Consensus Recommendations for an Integrated Diagnostic Approach to Peripheral Nerve Sheath Tumors Arising in the Setting of Neurofibromatosis Type 1

Authors

Calixto-Hope G Lucas
Andrea M Gross
Carlos G Romo
Carina A Dehner
Alexander J Lazar
Markku Miettinen
Melike Pekmezci
Martha Quezado
Fausto J Rodriguez
Anat Stemmer-Rachamimov
David Viskochil
Arie Perry

Publication Date

3-7-2025

Journal

Neuro-Oncology

Abstract

Consensus recommendations published in 2017 histologically defining atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) and malignant peripheral nerve sheath tumor (MPNST) were codified in the 2021 WHO Classification of Tumors of the Central Nervous System and the 2022 WHO Classification of Tumors of Soft Tissue and Bone. However, given the shift in diagnostic pathology toward the use of integrated histopathologic and genomic approaches, the incorporation of additional molecular strata in the classification of Neurofibromatosis Type 1 (NF1)-associated peripheral nerve sheath tumors should be formalized to aid in accurate diagnosis and early identification of malignant transformation and enable appropriate intervention for affected patients. To this end, we assembled a multi-institutional expert pathology working group as part of a "Symposium on Atypical Neurofibroma: State of the Science." Herein, we provide a suggested framework for adequate interventional radiology and surgical sampling and recommend molecular profiling for clinically or radiologically worrisome noncutaneous lesions in patients with NF1 to identify diagnostically-relevant molecular features, including CDKN2A/B inactivation for ANNUBP, as well as SUZ12, EED, or TP53 inactivating mutations, or significant aneuploidy for MPNST. We also propose renaming "low-grade MPNST" to "ANNUBP with increased proliferation" to avoid the use of the "malignant" term in this group of tumors with persistent unknown biologic potential. This refined integrated diagnostic approach for NF1-associated peripheral nerve sheath tumors should continue to evolve in concert with our understanding of these neoplasms.

Keywords

Humans, Neurofibromatosis 1, Consensus, Nerve Sheath Neoplasms, Practice Guidelines as Topic, Biomarkers, Tumor

DOI

10.1093/neuonc/noae235

PMID

39500722

PMCID

PMC11889724

PubMedCentral® Posted Date

11-6-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes