Intracranial Malignant Peripheral Nerve Sheath Tumors Not Associated with a Cranial Nerve: Systematic Review and Illustrative Case

Objective

Primary intracranial malignant peripheral nerve sheath tumors (MPNSTs) not associated with cranial nerves are rare and aggressive neoplasms. The rarity of presentation has precluded rigorous analysis of diagnosis, risk factors, treatment, and survival. We analyzed every reported case through exhaustive literature review. In addition, we present our own experience managed with resection, radiotherapy, and first use of targeted therapy in a tumor of this type for a BRAF mutation identified during next-generation sequencing.

Methods

Two databases, PubMed and Embase, and crossed references were queried for intracranial MPNSTs not associated with a cranial nerve. Extracted variables included demographics, risk factors, tumor characteristics, interventions, and outcomes. Univariate and multivariate analysis was performed to identify factors with survival benefit.

Results

A total of 56 patients (including the present case) were included from 743 literature results. There was a male/female ratio of 1.5:1 and mean diagnosis age of 29.7 ± 21.8 years. Seventy-one percent of cases were sporadic and 23% neurofibromatosis type 1 related. Median survival was 29 ± 22.1 months with 1-year survival of 60%. Factors associated on univariate analysis with reduced survival were subtotal resection (P = 0.05), older age (P = 0.023), triton histology (P < 0.001), and early recurrence (≤6 months) (P = 0.018). On multivariate analysis, gross total resection reduced mortality risk (P = 0.011), whereas triton histology (P = 0.017) and infratentorial tumor location (P = 0.037) increased mortality.

Conclusions

We present a systematic review of intracranial MPNSTs not associated with a cranial nerve. These tumors have poor prognosis and benefit from aggressive resection, multimodal treatment, and close follow-up. Next-generation sequencing can show molecular alterations for potential targeted therapy.

Introduction

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive mesenchymal neoplasms that originate from peripheral nerve sheaths sporadically^1,2 or arise from dedifferentiation of schwannomas or plexiform neurofibromas.1, 2, 3 They have a 5-year overall survival of 49% (16%–63%)⁴ and represent 3%–10% of soft-tissue sarcomas² arising at a frequency of 0.001% in the general population⁵ and 8%–16% of patients with neurofibromatosis type 1 (NF-1).^6,7 Most cases (71.3%) develop in the trunk or limbs, whereas 5.1% are intracranial.⁸

The intracranial MPNST is a dismal variant, with a median survival of 9–11 months^9,10 and 1-year survival of 33%.¹¹ Approximately 77% of intracranial MPNSTs arise from cranial nerves (CNs) (60% CN VIII and 27% CN V).¹¹ Consequently, intracranial MPNSTs not arising from a CN are particularly rare. These MPNSTs include intraparenchymal MPNSTs (also known as malignant intracerebral nerve sheath tumors),^12,13 with 25 cases previously identified in the literature,¹⁴ as well as sellar/suprasellar MPNSTs,¹⁵ intraventricular MPNSTs,^16,17 and extra-axial dural-based MPNSTs.^18,19

The cause, prevalence, and management of intracranial MPNSTs not associated with a CN are poorly understood. We review our experience with a malignant intracerebral nerve sheath tumor in a 23-year-old man not only to show the severity of the disease but also to document the first use of targeted therapy for its intracranial management as a result of genomic profiling. In addition, we performed a systematic review of the literature for intracranial MPNSTs not associated with a CN and identified significantly more cases than previously reported. Combining our case with those found in the literature, we analyzed the demographics, tumor histology, interventions, and outcomes of patients with non-CN MPNSTs to identify risk factors and treatment modalities affecting overall survival.