Table 1.

Histopathological features and diagnostic criteria for NF1-associated peripheral nerve sheath tumors

Diagnosis	Key Diagnostic Features*
Plexiform neurofibroma (PN)	Neoplastic proliferation of S100+ Schwann cells with wavy nuclear contours, diffusely enlarging and replacing a major nerve trunk. Thickened perineural sheath. Microenvironment consisting of fibroblasts with myxoid/collagenous matrix and infiltrating inflammatory cells (mast cells and other lineages). Well-developed, lattice-like CD34+ fibroblastic network.
Atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP)	Schwann cell neoplasm with at least 2 of 4 features: (1) hypercellularity as defined by nuclear overlap at high magnification; (2) cytologic atypia—enlarged nuclei at least 2-3× > normal, hyperchromasia, pleomorphism with irregular chromatin distribution, and/or multinucleated and ‘bizarre’ forms; (3) loss of neurofibroma architecture as defined by fascicular growth pattern or disruption of lattice like CD34+ fibroblastic network; (4) rare mitoses with a mitotic index >1/50 HPF but <3/10 HPF.
Malignant peripheral nerve sheath tumor (MPNST)	Features of ANNUBP with mitotic index of 3–9/10 HPF without necrosis (low grade MPNST). MPNST with a mitotic index >10/10 HPF or > 3/10 HPF with necrosis (high grade MPNST).

^*Adapted from Miettinen et al. Human Pathology (2017) 67, 1–10.