{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:22:28Z","timestamp":1789802548808,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Clear cell carcinoma with enteroblastic differentiation arising in the female genital tract is exceptionally rare, and its pathogenesis, diagnostic features, and therapeutic implications remain poorly understood. We report a rare case in a 67\u2010year\u2010old woman with tumor involvement of the cervix, uterine cavity, fallopian tubes, and ovaries, and highlight the value of multi\u2010site sequencing for resolving tumor origin and biological heterogeneity. Histologically, the tumor exhibited a fetal intestinal\u2010like morphology with glycogen\u2010rich clear cytoplasm. Immunohistochemistry revealed positive staining for HNF1\u03b2, with variable immunoreactivity for Glypican\u20103 and SALL4. Multi\u2010site whole\u2010exome sequencing revealed marked inter\u2010lesional genomic heterogeneity, divergent clonal evolution, and a molecular phylogenetic pattern supporting the fallopian tube as the most likely primary site. RNA sequencing further demonstrated a more immunogenic microenvironment in the fallopian tube lesion, characterized by increased infiltration of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and B cells and a higher immunophenoscore, suggesting potential sensitivity to immunotherapy. Comparison with previously reported cases also helped define immunophenotypic features of diagnostic relevance. Collectively, this case underscores the value of integrating clinicopathologic evaluation with multi\u2010site whole\u2010exome and transcriptomic sequencing to refine diagnosis, infer tumor origin, and identify potential therapeutic opportunities in this rare gynecologic tumor subtype.\n                  <\/jats:p>","DOI":"10.1002\/biof.70152","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T06:45:13Z","timestamp":1789800313000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clear Cell Carcinoma With Enteroblast\u2010Like Differentiation Involving Multiple Gynecologic Sites: An Integrated Clinicopathologic, Whole\u2010Exome, and Transcriptomic Analysis"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3466-4536","authenticated-orcid":false,"given":"Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-5858","authenticated-orcid":false,"given":"Xiangshan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pathology The First Affiliated Hospital of Anhui Medical University  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.4132\/jptm.2021.10.28"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12328-020-01209-1"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14158"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gynor.2014.03.001"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0756.2011.01622.x"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00795-022-00336-7"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2007.00901.x"},{"issue":"1","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13048-018-0426-8","article-title":"Alpha\u2010Fetoprotein\u2010Producing Ovarian Clear Cell Adenocarcinoma With Fetal Gut Differentiation: A Rare Case Report and Literature Review","volume":"11","author":"Chao W. T.","year":"2018","journal-title":"Journal of Ovarian Research"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001090"},{"issue":"1","key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13000-019-0852-y","article-title":"Primary Endocervical Gastric\u2010Type Adenocarcinoma: A Clinicopathologic and Immunohistochemical Analysis of 23 Cases","volume":"14","author":"Lu S.","year":"2019","journal-title":"Diagnostic Pathology"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cyt.12688"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9465375"},{"issue":"1","key":"e_1_2_13_14_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/PGP.0000000000000213","article-title":"The Application Value of HNF\u20101\u03b2 Transcription Factor in the Diagnosis of Ovarian Clear Cell Carcinoma","volume":"35","author":"Huang W.","year":"2016","journal-title":"International Journal of Gynecological Pathology"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2012.04267.x"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000436"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAT.0000000000000223"},{"key":"e_1_2_13_18_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.799163","article-title":"\u03b1\u2010Fetoprotein\u2010Producing Endometrial Carcinoma Is Associated With Fetal Gut\u2010Like and\/or Hepatoid Morphology, Lymphovascular Infiltration, TP53 Abnormalities, and Poor Prognosis: Five Cases and Literature Review","volume":"8","author":"Otani K.","year":"2022","journal-title":"Frontiers in Medicine"},{"issue":"1","key":"e_1_2_13_19_1","first-page":"112","article-title":"Gastric Adenocarcinoma With Enteroblastic Differentiation: An Overview","volume":"78","author":"Yamazawa S.","year":"2021","journal-title":"Histopathology"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-023-00563-x"},{"issue":"5","key":"e_1_2_13_21_1","doi-asserted-by":"crossref","DOI":"10.3802\/jgo.2022.33.e67","article-title":"Frequency and Clinical Features of Deficient Mismatch Repair in Ovarian Clear Cell and Endometrioid Carcinoma","volume":"33","author":"Tanaka T.","year":"2022","journal-title":"Journal of Gynecologic Oncology"},{"issue":"3","key":"e_1_2_13_22_1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.4274\/tjod.galenos.2023.62819","article-title":"Clear Cell Carcinoma of the Uterine Cervix; an Unusual HPV\u2010Independent Tumor: Clinicopathological Features, PD\u2010L1 Expression, and Mismatch Repair Protein Deficiency Status of 16 Cases","volume":"20","author":"Bulutay P.","year":"2023","journal-title":"Turkish Journal of Obstetrics and Gynecology"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-01027-5"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09203-8"}],"container-title":["BioFactors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.70152","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biof.70152","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.70152","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T06:45:15Z","timestamp":1789800315000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/biof.70152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/biof.70152"],"URL":"https:\/\/doi.org\/10.1002\/biof.70152","archive":["Portico"],"relation":{},"ISSN":["0951-6433","1872-8081"],"issn-type":[{"value":"0951-6433","type":"print"},{"value":"1872-8081","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70152"}}