膀胱小細胞神經内分泌癌合併尿路細胞上皮癌：病例分享
柯旭承¹、翁瑋駿¹、歐宴泉¹、童敏哲¹ 

童綜合醫療社團法人童綜合醫院 外科部 泌尿科  

Small cell neuroendocrine carcinoma with coexistence of high grade urothelial carcinoma of urinary bladder: a case sharing 

Hsu-Cheng Ko¹、Wei-Chun Weng ¹、Yen-Chuan Ou¹、Min-Che Tung ¹ 

¹ Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung City, Taiwan  

ABSTRACT 

Background: 

Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder is a rare entity, accounting for less than 1% of all bladder malignancies. It is characterized by an aggressive clinical course, rapid progression, and a high propensity for early metastasis, most commonly affecting older male patients. Histologically, a mixed phenotype is frequently observed, with SCNEC admixed with high-grade urothelial carcinoma in a substantial proportion of cases. Reported series indicate that coexistent urothelial carcinoma components are present in approximately 55% to 70% of bladder SCNEC cases.

Case presentation: 
A 76-year-old man with a medical history of hypertension and chronic hepatitis B presented to the outpatient clinic with several weeks of persistent hematuria. Ultrasonography of the bladder revealed a 3.7 × 2.5 cm mass at the dome with positive Doppler vascular signals. Cystoscopic evaluation followed by bipolar transurethral resection of bladder tumor (TURBT) was performed (Figure 1A, 1B). Histopathological examination confirmed SCNEC with focal areas of high-grade urothelial carcinoma and invasion into the lamina propria. Immunohistochemical staining was positive for synaptophysin and CD56.

Postoperative staging workup, including computed tomography (CT) and whole-body bone scintigraphy, showed no evidence of visceral, nodal, or osseous metastasis. The disease was staged as grade 3, cT1N0M0, stage I. The patient subsequently received three cycles of adjuvant chemotherapy with cisplatin and etoposide. Despite this, he developed recurrent high-grade papillary urothelial carcinoma, which proved refractory to intravesical Bacillus Calmette–Guérin (BCG) instillation and adjuvant cisplatin–gemcitabine chemotherapy. Nine months after the initial diagnosis, he underwent laparoscopic radical cystectomy with pelvic lymph node dissection and ileal conduit urinary diversion. At present, the patient remains disease-free, with no evidence of recurrence, two years following the initial diagnosis of bladder SCNEC.

Discussion:

SCNEC of the urinary bladder typically arises in older adults, demonstrates a male predominance, and most often presents with painless hematuria. It is a rare but highly aggressive malignancy, histologically characterized by small, round-to-oval cells with scant cytoplasm, nuclear molding, and brisk mitotic activity. As a member of the neuroendocrine tumor family, it closely parallels small cell lung carcinoma in both histopathologic and immunohistochemical features, including frequent expression of neuroendocrine markers such as synaptophysin, chromogranin, and CD56 [1,2]. Diagnosis is established based on morphologic criteria analogous to those applied in small cell lung carcinoma, supplemented by confirmatory immunohistochemistry.

Management is stage-specific and generally multimodal. In limited-stage disease, the preferred approach is neoadjuvant cisplatin/etoposide chemotherapy followed by radical cystectomy or, alternatively, definitive radiotherapy. Neoadjuvant chemotherapy (typically 4–6 cycles) has been shown to improve pathologic downstaging, reduce recurrence risk, and prolong both disease-free and overall survival [3]. Comparative series suggest superior outcomes with neoadjuvant chemotherapy plus cystectomy, yielding median overall survival (OS) of 45–64 months, compared with 23–29 months for concurrent chemoradiation; both approaches outperform monotherapy with surgery or radiotherapy alone [4].

For metastatic disease, platinum-based chemotherapy—most commonly cisplatin/etoposide—remains the standard of care, largely extrapolated from small cell lung cancer treatment paradigms. Despite this, the prognosis is dismal, with median OS typically less than 15 months [5]. Radiotherapy in this setting is most often employed for palliation of symptomatic metastatic lesions, such as those in bone or brain [6].

Conclusion: 
SCNEC of the urinary bladder of the urinary bladder is a rare and highly aggressive neoplasm that frequently presents in association with high-grade urothelial carcinoma. Current consensus recommends a multimodal treatment approach for both pure and mixed histologic subtypes. The standard strategy typically involves neoadjuvant platinum-based chemotherapy followed by radical cystectomy or, alternatively, definitive chemoradiation. Survival outcomes appear comparable between pure SCNEC and mixed SCNEC with urothelial carcinoma components.