Fusion as a Diagnostic Biomarker for Metaplastic Thymoma.

BACKGROUND

Metaplastic thymoma is a very rare tumor with only a few case reports documented in literature. Hence, its molecular features have not been well explored.

MATERIAL AND METHODS

Seventeen specimens of metaplastic thymoma were sequenced and retrospectively analyzed by fluorescence hybridization (FISH) and immunohistochemistry in the study. In addition, seven cases of micronodular thymoma with lymphoid stroma and nine cases of type A thymoma were also investigated.

RESULTS

Among these metaplastic thymomas, fifteen cases showed classical histological features, and two cases displayed characteristic micronodular-like growth patterns. DNA and RNA based next-generation sequencing identified and confirmed highly recurrent Yes Associated Protein 1 () - Mastermind Like Transcriptional Coactivator 2 () translocation (13/17, 76.5%) in metaplastic thymoma but not in micronodular thymoma with lymphoid stroma (0/7, 0%) and type A thymoma (0/9, 0%). In addition, six nonsense mutations were also detected in the metaplastic thymoma. FISH in microdissection specimens indicated that both epithelioid and spindle cell components harbored gene rearrangements.

CONCLUSIONS

Our study explored the genetic alterations in epithelioid and spindle cell components in metaplastic thymoma. Furthermore, gene rearrangements emerged as a potential diagnostic biomarker helpful for distinguishing metaplastic thymoma from type A and micronodular thymoma with lymphoid stroma.