Radiation-associated Malignant Peripheral Nerve Sheath Tumor with 26-year Latency

A BSTRACT Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that may appear as late complications of radiotherapy. Here we report the case of a 54-year-old woman with a history of breast cancer treated with mastectomy and adjuvant chemoradiotherapy at the age of 29 in 1994, who developed an MPNST 26 years later. Electromyography and magnetic resonance imaging localized a mass along the right brachial plexus. Positron emission tomography/computed tomography showed a retroclavicular fluorodeoxyglucose-avid lesion (6.1 cm × 4.0 cm; SUV ma × 10.0) and a smaller focus in the low right neck (SUV ma × 4.8). Histopathology confirmed high-grade MPNST; immunohistochemistry demonstrated S-100/CD57/CD99 positivity with a Ki-67 index of ~70%. Genomic profiling identified a somatic CDKN2A deletion without actionable variants. The patient underwent resection, adjuvant doxorubicin, radiotherapy, pazopanib, and ultimately right upper-limb disarticulation, followed by systemic therapy, achieving complete metabolic response before nodal relapse at 44 months; care then transitioned to palliation. This case highlights the potential for very long latency of radiation-associated sarcoma, the complementary value of molecular profiling even when nonactionable, and the importance of multidisciplinary, multimodality management.