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.

Surgical outcome of isolated benign peripheral nerve sheath tumors without neurofibromatosis

“…Some soft tissue tumors known as peripheral nerve sheath tumors (PNSTs) originate from components of the peripheral nervous system, such as Schwann cells, and perineural cells [1]. Benign peripheral nerve sheath tumors (BPNSTs) include schwannomas and neurofibromas.…”

“…They impact individuals of all ages and are solitary and intermittent. These are slow-growing, encapsulated tumors that may exhibit cystic degeneration or calcifications [1,4]. Malignant transformation of schwannomas is rare.…”

“…Malignant transformation of schwannomas is rare. Asymptomatic lesion of the skin or subcutaneous tissue of the head and neck, or in the flexor surfaces of the limbs is a common presentation of schwannomas [1]. Soft, skin-colored papules or tiny subcutaneous nodules are the outward manifestations of neurofibromas.…”

“…Cutaneous neurofibroma rarely causes pain and usually asymptomatic. About 8-13% of patients with neurofibromatosis type 1 (NF1) often develop MPNSTs, and they are typically linked to NF1, an autosomal dominant disorder [1,4,5]. Surgical resection remains the treatment of choice of BPNSTs because they may cause neural compromise, rapid growth, and pressure they apply to nearby structures.…”

Case report: Solitary mass of the sciatic nerve confirmed as a primary extranodal manifestation of diffuse large B-cell lymphoma in a geriatric patient

“…The majority of PNSTs are benign and histologically represent schwannomas or neurofibromas (1,3). Diagnostic work up includes ultrasound assessment, if accessible, followed by MRI imaging (4,5). Surgical removal aiming for preservation of nerve function is the therapy of choice in symptomatic and benign lesions (4).…”