BACKGROUND: Ameloblastic carcinoma and metastasising ameloblastoma are rare epithelial odontogenic tumours with aggressive features. Distinguishing between these two lesions is often clinically difficult but necessary to predict tumour behaviour or to plan future therapy. Here, we provide a brief review of the literature available on these two types of lesions and present a new case report of a young man with an ameloblastoma displaying metastatic features. We also use this case to illustrate the similarities and differences between these two types of tumours and the difficulties of their differential diagnosis. CASE PRESENTATION: Our histopathological analyses uncovered a metastasising tumour with features of ameloblastic carcinoma, which developed from the ameloblastoma. We profiled the gene expression of Wnt pathway members in ameloblastoma sample of this patient, because multiple molecules of this pathway are involved in the establishing of cell polarity, cell migration or for epithelial-mesenchymal transition during tumour metastasis to evaluate features of tumor behaviour. Indeed, we found upregulation of several cell migration-related genes in our patient. Moreover, we uncovered somatic mutation BRAF p.V600E with known pathological role in cancerogenesis and germline heterozygous FANCA p.S858R mutation, whose interpretation in this context has not been discussed yet. CONCLUSIONS: In conclusion, we have uncovered a unique case of ameloblastic carcinoma associated with an alteration of Wnt signalling and the presence of BRAF mutation. Development of harmful state of our patient might be also supported by the germline mutation in one FANCA allele, however this has to be confirmed by further analyses.

Department of Anatomy Histology and Embryology University of Veterinary Sciences Brno Czech Republic

Department of Clinical and Molecular Pathology Faculty of Medicine and Dentistry Palacky University and University Hospital in Olomouc Olomouc Czech Republic

Department of Hematooncology Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic

Department of Histology and Embryology Faculty of Medicine Masaryk University Brno Czech Republic

Department of Nuclear Medicine University Hospital Ostrava Ostrava Czech Republic

Department of Oncology Faculty of Medicine and University Hospital Ostrava Ostrava Czech Republic

Department of Oral and Maxillofacial Surgery University Hospital Ostrava Ostrava Czech Republic

Department of Pathological Morphology and Parasitology University of Veterinary Sciences Brno Czech Republic

Institute of Clinical and Molecular Pathology and Medical Genetics Faculty Hospital and Medical Faculty Ostrava Ostrava Czech Republic

Laboratory of Molecular Morphogenesis Institute of Animal Physiology and Genetics Czech Academy of Sciences Brno Czech Republic

See more in PubMed

Wright JM, Vered M. Update from the 4th Edition of the world health organization classification of head and neck tumours: odontogenic and maxillofacial bone Tumors. Head Neck Pathol. 2017;11(1):68–77. PubMed PMC

Kramer IR, Pindborg JJ, Shear M. The WHO Histological Typing of Odontogenic Tumours. A commentary on the Second Edition. Cancer. 1992;70(12):2988–94. PubMed

Kishore M, Panat SR, Aggarwal A, Upadhyay N, Agarwal N. Ameloblastic Carcinoma: A Case Report. J Clin Diagn Res. 2015;9(7):ZD27–8. PubMed PMC

Palanisamy JC, Jenzer AC. Ameloblastoma. StatPearls. Treasure Island (FL)2022.

Jing W, Xuan M, Lin Y, Wu L, Liu L, Zheng X, et al. Odontogenic tumours: a retrospective study of 1642 cases in a Chinese population. Int J Oral Maxillofac Surg. 2007;36(1):20–25. PubMed

Mosqueda Taylor A, Meneses Garcia A, Ruiz Godoy Rivera LM, Suarez Roa Mde L, Luna Ortiz K. Malignant odontogenic tumors. A retrospective and collaborative study of seven cases. Med Oral. 2003;8(2):110–21. PubMed

Ricard AS, Majoufre-Lefebvre C, Siberchicot F, Laurentjoye M. A multirecurrent ameloblastoma metastatic to the lung. Rev Stomatol Chir Maxillofac. 2010;111(2):98–100. PubMed

Pandiar D, Anand R, Kamboj M, Narwal A, Shameena PM, Devi A. Metastasizing Ameloblastoma: a 10 year clinicopathological review with an insight into pathogenesis. Head Neck Pathol. 2021;15(3):967–974. PubMed PMC

Collins AP, Mubarak N, Hemaidan HS, Hemaidan SM, Hemaidan A. Malignant Ameloblastoma with Hepatic Metastasis in a 38-Year-Old Haitian Woman. Ame J Case Rep. 2021;22:e929422. PubMed PMC

Ladeinde AL, Ajayi OF, Ogunlewe MO, Adeyemo WL, Arotiba GT, Bamgbose BO, et al. Odontogenic tumors: a review of 319 cases in a Nigerian teaching hospital. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;99(2):191–195. PubMed

Adebiyi KE, Odukoya O, Taiwo EO. Ectodermal odontogenic tumours: analysis of 197 Nigerian cases. Int J Oral Maxillofac Surg. 2004;33(8):766–770. PubMed

Gawande PD, Khande K, Agrawal G, Aditya A. Ameloblastic Carcinoma: a rare malignant Tumour in Maxillofacial Region. J Maxillofac Oral Surg. 2017;16(3):377–381. PubMed PMC

Cho BH, Jung YH, Hwang JJ. Ameloblastic carcinoma of the mandible: a case report. Imaging Sci Dent. 2020;50(4):359–363. PubMed PMC

Li J, Du H, Li P, Zhang J, Tian W, Tang W. Ameloblastic carcinoma: An analysis of 12 cases with a review of the literature. Oncol Lett. 2014;8(2):914–920. PubMed PMC

Yoon HJ, Hong SP, Lee JI, Lee SS, Hong SD. Ameloblastic carcinoma: an analysis of 6 cases with review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108(6):904–913. PubMed

Giridhar P, Mallick S, Upadhyay AD, Rath GK. Pattern of care and impact of prognostic factors in the outcome of ameloblastic carcinoma: a systematic review and individual patient data analysis of 199 cases. Eur Arch Otorhinolaryngol. 2017;274(10):3803–3810. PubMed

Alexander C, Maleki Z. Ameloblastic carcinoma with metastasis to the parotid gland. Diagn Cytopathol. 2018;46(2):162–164. PubMed

Abada RL, Kadiri F, Tawfik N, Benchakroun N, Bouchbika Z, Chekkoury AI, et al. Multiple metastases of a mandibular ameloblastoma. Rev Stomatol Chir Maxillofac. 2005;106(3):177–180. PubMed

Ribatti D, Tamma R, Annese T. Epithelial-mesenchymal transition in cancer: a historical overview. Transl Oncol. 2020;13(6):100773. PubMed PMC

Zhang J, Tian XJ, Xing J. Signal Transduction Pathways of EMT Induced by TGF-beta, SHH, and WNT and Their Crosstalks. J Clin Med. 2016;5(4):41. PubMed PMC

Luo J, Yao Y, Ji S, Sun Q, Xu Y, Liu K, et al. PITX2 enhances progression of lung adenocarcinoma by transcriptionally regulating WNT3A and activating Wnt/beta-catenin signaling pathway. Cancer Cell Int. 2019;19:96. PubMed PMC

Kioussi C, Briata P, Baek SH, Rose DW, Hamblet NS, Herman T, et al. Identification of a Wnt/Dvl/beta-Catenin –> Pitx2 pathway mediating cell-type-specific proliferation during development. Cell. 2002;111(5):673–685. PubMed

Ye B, Li L, Xu H, Chen Y, Li F. Opposing roles of TCF7/LEF1 and TCF7L2 in cyclin D2 and Bmp4 expression and cardiomyocyte cell cycle control during late heart development. Lab Invest J Tech Methods Pathol. 2019;99(6):807–18. PubMed PMC

Yoshioka Y, Toratani S, Ogawa I, Okamoto T. Ameloblastic carcinoma, secondary type, of the mandible: a case report. J Oral Maxillofac Surg. 2013;71(1):e58–62. PubMed

Pandey S, Bhutia O, Roychoudhury A, Arora A, Bhatt K. Literature review of 86 cases of mandibular ameloblastic carcinoma. Natl J Maxillofac Surg. 2018;9(1):2–7. PubMed PMC

Karakida K, Aoki T, Sakamoto H, Takahashi M, Akamatsu T, Ogura G, et al. Ameloblastic carcinoma, secondary type: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110(6):e33–e37. PubMed

Hall JM, Weathers DR, Unni KK. Ameloblastic carcinoma: an analysis of 14 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(6):799–807. PubMed

Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 2018;62:50–60. PubMed PMC

van der Wal T, van Amerongen R. Walking the tight wire between cell adhesion and WNT signalling: a balancing act for beta-catenin. Open Biol. 2020;10(12):200267. PubMed PMC

Miyake T, Tanaka Y, Kato K, Tanaka M, Sato Y, Ijiri R, et al. Gene mutation analysis and immunohistochemical study of beta-catenin in odontogenic tumors. Pathol Int. 2006;56(12):732–737. PubMed

Lei Y, Jaradat JM, Owosho A, Adebiyi KE, Lybrand KS, Neville BW, et al. Evaluation of SOX2 as a potential marker for ameloblastic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117(5):608–16 e1. PubMed

Siriwardena BS, Kudo Y, Ogawa I, Tilakaratne WM, Takata T. Aberrant beta-catenin expression and adenomatous polyposis coli gene mutation in ameloblastoma and odontogenic carcinoma. Oral Oncol. 2009;45(2):103–108. PubMed

Martinez-Martinez M, Mosqueda-Taylor A, Carlos-Bregni R, Pires FR, Delgado-Azanero W, Neves-Silva R, et al. Comparative histological and immunohistochemical study of ameloblastomas and ameloblastic carcinomas. Med Oral Patol Oral Cir Bucal. 2017;22(3):e324–e332. PubMed PMC

Sekine S, Sato S, Takata T, Fukuda Y, Ishida T, Kishino M, et al. Beta-catenin mutations are frequent in calcifying odontogenic cysts, but rare in ameloblastomas. Am J Pathol. 2003;163(5):1707–1712. PubMed PMC

Kawabata T, Takahashi K, Sugai M, Murashima-Suginami A, Ando S, Shimizu A, et al. Polymorphisms in PTCH1 affect the risk of ameloblastoma. J Dent Res. 2005;84(9):812–816. PubMed

Brown NA, Rolland D, McHugh JB, Weigelin HC, Zhao L, Lim MS, et al. Activating FGFR2-RAS-BRAF mutations in ameloblastoma. Clin Cancer Res. 2014;20(21):5517–5526. PubMed

Tanahashi J, Daa T, Yada N, Kashima K, Kondoh Y, Yokoyama S. Mutational analysis of Wnt signaling molecules in ameloblastoma with aberrant nuclear expression of beta-catenin. J Oral Pathol Med. 2008;37(9):565–570. PubMed

Garcia-Munoz A, Rodriguez MA, Liceaga-Escalera C, Liceaga-Reyes R, Carreon-Burciaga RG, Gonzalez-Gonzalez R, et al. Expression of the transcription factor PITX2 in ameloblastic carcinoma. Arch Oral Biol. 2015;60(6):799–803. PubMed

Hankey W, Frankel WL, Groden J. Functions of the APC tumor suppressor protein dependent and independent of canonical WNT signaling: implications for therapeutic targeting. Cancer Metastasis Rev. 2018;37(1):159–172. PubMed PMC

Kumamoto H, Ooya K. Immunohistochemical detection of beta-catenin and adenomatous polyposis coli in ameloblastomas. J Oral Pathol Med. 2005;34(7):401–406. PubMed

Guimaraes LM, Coura BP, Gomez RS, Gomes CC. The molecular pathology of odontogenic tumors: expanding the spectrum of MAPK pathway driven tumors. Front Oral Health. 2021;2:740788. PubMed PMC

Niu Z, Li Y, Chen W, Zhao J, Zheng H, Deng Q, et al. Study on clinical and biological characteristics of ameloblastic carcinoma. Orphanet J Rare Dis. 2020;15(1):316. PubMed PMC

Nobusawa A, Sano T, Yokoo S, Oyama T. Ameloblastic carcinoma developing in preexisting ameloblastoma with a mutation of the p53 gene: a case report. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;118(5):e146–e150. PubMed

Khojasteh A, Khodayari A, Rahimi F, Ghaderian MH, Jafarian M, Nayebi A, et al. Hypermethylation of p16 tumor-suppressor gene in ameloblastic carcinoma, ameloblastoma, and dental follicles. J oral Maxillofac Surg. 2013;71(1):62–65. PubMed

Li D, Xu S, Sun M, Qiao L, Wang L, Liu Y. MAID chemotherapy regimen as a treatment strategy for metastatic malignant ameloblastoma: a case report. Medicine. 2019;98(25):e15873. PubMed PMC

Chen G, Gao C, Gao X, Zhang DH, Kuan SF, Burns TF, et al. Wnt/beta-catenin pathway activation mediates adaptive resistance to BRAF inhibition in colorectal cancer. Mol Cancer Ther. 2018;17(4):806–813. PubMed PMC

Fennell LJ, Kane A, Liu C, McKeone D, Fernando W, Su C, et al. APC Mutation Marks an Aggressive Subtype of BRAF Mutant Colorectal Cancers. Cancers. 2020;12(5):1171. PubMed PMC

Dokal I. Fanconi's anaemia and related bone marrow failure syndromes. Br Med Bull. 2006;77–78:37–53. PubMed

Savino M, Borriello A, D'Apolito M, Criscuolo M, Del Vecchio M, Bianco AM, et al. Spectrum of FANCA mutations in Italian Fanconi anemia patients: identification of six novel alleles and phenotypic characterization of the S858R variant. Hum Mutat. 2003;22(4):338–339. PubMed

Rogers CD, Couch FJ, Brune K, Martin ST, Philips J, Murphy KM, et al. Genetics of the FANCA gene in familial pancreatic cancer. J Med Genet. 2004;41(12):e126. PubMed PMC

Litim N, Labrie Y, Desjardins S, Ouellette G, Plourde K, Belleau P, et al. Polymorphic variations in the FANCA gene in high-risk non-BRCA1/2 breast cancer individuals from the French Canadian population. Mol Oncol. 2013;7(1):85–100. PubMed PMC

Mamrak NE, Shimamura A, Howlett NG. Recent discoveries in the molecular pathogenesis of the inherited bone marrow failure syndrome Fanconi anemia. Blood Rev. 2017;31(3):93–99. PubMed PMC

Del Valle J, Rofes P, Moreno-Cabrera JM, Lopez-Doriga A, Belhadj S, Vargas-Parra G, et al. Exploring the Role of Mutations in Fanconi Anemia Genes in Hereditary Cancer Patients. Cancers. 2020;12(4):829. PubMed PMC

Chen H, Zhang S, Wu Z. Fanconi anemia pathway defects in inherited and sporadic cancers. Transl Pediatr. 2014;3(4):300–304. PubMed PMC

Xia Q, Zhao LY, Yan YD, Liao Y, Di YS, Xiao XY. A multiple primary malignancy patient with FANCA gene mutation: a case report and literature review. Front Oncol. 2020;10:1199. PubMed PMC

Wu J, Mu Q, Thiviyanathan V, Annapragada A, Vigneswaran N. Cancer stem cells are enriched in Fanconi anemia head and neck squamous cell carcinomas. Int J Oncol. 2014;45(6):2365–2372. PubMed PMC