{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:56:55Z","timestamp":1792000615765,"version":"4.4.0"},"reference-count":6,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T00:00:00Z","timestamp":1731196800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T00:00:00Z","timestamp":1731196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Med Mol Morphol"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>This report presents a rare case of a 45-year-old man diagnosed with a primary hepatic alpha-fetoprotein-producing neuroendocrine neoplasm, a condition rarely reported in the literature. The patient presented with initial symptoms of back and epigastric pain, after which multiple liver lesions were discovered on contrast-enhanced computed tomography, suggesting intrahepatic cholangiocarcinoma. Histopathological and immunohistochemical analyses confirmed the diagnosis of alpha-fetoprotein-producing neuroendocrine neoplasm that was further supported by genetic testing, which revealed <jats:italic>FGFR2<\/jats:italic> and <jats:italic>TP53<\/jats:italic> mutations commonly encountered in intrahepatic cholangiocarcinoma. Despite receiving various chemotherapeutic regimens, the patient exhibited a progressive disease. This case underscores the importance of accurate differential diagnosis from hepatocellular carcinoma and intrahepatic cholangiocarcinoma due to differences in treatment approaches and prognoses and highlights the necessity for increased awareness of AFP-producing primary hepatic neuroendocrine neoplasms among clinicians and pathologists. It emphasizes the significance of comprehensive histopathological evaluation, immunohistochemical profiling, and genetic analysis for precise diagnosis and tailored therapeutic strategies. Further research is warranted to elucidate the molecular mechanisms underlying this rare liver tumor subtype and develop targeted treatments.<\/jats:p>","DOI":"10.1007\/s00795-024-00408-w","type":"journal-article","created":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T07:25:34Z","timestamp":1731223534000},"page":"83-86","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Primary hepatic alpha-fetoprotein-producing neuroendocrine neoplasm harboring FGFR2 and TP53 mutations: a case report and literature review"],"prefix":"10.1007","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0253-7122","authenticated-orcid":false,"given":"Hirofumi","family":"Watanabe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodai","family":"Enda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiyoshi","family":"Fujishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Shirota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Ninomiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironobu","family":"Sasano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,10]]},"reference":[{"key":"408_CR1","doi-asserted-by":"publisher","first-page":"975","DOI":"10.2147\/OTT.S236728","volume":"13","author":"HF Huang","year":"2020","unstructured":"Huang HF, Jin PP, Yang HJ, Zhang CJ, Zhang X, Wang JS, Yu JJ, Zhang B, Zhang Y, Hu QD (2020) Primary hepatic neuroendocrine tumor mimicking ruptured hepatocellular carcinoma with AFP elevation: a case report and literature review. Onco Targets Ther 13:975\u2013979. https:\/\/doi.org\/10.2147\/OTT.S236728","journal-title":"Onco Targets Ther"},{"issue":"8","key":"408_CR2","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1016\/j.humpath.2014.03.014","volume":"45","author":"RP Graham","year":"2014","unstructured":"Graham RP, Barr Fritcher EG, Pestova E, Schulz J, Sitailo LA, Vasmatzis G, Murphy SJ, McWilliams RR, Hart SN, Halling KC, Roberts LR, Gores GJ, Couch FJ, Zhang L, Borad MJ, Kipp BR (2014) Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Hum Pathol 45(8):1630\u20131638. https:\/\/doi.org\/10.1016\/j.humpath.2014.03.014","journal-title":"Hum Pathol"},{"issue":"3","key":"408_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2022.100065","volume":"36","author":"SE Umetsu","year":"2023","unstructured":"Umetsu SE, Kakar S, Basturk O, Kim GE, Chatterjee D, Wen KW, Hale G, Shafizadeh N, Cho SJ, Whitman J, Gill RM, Jones KD, Navale P, Bergsland E, Klimstra D, Joseph NM (2023) Integrated genomic and clinicopathologic approach distinguishes pancreatic grade 3 neuroendocrine tumor from neuroendocrine carcinoma and identifies a subset with molecular overlap. Mod Pathol 36(3):100065. https:\/\/doi.org\/10.1016\/j.modpat.2022.100065","journal-title":"Mod Pathol"},{"issue":"8","key":"408_CR4","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1093\/qjmed\/hcaa018","volume":"113","author":"CY Wang","year":"2020","unstructured":"Wang CY, Lin JC, Li YF, Yang CW (2020) Alpha-fetoprotein producing pancreatic neuroendocrine tumour. QJM 113(8):565\u2013566. https:\/\/doi.org\/10.1093\/qjmed\/hcaa018","journal-title":"QJM"},{"issue":"2","key":"408_CR5","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1097\/JTO.0b013e3181623359","volume":"3","author":"K Takezawa","year":"2008","unstructured":"Takezawa K, Okamoto I, Fukuoka J, Tanaka K, Kaneda H, Uejima H, Yoon HE, Imakita M, Fukuoka M, Nakagawa K (2008) Large cell neuroendocrine carcinoma of the mediastinum with alpha-fetoprotein production. J Thorac Oncol 3(2):187\u2013189. https:\/\/doi.org\/10.1097\/JTO.0b013e3181623359","journal-title":"J Thorac Oncol"},{"issue":"1","key":"408_CR6","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/sj.bjc.6604428","volume":"99","author":"T Shah","year":"2008","unstructured":"Shah T, Srirajaskanthan R, Bhogal M, Toubanakis C, Meyer T, Noonan A, Witney-Smith C, Amin T, Bhogal P, Sivathasan N, Warner B, Hochhauser D, Caplin ME (2008) Alpha-fetoprotein and human chorionic gonadotrophin-beta as prognostic markers in neuroendocrine tumour patients. Br J Cancer 99(1):72\u201377. https:\/\/doi.org\/10.1038\/sj.bjc.6604428","journal-title":"Br J Cancer"}],"container-title":["Medical Molecular Morphology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00795-024-00408-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00795-024-00408-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00795-024-00408-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T10:39:34Z","timestamp":1739615974000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00795-024-00408-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,10]]},"references-count":6,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["408"],"URL":"https:\/\/doi.org\/10.1007\/s00795-024-00408-w","relation":{},"ISSN":["1860-1480","1860-1499"],"issn-type":[{"value":"1860-1480","type":"print"},{"value":"1860-1499","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,10]]},"assertion":[{"value":"27 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"This study was conducted according to the ethical standards and requirements of Tohoku University Hospital (Miyagi, Japan).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}