Rare Case of Urachal Neuroendocrine Carcinoma Reveals Potential for Targeted Therapy

In a newly published case report, Japanese researchers describe one of the few documented instances of neuroendocrine carcinoma (NEC) arising from the urachus, providing detailed pathological and genomic findings that hint at future therapeutic strategies.

The patient, a man in his 30s, presented with gross hematuria. Imaging located a nodular mass at the bladder dome; concurrent scans revealed multiple lung nodules consistent with metastatic disease. Initial transurethral resection was followed by open partial cystectomy and pelvic lymph node dissection. Histopathological evaluation confirmed a diagnosis of large‑cell NEC originating from the urachus, with infiltration into perivesical adipose tissue but negative margins and lymph nodes.

Immunohistochemistry supported the neuroendocrine phenotype: the tumor expressed chromogranin A and synaptophysin, and showed partial positivity for CD56. Notably, bladder mucosa overlying the tumor was free of malignant change, and no other primary malignancy was identified on extensive systemic evaluation, strengthening the conclusion that this was a primary urachal NEC.

What sets this case apart is the comprehensive genomic profiling (CGP) performed on the resected specimen. The analysis revealed an FGFR2–TACC2 gene fusion, a TP53 mutation (c.524G>A, p.Arg175His) at high allele frequency, and loss of Rb1. Given the known role of FGFR fusions in oncogenesis and the availability of FGFR inhibitors, the authors suggest that agents such as fucibatinib or pemigatinib could be considered, particularly in metastatic settings.

Because of current insurance limitations, the patient was initially treated with a conventional chemotherapy regimen—cisplatin plus etoposide (etoposide 100 mg/m² days 1–3, cisplatin 80 mg/m² day 1 every 3 weeks). The best achieved tumor response was stable disease. At nine months postoperatively, the patient remained alive and on chemotherapy.

Urachal cancer is rare—comprising less than 1 % of bladder malignancies—and NEC variants are exceedingly rare, with only a dozen or so prior cases in the literature. The prognosis is generally poor in advanced stage, and optimal systemic treatment remains undefined.

This case contributes an important data point by combining detailed pathology with genomic insights. It underscores that even in rare, aggressive tumors like urachal NEC, precision profiling may uncover targetable alterations. While the clinical benefit of FGFR inhibitors in this context remains speculative, this report supports further investigation of targeted therapy in high‑grade urachal tumors.