An unusual finding of an anaplastic meningioma in NF2-related schwannomatosis.

NF2-related schwannomatosis (NF2) is a rare autosomal-dominant genetic disorder characterized by bilateral vestibular schwannomas and multiple meningiomas. This case report presents the extremely rare occurrence of an anaplastic meningioma in a 12-year-old male with previously undiagnosed NF2. The patient presented with a history of abdominal pain and episodic emesis, gait unsteadiness, right upper and lower extremity weakness, and facial weakness. He had sensorineural hearing loss and wore bilateral hearing aids. MR imaging revealed a sizable left frontoparietal, dural-based meningioma with heterogeneous enhancement with mass effect on the brain and midline shift. Multiple additional CNS lesions were noted including a homogenous lesion at the level of T5 indicative of compression of the spinal cord. The patient underwent a frontotemporoparietal craniotomy for the removal of his large dural-based meningioma, utilizing neuronavigation and transdural ultrasonography for precise en bloc resection of the mass. Histopathology revealed an anaplastic meningioma, WHO grade 3, characterized by brisk mitotic activity, small-cell changes, high Ki-67 proliferation rate, and significant loss of P16. We report an anaplastic meningioma associated with an underlying diagnosis of NF2 for which we describe clinical and histopathological features.

A simplified technique for correction of complete ptosis secondary to palpebral neurofibromatosis.

PURPOSE: To present a simplified technique in management of complete ptosis secondary to neurofibromatosis. METHODS: This prospective, non-comparative, clinical interventional study included 13 patients with complete ptosis secondary to histologically proved plexiform neurofibromas. It was conducted at the Orbital Unit of Assiut University Hospital, the referral center of Upper Egypt in the period between June 2013 and October 2021. In all cases, a simplified technique of 5 surgical steps was applied: (A) Division of the involved eyelid surgically into three parts by drawing 2 curvilinear lines, the superior line 11 mm below and parallel to the lower eyebrow hairline and the inferior one 10 mm above the lid margin, (B) Resection (full-thickness) of the large middle part which involves the main pathology and lies between the 2 lines, (C) Preservation of the upper part with identification, dissection and clamping of the levator muscle, (D) Refinement of the lower part by removal of any tissue between the skin and the debulked tarsus and (E) Re-suturing of the upper and lower parts in layers; conjunctiva to conjunctiva, levator to tarsus (after resection of a part that corrects the ptosis) and skin to skin. RESULTS: Ptosis was completely corrected in 8 cases (61.5%) and residual mild ptosis occurred in 5 patients (38.5%). No exposure keratopathy or tumor growth was reported during the follow-up period of minimum 1 year. CONCLUSIONS: This simplified technique could be considered as a surgical basis for correction of complete ptosis in neurofibromatosis.

Schwannomatosis of the sciatic nerve: a case report.

Schwannomas are one of the most common peripheral nerve sheath neoplasms. These tumors, which are characteristically slow-growing and encapsulated, can occur in solitary or multiple forms. Although they usually occur sporadically, they can be seen with various genetic tumor predisposition syndromes such as neurofibromatosis type 2 (NF-2) or schwannomatosis. However, schwannomatosis is a relatively rare disease. We present a case of a 22-year-old patient with segmental schwannomatosis of the sciatic nerve and a comprehensive literature review.

Clinical features of multiple spinal schwannomas without vestibular schwannomas.

BACKGROUND: Multiple spinal cord tumors in a single patient are very rare and most often seen in cases of neurofibromatosis and associated disorders. Schwannomatosis, which is characterized by the development of multiple schwannomas without vestibular schwannomas, has been newly defined as a distinct form of neurofibromatosis. The purpose of the present study was to describe and review the clinical and radiological features and the management of patients with multiple spinal schwannomas without vestibular schwannomas. METHODS: Between 1986 and 2016, 19 patients with multiple spinal schwannomas without vestibular schwannoma were diagnosed and treated. Of the 19 patients, 13 were males, and 6 were females. The mean age at the first surgery for spinal schwannoma was 45.2 years old. The mean follow-up period was 123.4 months. The clinical features and radiological findings of the patients with multiple spinal schwannomas were retrospectively reviewed. RESULTS: Among the 19 patients, there were more than 140 spinal schwannomas. The most common area of spinal schwannoma was the thoracolumbar-lumbar region. Initial symptoms and chief complaints caused by spinal schwannomas were primarily pain in the trunk or extremities in 17 (89.5%) of 19 patients. More than 60 spinal schwannomas were surgically resected. Multiple spinal surgeries were required in six patients. In all 19 patients, surgical treatment has provided successful relief of symptoms and neurological recovery. CONCLUSIONS: Surgical treatment was safe and effective in patients with multiple spinal schwannomas without vestibular schwannomas. After surgery, we recommend that all patients be followed with magnetic resonance imaging to monitor for asymptomatic tumors or detect new tumors early.

Surgical management of peripheral nerve sheath tumours in children, with special consideration of neurofibromatoses.

INTRODUCTION: Peripheral nerve sheath tumours in children are a rare and heterogeneous group, consisting mostly of benign tumours as well as malignant neoplasms. Especially in the paediatric population, diagnostics and indication for therapy pose relevant challenges for neurosurgeons and paediatric neurologists alike. Most paediatric cases that need surgical intervention are associated to neurofibromatosis type 1 (NF1). METHODS: We retrospectively reviewed all paediatric cases treated at the Department of Neurosurgery in Tübingen between 2006 and 2017 for peripheral nerve sheath tumours. We analysed clinical signs, symptoms, histology, association to an underlying phacomatosis and sensory/motor function. RESULTS: Of the 82 identified patients, the majority had NF1 (76.8%). Nine children bore a sporadic tumour without underlying phacomatosis (11%), 8 had NF2 (9.8%) and 2 schwannomatosis (2.4%), A total of 168 surgical interventions were performed, and 206 tumours were removed. Indication for surgery was in most instances significant tumour growth (45.2%) followed by pain (33.9%). New deficits led to surgery in 12.5% of interventions; malignancy was suspected in 8.3%. Histopathology revealed mostly neurofibromas (82.5%), divided into cutaneous neurofibromas (10.7%), infiltrating plexiform neurofibromas (25.7%) and peripheral nerve-born neurofibromas (46.1%). 12.1% of tumours were schwannomas, 2.9% MPNST, 1.5% ganglioneuroma (n = 3) and 1 hybrid-neurofibroma and perineurinoma each. Leading symptoms, such as pain and motor and sensory deficits, improved after 125/166 interventions (74.4%), remained unchanged following 39 interventions (23.2%) and worsened in 4 occasions (2.4%). CONCLUSION: Surgery is safe and effective for (neurofibromatosis associated) peripheral nerve sheath tumours in the paediatric population; however, management needs a multidisciplinary setting. We propose early surgical resection in paediatric patients with peripheral nerve sheath tumours with significant growth, or pain, or motor deficit, or suspected malignancy.

Germline Mutations for Novel Candidate Predisposition Genes in Sporadic Schwannomatosis.

BACKGROUND: Schwannomatosis is a late-onset tumor predisposition syndrome associated with the development of many different types of malignancies. A relevant genetic mechanism can be explained by three mutational events. The first-hit mutation is a germline mutation, and the SMARCB1 mutation on chromosome 22 is the most well-known genetic abnormality in patients with schwannomatosis. LZTR1 is another major predisposing gene in 22q-related schwannomatosis that lacks SMARCB1 variants. Although these two variants account for the occurrence of most familiar schwannomatoses, the genetic causes of sporadic schwannomatosis for the most part remain unknown. Therefore, current molecular diagnostic criteria cannot completely explain the basis of this disease. The common genetic background between schwannomatosis and other related malignant tumors is also unclear. Moreover, it is not easy to explain various clinical manifestations by only two known mutations. QUESTION/PURPOSES: (1) Are there important sequences outside the SMARCB1 or LZTR1 region on chromosome 22 that might carry a first-hit mutational predisposition to sporadic schwannomatosis? Or are there alternative evolutionarily conserved loci that might carry a first-hit mutational predisposition? (2) Is the age of disease onset associated to such genetic variants? METHODS: This study was a retrospective chart review and prospective genetic study on patients with schwannomatosis who were treated surgically. The clinical criteria to diagnose schwannomatosis were as follows: (1) histologically proven nonvestibular schwannomas; (2) no evidence of vestibular schwannomas on 3-mm brain MRI. A total of 21 patients were treated between March 2006 and June 2015. Since nine patients did not visit the outpatient clinic during the recruitment period, we obtained blood samples from 12 patients with schwannomatosis for a genetic analysis. After two patients were excluded because of their family history of schwannomatosis, genetic analyses were finally performed on 10 patients. Then, those with NF2, SMARCB1 or LZTR1 variants were screened by whole exome sequencing. All 10 patients passed our screening strategy. There were eight men and two women, with a median (range) age of 43 years (24 to 66) at the time of diagnosis. To select candidate genes, common ethnic variants and frequent mutations in in-house exome sequencing data were removed to exclude the population-specific polymorphisms not found in other population and to generalize the findings. Frameshift, nonsense, and splice-site variants were deemed pathogenic. Missense variants were classified as potentially pathogenic, variants of uncertain significance, or benign using in silico (via computer simulation) prediction algorithms, Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping v2 (PolyPhen-2), and Combined Annotation Dependent Depletion (CADD). A variant was considered potentially pathogenic if two or more algorithms predicted the variant to be damaging and benign if none considered it damaging. Then, potentially pathogenic variants only in the genes associated with cancer-predisposition or DNA damage repair were classified as the pathogenic candidate variants of sporadic schwannomatosis. The predictions for pathogenic candidate variants were checked again on Clinical Interpretation of Genetic Variants (InterVar) based on the American College of Medical Genetics guidelines and validated against Mendelian clinically applicable pathogenicity scores (M-CAP scores). RESULTS: We detected 26 variants; 13 variants across 10 genes were predicted to be pathogenic and found in seven patients, two each in ARID1A, PTCH2, and NOTCH2 and one each in MSH6, ALPK2, MGMT, NOTCH1, CIC, TSC2, and CDKN2A. One frameshift deletion in PTCH2 met the criteria for pathogenic or likely pathogenic classification, as recommended by the American College of Medical Genetics guidelines. Six missense mutations were classified as possibly pathogenic variants based on M-CAP scores. Four predicted pathogenic missense variants were detected in DNA damage repair (DDR) genes. Three DDR genes were affected: ARID1A, MGMT, and MSH6. Among the nine predicted pathogenic mutations detected in known cancer-predisposing genes, one was a frameshift deletion and the others were missense mutations. Seven tumor suppressor genes were involved: PTCH2, ALPK2, CIC, NOTCH1, NOTCH2, TSC2, and CDKN2A. One patient with multiple pathogenic variants in two DDR genes, ARID1A and MSH6, received a schwannomatosis diagnosis at 33 years old. Each of the other patients who had single variants in the DDR gene received their diagnoses at 41 years of age. The age at diagnosis was 40 years or older in patients with variants in cancer-predisposing genes, except for one patient who had multiple variants in TSC2 and CDKN2A. The carrier of those variants received the diagnosis at 24 years old. CONCLUSIONS: This study identified first-hit candidate mutations predisposing patients to schwannomatosis that were not related to SMARCB1 or LZTR1 variations in a cohort of patients with sporadic schwannomatosis. Patients with sporadic schwannomatosis without SMARCB1 or LZTR1 genetic variation may have developed the disease because of genomic variants related to cancer initiation in areas other than chromosome 22. Seven of 10 patients had predicted pathogenic germline mutations in DDR and cancer predisposition genes. We detected multiple cancer-related mutations in each patient. The age at the time schwannomatosis was diagnosed might be associated with a combination of variants and characteristics of the genes containing the variants; however, we did not have enough patients to confirm this association. CLINICAL RELEVANCE: The germline mutations identified in this study and the ideas related to the age of disease onset may provide potential candidate variants for future research on sporadic schwannomatosis and help to revise the current clinical and molecular diagnostic criteria. Further in vivo and in vitro studies are needed for these variants.

[A Case of Familial Schwannomatosis Occurring as Intraorbital Schwannoma].

A 67-year-old male presenting with left exophthalmos and progressive visual disturbance was referred to our department. Tumors at the supraclavicular fossa and dorsal femoral region were resected at ages 27 and 45 years. His father and son had both been diagnosed with spinal tumors, and his son's tumor was pathologically diagnosed as a schwannoma. Brain MRI of his son demonstrated no intracranial tumor. Brain MRI of the patient revealed a multilobular tumor of 2 cm diameter compressing the optic nerve medially within the left muscle cone, and no other intracranial tumors. However, large masses lateral to the pharynx and intercostal nerve, as well as multiple spinal tumors were detected. Transcranial total resection of the intraorbital tumor was performed. The pathological diagnosis was consistent with a schwannoma. These clinical characteristics fulfilled the diagnostic criteria of familial schwannomatosis. The postoperative course was uneventful. His visual dysfunction and eye movement disorder resolved completely. The intraorbital tumor was believed to originate from the lacrimal nerve. Sequencing of all exons for SMARCB1 and LZTR1 using DNA extracted from the tumor did not reveal any mutations. This case is the third report on familial schwannomatosis in Japan.

Correction of Complex Neurofibromatosis Orbital and Globe Malposition Using the Orbital Box Segmentation Osteotomy With Patient-Specific Internal Orbit Reconstruction.

INTRODUCTION: Correction of severe orbital and globe malposition from neurofibromatosis remains a significant clinical challenge. Current techniques including zygoma osteotomy, bone grafting, or placement of orbital implants do not adequately address aberrant anatomy, under-correct the deformity, and are prone to relapse. The authors have developed the orbital box segmentation osteotomy to reduce vertical orbital height and translocate the orbit and use patient-specific custom internal orbital titanium implants to close the cranio-orbital communication-reestablishing both the external orbital shape and internal orbital volume. METHODS: Virtual surgical planning with contralateral mirror imaging was used to design symmetrical repositioning of the external orbit and to determine segmentation required to reduce the vertical excess and inferior rim malposition as well as for manufacturing patient-specific titanium implants. Orbital volume was measured from preoperative, virtual surgical simulation, and postoperative imaging using stereotactic software. Globe position was assessed using pre- and postoperative 3-dimensional photography software (Canfield). RESULTS: All patients (n = 3, mean age 12 years) demonstrated improved globe position and orbital contour with resolution of globe pulsatility. Virtual surgical planning predicted postoperative volumes within 0.8 cm ±â€Š0.5. Mean volume orbital change was 4.5 cm, change in conformation and distribution of orbital volume was present in all patients. Vertical globe position improved from 11.5 mm preoperatively to within 1 mm of the unaffected side postoperatively. One patient had surgical site infection, there is no evidence of relapse at mean 24-months follow-up. CONCLUSION: Segmental box osteotomy with internal orbital reconstruction redistributes orbital volume safely and accurately addresses globe malposition from neurofibromatosis.

[Surgery treatment of neurofibromatosis associated severe cervical kyphotic deformity: mid- and long-term follow-up and efficacy analysis].

Objective: To investigate the surgical strategy and mid-and long-term outcomes of neurofibromatosis associated cervical kyphotic deformity. Methods: Thirteen patients with neurofibromatosis associated cervical kyphotic deformity operated in Shanghai Changzheng Hospital from January 1998 to December 2015 were analyzed retrospectively. There were 7 males and 6 females in this group, aged from 12 to 61 years, with an average age of (28±15) years. Eight patients were treated with anterior surgery (Group A) and 5 patients were treated with combined anterior and posterior surgery (Group A+P). Cobb angle correction of cervical kyphosis and improvement of clinical symptoms were followed up. Clinical efficacy between the two groups was compared and analyzed. Chi-square test, Fisher exact test and independent sample t test were used for comparative analysis between the two groups. Results: All patients were operated successfully and finished follow up. The follow-up period was from 42 to 128 months ((80±22) months). After the surgery, neurological symptoms and pain were significantly improved in all patients. Compared with preoperative values, Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) score for pain at the last follow-up were significantly improved (t=7.63, -5.19, 8.63, -4.75, all P<0.01). Cervical kyphosis was significantly improved in all patients after surgery. In group A, the Cobb angle was improved from 64°±24° preoperatively to 12°±11° at the last follow-up, and the average correction rate of Cobb angle was 82.6%. In group A+P, the Cobb angle was improved from 55°±10° preoperatively to 7°±9° at the last follow-up, and the average correction rate of Cobb angle was 88.3%. The operation time, intraoperative blood loss and length of stay in group A were all significantly lower than those in group A+P (t=-6.32, -11.92, -6.52, all P<0.01). At the last follow-up, there was no significant difference in Cobb angle, JOA score and VAS score between the two groups (t=0.89, 0.94, 1.02, all P>0.05). Conclusions: Mid-and long-term results of anterior and combined anterior and posterior surgery for neurofibromatosis associated severe cervical kyphosis are satisfactory. Moderate correction strategy for cervical kyphosis is safe and effective. The incidence of complications of nerve injury can be reduced.

[Clinical features and surgical management of orbitotemporal neurofibromatosis].

Objective: To report the clinical features and surgical treatment of orbitotemporal neurofibromatosis. Methods: It was a retrospective case series study. The clinical records of 24 patients who were treated for orbitotemporal neurofibromatosis between April 2007 and July 2017 at Beijing Tongren Hospital, Capital Medical University were analyzed. Data collected included sex, age, laterality, periorbital deformities, surgical treatment, follow-up time, complication and recurrence. Results: Sixteen males and 8 females were included. Age at surgery was (15±7) years (4-30 years). All patients were unilaterally involved. Twenty-three patients (96%) had upper lid involvement and ptosis. Nine patients (38%) had lower lid involvement. Fourteen patients (58%) had lateral canthal disinsertion. Three patients (13%) had brow involvement, 10 patients (42%) had conjunctival involvement and 2 patients (8%) had lacrimal gland infiltration. All patients had tumor debulking procedure. Twenty-two patients (92%) had correction of ptosis. Fourteen patients (58%) required lid reconstruction and lateral canthus reattachment surgery. Three patients (13%) had correction of brow ptosis.One patient (4%) had skull and orbit reconstruction. The median follow-up time was 3.5 (1.0-10.0) years. All patients had improved appearance. Ptosis recurred in 6 patients, but were corrected with surgery. On the last follow-up, 7 patients were free of ptosis. In 14 patients, mild ptosis was noted, but the upper lid did not cover the pupil. In 2 patients the pupil was half covered. Only in 1 patient who had not received ptosis correction surgery the pupil was covered completely. Conclusions: The periorbital deformities of orbitotemporal neurofibromatosis include upper eyelid infiltration with ptosis, lateral canthal disinsertion and infiltration of lower eyelid, brow, conjunctiva and lacrimal gland. The appearance of patients with orbitotemporal neurofibromatosis can be significantly improved through oculoplastic surgery. (Chin J Ophthalmol, 2019, 55: 828-833).

Clinical experience of surgically treating giant neurofibromatosis-1.

The surgical treatment for giant neurofibromatosis-1 (NF-1) requires comprehensive measures. Presently, there is no systematic description of surgical treatment. Because of its high level of risk, we want to share our clinical experience. From 2011 to 2014, patients (n = 8, 5 female and 3 male patients, aging from 31 to 45 years-old) were included in the study. The tumours were located on the trunk (n = 5) or face (n = 3). In addition to routine examination, blood storage was also prepared. Preoperative consultation from related departments was critical at first. Related artery embolisation was also carried out. In the operation, we checked thromboelastography, based on which reasonable blood component transfusion was implemented. Autologous blood transfusion was also ready. An instrument of copper needle or ring ligation was used to reduce haemorrhage before the surgery. Protruding or drooping portions of the tumours were excised. A pressurised bandage was applied when the surgery was completed. After the surgery, besides the routine monitoring of vital signs, re-haemorrhage should be detected in time. Then, we should decide whether blood transfusion or surgery was required again. Expanders were implanted in one female patient with facial injuries before removing the tumour. Then, expanded flaps were applied to repair the secondary wound. According to the above clinical route, after an average of 1-year follow-up, no patients died, and other unforeseen events did not occur. Wounds healed well in all patients. The tumor was excised as much as possible. No facial nerve paralysis occurred in the facial sites. Expanded flaps necrosis WAS not encountered. It is essential to design the educational clinical route for treating NF-1 when a giant protruding tumour is advised to be excised, which can minimise the risk of surgery and assure us of the maximum range of resection.

Compressive myelopathy in severe angular kyphosis: a series of ten patients.

OBJECTIVE: Compressive myelopathy in severe angular kyphosis is rare and challenging for surgical treatment. The goal of this retrospective study was to report a series of ten patients with compressive myelopathy in severe angular kyphosis and the results of surgical decompression and correction of kyphosis. METHODS: Between 2010 and 2014, 10 patients were surgically treated for severe angular kyphosis with a progressive onset or a sudden onset of paraplegia in investigator group. In these ten patients (seven males and three females), the etiologic diagnosis included eight cases of congenital kyphosis and two of neurofibromatosis; the distribution of spine level was from C5 to T11; the duration from onset until surgery ranged from 1 to 120 months; follow-up ranged from 12 to 26 months (mean 18.5 months); the kyphosis angle of the patients ranged from 50° to 180°. Magnetic resonance imaging demonstrated the spinal cord thinning and compression at apex in most of patients. All patients underwent decompressive surgery by single-stage posterior vertebral column resection or both anterior corpectomy fusion and posterior fixation. Neurological status was evaluated using the ASIA impairment classification and the motor score. RESULTS: Postoperatively, all patients had different kyphosis correction rate from 24 to 100 %. Nine patients showed neurological improvement; one patient showed no improvement. Among them, one sudden onset ASIA A adolescent paraplegic patient improved to ASIA E within 1 year of follow-up. One ASIA C adolescent paraplegic patients deteriorated neurologically to ASIA A after surgery and improved to ASIA D with 12-month follow-up. CONCLUSIONS: Compressive myelopathy in severe angular congenital kyphosis is usually occurred high incidence rate at apex of upper thoracic spine (T1-T4). The duration from onset of paraplegia until surgery and the severity of paraplegia before surgery are two key factors for neurological prognosis after surgery.

Hemidiaphragmatic palsy following excision of cervical dumbbell neurofibroma in a patient with neurofibromatosis: Importance of assessing functional status of "non-limb" roots.

A 27-year-old male patient with neurofibromatosis type 1 who was operated on for a dumbbell neurofibroma of the cervical spine developed transient respiratory difficulty due to postoperative unilateral diaphragmatic palsy. This report emphasizes the need for preoperative assessment of residual function in involved non-limb roots, the role of intraoperative monitoring to take a decision on root sacrifice, and the need for optimizing respiratory function preoperatively, and describes a complication rarely reported in literature.

Use of Computed Tomography-Derived Prosthetics for Intraoperative Guidance of Tumor Resection.

Preoperative computed tomography (CT)-derived design and modeling provides a useful guide for a more accurate reconstruction of a variety of complex maxillofacial deformities. While the use of three-dimensional CT imaging has focused mainly on bony reconstruction, the use of this technique to facilitate soft tissue reconstruction represents an important innovation that can assist surgeons with preoperative planning and intraoperative decision-making. In this study, the authors report the novel use of three-dimensional CT scan modeling to facilitate the resection of a large maxillofacial neurofibroma in a patient with neurofibromatosis. In conjunction with an anaplastologist, the combined use of tangible models and aesthetic judgments significantly optimizes the quality of the initial resection and subsequent reconstruction. By utilizing an interdisciplinary approach, it is possible to achieve optimal symmetry in the setting of complex maxillofacial deformities.

Neurofibromatosis type 2 (NF 2) or schwannomatosis?--Case report study and diagnostic criteria.

INTRODUCTION: Neurofibromatosis type 2 (NF2) and schwannomatosis are entities that may, due to the similarity of clinical symptoms, cause diagnostic difficulties. Incidence rate of both diseases is similar and estimated between 1:25,000 and 1:40,000. The genes associated with the development of the aforementioned disorders are located on chromosome 22 and lay in proxmity. Schwannomatosis is characterized by an incomplete penetrance and the risk of its transmission to the offspring is significantly lower than in the case of NF 2. Schwannomatosis clinical characteristic is similar to the NF2, however vestibular schwannomas are not present. Therefore the imaging studies evaluated by an experienced radiologist play a key role in the diagnostic process. CASE REPORT: Forty two-year-old female hospitalized three times because of the tumors of the spinal canal was admitted to the Department of Neurosurgery and Peripheral Nerve Surgery in 2008 because of the cervical pain syndrome with concomitant headache. She was diagnosed with a schwannomatosis, recently distinguished, the third form of neurofibromatosis. MRI imaging revealed craniocervical junction tumor. Suboccipital craniectomy with concomitant C1-C2 laminectomy was done in order to remove the lesion. After the surgery the patient did not present any deficits in neurological examination and was discharged from hospital in good general condition. CONCLUSIONS: The patient was diagnosed with schwannomatosis, recently established neurofibromatosis entity which may resemble NF2 clinically. In patients after the age of 30, in whom we observe multiple schwannomas without the concomitant hearing impairment, the diagnosis of schwannomatosis is very likely.

Association of tumor location, extent of resection, and neurofibromatosis status with clinical outcomes for 221 spinal nerve sheath tumors.

OBJECT Intradural extramedullary spine tumors represent two-thirds of all primary spine neoplasms. Approximately half of these are peripheral nerve sheath tumors, mainly neurofibromas and schwannomas. Given the rarity of this disease and, thus, the limited analyses of clinical outcomes, the authors examined the association of tumor location, extent of resection, and neurofibromatosis (NF) status with clinical outcomes. METHODS Patients were identified through a search of the University of California, San Francisco, neuropathology database and a separate review of current procedural terminology codes. Data recorded included patient age, patient sex, clinical presentation, presence of NF, tumor type, tumor location, extent of resection (gross-total resection [GTR] or subtotal resection [STR]), and clinical follow-up. RESULTS Of 221 tumors in 199 patients (mean age 45 years), 53 were neurofibromas, 163 were schwannomas, and 5 were malignant peripheral nerve sheath tumors. The most common presenting symptom was spinal pain (76%), followed by weakness (36%) and sensory abnormalities (34%). Mean symptom duration was 16 months. In terms of spinal location, neurofibromas were more common in the cervical spine (74% vs 27%, p < 0.001), and schwannomas were more common in the thoracic and lumbosacral spine (73% vs 26%, p < 0.001). Rates of GTR were lower for neurofibromas than schwannomas (51% vs 83%, p < 0.001), regardless of location. Rates of GTR were lower for cervical (54%) than thoracic (90%) and lumbosacral (86%) lesions (p < 0.001). NF was associated with lower rates of GTR among all tumors (43% vs 86%, p < 0.001). The mean follow-up time was 32 months. Recurrence/progression was more common for neurofibromas than schwannomas (17% vs 7%, p = 0.03), although the mean time to recurrence/progression did not differ according to tumor type (45 vs 53 months, p = 0.63). As expected, GTR was associated with lower recurrence rates (4% vs 22%, p < 0.001). According to multivariate analysis, cervical location (OR 0.239, 95% CI 0.110-0.520) and presence of NF (OR 0.166, 95% CI 0.054-0.507) were associated with lower rates of GTR. In a separate model, only GTR (OR 0.141, 95% CI 0.046-0.429) was associated with tumor recurrence. CONCLUSIONS Resection is an effective treatment for spinal nerve sheath tumors. Neurofibromas were found more commonly in the cervical spine than in other regions of the spine and were associated with higher rates of recurrence and lower rates of GTR than other tumor types, particularly in patients with NF Types 1 or 2. According to multivariate analysis, both cervical location and presence of NF were associated with lower rates of GTR. According to a second multivariate model, the only variable associated with tumor recurrence was extent of resection. Maximal safe resection remains ideal for these lesions; however, patients with cervical tumors or NF should be counseled about their increased risk for recurrence.

Orbital schwannomatosis in the absence of neurofibromatosis.

PURPOSE: The aim of this study was to describe 3 cases of primary orbital schwannomatosis without associated systemic neurofibromatosis. METHODS: This is a retrospective interventional study of 3 patients who presented with multiple, distinct masses in the orbit (n = 3) as well as in the hemiface (n = 1). The clinical presentation, imaging features, surgical procedures, and outcomes were defined. RESULTS: Two women and a man presented with of exophthalmos and diplopia. Pain was the most prominent complaint in 2 patients. None of the patients had associated systemic neurofibromatosis by history or examination. Radiologic evaluation with computed tomography or magnetic resonance imaging of orbit revealed multiple well-demarcated intraconal and extraconal masses. Masses were excised, and histopathology confirmed all masses to be schwannomas. Postoperative follow-up was uneventful with alleviation of primary complaints in all patients. CONCLUSIONS: Multiple orbital schwannomas (primary orbital schwannomatosis) may be observed in patients without systemic association of neurofibromatosis. Management includes surgical excision of the tumors to achieve relief from their mass effects.

Stereotactic Radiosurgery and Radiotherapy for Vestibular Schwannoma in NF2-Related Schwannomatosis.

OBJECTIVES: To determine the long-term control rates and hearing outcomes for growing vestibular schwannoma in NF2-related schwannomatosis (NF2) treated with stereotactic radiosurgery (SRS) and fractionated radiotherapy (FRT). METHODS: Retrospective review of all patients treated with SRS/FRT between 1986 and2021 from a tertiary NF2 unit. Overall tumor control was defined as: (1) growth control (growth failure was defined as growth in any dimension of 3 millimetres or more from baseline post-SRS/FRT), and (2) treatment control (no need for further intervention). Loss of serviceable hearing was defined as a drop in speech discrimination score below 50% after SRS/FRT. RESULTS: There were 81 cases, with a mean duration of follow-up of 125 months. Overall control rate was 72% (58/81), with 80% (65/81) growth control and 74% (60/81) treatment control. There was a 5-year actuarial survival of 77% and 10-year survival of 71%. Forty-three percent (30/69) of cases did not have serviceable hearing at baseline. Of those remaining, 49% (19/39) preserved serviceable hearing during follow-up at a mean of 106 months. Actuarial survival for preservation of serviceable hearing at 5 and 10 years was 69% and 53%. There were poorer outcomes with increasing genetic severity, and with baseline tumor size >3 cm. No cases of SRS/FRT-related malignancy were identified at a mean follow-up of 10 years. CONCLUSION: Stereotactic radiosurgery/fractionated radiotherapy are an effective option to treat growing vestibular schwannoma in patients with NF2 with the potential for hearing preservation in a proportion of patients. LEVEL OF EVIDENCE: 4-Case Series Laryngoscope, 134:2364-2371, 2024.