Correspondence: Kazumi Suzuki MD, Department of Urology, Jichi Medical School, Minamikawachi-machi, Kawachi-gun, Tochigi 3290498, Japan. Email: email@example.com
Abstract A 69-year-old woman presented with difficulty in urination and bloody fluid discharge from the urethra. Based upon a diagnosis of primary urethral carcinoma, she underwent total cysto-urethrectomy and hysterectomy with pelvic lymph node dissection and urinary diversion of ileal conduit. Microscopically, the tumor was composed of mucinous adenocarcinoma and signet ring cell carcinoma. There was no recurrence 17 months after the surgery.
Primary adenocarcinoma of the urethra in women is a rare malignant tumor. Moreover, primary signet ring cell carcinoma (SRCC) of the urethra in women is extremely rare and only three cases have been reported.1,2 We report a case of advanced primary SRCC in the urethra of a female patient. She was treated with total cysto-urethrectomy and hysterectomy with pelvic lymph node dissection in addition to the urinary diversion of ileal conduit. She was followed up for 17 months.
A 69-year-old woman presented with difficulty in urination and discharge of bloody fluid from the urethra. A hard mass about 3 cm in diameter was palpable under the anterior vaginal wall. Bloody fluid was discharged from the meatus by pressing the hard mass. Serum tumor markers including squamous cell carcinoma (SCC) antigen, carbohydrate antigen 19–9 (CA19-9) and α-fetoprotein (AFP) were normal, but carcinoembryonic antigen (CEA) was slightly elevated. Pathological examination of the tumor resected by transurethral biopsy showed signet ring cell carcinoma (SRCC). Pelvic magnetic resonance imaging (MRI) showed a tumor arising from the proximal urethra infiltrated into the submucosal layer of the bladder neck and anterior vaginal wall (Fig. 1). Since gastrointestinal fiberscopy and systemic survey for distant metastases were negative, the diagnosis was primary urethral SRCC (clinical stage T3N0M0).3 The patient underwent total cysto-urethrectomy and hysterectomy with pelvic lymph node dissection in addition to the urinary diversion of ileal conduit. Microscopically, the tumor was composed of mucinous adenocarcinoma and SRCC without glandular metaplasia (Fig. 2). Immunohistochemical staining showed that both the mucinous adenocarcinoma and SRCC were positive for CEA (Fig. 3) but negative for prostate specific antigen (PSA). She did not receive any further treatment and remained well without any evidence of recurrence 17 months after the operation.
Adenocarcinoma of the female urethra is extremely rare, constituting 10% of all primary urethral malignancies in women.1 Only three cases of primary urethral adenocarcinoma containing SRCC have been reported (Table 1).1,2 Recent immunohistochemical studies and previous case reports suggest that adenocarcinoma including SRCC of the female urethra arise from paraurethral glands, Skene's ducts or urothelium with glandular metaplasia like the urinary bladder.1,2,4–7
Table 1. Reported cases of primary signet ring cell carcinoma of the urethra in women
Location and extent of tumors at presentation
DOD, died of disease; NED, no evidence of disease.
Frequency, difficulty in urination, nocturia and acute retention
Urethral mass fixed to symphisis pubis, vagina and bladder neck with left inguinal lymph node metastasis
T4N1 or 2 M0
Radiotherapy Anterior exenteration and left inguinal lymph node dissection Palliative chemotherapy
DOD (Lung metastasis)
Frequency and bloody vaginal discharge
Entire urethra, anterior vaginal wall, pelvic side walls and bladder neck with right inguinal lymph node metastasis
T3N1 or 2 M0
Enlarging mass at external urethral meatus and yellowish discharge
Polypoid tumor at external urethral meatus
Wide local excision (2 cm of distal urethra and anterior vulva) and bilateral inguinal lymph node dissection
4 (present case)
Difficulty in urination and bloody fluid from urethra
Anterior vaginal wall and bladder neck
Total cysto-urethrectomy and hysterectomy with pelvic lymph node dissection
Skene's ducts in women are the homolog of the prostate and tumors arising from them are similar to prostatic carcinoma.5 Thirty-nine cases of prostatic adenocarcinoma containing SRCC have been reported.8 Kuroda et al. found that the rate of PSA and CEA positive staining in primary prostatic SRCC was 91% (30/33 cases) and 45% (5/11 cases), respectively.8 Moreover, Zaviacic et al. reported a case of female para-urethral gland adenocarcinoma that was positive for PSA and prostate specific acid phosphatase.5
Chan et al. recently reported a case in which female urethral adenocarcinoma with SRCC arose from the intestinal metaplasia using cytokeratins 7 and 20 antibodies.2 They also noted that the SRCC was negative for PSA by immunohistochemical analysis.2 Murphy et al. demonstrated that female urethral columnar/mucinous adenocarcinoma arose from glandular metaplasia using a monoclonal antibody mAbDas1.4 Additionally, primary adenocarcinomas containing SRCC of the urinary bladder were thought to arise from the bladder mucosa with glandular metaplasia,6,7 and approximately 70% were positive for CEA but all were negative for PSA.6
Although the pathogenesis of urethral SRCC is not well known, that of SRCC of the urinary bladder or the prostate has been described as follows.6,9,10 If abundant mucin accumulates within the cytoplasm, the nucleus will become compressed giving it the characteristic signet ring appearance. Rupture of either the mucin-distended glands or individual cells produces the mucin pools that are characteristically observed in these neoplasms. Thus, SRCC of the urinary bladder or the prostate coexists with microacinar poorly differentiated adenocarcinoma cells and/or mucinous carcinoma cells that look like they are ‘floating in mucin lakes’.6,10,11 In the present case, the pathogenesis of the SRCC was thought to be similar to SRCC of the urinary bladder or the prostate because the tumor was composed of mucinous adenocarcinoma and SRCC.
The microscopic origin of SRCC could not be determined in this case because the tumor cell was immunohistochemically positive for CEA but negative for PSA and without coexistence of glandular metaplasia histologically. However, radiological findings including urethroscopy, pelvic CT and MRI supported the theory that the tumor had arisen from the proximal urethra. To our knowledge, this is the fourth report of primary SRCC in the female urethra.