MPNST

Malignant peripheral nerve sheath tumor (MPNST) is a rare, aggressive soft tissue sarcoma that arises from the protective coverings of peripheral nerves. It can develop de novo or from malignant transformation of a benign plexiform neurofibroma, most notably in people with neurofibromatosis type 1 (NF1).

Most patients present in adolescence to middle age. NF1-associated MPNSTs occur more frequently and tend to have a poorer prognosis.

Clinical features include a rapidly enlarging, painful mass along a major nerve pathway, often with new or worsening neurologic deficits such as weakness or sensory loss.

Imaging typically begins with magnetic resonance imaging (MRI), which shows a fusiform nerve-tumor extending along a nerve, with T2 hyperintensity and contrast enhancement. Positron emission tomography (PET) can help distinguish malignant from benign lesions and for staging. Definitive diagnosis requires biopsy, which reveals a high-grade spindle cell sarcoma with variable patterns; immunohistochemistry often shows S-100 protein positivity in about half of cases and SOX10 positivity in many. A high proliferative index is common. Genetic background frequently includes loss of function of the NF1 gene, with additional chromosomal alterations in many tumors.

Treatment centers on wide surgical excision with clear margins. Adjuvant radiotherapy is commonly used to reduce local recurrence. Chemotherapy is reserved for unresectable, recurrent, or metastatic disease, with regimens including ifosfamide and doxorubicin; responses are variable. Emerging approaches include targeted therapies such as MEK inhibitors, particularly in NF1-associated tumors, and participation in clinical trials.

Prognosis remains guarded. Reported 5-year survival ranges from the mid-30s to around 50%, with NF1-associated tumors carrying a worse outcome. Prognostic factors include tumor size, site, resectability, margin status, presence of metastasis at diagnosis, and NF1 status. Regular imaging surveillance after treatment is recommended to detect recurrence.