Primary urethral CCA is a rare and aggressive tumour found predominantly in women and may be associated with a urethral diverticulum [5]. The term CCA was proposed by Young and Scully in 1985 due to its histopathological spectrum similar to CCA of female genital tract. It may arise from either Müllerian rests or metaplastic urothelium. [4,5,6]
The main prognostic factors are location and depth of invasion. Anterior lesions tend to be superficial and have a good prognosis. Posterior lesions are deeply invasive and have higher rates of distant metastasis [7]. Compared with other urinary tract malignancies, the prognosis is poor. Patients often present with metastatic or locally advanced disease [5, 8]. Our patient presented with features of locally advanced disease, viz. obstructive symptoms, haematuria and bloody urethral discharge. Periurethral abscess and fistulae have also been documented to occur. [8]
Although our patient had a urethroscopy which shed more light on the diagnosis and ruled out benign urethral stricture as a differential diagnosis, a report from another centre in Southwestern Nigeria showed that only 7 percent of patients with suspected urethral strictures were able to have urethroscopies due to financial and resource-limited challenges [9]. Another report from Ethiopia highlighted the difficulties many Sub-Saharan or low-income nations face with access to endoscopy for routine diagnosis and/or therapeutics [10]. Endoscopic diagnosis is further recommended due to the presentation with visible haematuria [11]. The retrograde urethrogram, which is a cheaper and more readily accessible test in low-income nations, showed multiple filling defects which could have been neoplasms or inadvertent air bubbles, and the urethroscopy served as a complementary investigation to improve accuracy. [12]
Histologically, CCAs typically display tubulocystic, papillary, mucinous, villous and diffuse patterns [2, 13, 14]. Sun et al. [13] reported the papillary variant as the most common, followed by tubulocystic patterns. Typical cytological characteristics of clear cell adenocarcinoma include hobnail cells, flattened cells and cells with abundant clear cytoplasm. These cytologic features should aid in the distinction of CCA from benign nephrogenic adenoma, another rare but benign tumour. [13,14,15,16] CCA of the urethra exhibits positive immunohistochemical staining with PAS, paired box protein (PAX) 2, PAX8, cytokeratin (CK) 7, p16, p53, cancer antigen (CA) 125, cell adhesion molecule (CAM) 5.2, AE1/AE3 and stains negatively with prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), thrombomodulin, oestrogen, progesterone, CK20, p63, cluster of differentiation (CD) 10, polyclonal carcinoembryonic antigen (CEAp), Wilm’s tumour (WT) 1, alpha foetoprotein (AFP), S-100. [15, 17,18,19]
Due to the rarity of CCA of the urethra, the optimal treatment of the advanced disease is unknown [20]. Our patient declined any form of intervention, thus limiting the contribution of this report to intervention armamentarium. However, the scenario provided a natural history for the untreated case of primary urethral CCA. Cantrell et al. [21]treated their male patient with total pelvic radiation after staging pelvic lymphadenectomy. The patient died 26 months later. Seseke et al. [18] performed total urethrectomy with suprapubic urinary diversion. The patient died 30 months following his surgery. A case series of 15 CCA of various male genitourinary organs included two definite urethral and seven possible prostatic or prostatic urethral origins. This latter set was not included in the sum total of urethral cases reported in this write-up due to the uncertain origin. Therapies used included transurethral resections, targeted therapy with gefitinib, hormonal therapy and nivolumab immunotherapy. Poor prognosis occurred in those with ambiguous origin from the prostatic urethra or the prostate itself [22]. Other noted therapies for male urethral CCA include radical cystoprostatectomy, urethrectomy, bilateral inguinal and pelvic lymph node dissection and ileal conduit urinary diversion with adjuvant chemotherapy [20], partial penectomy with cystoprostatectomy and partial urethrectomy. [23]
There is a dearth of knowledge on the effectiveness of chemotherapy in the treatment of primary urethral CCA. Liu et al. [24] reported a case of metastatic urethral CCA in a male treated with maximal cystoscopic resection of the tumour and palliative systemic therapy (cisplatin and gemcitabine) intermittently for nearly 2 years. Second-line therapy with nab-paclitaxel was ineffective. Two other documented cases had no long-term follow-up. [4, 15]
