Role of a Promoter Mutation in TERT in Malignant Transformation of Pleomorphic Xanthoastrocytoma.

Abstract

Pleomorphic xanthoastrocytoma (PXA) is categorized as grade II, other astrocytic tumors per the 2016 World Health Organization classification. Despite being a relatively benign type of tumor, PXA often has an aggressive clinical course. The more malignant form of PXA is now known as anaplastic pleomorphic xanthoastrocytoma (A-PXA) and is categorized as a grade III tumor. Clinical and genetic factors associated with malignant transformation remain unclear. In particular, typical genetic expression patterns in PXA and A-PXA remain unidentified. We present a case of recurrent PXA in which malignant transformation followed a promoter mutation in TERT. In this case, genetic chronologic changes accompanying malignant transformation of PXA were thoroughly examined. The promoter mutation was detected in the second operative specimen after stereotactic radiosurgery (SRS) at the first tumor recurrence. Subsequently, a malignant transformation to the A-PXA occurred at the time of the second recurrence, and the tumor repeatedly recurred afterward. TERT promotor mutations may contribute to the malignant transformation of PXA; the mechanism of this mutation is unknown, but it may have been caused by SRS. Therefore, improvident use of radiation should be avoided to prevent the malignant transformation of PXA.