Malignant Peripheral Nerve Sheath Tumors of the Skull Base: The Mayo Clinic Cohort

Introduction: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, heterogenous soft-tissue sarcomas of nerve sheath origin. Their occurrence at the skull base is exceedingly rare and portend poor prognosis. Only single case reports have been published to date, rendering significant gaps in clinical understanding. Objective: To characterize the clinical spectrum, surgical and oncologic management, and outcomes of patients with intracranial MPNST at the Mayo Clinic Methods: A retrospective review of the institutional database was performed for MPNST. Patients with intracranial involvement were included regardless of primary site. Data included demographics, prior malignancies, tumor etiology, extent of resection, histopathologic markers, adjuvant therapies, recurrence, progression-free survival (PFS), and overall survival (OS). Univariate analyses were performed with t -tests and Fisher’s exact tests. Kaplan–Meier curves with log-rank testing were used to assess predictors of PFS and OS. Type 1 error was defined as p < 0.05. Results: Between 1985–2025, nine patients had intracranial disease: eight primary skull base tumors and one intracranial parenchymal metastasis from an extracranial MPNST. Within the skull base cohort ([ Fig. 1 ]), median age was 56.5 years with equal sex distribution. One patient had neurofibromatosis type 1. Etiology was spontaneous in 25% and radiation-induced in 75%, following treatment of paraganglioma, pituitary adenoma, optic glioma, and vestibular schwannoma 6.5 to 26 years prior to re-presentation (Figs. 2, 3). The vestibulocochlear nerve was the most common site of origin. Symptom duration ranged 2–4 months with multiple cranial neuropathies. Gross total resection was achieved in 50% of cases; cranial nerve sacrifice occurred in 37.5%. Tumors were largely firm and avascular. Histopathology consistently demonstrated loss of H3K27me3 expression, elevated K i -67, frequent S100/SOX10 negativity, and CDKN2A/B loss. 87.5% received adjuvant radiotherapy, most commonly proton beam therapy. Two patients trialed doxorubicin-based chemotherapy. Median time to local recurrence was 1.5 months occurring in 37.5% of cases. Distant metastases, involving the spinal cord, scalp, and/or lung, also occurred in 37.5%, with a median time to development of 4 months. At approximately one year, 25% had no evidence of disease, 12.5% had controlled progression, and 62.5% had died. Median PFS was 5 months (95% CI 4–9), and median OS was 11 months (95% CI 6–28). Gross total resection significantly improved PFS (15.6 versus 4.3 months, p = 0.022) and OS (28 versus 6–10 months, p = 0.03). NF1 status correlated with worse OS (6 versus 11 months, p = 0.014). Non-significant trends toward longer survival were observed in tumors arising from cranial nerve VIII and in de novo versus radiation-induced cases ([ Fig. 4 ]). Conclusion: Intracranial MPNSTs of the skull base should be considered in rapidly enlarging lesions causing acute cranial neuropathies with associated vasogenic edema. Early recognition and maximal resection—sometimes necessitating cranial nerve sacrifice and/or subpial brainstem dissection—are the strongest determinants of survival. Intraoperative frozen pathology with multiple specimens is critical for early identification of malignancy and for guiding resection strategy. Future studies incorporating molecular profiling are warranted to better define prognostic markers and known histopathologic variants and differentiate the clinical behavior of de novo versus radiation-induced disease. Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany