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.