Case Report Open Access
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World J Clin Cases. Sep 16, 2025; 13(26): 104876
Published online Sep 16, 2025. doi: 10.12998/wjcc.v13.i26.104876
Urothelial carcinoma arising in orthotopic ileal neobladder reconstruction: A case report
Miki Murakami, Hirotsugu Noguchi, Mari Kirishima, Takashi Tasaki, Ikumi Kitazono, Michiyo Higashi, Akihide Tanimoto, Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
Ryosuke Matsushita, Shuichi Tatarano, Hideki Enokida, Department of Urology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
ORCID number: Miki Murakami (0009-0000-7730-5257); Hirotsugu Noguchi (0000-0003-3738-9219); Ryosuke Matsushita (0000-0001-9399-956X); Shuichi Tatarano (0000-0003-4224-5084); Mari Kirishima (0000-0002-6997-8336); Takashi Tasaki (0000-0002-4211-3324); Ikumi Kitazono (0000-0002-6746-6695); Michiyo Higashi (0000-0003-2723-1063); Hideki Enokida (0000-0002-3050-9700); Akihide Tanimoto (0000-0001-7508-1624).
Co-first authors: Miki Murakami and Hirotsugu Noguchi.
Author contributions: Murakami M and Noguchi H performed the pathological analysis and wrote the initial draft of the manuscript; Matsushita R, Shuichi Tatarano, and Enokida H were the patient’s surgeons, reviewed the literature, and contributed to manuscript drafting; Kirishima M, Tasaki T, Kitazono I, and Higashi M performed the pathological examination, reviewed the literature, and contributed to manuscript drafting; Tanimoto A was responsible for revising the manuscript for important intellectual content; all authors have read and approved the final manuscript.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that there is no potential conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Akihide Tanimoto, MD, PhD, Professor, Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. akit09@m3.kufm.kagoshima-u.ac.jp
Received: January 5, 2025
Revised: April 18, 2025
Accepted: June 4, 2025
Published online: September 16, 2025
Processing time: 199 Days and 17.5 Hours

Abstract
BACKGROUND

An ileal neobladder is a standardized form of urinary diversion that provides acceptable outcomes in terms of long-term quality of life. Urothelial carcinomas (UCs) arising in the ileal neobladder are extremely rare, and few reports on this have been published in the English language.

CASE SUMMARY

We report a case of UC that developed in the ileal neobladder of a 63-year-old man. The patient was diagnosed with UC in situ and underwent radical cystoprostatectomy and ileal neobladder creation. Ten years after the surgery and neoadjuvant chemotherapy, an UC developed in the ileal neobladder.

CONCLUSION

Ileal neobladder urothelial carcinoma can originate from the implanted urothelium and the intestinal mucosa can migrate intraluminally.

Key Words: Bladder cancer; Urothelial carcinoma; Radical cystectomy; Ileal neobladder; Recurrence; Case report

Core Tip: The simultaneous or metachronous occurrence of multifocal tumors in the urinary tract is characteristic of urothelial carcinoma (UC), and many patients experience recurrence post-surgery. However, recurrence of UC in ileal neobladders is extremely rare. Most cases of UC in the ileal neobladder are initially diagnosed as muscle-invasive bladder cancers. In this case, the pathological stage of the resected bladder after neoadjuvant chemotherapy was UC in situ. Patients who have undergone ileal neobladder surgery should be carefully followed up for a long period because the exfoliated tumor cells could “seed and implant” in the bladder and non-urothelial epithelium.



INTRODUCTION

Bladder cancer was the 10th most common malignancy of the urinary tract worldwide in 2020, accounting for 3% of global cancer diagnoses. It is the 13th most common cause of cancer-related mortality worldwide, and its prevalence is particularly high in high-income nations. The risk factors for bladder cancer include advanced age, smoking, and occupational and environmental exposure to toxins[1]. The urothelial cells lining the bladder and urinary tract are exposed to several chemicals that can cause genetic mutations[1]. Transurethral resection of bladder tumors is the initial treatment for non-muscle-invasive bladder cancer (MIBC), and is essential for diagnosis and staging. The standard treatment for MIBC is radical cystectomy and ileal conduit or ileal neobladder construction preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumors in eligible patients[2]. Ileal neobladders have become the preferred form of urinary diversion in patients undergoing radical cystectomy because they are associated with a lower risk of secondary tumors than colonic neobladders[3]. Some cases of secondary adenocarcinoma developing in the ileal neobladder have been reported, as well as a few cases urothelial carcinoma (UC) replacing the bowel segment[4]. Although UCs are widely acknowledged to be multifocal, its etiology in urinary diversion remains unclear. Here, we report a unique case of UC that developed at the site of the ileal neobladder anastomosis after cystectomy for bladder cancer and NAC in a 63 year old man.

To the best of our knowledge, no case of UC in the ileal neobladder after radical cystectomy for UC in situ (UCIS) has ever been reported. This case suggests that any UC treated with an ileal neobladder should be carefully followed-up after radical cystectomy.

CASE PRESENTATION
Chief complaints

A 63-year-old man who had undergone radical cystoprostatectomy and ileal neobladder reconstruction 10 years previously presented with dysuria, hematuria, and nausea.

History of present illness

The patient’s symptoms started two months prior to admission. He had been treated for type 2 diabetes mellitus (T2DM) and diagnosed with chronic kidney disease.

History of past illness

Ten years prior, he was diagnosed with high-grade UC with muscle invasion of the urinary bladder. Laboratory data of creatinine (0.73 mg/dL, normal range: 0.6-1.1 mg/dL) and blood urea nitrogen (14.2 mg/dL, normal range: 8-22 mg/dL) were within normal limits. Computed tomography (CT) revealed no evidence of metastases. The patient received NAC consisting of two courses of cisplatin and gemcitabine. Radical cystoprostatectomy and ileal neobladder creation were performed. Histopathological findings revealed UCIS spreading from the apex to the trigone in the resected urinary bladder with no lymph node metastasis. No cancer was detected in the urethra and all surgical margins were negative. After the surgery, the patient was closely followed-up with urine cytology and imaging at regular intervals.

Personal and family history

The patient was on medications for hypertension, T2DM, and dyslipidemia. The patient had smoked 30 cigarettes per day for 30 years until the age of 50 years. There was no relevant family history.

Physical examination

Upon admission, the systolic blood pressure was 113 mmHg, diastolic was 70 mmHg, and respiratory rate was 18/minute. His body weight, height, and surface area were 58.3 kg, 150 cm, and 1.38 m2 respectively.

Laboratory examinations

Laboratory tests revealed elevated creatinine (1.63 mg/dL) and urine nitrogen levels (32.4 mg/dL). Urinalysis revealed increased red blood cell and leukocyte counts (19 cells/high-power field and 99 cells/high-power field, respectively).

Imaging examinations

Cystoscopic examination revealed a papillary tumor measuring 20 mm × 15 mm, located in the left lateral region of the ileal neobladder (Figure 1A). The tumor was not connected to the anastomotic site. CT confirmed there was no metastasis to the pelvic lymph nodes nor any tumorous regions in the bilateral kidney pelvises and ureters. The biopsy specimen revealed UC with a papillary structure. Based on the diagnosis of UC of the ileal neobladder, the patient underwent neocystectomy.

Figure 1
Figure 1 Cystoscopic and macroscopic appearance. A: Cystoscopy reveals a papillary tumor with white exudate adherent in the left lateral side of the ileal neobladder, which was located distal to the anastomosis (yellow arrowhead); B: Macroscopic appearance of the resected specimen showing an irregular papillary surface with exophytic growth pattern in the ileal neobladder measuring 20 mm × 15 mm. The tumor is located in the left wall of the ileal neobladder (yellow arrow); C: The cut surface of the tumor is grey to white in color.
Pathological examinations

Gross examination revealed papillary tumor proliferation in the left lateral region of the ileal neobladder measuring 20 mm × 15 mm (Figure 1B). There were no tumors in the anastomosis or the remaining urethra. The cut surface of the tumor was gray to white in color (Figure 1C). Histological examination revealed a high-grade papillary UC without glandular differentiation (Figure 2A and B). The tumor cells were arranged in papillae with fibrous stroma. The boundary between the UC and the surrounding normal intestinal mucosa was clearly demarcated. Invasion of the submucosa of the ileal neobladder was also observed. Immunohistochemical examination revealed that the tumor cells were positive for GATA binding protein 3 (Figure 2C), but negative for cluster of differentiation 10 (not shown). No UC was observed in the urethra. Background ileal mucosa showed moderate atrophic changes; however, no urothelial metaplasia was observed.

Figure 2
Figure 2 Microscopic and immunohistochemical findings. A: The loupe section shows that the papillary arrangement of urothelium with a fibrovascular core. [hematoxylin and eosin (HE) stain, magnification 10 ×]; B: Significant architectural and nuclear atypia, including loss of polarity (HE stain, magnification 200 ×); C: Immunohistochemical staining for GATA binding protein 3 reveals positivity in urothelial carcinoma (immunostaining, magnification 200 ×).
FINAL DIAGNOSIS

The final diagnosis was UC of the ileal neobladder.

TREATMENT

He underwent neocystectomy with lymphadenectomy and an ileal conduit reconstruction.

OUTCOME AND FOLLOW-UP

The patient was discharged 21 days postoperatively without any adverse events and received one-year postoperative chemotherapy with nivolumab. The patient was monitored at regular intervals by physical examination, urine cytology, and diagnostic imaging. The patient remained in stable condition without disease recurrence for 6 months after surgery.

DISCUSSION

Herein, we report a rare case of UC that developed in the ileal neobladder after radical cystoprostatectomy for UCIS. Primary malignancies after bladder substitution typically develop in the area of anastomoses with the remaining urinary tract or in the uretero-ileal or urethro-ileal anastomoses[5]. Although the most common histological subtype of malignancy in intestinal urinary diversion is adenocarcinoma[6], 20 cases of UC that developed in the ileal neobladder without urinary tract recurrence have been reported in the literature (Table 1)[4,7-15]. Most patients who develop neobladder carcinoma are initially diagnosed with high-grade UC with MIBC. Only one case of UCIS diagnosed before radical cystectomy has been reported; however, that case did not indicate where the recurrence occurred in the neobladder or urethra[7]. The recurrence period after the initial surgery ranges from 3 months to 161 months[4]. The UC recurrence rate in the urethra after radical cystectomy and ileal neobladder reconstruction ranges from 2.8% to 6%[16,17]. In our case, the patient was initially diagnosed with MIBC by transurethral resection of a bladder tumor and underwent NAC. The final diagnosis after radical cystoprostatectomy was UCIS without lymph node metastasis, and the ureteral margins were negative; however, UC developed in the ileal neobladder 10 years after surgery. This case shows that the initial diagnosis is important for predicting recurrence, even if the tumor volume is reduced after NAC.

Table 1 Clinical and pathological characteristics of cases of urothelial carcinoma developing in the ileal neobladder following initial resection.
Ref.
Number of case
Age/sex
Pathological diagnosis
Initial stage
Localization of recurrence
Recurrence period
Oberneder et al[7]6NSUCpTis-pT4aNSNS
Hadzi-Djokić et al[8]165/MUC, grade 2pT2Right wall12 years
Yamashita et al[9]174/MUC, high gradepT3aRight and anterior wall3 years
Cakmak et al[10]140/FUC, grade 2pT1Left wall (multifocal)11 years
Moeen et al[11]159/FUC, high gradepT2Bilateral wall (multifocal)18 months
Cherbanyk et al[12]166/MUC, grade 2-3pT3aAnterior and left wall9 years
Doshi et al[13]171/MUC, high gradepT3aLeft anterioinferior wall11 years
Pardalidis et al[14]156/MUC, grade 3pT3aNS10 years
Dadikhi et al[15]178/MUC, grade 3pT2Entier (multifocal)4 years
Collins et al[4]657/MUC, high gradepT2aNS30 months
57/MUC, sarcomatoidpT2bNS3 months
58/MUC, high gradepT2aNS41 months
80/MUC, glandularypT2bNS44 months
72/MUC, plasmacytoidypT3aNS12 months
79/MUC, micropapillarypT2bNS161 months
Present case163/MUC, high gradeypTis (pT2 befor neoadjuvant chemotherapy)Left wall112 months

Several studies have proposed two hypotheses to explain the mechanism of UC. The first is the “field carcinogenesis” theory, which posits that normal urothelial cells have malignant genetic background to develop UC[18]. The consequence is the multifocal occurrence of carcinoma in situ. Several molecular genetic studies support the theory that multifocal UCs result from clonal evolution of a single transformed cell[19,20]. The second hypothesis is that the exfoliated tumor cells seed and implant at another site in the urinary tract[21]. Papillary UC of the upper urinary tract frequently recurs in the bladder (15%-50%)[22]. The latter hypothesis explains the potential of UC implantation not only in the urothelium of the bladder, but also in the ileal mucosa of a neobladder[21].

The pathogenesis of the present case of UC that recurred in the small intestinal mucosa of ileal neobladder could be explained by the “seed and implantation” theory, because there was no recurrent UC lesion in the urinary tract or anastomosis site. Intraluminal tumor cell seeding as the source of multiple synchronous or metachronous urothelial tumors should be considered a potential factor contributing to the multifocal recurrence of UC in tissues other than the urothelium.

CONCLUSION

We have highlighted a rare case of UC of the ileal neobladder in this case report and highly recommend regular follow-up with standard management protocols for detecting early stage recurrence in the ileal neobladder.

Footnotes

Provenance and peer review: Unsolicited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Medicine, research and experimental

Country of origin: Japan

Peer-review report’s classification

Scientific Quality: Grade B, Grade B

Novelty: Grade B, Grade C

Creativity or Innovation: Grade B, Grade C

Scientific Significance: Grade B, Grade B

P-Reviewer: Zou YZ S-Editor: Luo ML L-Editor: A P-Editor: Zhang L

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