{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:16:40Z","timestamp":1790803000327,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T00:00:00Z","timestamp":1577059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>High\u2010grade appendiceal mucinous neoplasm (HAMN) was recently proposed as a disease entity histologically analogous to low\u2010grade appendiceal mucinous neoplasm (LAMN), but characterised by high\u2010grade cytological atypia. The pathogenesis and clinical features of HAMN have not been fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Nine cases of HAMN, eight LAMN, 10 appendiceal mucinous adenocarcinomas (MACA) and five appendiceal serrated polyps resected between 2008 and 2017 contributed by three medical centres underwent targeted next\u2010generation sequencing of 50 cancer\u2010related genes. The patients in each category had similar profiles with respect to gender, age, tumour stage and follow\u2010up intervals. Both LAMN and HAMN harboured mutations of <jats:italic>KRAS<\/jats:italic> [nine of nine and eight of eight (100%), respectively] and <jats:italic>GNAS<\/jats:italic> [five of eight (63%) and five of nine (56%), respectively] in significantly higher proportions than MACA [KRAS, seven of 10 (70%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04); <jats:italic>GNAS<\/jats:italic>: one of 10 (10%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.02)] and serrated polyps [<jats:italic>KRAS<\/jats:italic>, one of five (20%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0007); <jats:italic>GNAS<\/jats:italic>: none of five (0%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04)]. Four cases of HAMN, but none of LAMN, harboured mutations of <jats:italic>TP53<\/jats:italic> [four of nine (44%)] and\/or <jats:italic>ATM<\/jats:italic> [two of nine (22%)]. Three cases of HAMN (33%) showed extra\u2010appendiceal spread with retention of the same mutational profiles in the intra\u2010 and extra\u2010appendiceal components. The 10 cases of MACA harboured a similar prevalence of <jats:italic>TP53<\/jats:italic> mutations (<jats:italic>n<\/jats:italic>\u00a0=\u00a05, 50%) as HAMN but, unlike LAMN and HAMN, some harboured mutations in <jats:italic>PIK3CA<\/jats:italic>, <jats:italic>APC<\/jats:italic>, <jats:italic>FBXW7<\/jats:italic>, <jats:italic>PTEN<\/jats:italic> and <jats:italic>SMAD4<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HAMN and LAMN share high rates of <jats:italic>KRAS<\/jats:italic> and <jats:italic>GNAS<\/jats:italic> co\u2010mutations supporting a common histogenesis and distinguishing them from MACA. Acquisition of <jats:italic>TP53<\/jats:italic> or <jats:italic>ATM<\/jats:italic> mutations by HAMN may drive its progression to a more advanced phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13986","type":"journal-article","created":{"date-parts":[[2019,9,6]],"date-time":"2019-09-06T18:33:31Z","timestamp":1567794811000},"page":"461-469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Mutation profile of high\u2010grade appendiceal mucinous neoplasm"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5052-0632","authenticated-orcid":false,"given":"Xiaoyan","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester NY USA"},{"name":"Department of Medicine Icahn Medical Center at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Vavinskaya","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of California San Diego Health System San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine New York University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yansheng","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Medicine Icahn Medical Center at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine New York University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Valasek","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of California San Diego Health System San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruliang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine New York University New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros D","family":"Polydorides","sequence":"additional","affiliation":[{"name":"Department of Medicine Icahn Medical Center at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Houldsworth","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell\u2010Based Medicine Icahn Medical Center at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noam","family":"Harpaz","sequence":"additional","affiliation":[{"name":"Department of Medicine Icahn Medical Center at Mount Sinai New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000535"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13324"},{"key":"e_1_2_7_4_1","first-page":"122","volume-title":"WHO classification of tumours of the digestive system","author":"Carr NJ","year":"2010"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-40618-3_19"},{"key":"e_1_2_7_6_1","volume-title":"Digestive system tumours","author":"WHO classification of Tumours Editorial 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