Primary adenocarcinoma arising in an ileal neobladder is an exceptionally rare long-term complication following radical cystectomy. We report a rare case of intestinal-type adenocarcinoma arising in an ileal neobladder over 30 years after radical cystectomy.

A 70-year-old man, treated for muscle-invasive bladder cancer with radical cystectomy and ileal neobladder reconstruction 30 years ago, presented with gross hematuria for two weeks. He had been lost to follow-up for two decades. His comorbidities also included SLE, multiple myeloma, and chronic thrombocytopenia. Initial workup revealed microscopic hematuria, negative cytology, and no recurrence on CT. Cystoscopy in January 2024 revealed only fragile mucosal near the bladder neck; and the bleeding was initially attributed to thrombocytopenia. However, recurrent UTIs, mild incontinence, and hematuria persisted during the following period despite treatment. In January 2025, repeat cystoscopy revealed necrotic tumor-like lesions at the neck of neobladder and TURBT confirmed intestinal-type adenocarcinoma with mucin pools and pleomorphic gland-forming cells, with immunopositive for CK7, CK20, CDX2, and negative for GATA3. We planned a neobladder resection with a new ileal-conduit reconstruction, but a firm supraumbilical subcutaneous nodule was found and incision biopsy proved metastatic adenocarcinoma. Therefore, chemotherapy with fluorouracil and oxaliplatin was initiated from March 2025.

Adenocarcinoma arising from an ileal neobladder is a rare but serious long-term complication. Diagnosing it is challenging due to non-specific symptoms, altered anatomy, and the presence of significant comorbidities. Similar cases have been documented in patients with either ileal conduit or neobladder. The latency period for secondary adenocarcinomas can be up to 40 years, longer than that for typical urothelial carcinoma recurrence. These tumors tend to be aggressive, with 60% of patients having regional lymph node involvement and 20% distant metastasis. Chronic inflammation, recurrent infections, and prolonged urine exposure to intestinal mucosa may contribute to its development, with studies showing mucosal thinning, increased goblet cells, and villous atrophy in the intestinal mucosa of bladder substitution. Immunohistochemical staining is essential in confirming the tumor’s origin. There is no standard treatment for this condition. Radical resection of involved organs represents optimal treatment, if feasible, and multidisciplinary treatment is usually warranted.

This case illustrates a rare and delayed occurrence of adenocarcinoma in an ileal neobladder. It underscores the importance of long-term surveillance in patients with urinary diversions and considering neoplastic transformation in the differential diagnosis of unexplained hematuria or recurrent UTIs.