Lung tumors resembling jaw ameloblastomas with BRAF mutation

Researchers report three solitary lung tumors that show the same appearance and molecular change as ameloblastomas, a tumor type usually found in the jaw. Each tumor was a peribronchial mass several centimeters across and had characteristic cell patterns and BRAF V600E mutations confirmed by testing. Entrapped normal lung cells mimicked a second tumor component, but testing showed they were not part of the tumor. Dental and clinical exams found no hidden jaw tumors. So far, none of the cases have recurred or spread, and the authors consider how such jaw-like tumors might arise in the lung.

What the study examined

This work examined three lung tumors that showed the defining features of ameloblastoma, a tumor type normally found in the jawbones. The cases were collected through consultation at academic centers and were studied with careful pathology and molecular testing to compare them with their jaw counterparts.

The tumors presented as solitary peribronchial masses several centimeters in size. The investigators also checked for hidden jaw tumors using clinical examinations and panoramic dental x-rays, which were negative.

Key findings

The tumors shared a distinctive microscopic pattern: a loose central zone of bland squamoid-to-spindled cells with long intercellular connections and a surrounding layer of palisaded columnar cells showing focal reverse nuclear polarity at the edge where tumor met myxoid stroma. This pattern matches the appearance of ameloblastomas that arise in the mandible or maxilla.

• All tumors stained positive with an antibody test that detects the BRAF V600E protein change.
• Molecular testing confirmed the BRAF V600E mutation in each case, and broad next-generation sequencing was performed on two of the tumors.
• A pronounced overgrowth of trapped pneumocytes (normal lung cells) was present in some areas and initially suggested a two-part tumor, but lack of BRAF V600E labeling in those cells showed they were non-neoplastic lung tissue.
• No recurrences or metastases were observed during the follow-up reported in these cases.

Why it matters

These cases document a tumor in the lung that is histologically and molecularly identical to jaw ameloblastomas, expanding the recognized settings in which this tumor appearance can arise. The presence of the same BRAF V600E mutation links the lung tumors closely to their gnathic counterparts.

Recognizing this tumor pattern in the lung can help pathologists distinguish true neoplastic components from entrapped normal lung cells, and it raises questions about how a tumor with jaw-like features can develop in the respiratory tract. The authors discuss possible origins and emphasize the distinctiveness of this tumor type based on the collected cases.