In these cases, two patients with leiomyosarcoma were reclassified as dedifferentiated liposarcoma and therapy was changed to investigational MDM2 or CDK4 inhibitors, a third patient with sarcoma NOS was diagnosed as PEComa (TSC2 loss) and recommended an mTOR inhibitor, and a fourth patient with MPNST was reclassified as synovial sarcoma based on an SS18-SSX2 fusion and evaluated for NY-ESO-1-based T cell therapy. The gene discussed is TSC2; the disease is malignant peripheral nerve sheath tumor.