Abstract
Bladder cancer arising in a defunctionalized bladder after urinary diversion is rare. We report a 42-year-old man who developed pure small cell carcinoma 20 years after diversion for childhood trauma. Lower abdominal discomfort and increasing intravesical fluid accumulation prompted reevaluation. Preoperative biopsy was interpreted as urothelial carcinoma, whereas the cystectomy specimen revealed pure small cell carcinoma. He underwent radical cystectomy followed by adjuvant etoposide and cisplatin chemotherapy and remained recurrence-free for 15 years. This case highlights the importance of long-term follow-up, reassessment of new or worsening clinical findings, and recognition of potential sampling limitations of a small biopsy specimen.
Keywords: Defunctionalized bladder, Urinary diversion, Small cell carcinoma, Bladder cancer
Highlights
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To our knowledge, this is the first reported case of small cell carcinoma in a defunctionalized bladder.
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New or worsening findings should prompt evaluation for possible malignancy.
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A limited biopsy did not identify the small cell component preoperatively.
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Long-term follow-up is important after urinary diversion with bladder preservation.
1. Introduction
Retention of the native bladder after urinary diversion results in a defunctionalized bladder, which may be associated with long-term complications, including infection and fluid accumulation.1,2 However, because bladder cancer arising in a defunctionalized bladder is rare,3,4 its clinical characteristics remain poorly defined. Here, we report a case of small cell carcinoma arising in a defunctionalized bladder after urinary diversion for benign condition, in which the preoperative biopsy and cystectomy specimen showed discordant histological findings. We also review the literature focusing on the clinical presentation and characteristics of bladder tumors arising in the defunctionalized bladder.
2. Case presentation
An 8-year-old boy sustained a pelvic fracture and urethral disruption following a snowplow accident and was managed with cystostomy for a prolonged period. Fourteen years later, at the patient's request to discontinue the cystostomy catheter, urinary diversion with a Kock pouch was performed, while the native bladder was retained, resulting in a defunctionalized bladder. Fourteen years after urinary diversion (28 years after the initial injury), the patient developed diversion-related complications, including afferent limb stricture, pouch calculi, and recurrent pyelonephritis. Because these complications were difficult to manage, a right nephrostomy was performed, and catheterization of the pouch was also required. Approximately 16 years after urinary diversion, the patient presented with lower abdominal discomfort. Imaging studies demonstrated fluid accumulation within the defunctionalized bladder. Percutaneous aspiration yielded semen-like fluid and relieved the symptoms.
Nineteen years after urinary diversion, the fluid accumulation increased, and 1 year later, the patient was referred to our hospital. Magnetic resonance imaging demonstrated a 27× 26 × 29-mm mass within the defunctionalized bladder (Fig. 1). Antegrade cystoscopy of the defunctionalized bladder through the cystostomy tract revealed a bladder mass, and histopathological examination of the tumor biopsy was interpreted as urothelial carcinoma (G2). The patient underwent radical cystectomy of the defunctionalized bladder with standard pelvic lymph node dissection. The operative time was 5 h 30 min, and the estimated blood loss was 2210 mL. No perioperative blood transfusion was required. The postoperative course was uneventful, with no perioperative complications. Histopathological examination of the resected specimen (Fig. 2, Fig. 3) revealed pure small cell carcinoma (pT2aN0). Furthermore, immunohistochemical analysis showed positivity for CD56, synaptophysin, and cytokeratin AE1/AE3 in the cancer cells, with a Ki-67 (MIB-1) labeling index >95%. After the diagnosis of pure small cell carcinoma was established in the cystectomy specimen, the preoperative biopsy specimen was retrospectively re-reviewed by a pathologist; however, no morphological features of small cell carcinoma were identified. Postoperatively, adjuvant chemotherapy with etoposide and cisplatin (EP regimen: cisplatin 80 mg/m2 and etoposide 100 mg/m2) was administered for three cycles. Grade 4 leukopenia according to the Common Terminology Criteria for Adverse Events occurred during the first cycle, and the doses were reduced to 80% in subsequent cycles. The patient was subsequently followed with regular nephrostomy tube exchanges and catheterization of the Kock pouch. Thirty-four years after urinary diversion, percutaneous nephrolithotomy was performed for right renal calculi that made nephrostomy tube exchange difficult. The patient remained recurrence-free for 15 years after completing chemotherapy.
Fig. 1.
Magnetic resonance imaging of the defunctionalized bladder.
Axial (A) and coronal (B) magnetic resonance images demonstrating a bladder tumor measuring 27× 26 × 29 mm arising in the defunctionalized bladder (arrows).
Fig. 2.
Gross specimen of the resected bladder specimen.
Macroscopic examination of the cystectomy specimen revealed a bladder tumor measuring 36 mm in maximum diameter within the defunctionalized bladder. Arrow indicates the tumor.
Fig. 3.
Histopathological findings of the tumor arising in the defunctionalized bladder.
Histopathological examination demonstrated small cell carcinoma of the bladder (pT2aN0, Stage II). Hematoxylin and eosin staining showed diffuse proliferation of small atypical cells (A). Immunohistochemical staining was positive for CD56 (B), synaptophysin (C), and cytokeratin AE1/AE3 (D). The Ki-67 (MIB-1) labeling index exceeded 95% (E).
3. Discussion
Urinary diversion with retention of the native bladder may be selected for the management of benign conditions such as spinal cord injury, trauma, and neurogenic bladder, depending on the clinical context.1,3,5 As shown in Table 1 1, 2, 3, 4, 5, 6, 7, 8, 9, the defunctionalized bladder is associated with various long-term complications, including chronic inflammation, recurrent infection, pain and spasms, hemorrhage, and intravesical fluid accumulation.1,2,4 Infectious complications such as pyocystis are relatively common and may recur.4,5,8 In refractory cases, persistent infection, pain, or other complications may ultimately necessitate cystectomy.3,5,8 Although rare, malignant tumors have been reported in the defunctionalized bladder.6,7 Chronic inflammation and infection may contribute to tumor development8,10; therefore, bladder cancer should be considered a potential complication during long-term follow-up of patients with a defunctionalized bladder.
Table 1.
Summary of case series on clinical characteristics and complications of the defunctionalized bladder after urinary diversion.
| Author (Year) | Patients (n) | Follow-up after diversion (years) | Diversion Indication | Defunctionalized bladder complications | Cystectomy (n/total) | Cystectomy Indication | Malignancy (n/total) |
|---|---|---|---|---|---|---|---|
| Guerrier (1971) | 128 | NR | NR | infection, pain/spasm, other | 24/128 | NR | 1/128 |
| Albrich (1973) | 91 | 0.3–16 | Neurogenic/Congenital/Inflammatory/Benign disease | infection, pain/spasm, bleeding, other | 8/91 | bleeding | 2/91 |
| Eigner (1990) | 30 | Mean 3.6 | Neurogenic/Inflammatory/Radiation/Trauma/Benign disease | infection, pain/spasm, bleeding, other | 4/30 | infection (pyocystis) | 0/30 |
| Granados (1996) | 14 | 0.5–7 | Neurogenic/Inflammatory/Benign disease | infection, pain/spasm, bleeding, other | 1/14 | infection (pyocystis) | 0/14 |
| Adeyoju (1996) | 35 | Mean 5.2 (1–25) | Neurogenic/Inflammatory/Trauma/Congenital/Benign disease | infection, pain/spasm, bleeding | 4/35 | infection, pain/spasm, bleeding, other | 0/35 |
| Singh (1997) | 93 | Mean 5 (≥2) | Neurogenic (71/93)/Non-neurogenic (22/93) | infection | 5/93 | recurrent infection | 0/93 |
| Fazili (2006) | 24 | Median 4 (1–8) | Neurogenic/Non-neurogenic/Radiation/Benign disease | infection, bleeding | 6/24 | infection (pyocystis) | 0/24 |
| von Rundstedt (2010) | 9 | Median 10 | NR | infection, pain/spasm, bleeding | 1/9 | infection pain/spasm, bleeding | 2/9 |
| Lawrence (2013) | 60 | Mean 3.8 (0.8–8) | Neurogenic (28/60)/Non-neurogenic (32/60) | infection, pain/spasm | 0/60 | not performed | 0/60 |
Complications were categorized as infection, pain/spasm, bleeding, and other complications. Infection included pyocystis, empyema, recurrent urinary tract infection, and sepsis. Other complications included bladder distension, mucus retention, fistula formation, and miscellaneous reported events. Follow-up refers to the interval after urinary diversion.Abbreviations: NR, not reported.
As summarized in Table 2 6,7,9, 10, 11, 12, 13, reported initial symptoms of bladder cancer arising in the defunctionalized bladder include urethral bleeding, bloody or purulent discharge, recurrent infections, and lower abdominal pain or discomfort. However, these symptoms are also common complications of the defunctionalized bladder (Table 1) and are not specific to malignancy. Although these malignancies were diagnosed following clinical evaluation in several reported cases, some were incidentally identified in cystectomy specimens obtained for the management of complications (Table 2). These findings suggest that bladder cancer may remain clinically unrecognized during follow-up of patients with a defunctionalized bladder. Conversely, clinical symptoms may prompt further evaluation and lead to the diagnosis of malignancy (Table 2). In the present case, lower abdominal discomfort and increased intravesical fluid accumulation prompted reevaluation with endoscopic and imaging examinations, leading to the detection of the bladder tumor. Therefore, further evaluation, including endoscopic and imaging examinations, should be considered when patients with a defunctionalized bladder develop new or worsening clinical findings, such as bleeding, purulent discharge, or increased fluid accumulation. In addition, continued clinical attention to the defunctionalized bladder may be important during long-term follow-up.
Table 2.
Representative reported cases of bladder cancer arising in the defunctionalized bladder after urinary diversion.
| No. | Author (Year) | Age/Sex | Interval (years) | Symptoms/Evaluation | Detection | Histology | Treatment | Outcome |
|---|---|---|---|---|---|---|---|---|
| 1 | Guerrier (1971) | NR | NR | NR | NR | UC | Cx | NR |
| 2 | Albrich (1973) | NR | 2 | Urethral bleeding | Preoperative | NR | Unresectable | NR |
| 3 | Albrich (1973) | NR | 7 | Urethral bleeding | Preoperative | NR | Unresectable | NR |
| 4 | Moloney (1981) | 38/M | 16 | Intractable pyocystis | Incidental | SCC | Cx | Recurrence (2 years) |
| 5 | Moloney (1981) | 23/M | 11 | Pyocystis; bladder perforation | Incidental | SCC | Cx | DOD (6 weeks) |
| 6 | Moloney (1981) | 42/F | 15 | Vesicovaginal fistula, bloody vaginal discharge | Preoperative | UC | Cx | DOD (5 weeks) |
| 7 | Djavan (1995) | 31/M | 30 | Bloody urethral discharge; cystoscopy/TURBT | Preoperative | Mucinous adenocarcinoma | Cx | AWD |
| 8 | Djavan (1995) | 54/M | 8 | UTI, purulent urethral discharge | Preoperative | Adenocarcinoma | Debulking Cx | DOD |
| 9 | Taneous (2009) | 57/M | 30 | Blood-streaked mucous urethral discharge; Prostate biopsy/cystoscopy |
Preoperative | Mucinous adenocarcinoma | Cx → CRT | DOD (29 months) |
| 10 | von Rundstedt (2010) | NR | NR | NR | NR | NR | NR | NR |
| 11 | von Rundstedt (2010) | NR | NR | NR | NR | NR | NR | NR |
| 12 | Morikawa (2024) | 44/M | 26 | Urethral bleeding; imaging/biopsy | Preoperative | UC | NAC → Cx → adj. IO | NED (5 months) |
| 13 | Present case | 42/M | 20 | Lower abdominal discomfort, fluid retention; imaging/cystostomy drainage | Preoperative | Small cell carcinoma | Cx → adj. EP | NED (15 years) |
Detection indicates whether the diagnosis was established preoperatively or made incidentally after surgery. Interval refers to the time from urinary diversion to diagnosis.Abbreviations: adj., adjuvant; AWD, alive with disease; CRT, chemoradiotherapy; Cx, cystectomy; DOD, died of disease; EP, etoposide plus cisplatin; IO, immunotherapy; NAC, neoadjuvant chemotherapy; NED, no evidence of disease; NR, not reported; SCC, squamous cell carcinoma; TURBT, transurethral resection of bladder tumor; UC, urothelial carcinoma; UTI, urinary tract infection.
A key diagnostic challenge in the present case was the discrepancy between the preoperative biopsy and the cystectomy specimen. In this patient, conventional transurethral evaluation was limited because of the previous urethral disruption, and antegrade cystoscopy and biopsy were therefore used for tumor evaluation. The preoperative biopsy was interpreted as urothelial carcinoma, whereas the cystectomy specimen revealed pure small cell carcinoma. On retrospective review, no morphological features of small cell carcinoma were identified in the biopsy specimen. A previous study of urothelial carcinoma with variant histology showed that histological assessment can be affected by the extent of tumor sampling, particularly in limited biopsy specimens.14 The limited volume of the biopsy specimen may therefore have contributed to the histological discrepancy in the present case. Accordingly, when malignancy is suspected, evaluation with imaging and endoscopy, together with histopathological assessment, is important, and the potential sampling limitations of a small biopsy specimen should be recognized.
Various histological types of bladder cancer have been reported in the defunctionalized bladder, including urothelial carcinoma, adenocarcinoma, and squamous cell carcinoma (Table 2). Although urothelial carcinoma accounts for the vast majority of bladder cancers in general,15 several nonurothelial histological types have also been reported in the defunctionalized bladder (Table 2). Chronic inflammation and infection in the defunctionalized bladder may contribute to carcinogenesis through sustained cell proliferation and inflammation-associated DNA damage.16 To our knowledge, based on a PubMed literature search conducted on September 10, 2026, this is the first reported case of small cell carcinoma arising in a defunctionalized bladder. The present case may therefore expand the histological spectrum of malignancies reported in the defunctionalized bladder.
Small cell carcinoma of the bladder is a highly aggressive malignancy characterized by early systemic dissemination and poor prognosis.17 Because of its rarity, treatment recommendations are largely based on evidence extrapolated from small cell lung cancer, and multimodal treatment incorporating platinum-based chemotherapy is generally recommended.17 Among these regimens, etoposide plus cisplatin (EP) is a representative systemic chemotherapy regimen and is widely incorporated into multimodal treatment strategies for small cell carcinoma of the bladder.17,18 Because the small cell component was not identified in the preoperative biopsy specimen, neoadjuvant chemotherapy for small cell carcinoma was not administered. The definitive diagnosis of pure small cell carcinoma was established only after pathological examination of the cystectomy specimen, after which adjuvant EP chemotherapy was administered. The patient remained recurrence-free for 15 years following radical cystectomy and adjuvant EP chemotherapy. Although the contribution of adjuvant chemotherapy to this favorable outcome cannot be determined from a single case, the present case demonstrates the feasibility of multimodal treatment for localized small cell carcinoma of the bladder.
Long-term follow-up is important because the interval between urinary diversion and the diagnosis of bladder cancer in the defunctionalized bladder can be prolonged, with several reported cases diagnosed decades after diversion (Table 2). Given these long intervals, the incidence of bladder cancer may be underestimated in the case series summarized in Table 1. Therefore, appropriate follow-up duration and surveillance strategies should be further investigated to improve the detection of bladder cancer in the retained bladder.
The role of concomitant primary cystectomy during urinary diversion remains controversial because of concerns regarding perioperative morbidity and its impact on quality of life. Although concomitant cystectomy has been advocated in some reports, others suggest that it is not routinely required.4,5 Recent advances in surgical techniques, including robot-assisted approaches, suggest that concomitant cystectomy during urinary diversion for benign conditions may not increase perioperative morbidity.19 However, other reports have demonstrated relatively high complication rates and perioperative risks associated with cystectomy for non-bladder cancer conditions.20 Therefore, the surgical strategy should be individualized according to the patient's clinical background, taking into consideration the potential future risk of bladder cancer development and long-term complications.
4. Conclusion
We report a rare case of small cell carcinoma arising in a defunctionalized bladder after urinary diversion for benign condition, with long-term recurrence-free survival following multimodal treatment combining surgery and systemic therapy. Because symptoms of bladder cancer arising in a defunctionalized bladder can resemble those of common complications, careful long-term follow-up is important, and new or worsening clinical findings should prompt further evaluation for possible malignancy. When histological evaluation is based on a limited biopsy specimen, its potential sampling limitations should also be recognized.
CRediT authorship contribution statement
Taketoshi Nara: Writing – original draft, Investigation, Data curation, Conceptualization. Hiromi Sato: Supervision. Mizuki Kobayashi: Supervision. Ryohei Yamamoto: Supervision. Mitsuru Saito: Supervision. Shintaro Narita: Writing – review & editing, Conceptualization.
Ethics declaration
Written informed consent to take part in the study and to publish the article has been obtained from all participants or their legal representatives. The privacy rights of participants have been observed.
This study included organ or tissue donors. This study includes human biological material and consent was obtained by donors, or their next of kin or legal representatives, for use in this study and for publication of the article. The samples used in this research were not sourced from executed prisoners or prisoners of conscience.
This study was performed in compliance with relevant laws, regulatory frameworks and guidelines where the research took place. Ethics committee approval was not required under relevant laws and institutional guidelines. Ethics committee approval was not required for this single-patient case report in accordance with the institutional guidelines of Japanese Red Cross Akita Hospital and Akita University Graduate School of Medicine.
This research follows the CARE guidelines and the CARE checklist.
Informed consent
Written informed consent was obtained from the patient for publication of this case report and the accompanying images.
Data availability
The data are available from the corresponding author upon reasonable request but are not publicly available because of privacy and ethical restrictions.
Funding sources
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
We have nothing to declare.
Acknowledgments
We thank Dr. Naotake Shimoda, Dr. Yohei Horikawa, and Dr. Naoko Honma of the Japanese Red Cross Akita Hospital for their contributions to the treatment of urinary calculi in this patient. We are particularly grateful to Dr. Yohei Horikawa for his involvement from the early phase of treatment and to Dr. Tomonori Habuchi, former Professor of the Department of Urology, Akita University Graduate School of Medicine, for valuable advice regarding the overall treatment strategy throughout the clinical course.
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Associated Data
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Data Availability Statement
The data are available from the corresponding author upon reasonable request but are not publicly available because of privacy and ethical restrictions.