{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:00:54Z","timestamp":1790733654739,"version":"4.1.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"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:sec><jats:title>Background<\/jats:title><jats:p>Pancreatoblastoma is a rare malignant epithelial neoplasm of the pancreas that mainly occurs in children and involves abnormalities in the WNT\/\u03b2-catenin pathway, such as <jats:italic>CTNNB1<\/jats:italic> mutation. However, the molecular abnormalities in adult pancreatoblastoma are not well known.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case Presentation<\/jats:title><jats:p>An elderly man, who underwent elective distal pancreatectomy and splenectomy, was referred to our hospital with a mass in the tail of the pancreas. Histologically, the lesion revealed proliferation of clear, basophilic, and cartilaginous tumor cells with lymphatic metastasis. Each of the morphologically distinct tumor components showed different immunohistochemical patterns, indicating heterogeneous differentiation, including epithelial (both acinar and ductal), mesenchymal, and neuroendocrine differentiation. All tumor components showed nuclear expression of \u03b2-catenin and cyclin D1. Per next-generation sequencing (NGS), the clear and basophilic tumor cells shared mutations in <jats:italic>APC, GRM8<\/jats:italic>, <jats:italic>LAMP1<\/jats:italic>, and <jats:italic>AKA9<\/jats:italic>. Among the mutations, <jats:italic>APC<\/jats:italic>, c.1816_1817insA showed the highest frequency in both cell types, indicating that <jats:italic>APC<\/jats:italic> mutation was a driver mutation of the tumor. A diagnosis of PB was rendered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Summary<\/jats:title><jats:p>In conclusion, the clear and basophilic cells of the tumor were supposedly derived from the same clone and subsequently acquired additional mutations. This is the first report of clonal evolution in pancreatoblastoma.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.725290","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T16:00:45Z","timestamp":1630944045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["A Case of Adult Pancreatoblastoma With Novel APC Mutation and Genetic Heterogeneity"],"prefix":"10.3389","volume":"11","author":[{"given":"Yamato","family":"Suemitsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Mizukami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Yamakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Takamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Nakano-Narusawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Mukai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Takamatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Nakazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Mino-Kenudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Kumasaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197701)39:1<247::AID-CNCR2820390138>3.0.CO;2-F","article-title":"Morphogenesis of Pancreatoblastoma, Infantile Carcinoma of the Pancreas: Report of Two Cases","volume":"39","author":"Horie","year":"1977","journal-title":"Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1159\/000178877","article-title":"Pancreatoblastoma in Adults: A Review of the Literature","volume":"9","author":"Cavallini","year":"2009","journal-title":"Pancreatology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2227-684X.2015.04.05","article-title":"Clinicopathological Review of Pancreatoblastoma in Adults","volume":"4","author":"Omiyale","year":"2015","journal-title":"Gland Surg"},{"key":"B4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41698-018-0049-y","article-title":"Interaction Between Wnt\/beta-Catenin and RAS-ERK Pathways and an Anti-Cancer Strategy via Degradations of Beta-Catenin and RAS by Targeting the Wnt\/beta-Catenin Pathway","volume":"2","author":"Jeong","year":"2018","journal-title":"NPJ Precis Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/BF03195640","article-title":"APC Gene Mutations Causing Familial Adenomatous Polyposis in Polish Patients","volume":"49","author":"Plawski","year":"2008","journal-title":"J Appl Genet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9440(10)63008-8","article-title":"Distinctive Molecular Genetic Alterations in Sporadic and Familial Adenomatous Polyposis-Associated Pancreatoblastomas: Frequent Alterations in the APC\/beta-Catenin Pathway and Chromosome 11p","volume":"159","author":"Abraham","year":"2001","journal-title":"Am J Pathol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24017","article-title":"Identification and Characterization of a Novel Adenomatous Polyposis Coli Mutation in Adult Pancreatoblastoma","volume":"9","author":"Yamaguchi","year":"2018","journal-title":"Oncotarget"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e35826","DOI":"10.1371\/journal.pone.0035826","article-title":"Receptor Tyrosine Kinases Activate Canonical WNT\/beta-Catenin Signaling via MAP Kinase\/LRP6 Pathway and Direct Beta-Catenin Phosphorylation","volume":"7","author":"Krejci","year":"2012","journal-title":"PLoS One"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21854","article-title":"LEF1, TFE3, and AR are Putative Diagnostic Markers of Solid Pseudopapillary Neoplasms","volume":"8","author":"Kim","year":"2017","journal-title":"Oncotarget"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1515\/BC.2002.027","article-title":"TCF: Lady Justice Casting the Final Verdict on the Outcome of Wnt Signalling","volume":"383","author":"Brantjes","year":"2002","journal-title":"Biol Chem"},{"key":"B11","volume-title":"WHO Classification of Tumours of Endocrine Organs","author":"Lloyd","year":"2017"},{"key":"B12","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1097\/01.pas.0000184819.71752.ad","article-title":"Lipid-Rich Variant of Pancreatic Endocrine Neoplasms","volume":"30","author":"Singh","year":"2006","journal-title":"Am J Surg Pathol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1385\/ep:16:2:145","article-title":"Spindle Cell Pancreatic Endocrine Tumor Associated With Cushing\u2019s Syndrome","volume":"16","author":"Chetty","year":"2005","journal-title":"Endocr Pathol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880457","article-title":"Malignant Islet Cell Tumor With Sarcomatous Differentiation","volume":"14","author":"Emerson","year":"2001","journal-title":"Mod Pathol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-17-0560","article-title":"Genomic Landscape of Pancreatic Neuroendocrine Tumours: The International Cancer Genome Consortium","volume":"236","author":"Mafficini","year":"2018","journal-title":"J Endocrinol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2012.02791.x","article-title":"Intraductal Tubulopapillary Neoplasm of Pancreas With Stromal Osseous and Cartilaginous Metaplasia; a Case Report","volume":"62","author":"Jokoji","year":"2012","journal-title":"Pathol Int"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.10.008","article-title":"SOX9: A Useful Marker for Pancreatic Ductal Lineage of Pancreatic Neoplasms","volume":"45","author":"Shroff","year":"2014","journal-title":"Hum Pathol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1017802","article-title":"The Transcription Factor Sox9 has Essential Roles in Successive Steps of the Chondrocyte Differentiation Pathway and is Required for Expression of Sox5 and Sox6","volume":"16","author":"Akiyama","year":"2002","journal-title":"Genes Dev"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.725290\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T16:00:50Z","timestamp":1630944050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.725290\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,27]]},"references-count":18,"alternative-id":["10.3389\/fonc.2021.725290"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.725290","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,27]]},"article-number":"725290"}}