Nerve Neurofibroma Research Articles

Trigeminal Nerve Neurofibroma Presenting as Facial Swelling in Two 3-year-olds

Trigeminal Nerve Neurofibroma Presenting as Facial Swelling in Two 3-year-olds

Intratemporal facial nerve neurofibroma: a case report and review of literature

Facial nerve neurofibromas (FNN) are a rare benign tumor of facial nerve can arise from anywhere along the course of the facial nerve from the cerebellopontine angle (CPA) to the extracranial branches within the parotid. They are most commonly located in the parotid gland, and FNN in temporal bone are rarely reported. Intratemporal facial neurofibroma arise from facial nerve in internal auditory canal or in Fallopian canal. It usually manifests as progressive facial palsy, but also can present as sudden or repetitive facial palsy mimicking Bell’s palsy. We reported a case of intratemporal facial neurofibroma arising mainly from mastoid segment in 17-year-old female who presented with progressive facial palsy for 3 years. We briefly reviewed previous cases of intratemporal facial neurofibroma reported in the literature to provide a comprehensive understanding of this rare entity.

N°321 – A rare case of isolated cervical spinal nerve neurofibromas in a patient with a type 1 neurofibromatosis

N°321 – A rare case of isolated cervical spinal nerve neurofibromas in a patient with a type 1 neurofibromatosis

Ulnar Nerve Tuberculoma Mimicking as a Ulnar Nerve Schwannoma and Neurofibroma

Ulnar Nerve Tuberculoma Mimicking as a Ulnar Nerve Schwannoma and Neurofibroma

Neurofibroma of the Median Nerve Managed With Ultrasound Guided Nerve Block: A Case Report

Background: Median nerve neurofibroma can mimic carpal tunnel syndrome. In unilateral carpal tunnel syndrome, wrist imaging is suggested to exclude tumors. Diagnosis and management of peripheral nerve sheath tumors can be challenging.
 Case: This is a case report of 42-year-old female with median nerve neurofibroma who presented with excruciating pain as the main symptom. Though surgical excision is the preferred treatment, it is associated with the risk of functional deficit. In this case, patient was unwilling for surgery. This report highlights the evaluation of neurofibroma and the role of median nerve block in the symptomatic as well as functional improvement.
 Conclusion: Nerve block can be effective if neurofibroma presents with pain as the main symptom without any impairment of motor function or daily activities.

Simplifying the Surgical Classification and Approach to the Posterolateral Skull Base and Jugular Foramen Using Anatomical Triangles.

IntroductionLesions of the jugular foramen (JF) and postero-lateral skull base are difficult to expose and exhibit complex neurovascular relationships. Given their rarity and the increasing use of radiosurgery, neurosurgeons are becoming less experienced with their surgical management. Anatomical factors are crucial in designing the approach to achieve a maximal safe resection.Methods and methodsSix cadaveric heads (12 sides) were dissected via combined post-auricular infralabyrinthine and distal transcervical approach with additional anterior transstyloid and posterior far lateral exposures. Contiguous surgical triangles were measured, and contents were analyzed. Thirty-one patients (32 lesions) were treated surgically between 2000 and 2016 through different variations of the retro-auricular distal cervical transtemporal approaches.ResultsWe anatomically reviewed the carotid, stylodigastric, jugular, condylar, suboccipital, deep condylar, mastoid, suprajugular, suprahypoglossal (infrajugular), and infrahypoglossal triangles. Tumors included glomus jugulare, lower cranial nerve schwannomas or neurofibromas, meningiomas, chondrosarcoma, adenocystic carcinoma, plasmacytoma of the occipitocervical joint, and a sarcoid lesion. We classified tumors into extracranial, intradural, intraosseous, and dumbbell-shaped, and analyzed the approach selection for each.ConclusionJugular foramen and posterolateral skull base lesions can be safely resected through a retro-auricular distal cervical lateral skull base approach, which is customizable to anatomical location and tumor extension by tailoring the involved osteo-muscular triangles.

The intraoperative video of resecting a solitary cervical vagal nerve neurofibroma via endoscopic surgery

The intraoperative video of resecting a solitary cervical vagal nerve neurofibroma via endoscopic surgery

Treatment of Sympathetic Nerve Neurofibroma of the Neck and Approach to the Postoperative Pain

Treatment of Sympathetic Nerve Neurofibroma of the Neck and Approach to the Postoperative Pain

Integrated Multi-Omics Characterization of Neurofibromatosis Type 1 Related Peripheral Nerve Sheath Tumors Identifies Two Distinct Malignant Peripheral Nerve Sheath Tumors Subtypes with Sonic Hedgehog or WNT Pathway Activation

Abstract INTRODUCTION Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann-cell derived sarcomas and the leading cause of mortality in neurofibromatosis Type 1. In many cases, MPNSTs develop through malignant transformation of an underlying neurofibroma (NF). The genomic alterations and molecular pathways driving malignant transformation is not well understood. In this study, we leverage multi-platform genomic and epigenomic profiling of human NFs and MPNSTs to identify targetable molecular pathways that lead to malignant transformation. METHODS Fresh-frozen tumor (N = 108; 19 MPNSTs, 18 premalignant NFs, 37 benign peripheral nerve NFs, and 34 cutaneous NFs) and matched-controls were allocated for NGS platforms including methylation-profiling, RNA, whole exome and ChIP sequencing. In addition, functional validation of identified pathways was performed using CRISPR/cas9 knockout of relevant sonic hedgehog (SHH) and WNT pathway genes in immortalized neurofibroma cell lines. RESULTS Unsupervised consensus clustering of peripheral nerve tumors identified 4 distinct methylation subgroups, with MPNSTs clustering in either Methyl_Grp-2B or Methyl_Grp-3. Transcriptomic analysis of the MPNSTs, identified SHH pathway activation in Methyl_Grp-3 MPNSTs (NES = 1.9952, P < .0001, FDR < 0.001) and WNT pathway activation in Methyl_Grp-2B MPNSTs (NES = 1.7630, P < .0001, FDR = 0.0058). Single sample gene set enrichment analysis demonstrates that there is a strong negative correlation between SHH and WNT pathway activation in MPNSTs (r = −0.78, P = .007). Methyl_Gr-3 MPNSTs harbor more PTCH1 copy number loss (62.5% vs 0%, P < .05) and PTCH1 promoter hypermethylation (mean beta value: 0.2899 vs. 0.06119, P < .05). PTCH1 knockout in immortalized neurofibroma cell lines increased expression of SHH pathway target genes (GLI1, GLI2, and SMO), and increased cellular proliferation and invasiveness. CONCLUSION We found that MPNSTs can be classified into two molecular subgroups driven by SHH or WNT pathway activation. Furthermore, PTCH1 loss is one mechanism that mediates SHH pathway activation. These results suggest a targeted approach should be taken for treating MPNSTs, and SHH and WNT pathway inhibition may be promising avenue for therapeutic development.

Treatment of Sympathetic Nerve Neurofibroma of the Neck and Approach to the Postoperative Pain

Treatment of Sympathetic Nerve Neurofibroma of the Neck and Approach to the Postoperative Pain

Pediatric Intraparotid Neurofibroma: Rare Entity

Abstract Aim: This case report provide an awareness of intraparotid facial nerve neurofibroma as a cause of parotid masses and to describe their characteristics and management considerations. Material: It is a case report of a pediatric patients with intraparotid facial nerve neurofibromas which is a rare entity. Method: It was preoperatively diagnosed as intraparotid benign tumor likely to be pleopmorphic features on fine needle aspiration cytology.Tumors arising from the extratemporal course of the facial nerve are quite rare. The tumors arise from Schwann cells and include the schwannoma and the neurofibroma. Conclusion: The overwhelming benign nature of these lesions necessitates a conservative course of treatment. Histological diagnosis should be followed by a limited tumor excision with emphasis on retaining normal facial nerve function. Malignant lesions require wide excision with facial nerve grafting or facial nerve reanimation.

Abstract 1340: RAS pathway activation and sensitivity to therapeutic agents is correlated with NF1 residual activity in malignant peripheral nerve sheath tumors

Abstract Background: Malignant Peripheral Nerve Sheath Tumor (MPNST) is a malignant sarcoma that derives from a peripheral nerve or plexiform neurofibroma. Neurofibromatosis type 1 (NF-1) patients are particularly susceptible, with a higher risk, earlier onset, and worse prognosis. The major factor associated with MPNST and NF-1 is Neurofibromin 1, coded by the NF1 gene. NF1 mutation results in RAS hyperactivation. Chemotherapy for MPNST is currently limited, with poor prognosis for metastatic or unresectable tumors. Thus, the development of promising treatment solutions for MPNST to translate to clinical trials is required. Methods: Here, we seek to identify efficacious chemotherapeutic treatments for MPNST with a combination of drug screening and biological pathway analysis. We used our previously established preclinical system to test FDA approved or promising developmental agents against five cell line models for MPNST. We screened sixty agents with diverse mechanisms of action below published maximum plasma concentrations, and measured effects with a CellTiter-Glo viability assay. Promising agents were then tested in two-drug combinations, allowing for determination of synergism. We then examined the molecular effects of the top candidates with use of antibody arrays that permit detection of a series of phosphorylated proteins. Results: The group of most efficacious drugs was enriched with agents that target factors downstream of RAS, including MEK, mTOR, and PI3K inhibitors, with microtubule inhibitors, genotoxics, and HDAC inhibitors also demonstrating good results. Strong synergism was observed across our cell line models particularly in combinations containing the dual mTORC1/2 inhibitor INK128. Interestingly, drug sensitivity varied greatly between cell lines, correlating with relative NF1 protein and RAS-GTP levels. We analyzed the activation of the RAS pathway in response to drug treatment with antibody arrays and found that, following treatment, relative phosphorylation signal was more decreased compared to controls in cell lines with lower relative NF1 protein levels. Doxorubicin was able to reduce phosphorylation signal compared to controls to a level near comparable to targeted inhibitors, which could contribute to doxorubicin’s current usefulness against MPNSTs. Importantly, we identified combination treatments that were able to greatly reduce the relative phosphorylation signal of RAS pathway members versus control. Combinations containing INK128 resulted in the most pathway shutdown. These findings suggest that MPNSTs may be susceptible to combination treatments targeting RAS pathway members. Moreover, it may be possible to use pathway analysis as a diagnostic tool to predict drug tolerance. Citation Format: Elliot Kahen, Darcy Welch, Diana Yu, Christopher Cubitt, Jae Lee, Andrew Brohl, Damon R. Reed. RAS pathway activation and sensitivity to therapeutic agents is correlated with NF1 residual activity in malignant peripheral nerve sheath tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1340. doi:10.1158/1538-7445.AM2017-1340

Abstract 2536: Assessing combinations of FDA approved chemotherapy in malignant peripheral nerve sheath tumor (MPNST) cell lines

Abstract Background: Malignant Peripheral Neural Sheath Tumors (MPNST) are a type of sarcoma that arise spontaneously from a peripheral nerve or plexiform neurofibroma. Approximately 1 in 10 people with a constitutional mutation in the NF1 gene, a negative regulator of RAS function, develop MPNST with a peak incidence in the adolescent and young adult years. Available chemotherapy treatment for MPNST has low response rates, and the prognosis for unresectable or metastatic tumors is poor. A clinically relevant system to rapidly evaluate the efficacy of many agents and combinations of agents on MPNSTs which can be translated into clinical trials is needed. Methods: Here, we seek to identify promising single drug and combination therapies using FDA approved and other agents of interest via high-throughput screening platforms, based on established MPNST cell line models (SNF02.2, SNF10.1, SNF94.3, and SNF96.2). Taking into consideration past lessons learned from in vitro experiments, we designed stringent screening conditions that assess the candidate compounds and combinations at clinically-relevant concentrations and exposure times that mimic the in vivo pharmacokinetics in an effort to maximize the translational potential of these results. Fifty-four agents with roughly ¼ inhibitors of the RAS downstream pathways, another ¼ kinase inhibitors, and the remainder a representation of many classes of agents with diverse mechanisms of action were screened across 4 cell lines with biological replicates. The majority of the agents are FDA approved. Others are in active clinical trials, demonstrate a promising mechanism of action, or have published preclinical data in MPNST models. CellTiter Glo assays were used to assess cell viability at the maximal achievable serum concentration from phase I studies and at two lower concentrations. Promising agents were then studied in two-drug combinations to evaluate for synergy in addition to efficacy of the combination. The combinations were selected with careful attention to known drug-drug interactions, metabolism, schedule and non-overlapping toxicities. Results: Our screening results indicate that a number of FDA approved chemotherapy agents, evaluated at clinically relevant concentrations and exposure times, significantly reduced cell viability across all cell lines tested. These findings suggest promising opportunities for developing combination clinical trials. Citation Format: Elliott Kahen, Diana Yu, Christopher Cubitt, Dan Sullivan, Damon R. Reed. Assessing combinations of FDA approved chemotherapy in malignant peripheral nerve sheath tumor (MPNST) cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2536. doi:10.1158/1538-7445.AM2015-2536

Clinical characteristics and outcomes of intratemporal facial nerve neurofibromas

This study aimed to present clinical features and outcomes of 10 patients with intratemporal facial nerve neurofibromas. The ten patients underwent complete tumor removal, and nerve grafting was performed on 3 cases whose nerve integrity was sacrificed. They were followed up after surgery. All patients firstly complained of facial palsy, and progressive sensorineural hearing loss was also present in one case. Insidious onset of facial palsy was found in 6 of 10 cases (60.0%). There was multi-segment involvement in 5 of 10 cases (50.0%). During the follow-up of 4.2±1.5 ys (range, 2-6 ys), 1 of 6 cases who successfully maintained nerve integrity recovered to Grade III, and the others remained or recovered to Grade V or even Grade VI. In contrast, all of the 3 cases with nerve grafting recovered from Grade VI to Grade III or Grade IV. No tumor recurrence was noted. Facial nerve neurofibromas mainly presented with insidious facial palsy, and tended to affect multiple segments of facial nerve. It seemed that complete tumor removal and nerve grafting had better outcomes of facial nerve compared to complete tumor removal with nerve integrity preserved.

Endolaryngeal Excision of Recurrent Laryngeal Nerve Neurofibroma

ABSTRACT Vagal schwannomas, compromising 1% of head and neck neoplasms, are the commonest neurogenic tumors of the neck. Recurrent laryngeal nerve neurofibromas are even rarer. We report such a case, excised totally by an endolaryngeal approach. New trends in diagnosis and immunohistochemistry are discussed. How to cite this article Matta I, Shukla SC, Karnik P. Endolaryngeal Excision of Recurrent Laryngeal Nerve Neurofibroma. Int J Phonosurg Laryngol 2015;5(1):35-38.

Solitary Giant Neurofibroma of the Mental Nerve

Neurofibroma is a benign neoplasm derived from peripheral nerves whose etiology is still unclear. It may present as a solitary lesion or be associated with other diseases such as neurofibromatosis type I and II syndrome. This paper aims to report an extremely rare case of a solitary giant neurofibroma of the mental nerve whose etiology was related to a local trauma. A 14-year-old female patient presented an extensive left facial mass with a size of 7 × 5 × 4 cm, located between the teeth 33 and 37 in the mandible region. It has begun to grow 3 months after a local trauma. Imaging studies were suggestive of a soft-tissue lesion, with minimal bone changes and maintaining the integrity of the mandibular canal and mental foramen. Histopathological tests showed spindle cells with undulated and hyperchromatic nuclei, and sparse cytoplasm in a stroma composed of dense fibrous connective tissue. Immunohistochemistry revealed positive expression for the proteins S-100 and vimentin, confirming the diagnosis of neurofibroma. The patient underwent surgical removal of the lesion by intraoral approach and evolved with an excellent cosmetic result and no signs of recurrence after 2 years of follow up. We report a rare case of solitary giant neurofibroma whose etiology was related to a local trauma. To our knowledge, this is the first report of a mental nerve neurofibroma. Although the etiology remains unclear, we suggest the investigation of local trauma as a possible etiologic factor for solitary neurofibromas of the jaw.

Surgical experience of intratemporal facial nerve neurofibromas

Conclusions: The first presentation of intratemporal facial neurofibromas was variable, with facial palsy most common. The tumors often involve two or more segments of facial nerve. Outcomes of the tumors were closely related to nerve integrity, preoperative facial nerve function level, and follow-up period. Objective: The aim of this study was to present surgical experience of 11 cases with intratemporal facial neurofibroma. Methods: Clinical data of the 11 cases with the tumors was retrospectively collected and analyzed. They were followed up for 37.9 ± 1.7 months, range 13–59 months, except for one case that was only followed up for 5 months and was excluded from the analysis of outcomes. Results: Facial palsy was the first presentation in 10 cases, with repetitive facial palsy and vertigo in 1 case; 6 cases (54.5%) were insidious and 5 (45.5%) were sudden in terms of onset. Ear pain around the onset of facial palsy was found in four cases (36.4%). The tumor involved more than one segment in six cases. Among the non-grafted cases one patient with grade V facial nerve function recovered to grade III and another patient with grade VI facial nerve function recovered to grade IV, whereas only one case with grade VI recovered to grade IV among the grafted cases.

Diagnosis of neurofibromatosis type 1 after resection of intercostal nerve neurofibroma

We report a case of a 37-year-old man with an asymptomatic extraparenchymal mass in the left hemithorax. Complete surgical removal of the tumour was achieved through a minithoracotomy and histological analysis confirmed the diagnosis of myxoid neurofibroma. Given this histological diagnosis, the patient was re-examined and many café au lait spots (more than 6, larger than 15 mm in diameter) and neurofibromas (elastic tissue) were observed and the patient was diagnosed with neurofibromatosis (NF) type 1 (von Recklinghausen’s disease). We have found only eight case reports of neurogenic tumours originating from an intercostal nerve; only two of these corresponded to neurofibromas. Among these two patients, only one was a case of NF type 1 and, in contrast to our case, the diagnosis was reached prior to surgery. We present a very rare case of intercostal nerve neurofibroma leading to a definitive diagnosis of NF type 1.

Diagnosis of neurofibromatosis type 1 after resection of intercostal nerve neurofibroma

We report a case of a 37-year-old man with an asymptomatic extraparenchymal mass in the left hemithorax. Complete surgical removal of the tumour was achieved through a minithoracotomy and histological analysis confirmed the diagnosis of myxoid neurofibroma. Given this histological diagnosis, the patient was re-examined and many café au lait spots (more than 6, larger than 15 mm in diameter) and neurofibromas (elastic tissue) were observed and the patient was diagnosed with neurofibromatosis (NF) type 1 (von Recklinghausen’s disease). We have found only eight case reports of neurogenic tumours originating from an intercostal nerve; only two of these corresponded to neurofibromas. Among these two patients, only one was a case of NF type 1 and, in contrast to our case, the diagnosis was reached prior to surgery. We present a very rare case of intercostal nerve neurofibroma leading to a definitive diagnosis of NF type 1.

Vidian Nerve Neurofibroma Removed via a Transpterygoid Approach

Lesions originating in the vidian canal are extremely rare. Most frequently, they are extensions from contiguous carcinomas. We present a rare case of a vidian nerve neurofibroma and discuss its surgical management. A 62-year-old woman with a history of a basal cell skin cancer was evaluated for bilateral tinnitus. Imaging revealed a left-sided lesion at the medial aspect of the pterygoid process base, over the vidian canal. Under image-guidance, an endonasal endoscopic transpterygoid approach was performed. The histopathological examination supported the diagnosis of neurofibroma. Benign nerve sheath tumors of the vidian nerve should be considered in the differential diagnosis of a vidian canal lesion. Given the propensity of more aggressive tumors, a tissue diagnosis should be warranted in order to coordinate appropriate subsequent treatment. The expanded endonasal transpterygoid approach offers a safe, less invasive, and effective route to perform the excisional biopsy of such a lesion.