{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T08:04:17Z","timestamp":1768377857169,"version":"3.49.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Giant cell tumor of bone (GCTB) is a rare but locally aggressive neoplasm which most commonly arises in the epiphyses of long bones of young adults. Occurrence in the mandible is uncommon, and hormone secreting variants are extremely rare.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>We present the case of a 16-year-old female, who presented with progressive swelling and pain in the left mandible after extraction of adjacent teeth. On examination, she had a large ulcerated intraoral mass with marked tooth mobility; imaging revealed a 4.7-cm expansive lytic lesion with cortical erosions and displacement of the inferior alveolar canal. Histopathologic evaluation revealed sheets of mononuclear stromal cells interspersed with numerous osteoclast-like giant cells. Immunohistochemical stains showed strong positivity for H3G34W and p63. Genomic sequencing confirmed the presence of an H3-3A p.G35W hotspot mutation and also identified a pathogenic FANCA p.R951Q variant. Investigations prior to treatment showed an elevated serum \u03b2-human chorionic gonadotropin (\u03b2-hCG) level despite the patient being negative for pregnancy status. Following this the patient began denosumab therapy, which was associated clinical improvement, plus a decline in \u03b2-hCG, confirming the tumor as the source of hormone secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>There is only one other case that has been documented of a \u03b2-hCG\u2013producing GCTBoccurring in the base of the skull with secondary aneurysmal bone cyst\u2013like changes.This appears to be the first reported instance of \u03b2-hCG\u2013secreting GCTB in the gnathicbones. This case exemplifies the diagnostic challenges of rare presentations of GCTBand alerts clinicians to the potential misleading presentation of hormone expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12105-025-01883-y","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T13:18:27Z","timestamp":1768310307000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2-Human Chorionic Gonadotropin\u2013Secreting Giant Cell Tumor of Bone in the Mandible: Case Report and Comprehensive Literature Review"],"prefix":"10.1007","volume":"20","author":[{"given":"Andres","family":"Flores-Hidalgo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sholeh","family":"Bazrafshan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hether","family":"Khosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"1883_CR1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s11912-021-01047-5","volume":"23","author":"A Basu Mallick","year":"2021","unstructured":"Basu Mallick A, Chawla SP (2021) Giant cell tumor of bone: an update. Curr Oncol Rep 23:51","journal-title":"Curr Oncol Rep"},{"key":"1883_CR2","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3928\/01477447-20140124-08","volume":"37","author":"DF Amanatullah","year":"2014","unstructured":"Amanatullah DF, Clark TR, Lopez MJ, Borys D, Tamurian RM (2014) Giant cell tumor of bone. Orthopedics 37:112\u2013120","journal-title":"Orthopedics"},{"key":"1883_CR3","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1038\/ng.2814","volume":"45","author":"S Behjati","year":"2013","unstructured":"Behjati S, Tarpey PS, Presneau N, Scheipl S, Pillay N, Van Loo P et al (2013) Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet 45:1479\u20131482","journal-title":"Nat Genet"},{"key":"1883_CR4","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1097\/PAS.0000000000000512","volume":"39","author":"AHG Cleven","year":"2015","unstructured":"Cleven AHG, H\u00f6cker S, Briaire-de Bruijn I, Szuhai K, Cleton-Jansen A-M, Bov\u00e9e JVMG (2015) Mutation analysis of H3F3A and H3F3B as a diagnostic tool for giant cell tumor of bone and chondroblastoma. Am J Surg Pathol 39:1576\u20131583","journal-title":"Am J Surg Pathol"},{"key":"1883_CR5","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1007\/s12672-025-02880-x","volume":"16","author":"Q Bai","year":"2025","unstructured":"Bai Q, Chang X, Zou X, Zhang B (2025) Pulmonary metastasis of giant cell tumor of bone 29 years after local recurrence resection: implications for Long-Term surveillance. Discov Oncol 16:1108","journal-title":"Discov Oncol"},{"key":"1883_CR6","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.jbo.2018.07.003","volume":"12","author":"A Liede","year":"2018","unstructured":"Liede A, Hernandez RK, Tang E-T, Li C, Bennett B, Wong SS et al (2018) Epidemiology of benign giant cell tumor of bone in the Chinese population. J Bone Oncol 12:96\u2013100","journal-title":"J Bone Oncol"},{"key":"1883_CR7","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.canep.2016.03.014","volume":"42","author":"JM Amelio","year":"2016","unstructured":"Amelio JM, Rockberg J, Hernandez RK, Sobocki P, Stryker S, Bach BA et al (2016) Population-based study of giant cell tumor of bone in Sweden (1983\u20132011). Cancer Epidemiol 42:82\u201389","journal-title":"Cancer Epidemiol"},{"key":"1883_CR8","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jbo.2016.02.001","volume":"5","author":"F Lin","year":"2016","unstructured":"Lin F, Hu Y, Zhao L, Zhang H, Yu X, Wang Z et al (2016) The epidemiological and clinical features of primary giant cell tumor around the knee: a report from the multicenter retrospective study in China. J Bone Oncol 5:38\u201342","journal-title":"J Bone Oncol"},{"key":"1883_CR9","doi-asserted-by":"publisher","first-page":"5414","DOI":"10.1038\/s41467-020-18955-y","volume":"11","author":"P Lutsik","year":"2020","unstructured":"Lutsik P, Baude A, Mancarella D, \u00d6z S, K\u00fchn A, Toth R et al (2020) Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone. Nat Commun 11:5414","journal-title":"Nat Commun"},{"key":"1883_CR10","doi-asserted-by":"publisher","first-page":"e32995","DOI":"10.1097\/MD.0000000000032995","volume":"102","author":"R Wu","year":"2023","unstructured":"Wu R, Wu X, Weng X, Xiu Y, Xu G, Liu X et al (2023) Giant cell tumor of bone with H3F3B mutation: a case report. Med (Baltim) 102:e32995","journal-title":"Med (Baltim)"},{"key":"1883_CR11","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.oooo.2014.07.011","volume":"118","author":"CC Gomes","year":"2014","unstructured":"Gomes CC, Diniz MG, Amaral FR, Antonini Guimar\u00e3es BV, Gomez RS (2014) The highly prevalent H3F3A mutation in giant cell tumours of bone is not shared by sporadic central giant cell lesion of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol 118:583\u2013585","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol"},{"key":"1883_CR12","doi-asserted-by":"publisher","first-page":"3759","DOI":"10.1182\/blood-2010-08-299917","volume":"117","author":"M Castella","year":"2011","unstructured":"Castella M, Pujol R, Call\u00e9n E, Trujillo JP, Casado JA, Gille H et al (2011) Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations. Blood 117:3759\u20133769","journal-title":"Blood"},{"key":"1883_CR13","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1002\/cncy.22000","volume":"126","author":"I-M Schaefer","year":"2018","unstructured":"Schaefer I-M, Fletcher JA, Nielsen GP, Shih AR, Ferrone ML, Hornick JL et al (2018) Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy. Cancer Cytopathol 126:552\u2013566","journal-title":"Cancer Cytopathol"},{"key":"1883_CR14","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1007\/s13139-016-0423-z","volume":"50","author":"HJ Park","year":"2016","unstructured":"Park HJ, Kwon SY, Cho S-G, Kim J, Song H-C, Kim SS et al (2016) Giant cell tumor with secondary aneurysmal bone cyst shows heterogeneous metabolic pattern on 18F-FDG PET\/CT: a case report. Nucl Med Mol Imaging 50:348\u2013352","journal-title":"Nucl Med Mol Imaging"},{"key":"1883_CR15","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1097\/PAS.0000000000000859","volume":"41","author":"F Amary","year":"2017","unstructured":"Amary F, Berisha F, Ye H, Gupta M, Gutteridge A, Baumhoer D et al (2017) H3F3A (histone 3.3) G34W immunohistochemistry: a reliable marker defining benign and malignant giant cell tumor of bone. Am J Surg Pathol 41:1059\u20131068","journal-title":"Am J Surg Pathol"},{"key":"1883_CR16","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1097\/PAS.0000000000001555","volume":"45","author":"DA Kerr","year":"2021","unstructured":"Kerr DA, Brcic I, Diaz-Perez JA, Shih A, Wilky BA, Pretell-Mazzini J et al (2021) Immunohistochemical characterization of giant cell tumor of bone treated with denosumab: support for osteoblastic differentiation. Am J Surg Pathol 45:93\u2013100","journal-title":"Am J Surg Pathol"},{"key":"1883_CR17","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/S0009-9260(98)80166-9","volume":"53","author":"MJ Lee","year":"1998","unstructured":"Lee MJ, Sallomi DF, Munk PL, Janzen DL, Connell DG, O\u2019Connell JX et al (1998) Pictorial review: giant cell tumours of bone. Clin Radiol 53:481\u2013489","journal-title":"Clin Radiol"},{"key":"1883_CR18","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ocl.2005.08.005","volume":"37","author":"RE Turcotte","year":"2006","unstructured":"Turcotte RE (2006) Giant cell tumor of bone. Orthop Clin North Am 37:35\u201351","journal-title":"Orthop Clin North Am"},{"key":"1883_CR19","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1097\/CCO.0000000000000852","volume":"34","author":"L van der Heijden","year":"2022","unstructured":"van der Heijden L, Lipplaa A, van Langevelde K, Bov\u00e9e JVMG, van de Sande MAJ, Gelderblom H (2022) Updated concepts in treatment of giant cell tumor of bone. Curr Opin Oncol 34:371\u2013378","journal-title":"Curr Opin Oncol"},{"key":"1883_CR20","doi-asserted-by":"publisher","first-page":"153303381984000","DOI":"10.1177\/1533033819840000","volume":"18","author":"E Palmerini","year":"2019","unstructured":"Palmerini E, Picci P, Reichardt P, Downey G (2019) Malignancy in giant cell tumor of bone: A review of the literature. Technol Cancer Res Treat 18:1533033819840000","journal-title":"Technol Cancer Res Treat"},{"key":"1883_CR21","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s00428-009-0863-2","volume":"456","author":"M Alberghini","year":"2010","unstructured":"Alberghini M, Kliskey K, Krenacs T, Picci P, Kindblom L, Forsyth R et al (2010) Morphological and immunophenotypic features of primary and metastatic giant cell tumour of bone. Virchows Arch 456:97\u2013103","journal-title":"Virchows Arch"},{"key":"1883_CR22","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1002\/jso.24739","volume":"116","author":"M Rosario","year":"2017","unstructured":"Rosario M, Kim H-S, Yun JY, Han I (2017) Surveillance for lung metastasis from giant cell tumor of bone. J Surg Oncol 116:907\u2013913","journal-title":"J Surg Oncol"},{"key":"1883_CR23","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1177\/1066896914534466","volume":"22","author":"ME Lawless","year":"2014","unstructured":"Lawless ME, Jour G, Hoch BL, Rendi MH (2014) Beta-human chorionic gonadotropin expression in recurrent and metastatic giant cell tumors of bone: a potential mimicker of germ cell tumor. Int J Surg Pathol 22:617\u2013622","journal-title":"Int J Surg Pathol"},{"key":"1883_CR24","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s00256-013-1785-2","volume":"43","author":"VA Fitzhugh","year":"2014","unstructured":"Fitzhugh VA, Katava G, Wenokor C, Roche N, Beebe KS (2014) Giant cell tumor of bone with secondary aneurysmal bone cyst-like change producing \u03b2-human chorionic gonadotropin. Skeletal Radiol 43:831\u2013834","journal-title":"Skeletal Radiol"},{"key":"1883_CR25","doi-asserted-by":"publisher","first-page":"117566","DOI":"10.1016\/j.bone.2025.117566","volume":"199","author":"V Knechtova","year":"2025","unstructured":"Knechtova V, Mahdal M, Zambo IS, Skoda J, Neradil J (2025) Biomarkers and therapeutic targets in giant cell tumor of bone: a comprehensive review. Bone 199:117566","journal-title":"Bone"},{"key":"1883_CR26","doi-asserted-by":"publisher","first-page":"e23514","DOI":"10.1200\/JCO.2021.39.15_suppl.e23514","volume":"39","author":"M Taqi","year":"2021","unstructured":"Taqi M, Haider MZ, Tariq M, Gillani SF-HS, Ali M, Zamani Z et al (2021) Role of biogenetic markers in differentiation and prognosis of giant cell tumor: a systemic review. JCO 39:e23514\u2013e23514","journal-title":"JCO"},{"key":"1883_CR27","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1634\/theoncologist.2013-0432","volume":"19","author":"L van der Heijden","year":"2014","unstructured":"van der Heijden L, Dijkstra PDS, van de Sande MAJ, Kroep JR, Nout RA, van Rijswijk CSP et al (2014) The clinical approach toward giant cell tumor of bone. Oncologist 19:550\u2013561","journal-title":"Oncologist"},{"key":"1883_CR28","doi-asserted-by":"publisher","first-page":"1572560","DOI":"10.3389\/fonc.2025.1572560","volume":"15","author":"X Gao","year":"2025","unstructured":"Gao X, Wang S, Zhan X, Liu Y, Chen L, Sun J et al (2025) Case report: giant cell lesions in the maxillofacial region: diagnostic points and treatment strategies. Front Oncol 15:1572560","journal-title":"Front Oncol"},{"key":"1883_CR29","doi-asserted-by":"crossref","unstructured":"Zhang Z, Xu J, Yao Y, Chu S, Cheng H, Chen D, et al (2013) Giant celltumors of the skull: a series of 18 cases and review of the literature. J Neurooncol 115:437\u201344","DOI":"10.1007\/s11060-013-1242-z"},{"key":"1883_CR30","doi-asserted-by":"crossref","unstructured":"Freeman JL, Oushy S, Schowinsky J, Sillau S, Youssef AS (2016) Invasive Giant CellTumor of the Lateral Skull Base: A Systematic Review, Meta-Analysis, and Case Illustration. World Neurosurg 96:47\u201357","DOI":"10.1016\/j.wneu.2016.05.086"},{"key":"1883_CR31","doi-asserted-by":"crossref","unstructured":"Battoo AJ, Salih S, Unnikrishnan AG, Jojo A, Bahadur S, Iyer S, et al (2012) Oncogenic osteomalacia from nasal cavity giant cell tumor. Head Neck 34:454\u20137","DOI":"10.1002\/hed.21562"},{"key":"1883_CR32","doi-asserted-by":"crossref","unstructured":"Akyigit A, Karlidag T, Sakallioglu \u00d6\u00d6, Polat C, Keles E (2014) Giant cell tumor of bone involving thetemporomandibular joint and temporal bone. J Craniofac Surg 25:1397\u20139","DOI":"10.1097\/SCS.0000000000000876"},{"key":"1883_CR33","doi-asserted-by":"crossref","unstructured":"Inoue A, Ohnishi T, Kohno S, Nishikawa M, Nishida N, Ohue S (2016) Role of denosumab in endoscopic endonasaltreatment for juvenile clival giant cell tumor: A case report and review of the literature. World Neurosurg 91:674.e1\u20136","DOI":"10.1016\/j.wneu.2016.04.054"}],"container-title":["Head and Neck Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-025-01883-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12105-025-01883-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12105-025-01883-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T02:02:37Z","timestamp":1768356157000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12105-025-01883-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1883"],"URL":"https:\/\/doi.org\/10.1007\/s12105-025-01883-y","relation":{},"ISSN":["1936-0568"],"issn-type":[{"value":"1936-0568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]},"assertion":[{"value":"17 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Flores Hidalgo is a member of the Head & Neck Pathology Editorial Board. The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All study procedures were performed in accordance with the Declaration of Helsinki and Research Committee Regulations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}],"article-number":"12"}}