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

TL;DR

A rare case of ameloblastoma metastasizing to the lung 14 years after initial treatment is reported, highlighting the importance of clinical history and molecular analysis.

Contribution

This case highlights the diagnostic challenges of metastasizing ameloblastoma and the role of AKT1 mutation in such rare occurrences.

Findings

Metastasizing ameloblastoma was misdiagnosed as squamous cell carcinoma due to lack of clinical history.

Molecular analysis revealed an AKT1 mutation in both the primary and metastatic lesions.

Neoadjuvant treatment altered the tumor's morphology, complicating the diagnosis.

Abstract

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.

The online version contains supplementary material available at 10.1007/s12105-025-01844-5.

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