{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:13:33Z","timestamp":1788570813671,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"abstract":"\n Background<\/jats:title>\n The 6th edition of the WHO Classification of Digestive System Tumours distinguishes amphicrine\u2010like carcinomas (ALCs) from mixed neuroendocrine\u2010non\u2010neuroendocrine neoplasms (MiNENs). Acinar cell carcinomas (ACCs) with an intimately admixed and not separated neuroendocrine component comprising >30% of the tumour are classified as amphicrine\u2010like ACCs (AL\u2010ACCs). We characterised the genomic landscape of pancreatic ACCs and AL\u2010ACCs to validate current classification and identify therapeutic targets.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Among 2,151 pancreatic biopsy and resection cases that underwent targeted next\u2010generation sequencing using the OncoPanel AMC v4.3 or v4.5 (DNA\u2010based hybrid capture, targeting 323 genes (v4.3) or 343 genes (v4.5)), eight ACCs, seven AL\u2010ACCs originally diagnosed as MiNENs under the 5th edition of the WHO classification scheme, and four neuroendocrine tumours (NETs) were identified, diagnosed between 2020 and 2026.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Homologous recombination deficiency (HRD)\u2010associated alterations, involving\n BRCA1\/2<\/jats:italic>\n ,\n ATM<\/jats:italic>\n and\n FANCD2<\/jats:italic>\n , were identified in 87.5% (7\/8) of ACCs and 29% of AL\u2010ACCs. One ACC had an\n ATRX<\/jats:italic>\n nonsense mutation. Genomic heterogeneity was observed in molecular profiling of AL\u2010ACCs; two demonstrated a \u2018true hybrid\u2019 signature with co\u2010occurrence of lineage\u2010specific drivers:\n MEN1<\/jats:italic>\n deletion and splice site mutation (neuroendocrine\u2010associated),\n APC<\/jats:italic>\n ,\n SMAD4<\/jats:italic>\n and\n CTNNB1<\/jats:italic>\n alterations (exocrine\u2010associated). Two others exhibited \u2018ACC\u2010like\u2019 signatures, including missense\n BRCA1<\/jats:italic>\n and nonsense\n TP53<\/jats:italic>\n mutations and\n MDM4<\/jats:italic>\n and\n AKT3<\/jats:italic>\n amplifications, located on chromosome 1q, despite their neuroendocrine differentiation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Pancreatic ACCs frequently harbour HRD\u2010related alterations, suggesting potential for PARP\u2010inhibitor therapy. AL\u2010ACCs comprise molecularly heterogeneous groups, including true hybrid and ACC\u2010like patterns. Larger studies are required to elucidate the molecular distinction between true hybrid AL\u2010ACCs and those with single\u2010lineage alterations to refine their classification.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/his.70274","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:50:09Z","timestamp":1788569409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular profiling of pancreatic acinar cell carcinoma and amphicrine\u2010like carcinoma: high frequency of homologous recombination deficiency and molecular heterogeneity"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6054-0605","authenticated-orcid":false,"given":"Chankyung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Anatomical Pathology Royal Adelaide Hospital, SA Pathology Adelaide South Australia Australia"},{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences Adelaide University Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4752-8599","authenticated-orcid":false,"given":"Hyun\u2010Nam","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Pathology Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3597-1048","authenticated-orcid":false,"given":"Deokhoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0038-3959","authenticated-orcid":false,"given":"Byung\u2010Kwan","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Pathology Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0654-7392","authenticated-orcid":false,"given":"Jinho","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pathology Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-8455","authenticated-orcid":false,"given":"Changhoon","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Oncology Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-0138","authenticated-orcid":false,"given":"Dongwook","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7848-5923","authenticated-orcid":false,"given":"Kyu\u2010Pyo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oncology Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6156-8746","authenticated-orcid":false,"given":"Tae Jun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-5481","authenticated-orcid":false,"given":"Ki Byung","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Surgery Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5518-2249","authenticated-orcid":false,"given":"Seung Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Departments of Radiology and Research Institute of Radiology Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-4169","authenticated-orcid":false,"given":"Song Cheol","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery Asan Medical Center, University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8888-6007","authenticated-orcid":false,"given":"Seung\u2010Mo","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pathology Asan Medical 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