Genetic changes in the FH gene cause vagal paraganglioma.

Vagal paraganglioma (VPGL) is a rare neuroendocrine tumor that originates from the paraganglion associated with the vagus nerve. VPGLs present challenges in terms of diagnostics and treatment. VPGL can occur as a hereditary tumor and, like other head and neck paragangliomas, is most frequently associated with mutations in the SDHx genes. However, data regarding the genetics of VPGL are limited. Herein, we report a rare case of a 41-year-old woman with VPGL carrying a germline variant in the FH gene. Using whole-exome sequencing, a variant, FH p.S249R, was identified; no variants were found in other PPGL susceptibility and candidate genes. Loss of heterozygosity analysis revealed the loss of the wild-type allele of the FH gene in the tumor. The pathogenic effect of the p.S249R variant on FH activity was confirmed by immunohistochemistry for S-(2-succino)cysteine (2SC). Potentially deleterious somatic variants were found in three genes, SLC7A7, ZNF225, and MED23. The latter two encode transcriptional regulators that can impact gene expression deregulation and are involved in tumor development and progression. Moreover, FH-mutated VPGL was characterized by a molecular phenotype different from SDHx-mutated PPGLs. In conclusion, the association of genetic changes in the FH gene with the development of VPGL was demonstrated. The germline variant FH: p.S249R and somatic deletion of the second allele can lead to biallelic gene damage that promotes tumor initiation. These results expand the clinical and mutation spectra of FH-related disorders and improve our understanding of the molecular genetic mechanisms underlying the pathogenesis of VPGL.

Extracranial Hypoglossal Schwannoma: Case Report and Literature Review.

BACKGROUND: Schwannomas are solitary neurogenic tumors originating from the myelin sheath of peripheral nerves. Extracranial hypoglossal schwannomas comprise <5% of all head and neck schwannomas and can mimic submandibular salivary gland tumors. CASE REPORT: We report the diagnostic imaging, surgical treatment, and histopathological findings of a rare case of extracranial schwannoma of the hypoglossal nerve in a 73-year-old female, presented with an asymptomatic swelling in the left submandibular region that had been persisted for approximately three years. CONCLUSION: Accurate diagnosis of this rare clinical entity requires comprehensive diagnostics. The optimal therapeutic strategy is nerve-sparing surgical excision, although it can be challenging.

Preservation of cranial nerve function in large and giant trigeminal schwannoma resection: a case series.

BACKGROUND: Trigeminal schwannomas (TSs) are intracranial tumors that can cause significant brainstem compression. TS resection can be challenging because of the risk of new neurologic and cranial nerve deficits, especially with large (≥ 3 cm) or giant (≥ 4 cm) TSs. As prior surgical series include TSs of all sizes, we herein present our clinical experience treating large and giant TSs via microsurgical resection. METHODS: This was a retrospective, single-surgeon case series of adult patients with large or giant TSs treated with microsurgery in 2012-2023. RESULTS: Seven patients underwent microsurgical resection for TSs (1 large, 6 giant; 4 males; mean age 39 ± 14 years). Tumors were classified as type M (middle fossa in the interdural space; 1 case, 14%), type ME (middle fossa with extracranial extension; 3 cases, 43%), type MP (middle and posterior fossae; 2 cases, 29%), or type MPE (middle/posterior fossae and extracranial space; 1 case, 14%). Six patients were treated with a frontotemporal approach (combined with transmastoid craniotomy in the same sitting in one patient and a delayed transmaxillary approach in another), and one patient was treated using an orbitofrontotemporal approach. Gross total resection was achieved in 5 cases (2 near-total resections). Five patients had preoperative facial numbness, and 6 had immediate postoperative facial numbness, including two with worsened or new symptoms. Two patients (28%) demonstrated new non-trigeminal cranial nerve deficits over mean follow-up of 22 months. Overall, 80% of patients with preoperative facial numbness and 83% with facial numbness at any point experienced improvement or resolution during their postoperative course. All patients with preoperative or new postoperative non-trigeminal tumor-related cranial nerve deficits (4/4) experienced improvement or resolution on follow-up. One patient experienced tumor recurrence that has been managed conservatively. CONCLUSIONS: Microsurgical resection of large or giant TSs can be performed with low morbidity and excellent long-term cranial nerve function.

Functional vagal paraganglioma developing 15 years after resection of a retroperitoneal paraganglioma.

The patient, a 40-year-old woman, was diagnosed as having a functional right vagal paraganglioma (PGL) 15 years after undergoing resection for a retroperitoneal PGL. 123I-MIBG scintigraphy showed no accumulation, but as the blood noradrenaline and urinary normetanephrine concentrations were elevated, the tumor was judged as being functional, and surgery was scheduled. The patient was started on doxazosin infusion and embolization of the tumor feeding vessel was performed before the surgery. Intraoperative examination showed that the tumor was contiguous with the vagal nerve, necessitating combined resection of the vagal nerve with the tumor. Postoperatively, the catecholamine levels returned to normal range. Histopathologically, the tumor was diagnosed as a moderately differentiated, intermediate-malignant-grade PGL, with a GAPP score of 4 to 6. No non-chromaffin tissue was observed in the tumor background, so that the functional vagal PGL was considered as a sporadic metachronous tumor rather than as a metastasis from the retroperitoneal PGL. More than half of head and neck paragangliomas (HNPGLs) are reported to arise in the carotid body, and about 5% from the vagal nerve. In addition, HNPGLs rarely produce catecholamines. Herein, we consider the relationship with the previously resected retroperitoneal PGL based on a review of the literature.

An unexpected complication of hypoglossal schwannoma surgery: Cerebrospinal fluid leakage-A case report and literature review.

BACKGROUND: Extracranial hypoglossal schwannoma is a rare tumor primarily treated with surgical excision. This article aims to highlight the potential for unexpected complications intraoperatively, such as cerebrospinal fluid leakage from skullbase to neck. METHODS: A previously healthy 23-year-old male presented with tongue numbness. Magnetic resonance imaging revealed a 17 × 20 mm nodular lesion adjacent to the cervical segment of the internal carotid artery. Surgical excision was scheduled due to suspicion of a neurogenic tumor. RESULTS: Intraoperatively, despite careful handling, cerebrospinal fluid leakage was observed. Manipulation of the mass caused detachment of proximal nerve fibers, potentially indicating avulsion of the hypoglossal nerve from the brainstem or nearby. Clear fluid leakage from the skull base was also noted. CONCLUSION: Thorough preoperative evaluation and patient education regarding potential complications are crucial. This article presents an unexpected complication encountered during surgical excision of extracranial hypoglossal schwannoma, emphasizing the need for awareness and preparedness in such cases.

Operative management of trigeminal schwannomas: based on a modified classification in a study of 93 cases.

BACKGROUND: Advances in microscopic and endoscopic surgical techniques have outpaced traditional classification and transcranial surgical strategies, especially with reference to the treatment of trigeminal schwannomas (TSs). A modified TS classification is proposed and appropriate surgical strategies are discussed. METHODS: The cases of 93 patients who underwent surgical treatment in Beijing Tiantan Hospital in the previous 6 years were analyzed retrospectively, and a literature review was conducted. RESULTS: Classification is based on surgical direction. Tumors were classified as follows: type A, backward orientation, located in the orbit or orbit and middle cranial fossa (8 cases, 8.6%); type B, upward orientation, located in the pterygopalatine fossa, infratemporal fossa or pterygopalatine fossa, infratemporal fossa, and middle cranial fossa (23 cases, 24.7%); type C, forward and backward orientations, located in the middle cranial fossa, posterior cranial fossa or both (58 cases, 62.4%); and type D, located in multiple regions (4 cases, 4.3%). 91.40% of patients underwent gross total resection (GTR) with 29 cases receiving endoscopic resection of whom 93.10% (27/29) experienced GTR. CONCLUSION: The 93 cases were satisfactorily divided into four types, according to tumor location and surgical orientation, enabling safe and effective removal by appropriate surgery.

Report of a vagal paraganglioma at the cervicothoracic junction.

BACKGROUND: Vagus nerve paragangliomas are rare tumors, comprising 0.03% of head and neck neoplasms. These tumors are usually located cephalad to the hyoid bone, and there is only one previously reported case that arose from the lower third of the neck. METHODS: We describe the second reported case of a lower neck vagus nerve paraganglioma that was managed with a limited sternotomy for access and surgical removal. RESULTS: A 66-year-old male presented with a long-standing lesion of the cervicothoracic junction. CT, MRI, and Ga-68 DOTATATE PET/CT showed an avidly enhancing 5.2 × 4.2 × 11.5 cm mass extending from C6 to approximately T4 level. FNA confirmed the diagnosis. The patient underwent catheter angiography and embolization via direct puncture technique followed by excision of the mass via a combined transcervical and limited sternotomy approach. CONCLUSION: We describe an unusual case of vagal paraganglioma at the cervicothoracic junction with retrosternal extension requiring a sternotomy for surgical excision.

Predictors of Surgical Outcomes in Patients with Abducens Nerve Schwannoma: A Comprehensive Systematic Review and a Case Report.

BACKGROUND: Abducens nerve (AN) schwannomas are extremely rare tumors. Clinical characteristics and factors that influence postoperative outcomes are not well defined. OBJECTIVE: To characterize clinical features of AN schwannomas and predictors of surgical outcomes. METHODS: PRISMA-guided systematic review of the literature on AN schwannomas was performed. Subsequently, univariate and multivariate regression analyses were performed to identify the predictive value of variables that influence postoperative outcomes. RESULTS: A total of 42 studies with 55 patients were evaluated. The mean age at presentation was 43.9 ± 14.6 years. The most common presenting symptom was cranial nerve VI palsy (69.1%). Cavernous sinus (49.1%) and prepontine cistern (36.3%) were the most commonly involved locations. Complete recovery after surgery was seen in 36.3% at a median follow-up of 28.4 ± 25.8 months. Preoperative AN palsy (P < 0.001), suboccipital approach (P = 0.007), and subtotal resection of tumor (P = 0.044) were significant protective factors for postoperative complications. Prepontine location and postoperative complications were poor prognostic indicators of AN recovery (odds ratio [OR], 0.10, P = 0.030 and OR, 0.10, P = 0.028, respectively). Subtotal resection was significantly correlated with higher odds of AN recovery (OR, 6.06; P = 0.040). CONCLUSIONS: AN schwannomas are rare but serious tumors that can cause significant morbidity, with only approximately one third of patients showing complete recovery after surgery. The suboccipital approach was a protective factor for postoperative complications, especially when combined with subtotal resection. Knowledge of these factors along with tumor characteristics helps optimize surgical planning and preoperative counseling.

Endoscopic far-lateral supracerebellar infratentorial approach for resection of dumbbell-shaped trigeminal schwannoma: surgical techniques and preliminary results.

BACKGROUND: Trigeminal schwannomas (TSs) are mostly benign tumors. However, dumbbell-shaped TSs are most challenging for surgeons and pose a high surgical risk. OBJECTIVE: We describe the technique of the purely endoscopic far-lateral supracerebellar infratentorial approach (EFL-SCITA) for removing dumbbell-shaped TSs and further discuss the feasibility of this approach and our experience. METHODS: EFL-SCITA was performed for resection of 5 TSs between January 2020 and March 2023. The entire procedure was performed endoscopically with the goal of total tumor resection. During the operation, the tumor was exposed in close proximity and multiple angles under the endoscope, and the peri-tumor nerves were carefully identified and protected, especially the normal trigeminal fiber bundles around the tumor. RESULTS: All the tumors of 5 patients involved the middle and posterior cranial fossa, of which total removal was achieved in 2 patients and near-total removal in 3 patients. The most common preoperative symptoms were relieved after surgery. Two patients had postoperative mild facial paralysis (House-Brackmann grade II), and 1 patient had abducens palsy; both recovered during the follow-up period. Two patients experienced new postoperative facial hypesthesia, and 1 experienced mastication weakness, which did not recover. There was no tumor recurrence or residual tumor growth during the follow-up period in any of the patients. CONCLUSION: EFL-SCITA is a new and effective alternative for the surgical treatment of TSs. For dumbbell-shaped TSs, this approach provides sufficient surgical field exposure and freedom of operation.

Extracranial Facial Nerve Schwannoma-Histological Surprise or Therapeutic Planning?

Schwannomas (neurilemomas) are benign, slow-growing, encapsulated, white, yellow, or pink tumors originating in Schwann cells in the sheaths of cranial nerves or myelinated peripheral nerves. Facial nerve schwannomas (FNS) can form anywhere along the course of the nerve, from the pontocerebellar angle to the terminal branches of the facial nerve. In this article, we propose a review of the specialized literature regarding the diagnostic and therapeutic management of schwannomas of the extracranial segment of the facial nerve, also presenting our experience in this type of rare neurogenic tumor. The clinical exam reveals pretragial swelling or retromandibular swelling, the extrinsic compression of the lateral oropharyngeal wall like a parapharyngeal tumor. The function of the facial nerve is generally preserved due to the eccentric growth of the tumor pushing on the nerve fibers, and the incidence of peripheral facial paralysis in FNSs is described in 20-27% of cases. Magnetic Resonance Imaging (MRI) examination is the gold standard and describes a mass with iso signal to muscle on T1 and hyper signal to muscle on T2 and a characteristic "darts sign." The most practical differential diagnoses are pleomorphic adenoma of the parotid gland and glossopharyngeal schwannoma. The surgical approach to FNSs requires an experienced surgeon, and radical ablation by extracapsular dissection with preservation of the facial nerve is the gold standard for the cure. The patient's informed consent is important regarding the diagnosis of schwannoma and the possibility of facial nerve resection with reconstruction. Frozen section intraoperative examination is necessary to rule out malignancy or when sectioning of the facial nerve fibers is necessary. Alternative therapeutic strategies are imaging monitoring or stereotactic radiosurgery. The main factors which are considered during the management are the extension of the tumor, the presence or not of facial palsy, the experience of the surgeon, and the patient's options.

Perineural Spread of Tumor in the Skull Base and Head and Neck.

Perineural tumor spread (PNS) is a well-recognized entity in head and neck cancers and represents a mode of metastasis along nerves. The trigeminal and facial nerves are most affected by PNS, and their connections are reviewed. MRI is the most sensitive modality for detecting PNS, and their anatomy and interconnections are reviewed. MRI is the most sensitive modality for detecting PNS, and imaging features of PNS and important imaging checkpoints are reviewed. Optimal imaging protocol and techniques are summarized as well as other entities that can mimic PNS.

Radical resection of trigeminal schwannoma at the cerebellopontine angle with support of the digital robotic exoscope Synaptive Modus V system: A case report and literature review.

RATIONALE AND PATIENT CONCERNS: We report on a 67-year-old woman who experienced drowsy mental status, facial numbness, and hearing loss on the right side; the symptom gradually worsened over the last 4 years. Brain magnetic resonance imaging revealed a 4.8 × 1.8 × 2.6 cm lesion located in the right cerebellopontine angle. INTERVENTIONS: She underwent surgery with the retrosigmoid suboccipital approach and support from the digital robotic exoscope Synaptive Modus V system. To the best of our knowledge, this is the first reported case that used the robotic exoscope system in Vietnam, and also in Asia. DIAGNOSIS: We performed radical resection of the tumor, the surgery position and the pathology result concluded the diagnosis was trigeminal schwannoma. OUTCOMES: After 30 months of follow-up, she fully recovered and the magnetic resonance imaging showed radical resection of the tumor. LESSONS: The aim of this study is to share our experience with the robotic exoscope system, which can improve optical field and image resolution, hence creating an opportunity for surgery that otherwise is impossible. The application of this robotic exoscope system is a breakthrough in neurosurgery in developing countries, such as Vietnam.

[Trigeminal neuromas: modern diagnosis and treatment]. / Trigeminal'nye nevrinomy: sovremennaya diagnostika i lechenie.

Trigeminal neuroma (TN) is a benign neoplasm arising from trigeminal nerve sheath. The tumor can grow from any part of the nerve from the root in posterior cranial fossa to peripheral extracranial branches. Symptoms of trigeminal neuroma are variable and usually depend on location and dimensions of tumor. We present a review devoted to the problem of TN. Surgery was the only possible option in patients with TN for a long time. However, radiotherapy became one of the options and sometimes alternative to surgical treatment since the late 1980s. Besides active management of patients with TN, follow-up with regular radiographic control of small asymptomatic tumors also seems to be reasonable. When evaluating treatment outcomes, physicians consider quality of life and return to previous work and activity in addition to resection quality, neurological impairment, relapse-free period and tumor growth control. However, assessment of these indicators after certain treatment is rare. Thus, it is difficult to determine treatment strategy with maximum ratio of effectiveness and quality of life. Therefore, optimization of TN treatment is currently an urgent problem that requires further study.

Facial Nerve Schwannoma Extending to Jugular Foramen: A Case Report.

Facial nerve schwannoma (FNS) is a benign, slow-growing schwannoma that originates from Schwann cells. Facial nerve schwannoma is the most common tumor of the facial nerve but rare and only accounts for 0.15% to 0.8% of intracranial neurinomas. It may be manifested as asymmetric hearing loss, facial palsy, and hemifacial spasm. A 56-year-old woman was transferred to our department, because of pain behind the right ear and spasm of the right lateral muscle for more than 2 years and pulsatile tinnitus for half a year. Based on the preoperative medical history, physical signs, and auxiliary examination, it was diagnosed with jugular foramen (JF) space-occupying lesion. We removed the tumor through the infratemporal fossa type A approach and found that the tumor originated from the facial nerve. After the tumor resection, sural nerve transplantation was performed. The patient demonstrated postoperative facial palsy (House-Brackman grade VI) and was smoothly discharged after good recovery. Facial nerve schwannoma rarely invades the JF, and the most common tumor in the JF is the glomus jugular tumor, followed by the posterior cranial schwannoma. They have common symptoms, making it difficult to obtain a correct diagnosis. Clinical data, medical history, and auxiliary examinations should be carefully analyzed to avoid misdiagnosis or mistreatment. Infratemporal fossa type A approach is an effective method for treating FNS of JF.

Diagnosis and management of hypoglossal nerve-derived schwannoma in the floor of mouth: a case series.

BACKGROUND: Schwannomas or neurilemmomas are well-encapsulated, benign, solitary, and slow-growing tumors that originate from Schwann cells of the nerve sheath. Extracranial schwannoma is reported to have a relatively high incidence in the tongue while an extremely low incidence in the floor of mouth. In the current study, we presented the first case series of hypoglossal nerve-derived schwannoma in the floor of mouth in Asia. METHODS: A retrospective study of 9 surgical cases of hypoglossal nerve-derived schwannoma in the floor of mouth was performed. The patient and tumor characteristics were evaluated by physical, radiological and pathological examination. Details of operation and complications were also recorded. RESULTS: Hypoglossal nerve-derived schwannoma in the floor of mouth showed a well-defined boundary with a firm texture, smooth surface and good mobility on palpation. The median maximum diameter of the tumors was 4.3 cm (range 2.8-7.0 cm). The median operative time and bleeding volumes were 89.4 min (range 47-180 min) and 99.2 mL (range 15-200 mL), respectively. All cases received complete surgical excision. CONCLUSION: In this study, we presented the diagnosis and management of hypoglossal nerve-derived schwannoma in the floor of mouth for the first time in Asia. The study provided us with a recommendation for consideration of the diagnosis of hypoglossal schwannoma when a patient presents with a mass in the floor of mouth.

Malignant Nerve Sheath Tumor of the Hypoglossal Nerve in a Maltese Dog.

A 4 yr old male Maltese dog presented with a 1 wk history of intermittent neck pain and progressive difficulty walking. Neurologic evaluation was consistent with a left-sided brainstem lesion. On oral examination, left lingual hemiatrophy was evident suggesting hypoglossal nerve involvement. A dumbbell-shaped extra-axial mass in the left side of the caudal fossa extending extracranially through the hypoglossal canal was detected by MRI. At postmortem histologic examination, the hypoglossal nerve was diffusely infiltrated by fusiform neoplastic cells arranged in Antoni A and Antoni B patterns. This is the first description of a malignant nerve sheath tumor selectively involving the hypoglossal nerve in a dog.

Middle fossa approach for a facial nerve schwannoma: how I do it.

BACKGROUND: Facial nerve schwannomas can extend to the middle fossa or the cerebellopontine angle through the labyrinthine and cisternal segments of the facial nerve. The middle fossa approach (MFA) and its extensions provide a wide approach to deal with a large variety of lesions located in the middle and posterior cranial fossa junction. METHODS: We describe the MFA along with its advantages and limitations to treat a facial nerve schwannoma involving the middle and posterior cranial fossa. CONCLUSIONS: The MFA is a well-established route to surgically deal with tumors located in and around the proximal four segments of the facial nerve.

Aspiration cytology of facial nerve schwannoma of parotid gland: A rare diagnosis.

Schwannoma is a benign nerve sheath tumour rarely found in the head and neck region and much less commonly found in the intraparotid facial nerve. It is a slow-growing encapsulated tumour arising from differentiated Schwann cells or axonal nerve sheath. It can occur anywhere along the course of the facial nerve. Patients most commonly present with an asymptomatic swelling, in the absence of any signs of facial nerve palsy. Accordingly, diagnosis is usually difficult before surgical removal and histopathological examination. Here, we report a rare case of facial nerve schwannoma (FNS), diagnosed on fine needle aspiration cytology, in a 35-year-old male who presented with a painless, gradually increasing swelling in the right infra-auricular region for the last 2 years. His general examination revealed no signs of facial muscle weakness. The cytodiagnosis of intraparotid FNS was further confirmed by immunohistochemistry on cell block.

Surgical Technique and Nuances of Resection of a Trochlear Schwannoma: Operative Video.

Cranial nerve schwannomas accounts for around 8% of all benign intracranial tumors, arising most commonly from the vestibular nerve, followed by the trigeminal nerve and other lower cranial nerves. However, trochlear schwannoma in a patient without neurofibromatosis-2 are extremely rare and to date, fewer than 100 cases have been reported in the literature. They are either asymptomatic or present with ophthalmologic or neurologic symptoms. Diplopia is the most common initial symptom. As the tumor grows, it can compress the surrounding brainstem and other cranial nerves, causing neurologic symptoms. Asymptomatic lesions are detected incidentally following imaging for some other reason. There are no clear guidelines for the management of these tumors. In general, small asymptomatic tumors are closely observed by serial imaging and symptomatic or larger tumors are managed by surgical excision and/or stereotactic radiosurgery.1-7 Here we present a 41-year-old female patient with incidentally detected left trochlear schwannoma during the follow-up magnetic resonance imaging (MRI) scans. She was followed up regularly with multiple repeat MRI. Recently she started complaining of occasional headaches, and MRI showed a left peimesencephalic cistern tumor causing mass effect on the ipsilateral midbrain. There was also significant brainstem edema. Hence she underwent left retromastoid suboccipital craniectomy, lateral supracerbellar approach, and complete excision of the tumor. Postoperatively the patient had an uneventful recovery without any new neurologic deficits. At 6 months' follow-up the patient is doing well.