Brain Tumor Res Treat.  2024 Jul;12(3):192-199. 10.14791/btrt.2024.0023.

Malignant Transformation of Meningioma With TERT Promoter Mutation: A Case Report

• Hong Y
• Han N
• Gwak HS

• KMID: 2558438
• DOI: http://doi.org/10.14791/btrt.2024.0023

Abstract

High-grade meningiomas make up a relatively minor proportion of meningiomas, which are one of the most common types of primary intracranial tumors in adults. Though rare, a considerable portion of highgrade meningiomas arise from malignant transformation of benign meningiomas. The 2021 World Health Organization (WHO) classification criteria introduced molecular markers in the diagnosis and grading of central nervous system (CNS) tumors and assigned certain genomic mutations to grade 3 meningiomas. We report a case of a 54-year-old male patient who underwent stepwise malignant transformation of meningioma from WHO grade 1 to grade 3 within 10 years, during the course of five surgeries followed by adjuvant stereotactic radiosurgery and radiotherapy. We performed next-generation sequencing (NGS) on the most recent grade 3 meningioma specimen and found that it carried a telomerase reverse transcriptase promoter (TERTp) mutation (c.-124C>T) in accordance with the 2021 WHO criteria for grade 3 meningiomas. We then retrospectively examined the previous grade 1 and 2 specimens and found them to have the same mutation. We reviewed the significance of molecular markers in the diagnosis of meningiomas, possible genetic alterations associated with their malignant transformation, and what measures could be taken to effectively manage meningiomas considering NGS findings.

Keyword

Meningioma; Telomerase; Mutation; Genomics; Recurrence; Radiation

Figure

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  Fig. 1 Initial CT, MRI, and histopathologic findings of the right frontal lesion at the first operation in 2013. Axial view of preoperative non-contrast CT (A) and T1-weighted gadolinium-enhanced MRI (B) shows a lobulated, well-circumscribed right frontal mass with homogeneous contrast enhancement. The histopathology slide (C) shows typical meningothelial whorls with increased cellularity, and tumor cells are composed in a syncytial pattern with eosinophilic cytoplasm and indistinct cell borders suggestive of WHO grade 1 meningothelial meningioma (hematoxylin and eosin, ×100).

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  Fig. 2 Follow-up MRI showing new lesions treated by radiotherapies (RTs) in 2015 and 2017. A: Two years after the initial operation, a newly appeared middle frontal convexity lesion was treated by fractionated stereotactic RT of 3,000 cGy/3 fractions. B: One and a half years after the RT, follow-up MRI showed a newly appeared right temporal dural-based mass, and stereotactic radiosurgery with a 1,800 cGy marginal dose was delivered.

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  Fig. 3 MRI and histopathologic findings of recurrent lesions at the second operation in 2019. Axial views of preoperative T1-weighted gadolinium-enhanced MRI lesions at the right high frontal (A), middle frontal (B), Sylvian (C), and temporal convexity (D) areas. On the histopathology slides, the previously irradiated (arrows in B and C) middle frontal (F) and Sylvian (G) lesions show treatment-related changes of marked hyalinization with low cellularity. Microscopic findings of the newly appeared middle frontal (E) and temporal convexity (H) lesions (especially the latter) show increased mitoses and prominent nucleoli, compatible with WHO grade 2 atypical meningioma (hematoxylin and eosin, ×100).

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  Fig. 4 MRI and histopathologic findings of recurrent lesions at the fifth operation in 2023. Axial views of the preoperative T1-weighted gadolinium-enhanced MRI reveal lesions at the right frontal convexity (red arrow) (A), temporal convexity with necrotic changes (previously irradiated; red arrow) (B), and temporal base with cystic changes (C). Histopathologic examinations show (D) a right frontal lesion (×100), (E) a temporal base lesion with patternless growth (×100), and (F) prominent nucleoli and increased mitoses (×200) suggestive of WHO grade 3 anaplastic meningioma (hematoxylin and eosin).

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