{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:00:11Z","timestamp":1785214811080,"version":"3.55.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Large cell neuroendocrine carcinoma (LCNEC) is the rarest high-grade neuroendocrine carcinoma (NEC) of the urinary bladder. It can be observed in mixed neuroendocrine\/non-neuroendocrine neoplasm (MiNEN), which is predominantly associated with urothelial carcinoma (UC) and less frequently with adenocarcinoma. Here, we report a primary MiNEN of the urinary bladder, composed of LCNEC and enteric-type adenocarcinoma. The patient was a 58-year-old male who initially presented with painless hematuria and dysuria. Transabdominal ultrasonography demonstrated a 4.8 \u00d7 2.4\u00a0cm hypoechoic lesion arising from the posterior bladder wall. Histologically, the tumor showed distinct yet closely apposed components of LCNEC and enteric-type adenocarcinoma. Immunohistochemically, the LCNEC component was positive for neuroendocrine markers, including CD56, chromogranin, synaptophysin, and INSM1, while the adenocarcinoma component was positive for CK20 and CDX2. Notably, both components showed aberrant P53 expression (P53-null pattern), supporting a shared clonal origin with divergent differentiation. After progression following initial platinum-based chemotherapy, the patient achieved a radiographic partial response (PR) of pulmonary metastases after treatment with enfortumab vedotin plus pembrolizumab administered with radiotherapy. Our case highlights the diagnostic importance of recognizing a high-grade neuroendocrine component in bladder tumors. Furthermore, antibody-drug conjugates and immune checkpoint inhibitors may merit further study in this rare entity.<\/jats:p>","DOI":"10.3389\/fonc.2026.1811895","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:26:12Z","timestamp":1785212772000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Primary MiNEN of the urinary bladder with large cell neuroendocrine carcinoma and enteric-type adenocarcinoma: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaofei","family":"Xiu","sequence":"first","affiliation":[{"name":"Department of Pathology, the Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Economics and Management, the Hebei Vocational College of Labour Relations","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Radiology, the Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, the Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zinan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology, the Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pathology, the Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhui","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pathology, the Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology, the Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.14213","article-title":"Urinary tract large cell neuroendocrine carcinoma: diagnostic, prognostic and therapeutic issues","volume":"40","author":"Sanguedolce","year":"2020","journal-title":"Anticancer Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000002656","article-title":"Neuroendocrine carcinoma of the bladder: do they have a worse prognosis? 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