Practical guideline for malignant peripheral nerve sheath tumors

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare, aggressive, and heterogenous subtype of soft tissue sarcoma that arise from the peripheral nerves or associated sheaths. They account for approximately 5-10% of all soft tissue sarcomas, characterized by rapid growth, a significant propensity for local recurrence, and early metastasis. Nearly 50% of MPNSTs are associated with genetic predisposition of neurofibromatosis type 1 (NF1). Their prognosis is worse than sporadic with 5-year overall survival (OS) rate 34%–50%.1 Recent study on a Chinese cohort found malignant transformation rate of 8.2% in NF1 patients, higher than Western and imposing severe economic burden on the domestic medical system.2 Sporadic MPNSTs typically present at around 50 years, later compared to 25–35 years in NF1 patients. Radiation-induced MPNSTs often appear decades after exposure associated with the poorest outcomes. Owing to restricted understanding of the etiology and pathogenesis brought by rarity and heterogeneity, the therapeutic landscape slowly shifts with dismal prognosis. This guideline summarizes practical approach to diagnosis, treatment, and underscores the importance of a multidisciplinary approach, with clinical trials representing a key therapeutic avenue.

This guideline was developed by synthesizing peer-reviewed literature, including clinical trials, observational cohorts, and international sarcoma group statements including SARC and EORTC. The formulation of recommendations followed a structured, iterative process of expert deliberation. Recommendations were categorized using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Statements without grading were considered justified standard clinical practice by the authors.