Metastasizing Ameloblastoma Mimicking Squamous Cell Carcinoma of the Lung and Harboring an AKT1 Mutation

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's 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 AKT1 (c.49G > A p.(Glu17Lys) COSMIC ID: COSM33765) but no mutations in the BRAF 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.