Primary urothelial carcinoma of the prostate: A rare case report.

RATIONALE: Prostatic urothelial carcinoma is a rare disease. Medical misdiagnosis rates remain high because there are no specific clinical symptoms or imaging features, which decreases patient survival. We report a case of prostatic urethral cancer confirmed by transrectal ultrasound-guided prostate biopsy because of an abnormal digital rectal exam. PATIENT CONCERNS: A 55-year-old man was referred to our hospital due to lower urinary tract symptoms that lasted for 5 years. DIAGNOSES AND
INTERVENTIONS: On digital rectal examination, a hard and enlarged prostate was detected. Computed tomography, bone scintigraphy, and magnetic resonance imaging indicated benign prostatic hyperplasia. The patient underwent transrectal ultrasound-guided prostate biopsy. From the histopathological examination and immunohistochemical markers, a diagnosis of high-grade prostatic urothelial carcinoma was made. We excluded the possibility of urothelial cancer originating in the bladder lining after transurethral resection of the bladder. Radical cystoprostatectomy was performed, followed by 6 cycles of cisplatin and gemcitabine chemotherapy. Postoperative pathology showed primary urothelial carcinoma of the prostate. OUTCOMES: The patient recovered smoothly after surgery. After a 6-month follow-up, no evidence of local recurrence or metastatic disease was found. LESSONS: This case reminds clinicians that, for middle-aged men with suspicious digital rectal examinations, a diagnosis of prostatic urothelial carcinoma should be considered. Initial radical surgery followed by combination chemotherapy is suggested for therapeutic management.

Introduction

Primary urothelial carcinoma of the prostate is a rare solid malignant tumor that exhibits highly aggressive biological behavior and has a poor prognosis. Due to the high aggressiveness and strong tendency of local recurrence and distant metastasis to organs such as the bladder, seminal vesicle, and ureter, the overall prognosis of prostatic urothelial carcinoma is poor. These patients all die within 2 years of diagnosis.[

Only limited data on this malignancy have been reported.[ Due to the lack of specificity, the diagnosis of prostatic urothelial carcinoma is mainly based on pathology and immunohistochemistry. For instance, CK7, P63, and GATA-3 expression are critical evidence for diagnosis.[

There are many treatment strategies for prostatic urothelial carcinoma, including surgery, adjuvant chemotherapy, and radiotherapy. Owing to the high aggressiveness and obvious tendency of local recurrence and remote metastases, the overall prognosis of prostatic urothelial carcinoma is poor.[ We present the clinical characteristics, histopathological and immunohistochemical findings, and treatment outcomes in a new case of prostatic urothelial carcinoma in a 55-year-old man.

Case report

A 55-year-old man was referred to our hospital because of a 5-year history of lower urinary tract obstructive symptoms. Apart from hepatitis B that was treated 10 years previously, no accompanying disease was present. Abdominal examination was unremarkable, and digital rectal examination showed an enlarged and hard prostate with a prostate-specific antigen (PSA) of 0.01 ng/mL. The patient underwent further evaluation, including bone scintigraphy, and magnetic resonance imaging (MRI) (Fig. 1), which revealed no metastasis.

Figure 1

MRI concluded benign prostatic hyperplasia. MRI = magnetic resonance imaging.

Subsequently, he underwent transrectal ultrasound-guided biopsy of the prostate. Histopathological examination showed high-grade prostatic urothelial carcinoma [Immunohistochemistry: CK5/6(−), CK7(+), CgA(−), GATA-3(+,55%), P40(+), P504s(−), P63(+), PSA(−), Syn(−), uroplakim III(+), and CD56(−)] (Figs. 2 and 3).

Figure 2

Transrectal prostatic biopsy and negative pathological staining. A. Transrectal prostatic biopsy (HE × 100) B. Transrectal prostatic biopsy (HE × 400) C. Diffusely negative staining for PSA.D. Diffusely negative staining for P504 s. MRI = magnetic resonance imaging.

Figure 3

Positive pathological staining. A. Diffusely positive staining for GATA-3. B. Diffusely positive staining for Uroplakim III. C. Diffusely positive staining for CK7. D. Diffusely positive staining for P63.

The patient subsequently underwent transurethral resection of the bladder, which revealed normal urethral mucosa and bladder tissue. Soon after, the patient was readmitted to the urology department and experienced severe dysuria. All of his laboratory data were within the normal ranges, except for a slight increase in reticulocyte (1.61%). Considering his pathological outcome and general health, radical cystoprostatectomy was performed. Ten days after the successful operation, the patient was discharged without any complications. The results of the histopathological examination showed primary urothelial carcinoma of the prostate (Fig. 4A and B). Furthermore, the tumor had invaded the prostatic stroma, duct, acinar, bladder mucosa, and right seminal vesicle. One and 3 lymph node metastases were found around the left and right iliac vessels, respectively (Fig. 4C). After radical surgery, the patient underwent 6 cycles of cisplatin and gemcitabine without any evident harmful reactions. Computed tomography (CT) found no tumor recurrence during the 6-month follow-up period (Fig. 4D). Informed consent was signed by the patients for the publication of related images and this report.

Figure 4

Postoperative pathology and imaging data A. Postoperative prostate tissue (HE × 100) B. Postoperative prostate tissue (HE × 400). C. Postoperative gross specimen, Left lymph node (red arrow), right lymph node (blue arrow) and Right ureteral stump (green arrow) D. Postoperative CT image. CT = computed tomography.

Discussion

Primary urothelial carcinoma of the prostate, first reported by Ende et al[ in 1963, is an extremely rare tumor, accounting for about 1% to 5% of all prostatic carcinomas.[ It manifests in middle-aged men, with a mean age of 54 at diagnosis, and patients are almost 10 years younger than prostatic adenocarcinoma patients.[ Prostatic urothelial carcinoma presents with nonspecific symptoms, including obstructive voiding, hematuria, and other symptoms similar to the main manifestations of benign prostatic hyperplasia or prostatic adenocarcinoma.[ Digital rectal examination always reveals that the prostate is enlarged and hard. Laboratory parameters are mostly within normal ranges, and CT, bone scintigraphy, and MRI also do not display any characteristic signs.[

Due to the need to improve the accuracy of preoperative detection, transrectal prostate biopsy and transurethral resection biopsy of the lower urinary tract are recommended to detect the presence of transitional cell carcinoma.[ There is a wide spectrum of recommendations for expanding the scope of transurethral resection biopsy. Liedberg et al[ recommend the range of transurethral resection biopsy include the area around the verumontanum. Donat et al[ recommend examining the bladder neck, trigone, and prostatic urethra by transurethral loop biopsies, along with an ultrasound-guided biopsy of the prostate.

The diagnosis of prostatic urothelial carcinoma is mainly grounded in the combination of histopathology and immunohistochemistry. Pathological examination always shows invasion into the prostate, and the tumor forms many small nests, often with marked nuclear pleomorphism and variably present nucleoli. Immunohistochemically, prostatic urothelial carcinoma is frequently positive for CK7 and CK20,[ a vital clue for diagnosis. Moreover, prostatic urothelial carcinoma is generally negative for PSA and P504 s, which is also significant for differential diagnosis.[ In addition, almost two-thirds of prostatic urothelial carcinomas have P63 and HMWCK expression. Other markers such as GATA-3 and uroplakim III have also been detected.[

Treatment strategies for prostatic urothelial carcinoma are multimodal, including surgery, adjuvant chemotherapy, and radiotherapy. Walsh et al[ reported that urothelial carcinoma infiltration of different anatomical locations within the prostate (i.e., the mucosa, acini, ducts, and stroma) was closely correlated with treatment method and prognosis. Several reports have found that complete resection of the visible tumor and intravesical instillation of Bacillus Calmette-Guérin (BCG) is the preferred treatment for carcinoma in situ (CIS) in the prostatic urethral mucosa.[ Treatment of urothelial carcinoma invading the prostatic ducts is still a controversial issue. Many scholars advocate radical surgery in patients with ductal invasion,[ whereas Palou Redorta et al reported that patients with CIS involving the prostatic ducts could be treated with intravesical BCG, which has a 70% complete response rate.[ When prostatic stromal invasion is identified, radical cystoprostatectomy should be performed. Furthermore, many patients undergo cystoprostatectomy as the initial treatment, which has a survival advantage.[ Little information is available about the results of chemotherapy in patients with prostatic urothelial carcinoma. The current adjuvant chemotherapy regimens of prostatic urothelial carcinoma include doxorubicin, cyclophosphamide, and cisplatin substituted by gemcitabine and cisplatin.[ When the tumor is confined to the prostate tissue or pelvis, radiotherapy is also recommended.[

Conclusion

Prostatic urothelial carcinoma is a very rare disease with high aggressiveness and poor prognosis. In middle-aged men with suspicious dysuria or a firm prostate, a diagnosis of prostatic urothelial carcinoma should always be considered. The gold standard to diagnose prostatic urothelial carcinoma is grounded in histologic and immunohistochemical analysis. Combined radical surgery with chemotherapy is recommended to manage the disease.

Author contributions

Investigation: Zhaoxiang Lu.

Methodology: Jun Zhou, Zhaoxiang Lu, Chaozhao Liang.

Resources: Jun Zhou.

Supervision: Cheng Yang, Sheng Tai.

Validation: Li Zhang, Yu Yin.

Writing – original draft: Zhaoxiang Lu.

Writing – review & editing: Chaozhao Liang.