Significance of YAP1-MAML2 rearrangement and GTF2I mutation in the diagnosis and differential diagnosis of metaplastic thymoma

Background: Metaplastic thymoma (MT) is a very uncommon thymoma type, with biphasic differentiation as one of its histological characteristics. This histological pattern, however, can also be mistaken for type A thymoma and the A component in type AB thymoma.

Methods: Postoperative specimens were collected from five MT and four type A thymomas with a retrospective analysis involving immunohistochemistry, fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS).

Results: The histological morphology of the MT overlapped with that of the type A thymoma. With immunostains, the former's spindle cell components expressed vimentin and EMA, but not CD20. In MT, 3/5 cases had the nuclear expression of YAP1. The spindle cell component of the type A thymoma was found to express CD20. In all five cases of MT, FISH detection revealed YAP1-MAML2 fusion, which was not found in any type A thymoma cases. NGS sequencing confirmed YAP1-MAML2 rearrangement in all five cases of MT, and mutations in POLE and HRAS were also found in two cases, respectively. GTF2I c.74146970 T > A mutations were found in all cases of type A thymoma, and HRAS and NRAS mutations were found in two cases, but no YAP1-MAML2 rearrangement was evident.

Conclusions: For the diagnosis and differential diagnosis of challenging cases, the YAP1-MAML2 rearrangement and GTF2I mutation were both significant molecular events specific to MT and type A thymoma, respectively.