Defining and managing NF1-related peripheral nerve sheath tumors at risk for malignant transformation: Consensus from the Atypical Neurofibroma Symposium.

People with neurofibromatosis type 1 (NF1) are at risk for developing peripheral nerve sheath tumors (PNSTs) ranging from benign neurofibromas to high-grade sarcomas. PNSTs known as atypical neurofibromas are at increased risk for malignant transformation. In 2017 the term ANNUBP (atypical neurofibromatous neoplasm of uncertain biologic potential) was proposed for PNSTs at increased risk for malignant transformation based on histopathologic features. Subsequently it was recognized that PNSTs not meeting ANNUBP criteria could still have concerning clinical, imaging and molecular features. A State of the Science conference addressed how to define these pre-cancerous PNSTs and reached consensus regarding clinical management and priority areas of research. Key recommendations from this symposium include: (1) using a combination of histologic, molecular and imaging features to define pre-malignant "at-risk" PNST; (2) recognizing that people with NF1 may be divided into "higher-risk" and "average-risk" for MPNST based on features such as their germline NF1 variant, internal tumor burden and history of malignancy or radiotherapy and; (3) the need to validate consensus screening and surveillance strategies based on personal and tumor-related risk factors. These recommendations will advance the ability to standardize care, and potentially fuel research that enables early diagnosis, prevention of malignant transformation and improved outcomes.