Comprehensive Review of Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 2: Systematic Review, Case Series and SEER Database Analysis

Introduction: Malignant peripheral nerve sheath tumors (MPNSTs) are rare, aggressive soft tissue sarcomas often linked to neurofibromatosis type 1 (NF1), with occurrence in neurofibromatosis type 2 (NF2) less understood. This study delineates characteristics, prevalence, and outcomes of MPNSTs in NF2 or familial schwannomatosis (FS) patients through a systematic review, case series, and SEER database analysis.

Methods: This retrospective case series from two large academic institutions spanned 2011–2024, focusing on NF2/FS patients with MPNSTs confirmed by clinical/genetic diagnosis and histopathology. Data from electronic records included clinical features, tumor characteristics, and outcomes, with systematic review/SEER data providing broader epidemiological insights. Treatment strategies and outcome measures assessed survival and recurrence as primary endpoints.

Results: From 307 articles reviewed, 11 discussed 13 confirmed cases of MPNSTs in NF2/FS, with an additional two cases identified from the SEER database. Five additional cases were added from our series. Notable cases included a 79-year-old male with NF2 and a history of cranial radiation who developed a rapidly enlarging MPNST in the thigh, confirmed via biopsy. Another patient, a 33-year-old with familial schwannomatosis, underwent successful resection of multiple schwannomas, including a palmar lesion identified as an epithelioid MPNST. Those undergoing gross-total resection demonstrated markedly better overall survival (OS) and progression-free survival (PFS) compared to those with partial resection or biopsy alone. Plexiform schwannomas were more likely to undergo biopsy alone thus carried a similar poor prognosis. The presence of p53 mutations also indicated a worse prognosis.

Conclusion : This study highlights the presence of MPNSTs in NF2 and FS patients, a rare entity, emphasizing that gross-total resection markedly improves survival compared to less complete interventions. The presence of p53 mutations and histories of radiation predict poorer outcomes, though not statistically so as the series is underpowered, underscoring the need for vigilant surveillance and tailored therapeutic strategies. Future efforts should focus on understanding molecular drivers to develop targeted treatments and enhance patient prognosis.