Malignant Peripheral Nerve Sheath Tumor (MPNST)

Malignant Peripheral Nerve Sheath Tumor (MPNST) is an aggressive, highly metastatic form of soft tissue sarcoma that arises from peripheral nerves or their connective tissue sheaths, such as Schwann cells. It is strongly associated with Neurofibromatosis Type 1 (NF1), where roughly half of cases develop from pre-existing plexiform neurofibromas following the loss of the tumor suppressor neurofibromin. At the molecular level, MPNSTs are characterized by a complex genomic landscape often involving the loss of CDKN2A and the Polycomb Repressive Complex 2 (PRC2) subunits, EED or SUZ12, which leads to a diagnostic loss of trimethylation at Lysine 27 of Histone 3 (H3K27me3). Because MPNST is a clinical disease entity rather than a single molecular receptor, therapeutic strategies target the signaling pathways deregulated within the tumor, such as the RAS/MAPK and PI3K/AKT/mTOR pathways. Conventional treatment relies on surgical resection with wide margins, though systemic therapies including anthracycline-based chemotherapies and targeted MEK inhibitors are frequently utilized in clinical and investigational settings. Despite these interventions, the prognosis remains poor due to the tumor's rapid progression and limited response to existing pharmacological agents.

Other names

Malignant schwannomaNeurogenic sarcomaNeurofibrosarcomaMalignant neurilemoma

Treatment typically involves cytotoxic chemotherapy (DNA intercalation and alkylation), MEK inhibition to address RAS pathway overactivation, or mTOR inhibition to target downstream signaling in NF1-deficient cells.