Hybrid peripheral nerve sheath tumors show combined features of more than one type of conventional benign peripheral nerve sheath tumors. There are few cases reported of hybrid peripheral nerve sheath tumors in the head and neck region. A 68-year-old female patient was referred for evaluation of an oral swelling lasting five years. Intraoral examination revealed a small mobile nodule located in the lower vestibule. The patient underwent excisional biopsy and microscopic evaluation showed typical features of neurofibroma enclosing areas with palisading nuclei compatible with Antoni A pattern, which are seen in schwannomas. These regions showed strong and diffuse immunoreactivity for S100 protein and moderate positivity in the neurofibroma area. CD34 was positive in the neurofibroma area and entrapped axons were positive for neurofilament. The final diagnosis was oral hybrid neurofibroma-schwannoma tumor. Hybrid peripheral nerve sheath tumors, although extremely rare, may arise within the oral cavity. To the best of our knowledge, this is the first neurofibroma-schwannoma tumor reported in the oral cavity. Recognizing hybrid peripheral nerve sheath tumors as a distinct clinicopathological entity is important because they may also be associated with syndromic disorders.

The neurofibromatoses comprise three different genetic conditions causing considerable morbidity and mortality: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). This review summarizes recent and ongoing clinical trials involving patients with neurofibromatoses to better understand the current state of clinical trial research centered around these conditions and inform areas of need.
A search was conducted using the Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases. Inclusion and exclusion criteria were designed to identify clinical trials focused on patients with NF1, NF2, or SWN completed in or after 2010 and in process as of December 31, 2021. Information was collected using standardized guidelines.
A total of 134 clinical trials were included, with 75 (56%) completed and 59 (44%) in process. For completed trials, 74% (n = 56) involved patients with NF1, and of those based on specific tumors (n = 26, 46%), the majority focused on plexiform neurofibromas (PNs) (n = 12, 46%). For ongoing trials, 79% (n = 47) involve patients with NF1, and of those based on specific tumors (n = 29, 61%), the majority are focused on PNs (n = 13, 45%).
Both recent and ongoing clinical trials have primarily focused on patients with NF1 and the treatment of PNs. This research has led to the first FDA-approved drug for NF1-PN and has changed management of these tumors, allowing for systemic therapy rather than reliance on only a surgical modality. Trials evaluating comorbid psychiatric conditions and quality of life among patients with any of the neurofibromatoses appear less common. These areas may warrant focus in future studies to improve clinical management.

Schwannomatosis is a rare subset of neurofibromatosis. It is a disease process with a predisposition to schwannomas in the absence of bilateral vestibular schwannomas, which differentiates it from neurofibromatosis 2 (NF2). It is occasionally associated with certain tumors such as malignant peripheral nerve sheath tumors or rhabdoid tumors. Currently, there is limited literature to suggest an association between schwannomatosis and glioblastoma (GB). We present a case of a 55-year-old female with a history significant for schwannomatosis who presented after a witnessed first-time seizure with left facial weakness and slurred speech. She was found to have a 3 cm right-sided ring-enhancing lesion that was excised and found to be a grade IV Isocitrate dehydrogenase (IDH) wildtype GB.

UNASSIGNED: There is a paucity of literature that comprehensively analyzes previous and current clinical trials targeting neurofibromatoses-related tumors. This article aims to provide readers with drug development efforts targeting these tumors by analyzing translational and clinical findings.
UNASSIGNED: This systematic review was written according to the PRISMA guidelines. Inclusion criteria were clinical trials involving patients with neurofibromatosis type 1, type 2, or schwannomatosis that were treated with therapies targeting neurofibromatoses-associated tumors and that were registered on clinicaltrials.gov. In addition, a search was performed in PubMed, Web of Science, Google Scholar, and Embase European for articles fully describing these clinical trials.
UNASSIGNED: A total of 265 clinical trials were registered and screened for eligibility. Ninety-two were included in this systematic review involving approximately 4636 participants. The number of therapies analyzed was more than 50. Drugs under investigation mainly act on the MAPK/ERK and PI3K/AKT/mTOR pathways, tumor microenvironment, or aberrantly over-expressed cell surface receptors. Selumetinib was the most effective medication for treating a neurofibromatosis type 1-associated tumor with approximately 68%-71% partial response for inoperable or progressive plexiform neurofibromas in children 2 years of age and older and bevacizumab for a neurofibromatosis type 2-related tumor with approximately 36%-41% partial response for vestibular schwannomas in patients 12 years of age and older.
UNASSIGNED: This systematic review presents the results of previous clinical investigations and those under development for neurofibromatoses-associated tumors. Clinicians may use this information to strategize patients to appropriate clinical trials.

Neurofibromatosis (NF) is the umbrella term for neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SWN). EU-PEARL aims to create a framework for platform trials in NF. The aim of this systematic review is to create an overview of recent clinical drug trials in NF, to identify learning points to guide development of the framework. We searched Embase, Medline and Cochrane register of trials on October 1, 2020 for publications of clinical drug trials in NF patients. We excluded publications published before 2010, systematic reviews, secondary analyses and studies with <10 patients. Data was extracted on manifestations studied, study design, phase, number of participating centres and population size. Full-text review resulted in 42 articles: 31 for NF1, 11 for NF2, none for SWN. Most NF1 trials focused on plexiform neurofibromas (32%). Trials in NF2 solely studied vestibular schwannomas. In NF1, single-arm trials (58%) were most common, and the majority was phase II (74%). For NF2 most trials were single-arm (55%) and exclusively phase II. For both diseases, trials were predominantly single-country and included five centres or less. Study population sizes were small, with the majority including ≤50 patients (74%). In conclusion, NF research is dominated by studies on a limited number out of the wide range of manifestations. We need more trials for cutaneous manifestations and high-grade gliomas in NF1, manifestations other than vestibular schwannoma in NF2 and trials for SWN. Drug development in NF may profit from innovative trials on multiple interventions and increased international collaboration.

UNASSIGNED: Schwannomas are rare benign tumors affecting the peripheral nerves. They can grow in clusters when associated with neurofibromatosis Type II or with schwannomatosis. Typically, patients present with a palpable painless mass. However, some patients, on the other hand, present with symptomatic lesions that resemble a focal nerve compression caused by the encapsulating nature of these tumors. Surgical excision is an excellent solution for solitary symptomatic lesions. However, multiple schwannomas affecting the same nerve add another level of complexity to the surgery since these secondary masses can be too small to be detected on physical examination. A high index of suspension for schwannomatosis complemented with magnetic resonance imaging (MRI) ensures a more efficient pre-operative workup that can save the patient potentially an additional visit to the operating room.
UNASSIGNED: This is a case of a 36-year-old right-handed female presented to our clinic with a several-years history of a painful mass in her forearm. On physical examination, she had a palpable painful mass that was Tinel positive with pain and paresthesia radiating distally over the median nerve distribution. A subsequent MRI scan showed a second smaller mass distally adjacent to the main lesion along with the median nerve, both appearing to be schwannomas of the median nerve. In this case report, we discuss the patient presentation, diagnostic workup and radiographic finding, surgical technique, and pathological findings in addition to a review of the literature regarding multiple schwannomas affecting the upper extremity.
UNASSIGNED: Schwannomas are rare benign tumors affecting the peripheral nerves. Despite their solitary nature, a handful of cases are reported in the literature that describes multiple masses encapsulating the same nerve. MRI is utilized to allow proper pre-operative planning and more accurate localization of these tumors to avoid an unplanned return to the operating room.

UNASSIGNED: Intramedullary spinal schwannomas constitute only 0.3% of primary spine tumors. We could identify only 13 such cases involving the conus that were not associated with neurofibromatosis (NF). Here, we report a 70-year-old male without NF who was found to have a paraparesis due to a schwannoma of the thoracolumbar junction/conus (D11-L2).
UNASSIGNED: A 70-year-old male presented with an L1-level paraparesis with urinary incontinence. The magnetic resonance showed an intramedullary mass of 85 × 10 mm extending from D11 to L2; it demonstrated significant patchy enhancement. The patient underwent a D12 and L1 laminectomy with gross total excision of the mass that proved to be a schwannoma. Three months postoperatively, he was able to ambulate with support, and regained sphincter function.
UNASSIGNED: Intramedullary schwannomas involving the conus/thoracolumbar junction are rare, and can be successfully excised resulting in good outcomes.

UNASSIGNED: Schwannomatosis is a relatively rare disorder and is related to neurofibromatosis type 2. Although there is clinical overlap between schwannomatosis and neurofibromatosis type 2, these diseases have to be regarded as separate entities due to the genetic origin and course of the disease.
UNASSIGNED: A comprehensive review of the literature was conducted for relevant studies using Pubmed and Cochrane databases to discuss the epidemiology, clinical presentation, diagnostic criteria, pathological and imaging features, treatment and genetics of schwannomatosis.
UNASSIGNED: Germline mutations SMARCB1 and LZTRI together with the NF2 gene play a role in the pathophysiology of schwannomatosis. The most common symptom is pain with affection of the spine and peripheral nerves in the majority of patients. High quality contrast enhanced MRI scan is the imaging modality of choice. Treatment is conservative if asymptomatic and surgical if symptomatic. The goal is symptom control with preservation of neurological function.
UNASSIGNED: Schwannomatosis is a relatively rare disorder in which the main goal is to preserve neurological function.

BACKGROUND: Schwannomatosis is defined as multiple schwannomas without presence of neurofibromatosis and is a rare pathology. In vast majority of cases the schwannomas grow from different nerve roots or peripheral nerves.
METHODS: A 52-year-old woman presented with multiple intradural schwannomas arranged in a chain along the spinal canal causing significant compression. The lesions were successfully removed using a left side en-bloc hemilaminectomy technique in order to preserve maximal stability of the posterior column. Back and leg pain resolved completely. Tendon reflexes returned to normal shortly. There was decreased pain sensation in the distribution of the left L3 spinal root.
CONCLUSIONS: The traditional surgical strategy for posterior approach by laminectomy or laminotomy is sometimes complicated with instability or deformation of the vertebral column that requires surgical stabilization. We performed a one side en-bloc hemilaminectomy thus maintaining the integrity of the muscles and ligaments on the opposite side and preserving maximal stability of the vertebral column. Densely adherent tumors required careful sharp dissection and separation under neurosurgical monitoring and stimulation for recognition and preservation of spinal roots. An additional tumor was discovered by exploration of the spinal canal using an endoscope.
CONCLUSIONS: Multiple spinal cord schwannomas that are growing along the same part of the vertebral column can be safely removed by one-sided hemilaminectomy with preservation of the integrity of the muscles and ligaments on the opposite side and thus maintain spinal stability. The 30° endoscope can be a good tool for visual exploration of the spinal canal.

Schwannomatosis is a recently recognized distinct form of neurofibromatosis (NF). It is a rare condition, the incidence of which varies between 1/400,000 and 1/1.7 million. An important feature of schwannomatosis is the presence of multiple intracranial, spinal, and peripheral schwannomas in the absence of acoustic neuromas. Schwannomatosis presenting with intraosseous schwannoma of the mandible is even rarer, and only a few cases have been reported. It usually affects individuals in the third to fifth decade of life. Usually, it is sporadic in origin, but in 20% of patients, it can be familial. As a diagnostic criterion, NF2 gene is not involved in schwannomatosis. We report a case of a 48-year-old male presenting with facial pain and difficulty in chewing, and subsequent development of spastic paraplegia. Magnetic resonance imaging scan of head and neck revealed mass lesion involving infratemporal region on the left side, intraosseous lesion of the mandible, and multiple mass lesions in the neck. Acoustic nerves were not involved. Mutagen-induced chromosome sensitivity analysis test suggested no predisposition for malignancy. His clinical features are suggestive of schwannomatosis, which is a recently recognized distinct form of NF.