{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:11:00Z","timestamp":1792012260425,"version":"4.4.0"},"reference-count":45,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:00:00Z","timestamp":1760227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Colorectal neuroendocrine carcinomas (NECs) are rare, aggressive tumors with poorly defined clinicopathologic and molecular features. Their biological behavior and optimal treatment strategies remain unclear. Additionally, a subset of anorectal NECs may be associated with high-risk human papillomavirus (HPV) infection, suggesting potential heterogeneity in pathogenesis. Methods: We retrospectively reviewed 12 cases of colorectal NECs. Clinical outcomes, histologic morphology, immunohistochemistry, molecular profiling, including common oncogenic mutations, and HPV status were analyzed. Results: Seven cases demonstrated small cell NECs, and five showed large cell NECs. The majority of NECs (n = 9) arose in the rectum. TP53 mutations were the most common (75%), followed by KRAS, RB1, FBXW7, and BRAF mutations. One case demonstrated mismatch repair (MMR) deficiency. High-risk HPV was detected in one rectal NEC, which lacked common oncogenic mutations and was the only long-term survivor (54 months). p16 expression did not correlate consistently with HPV in situ hybridization (ISH) status. Among small cell NECs with follow-up, platinum-based chemotherapy resulted in significantly longer survival than FOLFOX (13.5 vs. 4 months, p = 0.0209). Conclusions: Colorectal NECs display histologic and molecular heterogeneity. The tumors of small cell NECs potentially benefit more from platinum-based chemotherapy. HPV-associated NECs may represent a distinct subset with better prognosis, but p16 is not a reliable surrogate marker. Routine subclassification into small vs. large cell types and comprehensive molecular profiling, including HPV testing, may aid clinical decision-making and prognostication.<\/jats:p>","DOI":"10.3390\/diagnostics15202569","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:48:21Z","timestamp":1760420901000},"page":"2569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Infrequent HPV Infection in Colorectal Neuroendocrine Carcinoma: Molecular and Histologic Characteristics"],"prefix":"10.3390","volume":"15","author":[{"given":"Xi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s10350-003-0038-1","article-title":"Neuroendocrine carcinomas of the colon and rectum","volume":"47","author":"Bernick","year":"2004","journal-title":"Dis. 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