Malignant transformation of plexiform neurofibroma to high-grade malignant peripheral nerve sheath tumor in neurofibromatosis Type 1: Case report and brief literature review

Malignant peripheral nerve sheath tumors (MPNSTs) represent a life-threatening complication of neurofibromatosis type 1 (NF1), often arising from the malignant transformation of pre-existing plexiform neurofibromas. We present the case of a 32-year-old male with NF1 who developed a rapidly enlarging, painful thigh mass at the site of a previously debulked plexiform neurofibroma. Imaging and core needle biopsy confirmed a high-grade MPNST. Molecular and immunohistochemical (IHC) profiling revealed biallelic NF1 inactivation, CDKN2A homozygous deletion, TP53 mutation, and the characteristic loss of H3K27 trimethylation (H3K27me3). The patient was treated with neoadjuvant chemoradiation followed by wide local excision with en bloc sciatic nerve sacrifice, achieving R0 margins and greater than 90% tumor necrosis. Three years post-resection, he developed a local recurrence and oligometastatic pulmonary disease. Rather than pursuing palliative care, a curative-intent salvage strategy was adopted, comprising systemic chemotherapy followed by surgical re-excision and video-assisted thoracoscopic surgery (VATS) metastasectomy. The patient remains disease-free for two years following the salvage treatment. This case underscores the aggressive clinical course of NF1-associated MPNSTs and highlights the critical role of sustained multidisciplinary management. Furthermore, it demonstrates that aggressive surgical salvage for oligometastatic recurrence can yield prolonged survival, challenging the historically dismal prognosis associated with metastatic MPNST.