Advances and challenges in the treatment of neurofibromatosis type 1 related plexiform neurofibromatosis in the head and neck

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene located at 17q11.2. Plexiform neurofibromas (PN) are one of the common clinical manifestations of NF1, known as NF1-related plexiform neurofibromas (NF1-PN). Head and neck NF1-PN account for 42.9% of all cases. Tumors grow rapidly during childhood and adolescence, and they can exhibit widespread growth, causing severe head, face, and neck deformities, organ dysfunction, and even loss of function. NF1-PN have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs), known as NF1-associated MPNST (NF1-MPNST). Histopathology is the gold standard for diagnosing NF1-PN, magnetic resonance imaging (MRI) is the preferred imaging examination for NF1-PN, and PET/CT examination is a reliable method for early detection and diagnosis of NF1-MPNST. Genetic testing plays an important role in early diagnosis of tumors, monitoring tumor progression, genetic counseling, and molecular level treatment and management of the disease. This article proposes the goals and principles for treating NF1-PN in the head and neck region. The main treatment methods currently used are surgery and medication. Surgical treatment includes surgical resection, and tissue flap repair or allogeneic transplantation of composite tissue after surgical resection. The mitogen-activated protein kinase inhibitors (MEK) inhibitor Selumetinib is an effective medication used to treat NF1-PN patients aged 3 years and older with symptoms and who are unable to undergo surgery. A Phase Ⅱb trial of mirdametinib, a small-molecule inhibitor, has been completed in adults and children, and it is considered well tolerated in both groups. CRISPR/Cas9 technology is expected to become an effective means of NF1-PN gene therapy. The treatment method of NF1-MPNST is similar to that of soft tissue sarcoma. However, the safety of complete resection of extra-large tumors, protection of important tissues and organs during surgery, effective control of intraoperative bleeding, reconstruction of soft and hard tissue defects in the head and neck; prospective, multicenter, randomized, double-blind, controlled clinical trials of MEK inhibitors, as well as the use of CRISPR/Cas9 technique for gene therapy NF1-PN, are all current challenges. This article summarizes recent advances and ongoing challenges in the treatment of head and neck NF1-PN, aiming to provide a reference for clinicians and researchers.