{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T04:56:07Z","timestamp":1767588967946,"version":"3.48.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"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":["Head and Neck Pathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We present a case of a 41-year-old non-smoker male patient presenting with ameloblastoma which metastasized to the lung 14 years post excision of the primary mandibular tumor. A biopsy of the pulmonary mass was initially diagnosed as squamous cell carcinoma by a non-specialist pathologist who was not provided a history of the patient\u2019s prior ameloblastoma diagnosis. The patient subsequently underwent neoadjuvant chemo-immunotherapy followed by surgical resection of the lung mass. The definitive diagnosis of metastasizing ameloblastoma (MA) was made on the surgical resection and compared to the original mandible lesion. Confounding morphological features were attributed to the impact of neoadjuvant treatment. Molecular analysis of the metastasis and original jaw lesion revealed a mutation of\n                    <jats:italic>AKT1<\/jats:italic>\n                    (c.49G\u2009&gt;\u2009A p.(Glu17Lys) COSMIC ID: COSM33765) but no mutations in the\n                    <jats:italic>BRAF<\/jats:italic>\n                    gene were identified. This case illustrates the critical necessity of a thorough clinical history of previous neoplasia, even many years following treatment, as well as the role of molecular profiling for identifying novel targeted treatment options.\n                  <\/jats:p>","DOI":"10.1007\/s12105-025-01844-5","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T06:54:39Z","timestamp":1761548079000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metastasizing Ameloblastoma Mimicking Squamous Cell Carcinoma of the Lung and Harboring an AKT1 Mutation"],"prefix":"10.1007","volume":"19","author":[{"given":"James","family":"Arrich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Forrest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Lofthouse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asterios","family":"Triantafyllou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith D.","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Haragan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"1844_CR1","volume-title":"WHO classification of tumors: head and neck tumors","author":"WHO Classification of Tumors Editorial Board","year":"2024","unstructured":"WHO Classification of Tumors Editorial Board (2024) WHO classification of tumors: head and neck tumors, vol 9, 5th edn. The International Agency for Research on Cancer (IARC), Lyon","edition":"5"},{"issue":"2","key":"1844_CR2","doi-asserted-by":"publisher","first-page":"e0117789","DOI":"10.1371\/journal.pone.0117789","volume":"10","author":"A Rizzitelli","year":"2015","unstructured":"Rizzitelli A, Smoll NR, Chae MP, Rozen WM, Hunter-Smith DJ (2015) Incidence and overall survival of malignant ameloblastoma. PLoS ONE 10(2):e0117789","journal-title":"PLoS ONE"},{"issue":"6","key":"1844_CR3","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.jobcr.2023.10.006","volume":"13","author":"G Sarode","year":"2023","unstructured":"Sarode G, Gondivkar SM, Gore A, Anand R, Sengupta N, Mehta V et al (2023) Clinico-pathological and prognostic overview of metastasizing ameloblastoma: an overview of the systematic reviews. J Oral Biol Craniofac Res 13(6):751\u2013757","journal-title":"J Oral Biol Craniofac Res"},{"issue":"7","key":"1844_CR4","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1111\/jop.13334","volume":"51","author":"BR Chrcanovic","year":"2022","unstructured":"Chrcanovic BR, Martins-Chaves RR, Pontes FSC, Fonseca FP, Gomez RS, Pontes HAR (2022) Comparison of survival outcomes between ameloblastic carcinoma and metastasizing ameloblastoma: A systematic review. J Oral Pathol Med 51(7):603\u2013610","journal-title":"J Oral Pathol Med"},{"issue":"2","key":"1844_CR5","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/0030-4220(84)90207-X","volume":"57","author":"PJ Slootweg","year":"1984","unstructured":"Slootweg PJ, M\u00fcller H (1984) Malignant ameloblastoma or ameloblastic carcinoma. oral surgery, oral medicine. Oral Pathol 57(2):168\u2013176","journal-title":"Oral Pathol"},{"issue":"12","key":"1844_CR6","doi-asserted-by":"publisher","first-page":"2962","DOI":"10.1016\/j.joms.2010.05.084","volume":"68","author":"SD Van Dam","year":"2010","unstructured":"Van Dam SD, Unni KK, Keller EE (2010) Metastasizing (malignant) ameloblastoma: review of a unique histopathologic entity and report of Mayo clinic experience. J Oral Maxillofac Surg 68(12):2962\u20132974","journal-title":"J Oral Maxillofac Surg"},{"issue":"3","key":"1844_CR7","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1007\/s12105-020-01258-5","volume":"15","author":"D Pandiar","year":"2021","unstructured":"Pandiar D, Anand R, Kamboj M, Narwal A, Shameena PM, Devi A (2021) Metastasizing ameloblastoma: A 10 year clinicopathological review with an insight into pathogenesis. Head Neck Pathol 15(3):967\u2013974","journal-title":"Head Neck Pathol"},{"issue":"6","key":"1844_CR8","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/j.tripleo.2010.12.018","volume":"111","author":"RKG Dissanayake","year":"2011","unstructured":"Dissanayake RKG, Jayasooriya PR, Siriwardena DJL, Tilakaratne WM (2011) Review of metastasizing (malignant) ameloblastoma (METAM): pattern of metastasis and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 111(6):734\u2013741","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"issue":"6","key":"1844_CR9","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/j.jcms.2013.11.009","volume":"42","author":"G Jayaraj","year":"2014","unstructured":"Jayaraj G, Sherlin HJ, Ramani P, Premkumar P, Natesan A, Ramasubramanian A et al (2014) Metastasizing Ameloblastoma - a perennial pathological enigma? Report of a case and review of literature. J Craniomaxillofac Surg 42(6):772\u2013779","journal-title":"J Craniomaxillofac Surg"},{"issue":"3","key":"1844_CR10","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1002\/1097-0142(19890801)64:3<776::AID-CNCR2820640335>3.0.CO;2-8","volume":"64","author":"EH Laughlin","year":"1989","unstructured":"Laughlin EH (1989) Metastasizing ameloblastoma. Cancer 64(3):776\u2013780","journal-title":"Cancer"},{"issue":"5","key":"1844_CR11","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.ijom.2021.07.016","volume":"51","author":"X Yang","year":"2022","unstructured":"Yang X, Zhou K, Tao Y, Ge S, Shang W, Song K (2022) Treatment efficacy and prognosis of pulmonary metastasizing ameloblastoma: a systematic review. Int J Oral Maxillofac Surg 51(5):579\u2013590","journal-title":"Int J Oral Maxillofac Surg"},{"issue":"6","key":"1844_CR12","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s12032-023-01993-z","volume":"40","author":"M Ebeling","year":"2023","unstructured":"Ebeling M, Scheurer M, Sakkas A, Pietzka S, Schramm A, Wilde F (2023) BRAF inhibitors in BRAF V600E-mutated ameloblastoma: systematic review of rare cases in the literature. Med Oncol 40(6):163","journal-title":"Med Oncol"},{"key":"1844_CR13","doi-asserted-by":"crossref","unstructured":"Lynch MM, Hermida-Viveiros P, Stencel S, Knott H, Al-Maryati R, Obeidin F et al (2025) Durable disease regression with Copanlisib treatment in PI3K-mutated metastasizing ameloblastoma: A case report. Rare Tumors. ;17","DOI":"10.1177\/20363613241309961"},{"key":"1844_CR14","doi-asserted-by":"crossref","unstructured":"Chen Y, Huang L, Dong Y, Tao C, Zhang R, Shao H et al (2020) Effect of AKT1 (p. E17K) hotspot mutation on malignant tumorigenesis and prognosis. Front Cell Dev Biol. ;8","DOI":"10.3389\/fcell.2020.573599"},{"issue":"3","key":"1844_CR15","doi-asserted-by":"publisher","first-page":"100682","DOI":"10.1016\/j.modpat.2024.100682","volume":"38","author":"C Mar\u00edn-M\u00e1rquez","year":"2025","unstructured":"Mar\u00edn-M\u00e1rquez C, Adisa AO, Niklander SE, Kirby J, Hunter KD (2025) Genomic and transcriptomic analysis of ameloblastoma reveals distinct molecularly aggressive phenotypes. Mod Pathol 38(3):100682","journal-title":"Mod Pathol"},{"issue":"2","key":"1844_CR16","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1111\/jop.12103","volume":"43","author":"RL Cecim","year":"2014","unstructured":"Cecim RL, Carmo HAF, Kataoka MSS, Freitas VM, de Melo Alves J\u00fanior S, Pedreira EN et al (2014) Expression of molecules related to AKT pathway as putative regulators of ameloblastoma local invasiveness. J Oral Pathol Med 43(2):143\u2013147","journal-title":"J Oral Pathol Med"},{"key":"1844_CR17","doi-asserted-by":"publisher","first-page":"2839","DOI":"10.2147\/OTT.S298697","volume":"14","author":"T Zhao","year":"2021","unstructured":"Zhao T, Tian Y, Ding X, Liu L, Tan B, Yang B et al (2021) Genetic analysis and targeted therapy using buparlisib and MK2206 in a patient with triple metachronous cancers of the kidney, prostate, and squamous cell carcinoma of the lung: A case report. Onco Targets Ther 14:2839\u20132845","journal-title":"Onco Targets Ther"}],"container-title":["Head and Neck Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-025-01844-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12105-025-01844-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-025-01844-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T04:53:45Z","timestamp":1767588825000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12105-025-01844-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,27]]},"references-count":17,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1844"],"URL":"https:\/\/doi.org\/10.1007\/s12105-025-01844-5","relation":{},"ISSN":["1936-0568"],"issn-type":[{"type":"electronic","value":"1936-0568"}],"subject":[],"published":{"date-parts":[[2025,10,27]]},"assertion":[{"value":"19 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2025","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 no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"For a case report formal consent or ethical review is not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Not applicable. In keeping with the instructions to authors, all patient identifiable data has been removed and the only images included are radiology and pathology, for which it is not necessary to obtain consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate\/for Publication"}}],"article-number":"120"}}