Primary signet ring cell carcinoma of the female urethra: A case report

Abstract

BACKGROUND

Primary signet ring cell carcinoma of the urethra in women is an exceedingly rare malignancy. It was first reported in postmenopausal women in 1987, and only five patients have been reported to date.

CASE SUMMARY

A 61-year-old woman presented with irregular vaginal bleeding, and subsequent evaluation identified a tumor located in the distal urethra. Upon diagnosis of primary urethral carcinoma, she underwent a distal urethrectomy. Histopathological analysis demonstrated that the tumor consisted of a combination of intestinal adenocarcinoma and signet ring cell carcinoma. At the 12-month postoperative follow-up, there was no evidence of disease recurrence.

CONCLUSION

This case report highlights the exceptional rarity of female urethral signet ring cell carcinoma, emphasizing the importance of early clinical detection and the necessity for precise and conservative surgical intervention.

Key Words: Signet ring cell carcinoma; Vaginal mass; Urethral mass; Female urethra; Case report

Core Tip: Primary signet ring cell carcinoma of the urethra in women is an exceedingly rare malignancy. A 61-year-old woman presented with irregular vaginal bleeding. She was found to have a tumor located in the distal urethra. Based upon a diagnosis of primary urethral carcinoma, she underwent distal urethrectomy. Microscopically, the tumor was composed of intestinal adenocarcinoma and signet ring cell carcinoma. No recurrence was observed 12 months after surgery.

INTRODUCTION

Urothelial carcinoma represents the predominant form of urethral cancer, with squamous cell carcinoma being the second most frequent form. Of all urethral cancer cases, 16.4% are classified as adenocarcinoma[1]. The primary urethral cancer exhibits an incidence rate of 4.3 per million among men, in contrast to 1.5 per million among women in the United States, highlighting a pronounced predilection for older males[2,3]. Primary signet ring cell carcinoma of the urethra in women is an exceedingly rare malignancy[4]. It was first reported in postmenopausal women in 1987, and only five patients have been reported to date[5,6]. Signet ring cell carcinoma was named due to its signet ring-like appearance.

CASE PRESENTATION

Chief complaints

A 61-year-old multiparous female had a vaginal mass detected 2 years previously, and had recently developed irregular vaginal bleeding for 2 months.

History of present illness

The patient was admitted to the hospital on January 31, 2024, and reported no associated symptoms of urinary frequency, urgency, or stranguria.

History of past illness

Ten years ago, the patient underwent a Manchester operation (including partial cervical resection, anterior and posterior vaginal wall repair, and cardinal ligament shortening) at a local hospital due to pelvic organ prolapse. The patient had no prior history of malignancies, hypertension, or diabetes.

Personal and family history

The patient was a multiparous woman with a history of two full-term deliveries and one abortion. She experienced menopause at the age of 55 years. Her father had a history of hypertension, while her two sisters and one brother were in good health.

Physical examination

Gynecological examination identified a 2 cm mass situated at the urethral orifice, exhibiting a medium texture and the absence of surface bleeding (Figure 1). No masses or abnormal bleeding were detected in the cervix or vagina. No enlarged lymph nodes were palpable in the inguinal region.

Figure 1 Gross specimen of the complete urethral tumor tissue which is approximately 2 cm in diameter.

Laboratory examinations

Tumor marker levels were within the normal range, including carbohydrate antigen 125, carbohydrate antigen 153, carbohydrate antigen 19-9, α-fetoprotein, and carcinoembryonic antigen.

Imaging examinations

Pelvic enhanced computed tomography (CT) was conducted to assess the pelvic and abdominal cavities, and showed no evidence of lymph node metastasis. In addition, cystoscopy findings were unremarkable. There were no abnormalities on gastrointestinal endoscopy, breast color Doppler ultrasound and lung CT examination.

Therapeutic intervention

The patient underwent a distal urethral resection after multidisciplinary diagnosis and treatment planning. The patient did not receiveundergo adjuvant radiotherapy or chemotherapy according to the European Association of Urology Guidelines on Primary Urethral Carcinoma-2020 Update.

Genetic testing

The patient declined genetic testing due to financial constraints.

Biopsy and pathology examinations

Final pathological examination confirmed the presence of intestinal adenocarcinoma and signet ring cell carcinoma, measuring 2.0 cm in size, located in the urethra, with negative surgical margins. No cancer accumulation was found in the external urethral tissue (Figure 2).

Figure 2 Hematoxylin and Eosin staining. Original magnification of 200 ×.

FINAL DIAGNOSIS

Primary signet ring cell carcinoma of the female urethra T1N0M0.

TREATMENT

The patient underwent a distal urethral resection after multidisciplinary diagnosis and treatment planning. The patient did not receive adjuvant radiotherapy or chemotherapy.

OUTCOME AND FOLLOW-UP

At the 12-month follow-up, no evidence of recurrence was observed, and lifelong follow-up is recommended for potential disease progression.

DISCUSSION

Primary urethral malignant tumors are rare, with a higher incidence in males compared to females. Risk factors include long-term urethral catheterization, chronic urinary tract infections, urethral strictures, sexually transmitted diseases, and a history of radiotherapy. In women, it may be associated with recurrent lower urinary tract infections or urethral diverticulum[7]. In female patients, tumors were located in the proximal urethra in 28.9% of cases, the distal urethra in 68.9%, and both proximal and distal urethra in 2.2%[2]. The 5-year overall survival rate for primary urethral malignant tumors is 61%. Among the histological subtypes, squamous cell carcinoma has a relatively better prognosis, with a 5-year overall survival rate of 64%, while adenocarcinoma has the poorest prognosis, with a 5-year overall survival rate of only 31%[8]. Studies suggest that female patients often have a worse prognosis compared to male patients at the time of diagnosis[3].

The most common histological types are squamous cell carcinoma and transitional cell carcinoma, while adenocarcinoma represents 16.4% of cases[1]. Histologically, adenocarcinoma is subdivided into intestinal, mucinous, clear cell, and signet ring cell types. Consequently, primary signet ring cell carcinoma of the female urethra is exceedingly rare[9]. Our case represents the sixth reported instance of female urethral signet ring cell adenocarcinoma in the English literature. As previously mentioned, the patient had no urinary system-related risk factors but had a history of pelvic organ prolapse and underwent surgical treatment for the condition.

The common symptoms of urethral malignant tumors include dysuria (48%), hematuria (62%), perineal mass (52%), urinary urgency (20%), pelvic pain (33%), and fistula (10%) among others[7]. The patient initially presented with no obvious urinary symptoms but was treated for irregular vaginal bleeding, which was likely related to the tumor's location. This incidental finding allowed for early detection and prompt treatment of the condition[8]. The patient could have received earlier treatment, as she had noticed the mass two years previously but only sought medical attention after developing symptoms of vaginal bleeding.

Signet ring cell carcinoma was named due to its signet ring-like appearance. This unique adenocarcinoma variant is defined by cells with abundant cytoplasmic mucin, which pushes the nucleus to the cell periphery. According to the 2010 World Health Organization classification, signet ring cell carcinoma is not classified as an independent histological subtype but is included within the poorly cohesive carcinoma category[10]. Signet ring cell adenocarcinoma is most frequently found in the gastrointestinal tract, followed by the breast and lung. Its occurrence in the urethra is exceedingly rare. Therefore, when diagnosing primary signet ring cell adenocarcinoma of the urethra, it is essential to perform upper and lower gastrointestinal endoscopy, breast examination, and lung CT imaging to rule out primary tumors in these organs. The diagnosis of primary urethral malignancy typically requires endoscopic evaluation and biopsy for definitive confirmation[7]. Magnetic resonance imaging is the preferred imaging modality for local and locoregional evaluation of confirmed or suspected tumors[7].

Endoscopic transurethral resection is not recommended for distal tumors due to its low local control rate, with recurrence rates as high as 50% within 17 months[7,11]. For stage T2 tumors of the distal urethra, distal urethral resection can be considered as a conservative treatment option if surgical margins are negative[12]. Studies report a 5-year recurrence-free survival rate of 65% and a 5-year disease-specific survival rate of 82% for this approach[7,13]. For malignant tumors of the posterior urethra in women, conservative surgery is not recommended, and radical cystectomy should be the preferred approach[7,12].

Cisplatin-based neoadjuvant chemotherapy is recommended prior to radical surgery for the management of proximal T2N0 urethral cancer. Multidisciplinary diagnosis and treatment are essential for all patients presenting with locally advanced disease (T3N0-2M0). In male patients with locally advanced squamous cell carcinoma, a regimen of radical radiotherapy augmented with radiosensitizing chemotherapy is advocated to achieve curative intent while preserving genital integrity. For patients experiencing local urethral recurrence, options such as salvage surgery or radiotherapy may be considered. In cases of distant metastatic disease, systemic therapy tailored to the specific characteristics of the tumor should be assessed and implemented as appropriate[12].

Compared with other reports, this case is the youngest and has the earliest stage. We expect her to have a better prognosis (Table 1).

Table 1 Reported cases of primary signet ring cell carcinoma of the urethra in women.

No.	Age (years)	Symptoms	Symptom duration	Location and extent of tumors at presentation	Stage (TNM)	Treatment	Follow up	Status
Suzuki et al[6]	70	Frequency, difficulty in urination, nocturia and acute retention	6 weeks	Urethral mass fixed to the symphysis 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	18 months	DOD
Suzuki et al[6]	66	Frequency and bloody vaginal discharge	9 months	Entire urethra, anterior vaginal wall, pelvic side walls and bladder neck with right inguinal lymph node metastasis	T3N1 or 2 M0	No treatment	6 months	Presumably DOD
Suzuki et al[6]	72	Enlarging mass at the external urethral meatus and yellowish discharge	4-6 months	Polypoid tumor at the external urethral meatus	TaN0M0	Wide local excision (2 cm of distal urethra, urethral meatus and anterior vulva) and bilateral inguinal lymph node dissection	7 months	NED
Suzuki et al[6]	69	Difficulty in urination and bloody fluid from urethra	24 months	Anterior vaginal wall and bladder neck	T3N0M0	Total cysto-urethrectomy and hysterectomy with bloody fluid pelvic lymph node dissection	17 months	NED
Grimsby et al[5]	81	Suprapubic pain, urethral discharge, urinary frequency, urgency, and stranguria	No report	A firm tender mass at 7 o’clock in the urethra	T4N0M0	Robotic assisted radical cystectomy, bilateral pelvic lymph node dissection	1 month	DOD
6 (present case)	61	Irregular vaginal bleeding	2 months	2 cm mass situated at the urethral orifice	T1N0M0	Distal urethral resection	12 months	NED

DOD: Died of disease; NED: No evidence of disease.

CONCLUSION

This case highlights the exceptional rarity of female urethral signet ring cell carcinoma, emphasizing the importance of early clinical detection and the necessity for precise, conservative surgical intervention. Irregular vaginal bleeding in females should not be exclusively attributed to gynecological conditions, as it may also signal the presence of a urinary tract neoplasm, necessitating a comprehensive multidisciplinary assessment for accurate diagnosis. Given the exceedingly low incidence of female urethral signet ring cell carcinoma, it is imperative to amass and analyze data from multiple centers to advance our understanding and management of this condition.

ACKNOWLEDGMENTS

The authors are grateful to the staff of the Pathology Department of Jinhua People’s Hospital, Zhejiang Province, China.