Primary mucinous cell adenocarcinoma of female urethra
- 1 Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
- 2 Department of Urology, Western General Hospital, Edinburgh, UK
- 3 Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
- Correspondence to Dr Hira Lal; hiralal2007@yahoo.co.in
Abstract
Primary adenocarcinoma of the female urethra is a rare entity. Its incidence increases with age with the highest rate in women aged more than 65 years. Adenocarcinoma of the urethra is more common among women than men and is associated with a relatively poor prognosis. We report a case of primary adenocarcinoma of the urethra and review the literature with emphasis on the diagnosis, management and outcome of this rare tumour.
Background
Primary urethral carcinoma (PUC) is considered rare cancer and primary adenocarcinoma of the urethra is even rarer. Signs and symptoms of PUC are neither diagnostic nor pathognomonic. MRI of the pelvis is the radiological investigation of choice for the local extent of the tumour along with CT thorax and abdomen for metastatic workup. Multimodal therapy which includes surgery, chemotherapy and radiotherapy is the part and parcel of the management of locally advanced disease. We hereby describe a case of primary urethral adenocarcinoma in a young woman and discuss its evaluation and management.
Case presentation
A woman in her late 20s complained of a 6-month history of lower urinary tract symptoms (LUTS) and intermittent gross haematuria. There was no history of lithuria, turbiduria, urethral discharge, fever, urinary incontinence and dyspareunia. She had no history of any medical risk factors or addiction. The general physical examination was normal. Examination of external genitalia revealed pulled back external urethral meatus.
Investigations
Urinalysis revealed multiple RBCs and 4–5 pus cells and urine cultures were sterile. Office cystoscopy revealed a posterior wall of the proximal urethra irregular with suspicious growth; the distal urethra and bladder were normal. Vaginoscopy did not reveal any abnormality. A cold cup biopsy of urethral growth was taken. Histological examination of biopsy shows tissue lined by stratified squamous epithelium and subepithelium displaying a tumour composed of closely packed malignant glands lined by columnar cells displaying markedly pleomorphic hyperchromatic nuclei, conspicuous nucleoli and a moderate amount of cytoplasm, with brisk mitosis.
MRI of the pelvis showed an ill-defined asymmetrical heterogeneously enhancing urethral wall thickening (max thickness ~16 mm along posterior aspect up to a length of ~3.3 cm) extending up to the bladder neck. Lesion shows diffusion weighted (DW1) restriction and its fat plane with vagina is maintained (figure 1). A few subcentimetric bilateral inguinal and internal iliac nodes are seen. Uterus, bilateral ovaries and pelvic floor muscles were normal. Chest X-ray was normal.
Axial T1 fast spoiled gradient echo image (A) showing hypointense lesion, axial T2 fast spin echo image (B) show circumferential thickening of the proximal urethra with corresponding diffusion weighted imaging (DWI) (C) showing diffusion restriction and corresponding apparent diffusion coefficient map (ADC MAP) (D).
Treatment
This cancer is devastating with poor prognosis and aggressive biology leading to metastatic spread both locally and distantly. For these reasons, the female urethral cancers may require surgical debulking and multimodal therapies. In our case a mutual decision of radical surgery was made. The examination under anaesthesia was done which include bimanual palpation to rule out any colorectal or gynaecological malignancy. An anterior pelvic exenteration including radical urethrectomy with bilateral pelvic lymph node dissection, anterior vaginal wall resection and vaginoplasty was conducted with a continent cutaneous pouch. The patient tolerated the procedure well, and her postoperative course was uncomplicated. Pathological examination of the surgical specimen showed urethral adenocarcinoma (figure 2), involving the adjacent bladder neck, ectocervix and anterior vaginal wall. The urethral resection margin was involved by the tumour. Bilateral ureteric resection margins, bilateral fallopian tubes and uterus were normal. Perineural invasion was seen. Bilateral obturator lymph nodes, bilateral external and internal iliac, and presacral lymph nodes were free from tumour. The tumour, node, metastases (TNM) classification was stage II (pT3 pN0 M0). Because of positive urethral margins and anterior vaginal wall involvement, the patient was planned for adjuvant radiotherapy and chemotherapy. The patient received 50 Gy/25# to the pelvis using three-dimensional conformal radiotherapy technique using four fields (box field) and bilateral parallel opposed collimated fields with unequal weightage using dual-energy beams (6 MV) technique on CLINAC 2100 CD with concurrent cisplatin-based chemotherapy.
Urethral adenocarcinoma (low magnification) (A). Areas contained adenocarcinoma glands floating in pools of mucin, which prompted the diagnosis of adenocarcinoma with mucinous features (B-C). Metaplastic mucin-filled goblet cells can be seen intermixed with the normal urothelium (C).
Outcome and follow-up
The patient is doing well, and there is no recurrence so far after 1 year of follow-up. Chemotherapy and radiotherapy have been completed and the patient is currently under 3 monthly follow-up as per the institute’s protocol.
Discussion
PUC is a rare cancer and primary adenocarcinoma of the urethra is even rarer. It accounts for 0.02% of all female cancers and corresponds to 0.003% of all cancers occurring in the female urogenital tract.1 Around the lower end of the female urethra and on the anterior vaginal wall are located Skene’s ducts and glands (also called periurethral glands) which originate from the urogenital sinus. It has been postulated that primary adenocarcinomas of the female urethra originate from these periurethral glands.2 In PUC, the overall male-to-female ratio is ~3:1, but in the case of adenocarcinoma women are more commonly affected than their male counterparts. The incidence increases with age, with the highest rate in women more than 65 years of age.3 Around 10% of malignant cancers of female urethra have been reported as adenocarcinoma, but some reports even claim that adenocarcinoma is now the most common histological variety in female PUC.4 Risk factors like recurrent urinary tract infections (UTI), urethral diverticulum, sexually transmitted disease and prior radiotherapy are correlated with transitional cell carcinoma and squamous cell carcinoma of the urethra. The risk factors in female urethral adenocarcinoma are largely unknown, clear cell adenocarcinoma may have a congenital origin.5
Urethral adenocarcinoma has been divided into two primary histological subtypes: columnar cell/mucinous (intestinal) and clear cell type. Columnar cell urethral adenocarcinoma usually contains abundant extracellular mucin, resembling mucinous carcinoma of the colon and rectum. Mucinous lesions are composed of cells with eosinophilic cytoplasm, round to oval nuclei, and usually single large nucleoli, and sometimes positive for carcinoembryonic antigen. Clear-cell adenocarcinoma generally has architectural patterns formed by irregular, often microcystic, glands, papillary structures and occasional solid sheets, and some of these cases are positive for cytokeratin 7, p63 and prostate-specific antigen.6
Signs and symptoms of female urethral adenocarcinoma are neither diagnostic nor pathognomonic. Females may report recurrent UTI, irritative LUTS, perineal pain, dysuria, urinary retention or overflow incontinence and dyspareunia. Obstructive LUTS and haematuria are less common as most patients present with locally advanced stage.7 Early evaluation of symptomatic cases therefore must include a thorough physical examination, including genitalia and rectal examination with palpation of the perineum and bilateral inguinal region. Cytological assessment of urine specimen according to the Paris system should be conducted in suspicious cases, although sensitivity and specificity for urethral adenocarcinoma per se have not been clearly mentioned.8 Cysto-vaginoscopy and cold cup biopsy of the suspicious lesion are needed to confirm the diagnosis, establish histology and grade, localisation of cancer and determine the concurrent bladder cancer.9 Radiological imaging aims to assess local tumour extent and detect metastasis. MRI has been reported to have good accuracy in mapping the extent of local disease for surgical planning, regional lymph node metastasis and monitoring response to neoadjuvant chemoradiotherapy. Urethral cancers are typically hypointense on T1-weighted images and relatively hyperintense on T2-weighted images.10 CT can be used for distant staging with CT of the thorax and abdomen in all patients with invasive disease (>cT1N0M0).11 If imaging of the rest of the urothelium is required, CT urography should be performed. Poor prognostic factors in PUC are advanced age (>65 years), stage, grade, nodal involvement and metastasis, tumour size and proximal tumour location, underlying histology, presence of concomitant bladder cancer, location of recurrence (urethral vs non-urethral).12 When compared with squamous cell carcinoma and transitional cell carcinoma, adenocarcinoma of the female urethra has a statistically significant lower cause-specific survival and recurrence-free survival. Consensus on management and outcome predictors have been slow to emerge because of the rarity of PUC in the female population. Although rare but PUC is associated with poor prognosis and aggressive biology which can lead to metastatic spread. Therefore, female urethral cancers may require a combination of surgical debulking and multimodal therapies. Treatment options irrespective of histological type, include local excision, radical urethrectomy and anterior pelvic exenteration, with or without neoadjuvant and adjuvant radiation or chemotherapy. In localised PUC primary radical urethrectomy has been advised to provide the highest chance of local cure. Bladder neck closure with appendicovesicostomy for the primary distal urethral region provides a satisfactory functional outcome. An ablative surgical technique like transurethral resection has been used for small distal urethral tumours. Radiation monotherapy in localised PUC has been used as an alternative to urethral surgery but local toxicity is the limiting factor. No difference has been reported in external beam radiation therapy (EBRT) versus interstitial brachytherapy for local tumour control. There is no recommendation for systemic therapy for localised disease.13
In locally advanced PUC (T3-4, N0-2, M0) the role of multimodality therapy is now well established which consists of definitive surgery plus chemotherapy with the option of additional radiotherapy (RT). An analysis of recent case reports on female urethral adenocarcinoma gives a hint about various modalities of treatment (table 1) which shows various modalities used depending on the clinical situation and hospital protocols.
Analysis of recent case reports on female urethral adenocarcinoma
| S. no | Age | Year of presentation | Site of tumour | Treatment |
|---|---|---|---|---|
| 1. | 75 | 2003 | Proximal urethra | Chemotherapy + radiotherapy + total urethrectomy and excision of the anterior vaginal wall and Klauber vesicostomy.16 |
| 2. | 48 | 2008 | Proximal urethra | Anterior pelvic exenteration.17 |
| 3. | 60 | 2015 | Distal urethra | Radical cystectomy + ileal conduit.18 |
| 4. | 54 | 2016 | Proximal urethra | Radical vulvectomy and ureterectomy, + two sessions of radiotherapy.19 |
| 5. | 60 | 2018 | Proximal urethra | Chemoradiation20 |
| 6. | 76 | 2021 | Entire urethra | Anterior pelvic exenteration.21 |
Ethics statements
Patient consent for publication
Footnotes
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Twitter @RaviBanthia_uro
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Contributors RB conceived the manuscript and this report was supervised by HL. HL provided the MR images. RB and ND prepared the manuscript. HL reviewed the manuscript. Consent was taken by RB. UPS performed the surgery. The final draft was read and approved by all the authors.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
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