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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. 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). 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 &gt; 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. 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.

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