Recurrent TRAF7-mutated meningioma: Molecular evolution and therapeutic insights

Abstract

Meningiomas are the most common primary intracranial tumors, with TRAF7 mutations identified in ~25% of cases. These mutations, associated with NFκB pathway activation, are linked to higher recurrence rates than other low-grade-associated mutations. We report a 49-year-old Caucasian woman with recurrent TRAF7-mutated World Health Organization Grade 2 meningiomas. Initially diagnosed with World Health Organization Grade 1 meningiomas in 2015, her disease progressed to Grade 2 chordoid meningioma by 2021. Molecular profiling revealed a TRAF7 exon 20 (p.R653Q) mutation and PMS2 deletion. Multiple surgical resections, radiation, and systemic therapies, including lanreotide, bevacizumab, and pembrolizumab, were employed, with pembrolizumab showing a favorable response due to mismatch repair deficiency. This case highlights the molecular and histological evolution of TRAF7-mutated meningiomas and the potential of immunotherapy in recurrent cases. The absence of targeted therapies for TRAF7-positive tumors underscores the need for mutation-specific clinical trials.

Keywords: TRAF7 mutation; case report; immunotherapy; meningioma; pembrolizumab; recurrence.

Figure 1.

Histopathological images of meningiomas. (a–c) H&E, 5×, 20×, 4×, left temporal bone (March 04, 2019). (d–f) H&E, 5×, 20×, 40×, left orbital skull (March 04, 2019). (g–i) H&E, 5×, 20×, 40×, temporal meningioma (December 03, 2019). (j–l) H&E, 5×, 20×, 40×, left tentorial meningioma (November 30, 2021).

Figure 2.

Imaging studies. (a) Ga-68 DOTATATE PET–CT, axial, 2020. (b) MRI brain T1 RAGE axial with gadolinium, 2021. (c) MRI orbit T1 axial TSE FS with gadolinium, 2021. (d) MRI brain T1 coronal RAGE 3D non-IR, 2025. CT: computed tomography; MRI: magnetic resonance imaging; PET: positron emission tomography.