Table 2.

2024 Proposed Integrated Consensus Classification Scheme

Diagnosis	Histologic features	Molecular features
NF	Lacks histologic features sufficient for the diagnosis of ANNUBP or MPNST	Lacks molecular features sufficient for the diagnosis of ANNUBP or MPNST
ANNUBP	At least 2 of 4 features with or without CDKN2A/B inactivationa: (a) cytologic atypia, (b) loss of neurofibroma architecture, (c) hypercellularity, or (d) mitotic index > 1/50 HPFs and <3/10 HPFs	CDKN2A/B homozygous inactivationb with or without any ANNUBP histologic features OR CDKN2A/B heterozygous inactivation in combination with ≥1 ANNUBP histologic feature (a-d) AND Lacks molecular features sufficient for the diagnosis of MPNST
ANNUBP with increased proliferation	ANNUBP but with mitotic index 3–9/10 HPFs AND Lacks necrosis	Lacks molecular features sufficient for the diagnosis of MPNST
MPNST	At least 10 mf/10 HPFs OR 3–9 mf/10 HPFs combined with necrosis	SUZ12/EED inactivating mutation, TP53 inactivating mutation, or significant aneuploidy (segmental gain or loss of at least 8 different chromosome arms)b

ANNUBP = atypical neurofibromatous neoplasm of uncertain biologic potential; HPFs = high-power fields; MPNST = malignant peripheral nerve sheath tumors; NF = neurofibroma.

^a CDKN2A/B homozygous or heterozygous inactivation is not required to define an ANNUBP if 2 of the 4 histologic criteria are present.

^bPresence of these molecular features is sufficient to make the diagnosis of ANNUBP or MPNST even in the absence of concerning histologic features.