Clear cell adenocarcinoma of a female urethra: A case report and review of the literature.

CONTEXT: Clear cell adenocarcinoma of the urethra is an extremely rare tumour. Its histogenetic derivation remains controversial. CASE REPORT: We report a new case of clear cell adenocarcinoma of the proximal urethra in a 56-year-old woman who presented with grossly hematuria. Urethral cystoscopy revealed a tumour protruding from the posterior urethral wall at the bladder neck. Treatment consisted of urethrocystectomy with pelvic lymph node dissection. Histologically, the neoplasm consisted of clear cell adenocarcinoma of the urethra.
CONCLUSION: It appears that female urethral adenocarcinoma has more than one tissue of origin.

Introduction

Clear cell adenocarcinoma (CCA) of the female urethra is very rare; most information has been gained from single case reports and small case series[1]. We report a new case in a 57-year-old woman and discuss the clinico-pathologic pattern.

Case Report

A 56-year-old woman presented with gross hematuria. On physical examination, bleeding from the urethra meatus was seen. Urethral cystoscopy revealed a tumour protruding from the posterior urethral wall at the bladder neck. Computed tomography scan of the pelvis revealed a severe thickening of the bladder wall (Fig. 1). The patient underwent transurethral biopsy of the tumour that showed an invasive poorly differentiated carcinoma of the urethra.

Fig. 1

Computed tomography scan: severe thickening of the bladder wall

A total urethrocystectomy was performed including anterior vaginal wall and pelvic lymph node dissection. An ileal conduit was chosen for urinary diversion. Grossly, the tumour was measuring 2.5×2×2cm and invaded all the urethral layers. The bladder mucosa was not involved.

Histological examination revealed a tumour composed of nests and papillary structures (Fig. 2) that were lined with cells having clearly cytoplasm with hobnail cells in some areas of the tumour (Fig. 3); these cells showed severe cytologic atypia and high mitotic rate; tumour cells invaded all the urethral layers, but didn’t involve the bladder.

Fig. 2

Clear cell carcinoma composed of nests and papillary structures (HE × 40)

Fig. 3

papillary structures lined by cells with clearly cytoplasm and pleomorphic nuclei (HE × 400)

Immunohistochemical staining, using the two-step indirect imunoperoxydase technique with antibodies to prostate-specific antigen (PSA; DAKO, L-1838) showed no cytoplasmic reaction in the tumour cell. No lymph node metastasis was detected. The patient didn’t receive any adjuvant therapy. She was free of disease three months after surgery.

Discussion

CCA of the urethra is an extremely rare tumour[2]. Most information has been gained from single case reports and small case series[123]. It mainly affects women and up to half of the cases develop in the context of a urethral diverticule[45].

The histogenesis of CCA of the female urethra remains controversial[6]. Konnack[7] reported the first case in 1973, using the term “mesonephric carcinoma”, and suggested that the tumour probably arises from the mesonephric duct or intermediate mesodermal vestiges. However, some authors[6] insisted on the mullerian origin of this tumour. In 1984, Pollen and Dreilinger[8] strongly supported the homogeneity between the female paraurethral duct and male prostate gland on finding positive immunohistochemical staining using antibodies to PSA (prostate-specific antigenin) and PAP (prostatic acid phosphatase). They have advocated that the tumour arises from the female para-urethral duct. In our case, tumour cells were negative for PSA. More recently, Zaviaci et al[9] reported a neoplasma with similar histologic appearance and immunohistochemical characteristics as adenocarcinoma of Skene's paraurethral glands and ducts.

The present findings support the theory that the female clear cell adenocarcinoma arises from the paraurethral duct[4]. However, it appears that female urethral adenocarcinoma has more than one tissue of origin with minority arising from the Skene's glands[10]. Morphologically, CCA of the urethral must be differentiated from nephrogenic adenoma of the urethra especially on biopsy. The predominance of clear cells, severe cytological atypia, high mitotic rate and necrosis favoured the diagnosis of CCA.

Because of the rarity of CCA in the urethra, the optimal treatment is unknown[211]. It seems to be based on the localisation of the primary tumour and the presence of metastasis. Radical cystourethrectomy with or without irradiation was performed in most cases[11]. The response to chemotherapy is also unclear[1112]. In our case, the patient didn’t receive any adjuvant therapy.