Abstract
Primary large cell neuroendocrine carcinoma (LCNEC) of the bladder is an extremely rare and highly aggressive malignancy with a poor prognosis, bringing major challenges to clinical diagnosis and treatment. We report the case of a 77-year-old man who presented with recurrent gross hematuria for more than 8 months, accompanied by urinary frequency, urinary urgency, and lumbosacral pain. Imaging revealed a large soft-tissue mass on the posterior bladder wall without pathognomonic imaging findings. Urine exfoliative cytology revealed atypical tumor cells with large cellular size, high nucleocytoplasmic ratio, scant cytoplasm, and marked nuclear atypia. Given the advanced age and multiple underlying comorbidities, the patient underwent transurethral resection of the bladder tumor. Histopathologically, the tumor was arranged in diffuse sheets with organoid architecture, composed of large polygonal cells with prominent atypia, active mitosis, focal necrosis, and intravascular tumor thrombi. Immunohistochemically, CK-Pan showed a paranuclear punctate expression pattern; neuroendocrine markers INSM1, Syn, and CD56 were diffusely positive; Ki-67 showed a high proliferation index; and P53 displayed diffuse strong expression. The final diagnosis of primary bladder LCNEC was confirmed by integrated morphological and immunohistochemical findings, with preoperative contrast-enhanced CT defining an advanced clinical stage of cT3N0M0 (American Joint Committee on Cancer, AJCC 8th edition). The patient received postoperative adjuvant chemotherapy, and tumor recurrence was identified at the 3-month follow-up with a stable general condition during the observational period. This case indicates that bladder LCNEC lacks specific clinical and imaging manifestations. Urine exfoliative cytology is a valuable non-invasive ancillary tool for detecting high-grade malignant cells in the urinary tract, whereas combining histopathology and immunohistochemistry remains the gold standard for definitive diagnosis. Surgical resection combined with individualized chemotherapy constitutes the main therapeutic regimen, and close long-term follow-up is indispensable for this highly aggressive tumor. Further clinical studies are required to optimize therapeutic strategies and improve patient prognosis.