(35) Management and Treatment of Ameloblastic Carcinoma: A Case Report of Cancerous Transformation of Ameloblastoma

Abstract: Ameloblastic carcinoma (AC) is a malignant form of ameloblastoma characterized by aggressive behavior, rapid growth, and local invasion. It is an extremely rare malignancy, representing 30% of malignant odontogenic tumors, which collectively comprise less than 2% of all odontogenic tumors (Vared et al; Robinson et al). AC typically arises de novo; however, rare cases of malignant transformation from pre-existing benign ameloblastoma have been reported (Yoon HJ et al.). While surgical resection remains the cornerstone of treatment, the lack of standardized protocols for adjuvant chemoradiotherapy complicates disease management due to its rarity (Saluja et al). 

We report a 43-year-old male diagnosed with recurrent and regionally metastatic AC originating from a pre-existing ameloblastoma. Initial surgical resection resulted in pT4aN2b AC, with negative margins, 2 out of 47 lymph nodes positive for metastasis, negative extranodal extension (ENE)/perineural invasion (PNI), and positive lymphovascular invasion (LVI). Disease recurrence was noted at 3 months postoperatively, affecting the left zygoma, orbit, and maxilla, necessitating a second radical resection with orbital exenteration, infratemporal fossa resection, resection of the anterior cranial fossa using surgical image-guided navigation, and reconstruction with a scapular free flap. Given the aggressive recurrence, a multidisciplinary tumor board recommended adjuvant radiation and further molecular studies to assess targeted therapy options. 

AC is a rare and aggressive odontogenic malignancy with a recurrence rate of approximately 30% (Giridhar et al). It has a metastatic potential of 20-30%, with regional metastasis to the cervical lymph nodes occurring in 25% of metastatic cases and distant metastasis to the lungs in 75% of cases. Metastases to the brain, bones, and liver have also been documented (Hennocq et al; Hou et al; Giridhar et al; Yoon HJ et al). AC is associated with several genetic mutations, most notably the BRAF V600E mutation, which is present in up to 90% of ameloblastic lesions and serves as a key therapeutic target. Additional mutations in p53, PD-L1, and CTNNB1 (beta-catenin) have been identified, contributing to tumor aggressiveness, recurrence, and potential resistance to therapy (Ganiyev et al; Mouselhy et al; Oh et al; Bartels et al). 

Radical surgical resection with negative margins remains the gold standard for treatment, with adjuvant radiotherapy recommended in high-risk cases. Chemotherapy remains experimental, while targeted therapy (BRAF/MEK inhibitors) is being explored as a potential therapeutic approach, though clinical outcomes remain under investigation. Genetic profiling may help guide therapy selection, but its routine use in AC management has yet to be standardized. In addition to surgical and pharmacotherapeutic strategies, close monitoring and long-term follow-ups are recommended to improve patient outcomes (Hall et al; Larranaga JJ et al; Cho BH et al). 

AC requires a multidisciplinary approach to optimize treatment outcomes and enhance quality of care. Future directions include exploring targeted therapies and immunotherapy to improve survival rates. Our case highlights the importance of close monitoring and aggressive surgical intervention in recurrent cases of AC.

1. Vered, M., Wright, J.M. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Odontogenic and Maxillofacial Bone Tumours. Head and Neck Pathol 16, 63–75 (2022). doi.org/10.1007/s12105-021-01404-7 
2. Robinson L, Abreu LG, Fonseca FP, Hunter KD, Ambele MA, van Heerden WFP. Ameloblastic carcinoma: A systematic review. J Oral Pathol Med. 2024 Mar;53(3):174-181. doi: 10.1111/jop.13517