Diagnosis and Treatment of Peripheral and Cranial Nerve Tumors with Expert Recommendations: An EUropean Network for RAre CANcers (EURACAN) Initiative

Abstract

The 2021 WHO classification of the CNS Tumors identifies as "Peripheral nerve sheath tumors" (PNST) some entities with specific clinical and anatomical characteristics, histological and molecular markers, imaging findings, and aggressiveness. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is particularly low due to the rarity, and drawn recommendations accordingly. Tumor diagnosis is primarily based on hematoxylin and eosin-stained sections and immunohistochemistry. Molecular analysis is not essential to establish the histological nature of these tumors, although genetic analyses on DNA extracted from PNST (neurofibromas/schwannomas) is required to diagnose mosaic forms of NF1 and SPS. MRI is the gold-standard to delineate the extension with respect to adjacent structures. Gross-total resection is the first choice, and can be curative in benign lesions; however, the extent of resection must be balanced with preservation of nerve functioning. Radiotherapy can be omitted in benign tumors after complete resection and in NF-related tumors, due to the theoretic risk of secondary malignancies in a tumor-suppressor syndrome. Systemic therapy should be considered in incomplete resected plexiform neurofibromas/MPNSTs. MEK inhibitor selumetinib can be used in NF1 children ≥2 years with inoperable/symptomatic plexiform neurofibromas, while anthracycline-based treatment is the first choice for unresectable/locally advanced/metastatic MPNST. Clinical trials on other MEK1-2 inhibitors alone or in combination with mTOR inhibitors are under investigation in plexiform neurofibromas and MPNST, respectively.

Keywords: MEK inhibitors; cauda equine neuroendocrine tumor; hybrid nerve sheath tumor; mTOR inhibitors; malignant peripheral nerve sheath tumor; neurofibroma; perineurioma; plexiform neurofibroma; schwannoma.

Figure 1

(A) Perineurioma: coronal three-dimensional (3D) proton density sequence of the wrist after fat suppression displays a fusiform enlargement of the radial nerve. (B) Malignant peripheral nerve sheath tumor: Three-dimensional T1-weighted spin echo sequence after contrast injection and fat suppression (upper image) shows a contrast-enhanced lesion in the right internal auditory canal and geniculate ganglion. High-resolution 3D T2-weighted sequence (lower image) reveals intra-cochlear extension of the tissue mass. (C) Malignant intracerebral nerve sheath tumor: 3D FLAIR sequence in the axial plane (upper image) and 3D T1-weighted spin echo sequence after contrast injection shows two intra-axials, enhancing lesions. The biggest lesion, located in the left superior frontal region, is highly heterogeneous, with hemorrhagic and cystic components, and is surrounded by FLAIR hyperintensity. The second, smaller lesion of the right hemisphere is hardly visible on the FLAIR image while it strongly enhances after contrast administration. (D) Cauda equine neuroendocrine tumor: sagittal T1-weighted sequence after contrast injection and fat suppression of the lumbar spine displays a well-defined intradural extramedullary contrast, enhancing lesions.