locally advanced cases [5, 10]. Our patient had both obstructive and irritative symptoms with a fungating urethral mass, associated foul-smelling vaginal discharge, and contact bleeding on examination.

A complete history, physical examination, examination under anesthesia, and serum workups such as a complete blood count, serum creatinine and urea, urinalysis, and urine cytology are all part of the patient assessment and workup process. Abdominal-pelvic MRI, CT, and ultrasonography scans can all be performed; however, MRI is the preferred method for determining the location, size, and local infiltration of the tumor. A CT scan of the abdomen, chest, and pelvis is recommended for staging with pre- and post-contrast images for assessment of the entire urinary tract [11].

A cystoscopy with urethral tumor biopsy is diagnostic [2, 12]. A PET CT scan can also be used for staging workup, as done in our case if available.

Tumor spread can be local or distant metastasis. In local infiltration, it more commonly spreads to the vagina, urinary bladder, or other periurethral tissues, whereas in distant metastasis, it spreads more commonly to the lungs, liver, bone, and brain [2, 13].

In our case, there was a tumor spread to the bladder neck and periurethral tissue with inguinal lymphadenopathy.

Marital status should be flagged as it was shown that unmarried women tend to present with more locally advanced diseases and unmarried men do not benefit from multimodal therapy, though both groups require pre- and post-treatment counseling and follow-up. Furthermore, Morra and colleagues noted that there was lower cancer-specific survival in married women in comparison to married men [14, 15].

Management of female urethral adenocarcinoma depends on several factors, such as the stage of the tumor, the histological grade, as well as the location. It can be monotherapy or multimodal therapy [16]. Distal focal tumors tend to have a better prognosis than proximal infiltrating or distant metastatic tumors. In the surgical management of proximal female urethral adenocarcinoma, a complete or partial urethrectomy can be done. In distal tumors, a urethra-sparing surgery, urethrectomy, or radiotherapy can be done, and the patient should be followed up for possible salvage surgery or radiotherapy in case of recurrence. In advanced tumors, neoadjuvant chemotherapy and surgery or chemoradiotherapy or surgery and adjuvant radiotherapy can be done. The decision to do chemotherapy is best advised after a MDT discussion [17, 18].

Junjie et al. [9], however, reported that in their second case in the paper they published, the patient was not routinely followed up following surgical resection. Additionally, the patient refused adjuvant multimodal therapy and eventually developed distant metastasis, necessitating palliative care, even after the tumor recurrence was discovered a few years later with a second surgery performed. This highlights that in cases of systemic or locally advanced disease, multimodal therapy is necessary, as is routine patient follow-up to ensure the best possible care. In our patient with a locally invasive disease, a chemoradiotherapy model of treatment was used, and the patient had radiation proctitis as a complication, as reported by [11].

Chemotherapy has shown survival benefits in adenocarcinoma and other variants of urethral cancers but not in squamous cell carcinoma. Unconventional nonmetastatic urethral malignancy histology harbors 106-month survival benefit, while the metastatic unconventional has only 10 months [18, 19].

4 Conclusions

Female urethral adenocarcinoma being uncommon, it requires a comprehensive investigation when it is suspected, particularly in those who have nonspecific or recurrent lower urinary tract symptoms. MRI is the ideal imaging method for determining the location, size, and local infiltration of the tumor. Management should involve a MDT. Monotherapy or multimodal therapy can be used depending on the disease's location, histological grade, and clinical stage. Localized distal urethral cancers are said to have a better prognosis. Follow-up is paramount to monitor recurrence.

Author Contributions

Omar Darboe: conceptualization, writing – original draft. Bartholomeo Nicholaus Ngowi: writing – review and editing. Gideon Mwasakyalo: writing – review and editing. Christine Mwakio: formal analysis. Rosemary Wangari Kamau: formal analysis. Adan S. Bashir: writing – review and editing. Waithera David: writing – review and editing. Paul Juma Irungu: writing – review and editing.

Consent

A written informed consent was obtained for the patient's clinical information to remain anonymous.

Conflicts of Interest

The authors declare no conflicts of interest.