DOCSLIB.ORG

An Intraventricular Schwannoma with Associated Hydrocephalus and Ventricular Entrapment: Acasereport

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
An Intraventricular Schwannoma with Associated Hydrocephalus and Ventricular Entrapment: Acasereport THIEME e32 Case Report An Intraventricular Schwannoma with Associated Hydrocephalus and Ventricular Entrapment: ACaseReport Sheilah M. Curran-Melendez1 Melanie Fukui1 William Bivin2 David Oliver-Smith3 1 Department of Radiology, Allegheny Health Network, Address for correspondence Sheilah M. Curran-Melendez, MD, Pittsburgh, Pennsylvania, United States Department of Radiology, Allegheny Health Network, 320 E 2 Department of Pathology, Allegheny Health Network, North Avenue, Pittsburgh, PA 15212, United States Pittsburgh, Pennsylvania, United States (e-mail: [email protected]). 3 Department of Neurosurgery, Allegheny Health Network, Pittsburgh, Pennsylvania, United States J Neurol Surg Rep 2015;76:e32–e36. Abstract Intraventricular schwannomas are rare primary brain tumors, with fewer than 25 cases reportedintheliterature.Here,wepresentthecaseofa20-year-oldmalepatientwitha 2 year history of blurry vision and dysesthesia involving his right occiput and upper neck. Keywords Imaging demonstrated a homogeneously enhancing mass located within the atrium of ► ventricles the right lateral ventricle with associated right lateral ventricular entrapment. Pathology ► brain confirmed the tumor to be an intraventricular schwannoma. Imaging findings, presen- ► schwannoma tation, complications, and treatment options for intraventricular schwannomas are ► hydrocephalus described. Case Presentation temporal horn intraventricular mass, with surrounding white matter edema and dilation of the right lateral ventricle. A 20-year-old male patient without significant medical his- Subsequent evaluation with an enhanced magnetic resonance tory presented to an urgent care facility for the evaluation of imaging (MRI) of the head included T2, T2Ã, fluid-attenuated intermittent blurry vision which had been present for ap- inversion recovery, diffusion-weighted, and T1-unenhanced proximately 2 years. The patient additionally complained of images in the axial plane. Unenhanced T1-weighted images dysesthesia: a burning sensation, located at the upper neck were acquired in the sagittal plane, as well as enhanced and right occiput, intermittent in occurrence and lasting only T1-weighted images in the axial, coronal, and sagittal planes. a few seconds, but increasing in intensity and severity over In aggregate, these images showed a 2.1  1.9  2.6 cm the previous 2 months. (transverse  anterior-posterior  superior-inferior) mass, Physical examination found the patient to be awake, alert, located within the atrium of the right lateral ventricle. The and oriented. Pupils were equal, round, and reactive to light mass demonstrated mild T1 hypointensity (►Fig. 1A)with and accommodation. A fundoscopic examination was not areas of heterogeneous T2 hyperintensity (►Fig. 2A). performed. Cranial nerves II–XII were intact; specifically, Foci of susceptibility artifact within the mass (►Fig. 3) extraocular motion was intact. Reflexes and range of motion were suggestive of calcification or hemosiderin deposition were normal, and the strength of the bilateral upper and from previous hemorrhage. Postcontrast images displayed lower extremities was 5/5. Sensation, proprioception, muscle homogeneous enhancement (►Fig. 1B, C). Within the white tone, and gait were intact. matter of the surrounding right parietal and inferior right Initial radiologic evaluation included an unenhanced com- temporal lobes, there was a large amount of edema puted tomography (CT) scan of the head which showed a right (►Fig. 2A). Asymmetric enlargement of the right lateral received DOI http://dx.doi.org/ © 2015 Georg Thieme Verlag KG June 23, 2013 10.1055/s-0034-1395493. Stuttgart · New York accepted after revision ISSN 2193-6366. August 6, 2014 published online January 16, 2015 Intraventricular Schwannoma Curran-Melendez et al. e33 Fig. 1. T1-weighted magnetic resonance imaging of the brain before (A) and after (B, C) the administration of gadolinium-based contrast demonstrate a midly T1 hypointense, avidly enhancing mass within the right lateral ventricle. Fig. 2 . T2-weighted magnetic resonance imaging of the brain demonstrate a heterogeneously hyperintense mass within the right lateral ventricle. Enlargement of the posterior horn of the right lateral ventricle with surrounding white matter edema is consistent with ventricular entrapment. ventricle (►Fig. 2B), particularly at the level of the right adherent to the medial aspect of the right lateral ventricle temporal horn, was suggestive of ventricular entrapment. wall. Areas of moderate calcification were noted. The third and fourth ventricles were normal in size. The Pathologic evaluation demonstrated densely packed fas- primary radiographic consideration was a meningioma, al- cicles of spindle cells with elongated nuclei representing though ependymoma and choroid plexus papilloma were in Antoni A tissue (►Fig. 4). These were mixed with areas of the differential. loosely packed, hypocellular foci of spindle cells with small, The patient underwent surgical resection of the tumor round nuclei within myxoid matrix. This was consistent with through a right parietal craniotomy, with a transparietal Antoni B tissue (►Fig. 5). approach, and intraventricular shunt placement for treat- Positive S-100 staining confirmed the Schwann cell origin ment of associated ventricular entrapment. Gross examina- of the tumor while the negative epithelial membrane antigen tion demonstrated the tumor to be well encapsulated and confirmed that the tumor was not meningeal in origin. Glial Journal of Neurological Surgery Reports Vol. 76 No. R1/2015 e34 Intraventricular Schwannoma Curran-Melendez et al. Fig. 5 Hematoxylin-eosin staining viewed at Â200 magnification demonstrates a loosely packed, hypocellular focus of spindle cells with small, round nuclei in a myxoid matrix (Antoni B). à Fig. 3 T2 -weighted magnetic resonance imaging of the brain 2 demonstrates susceptibility artifact within the mass, representing foci located in the region of the cerebellopontine angle. They of calcification. have also been associated with spinal nerve roots and have been found in the retroperitoneum and mediastinum. Rarely, schwannomas have been noted to arise from intracranial locations, a subset of which have been described as intraven- tricular in location. The earliest reported case of an intraventricular schwan- noma was described by Marchand et al in 1957.3 Since then 23 cases have been reported in the literature (►Table 1). Among these cases there is almost a 2:1 male-to-female predominance. The median age of presentation is 31 years, with a reported age range of 7 to 78 years. Overall, 21 of the reportedcaseswerebenigninetiologywithonly2reported cases demonstrating malignant features.3,4 These lesions are most often located within the lateral ventricles (70%) but have also been found in the fourth (26%) and third (4%) ventricles. The most common complication associated with intraventricular schwannoma is the presence of hydrocephalus. Fig. 4 Hematoxylin-eosin staining viewed at Â200 magnification The clinical presentation of an intraventricular schwan- demonstrates densely packed fascicles of spindle cells with elongated noma often varies but most commonly involves headache, nuclei (Antoni A). nausea, and vomiting. Brachial-crural hemiparesis, seizures, vertigo, and visual symptoms such as homonymous hema- nopsia and transient scintillating scotomas have also been fibrillary acidic protein was also positive, a marker which may reported. These lesions may also be asymptomatic and only be variably positive in schwannomas, but which is often detected incidentally, through papilledema or retinal hemor- positive in intracranial schwannomas. MIB-1 stain demon- rhage seen on an ophthalmic screening examination. strated low nuclear positivity, consistent with a benign Currently, the etiology of intraventricular schwannomas process. is unknown, although three theories are often mentioned The patient is currently 9 months out from surgical resec- in the literature. The most popular theory postulates that tion of the tumor without radiographic evidence of residual intraventricular schwannomas are the result of hyper- or recurrent tumor. plastic transformation of Schwann cells associated with peripheral or autonomic nerve fibers located within the 5 fi Discussion choroid plexus. This theory is supported by the identi - cation of peripheral nerve fibers within the choroid plexus Schwannomas account for 8% of all primary brain tumors.1 of the fourth ventricle.6 Another theory is neoplastic trans- Most schwannomas are associated with cranial nerves, most formation of ectopic neural crest cells located within the commonly cranial nerves VIII, V, and VII, and 80 to 90% are ventricles due to disorganized embryogenesis,7,8 atheory Journal of Neurological Surgery Reports Vol. 76 No. R1/2015 Intraventricular Schwannoma Curran-Melendez et al. e35 Table 1 Reported cases of intraventricular schwannoma Age (y) Gender Location Benign/malignant Year Citation 44 Male Lateral (occipital) Benign 1990 Ost et al5 21 Male Lateral (temporal) Benign 1975 Van Rensburg12 63 Female Lateral Benign 1975 Ghatak13 8 Male Lateral Benign 1988 Pimentel et al14 40 Male Lateral (temporal) Malignant 1995 Jung et al4 15 Male Lateral Benign 1965 David et al15 7 Male Fourth Benign 1990 Redekop et al16 16 Male Lateral (trigone) Benign 2004 Dow et al7 15 Male Lateral (occipital) Benign 2008 Benedict et al11 21 Male Lateral Benign 2003 Erdogan et al17 21 Female Third Benign 2006 Messing-Jünger et al18 71 Female Fourth Benign 2009 Oertel
Load more

Recommended publications
  • Neurofibromatosis Type 2 (NF2)
    International Journal of Molecular Sciences Review Neurofibromatosis Type 2 (NF2) and the Implications for Vestibular Schwannoma and Meningioma Pathogenesis Suha Bachir 1,† , Sanjit Shah 2,† , Scott Shapiro 3,†, Abigail Koehler 4, Abdelkader Mahammedi 5 , Ravi N. Samy 3, Mario Zuccarello 2, Elizabeth Schorry 1 and Soma Sengupta 4,* 1 Department of Genetics, Cincinnati Children’s Hospital, Cincinnati, OH 45229, USA; [email protected] (S.B.); [email protected] (E.S.) 2 Department of Neurosurgery, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] (S.S.); [email protected] (M.Z.) 3 Department of Otolaryngology, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] (S.S.); [email protected] (R.N.S.) 4 Department of Neurology, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] 5 Department of Radiology, University of Cincinnati, Cincinnati, OH 45267, USA; [email protected] * Correspondence: [email protected] † These authors contributed equally. Abstract: Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the NF2 gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression.
    [Show full text]
  • Information About Mosaic Neurofibromatosis Type 2 (NF2)
    Information about mosaic Neurofibromatosis type 2 (NF2) NF2 occurs because of a mutation (change) in the NF2 gene. When this change is present at the time of conception the changed gene will be present in all the cells of the baby. When this mutation occurs later in the development of the forming embryo, the baby will go on to have a mix of cells: some with the “normal” genetic information and some with the changed information. This mix of cells is called mosaicism. Approximately half the people who have a diagnosis of NF2 have inherited the misprinted NF2 gene change from their mother or father who will also have NF2. They will have that misprinted gene in all the cells of their body. When they have their children, there will be a 1 in 2 chance of passing on NF2 to each child they have. However about half of people with NF2 are the first person in the family to be affected. They have no family history and have not inherited the condition from a parent. When doctors studied this group of patients more closely they noticed certain characteristics. Significantly they observed that fewer children had inherited NF2 than expected some people in this group had relatively mild NF2 NF2 tumours in some patients tended to grow on one side of their body rather than both sides that when a blood sample was tested to identify the NF2 gene, the gene change could not be found in 30-40% of people This lead researchers to conclude that this group of people were most likely to be mosaic for NF2 i.e.
    [Show full text]
  • Simultaneous Neurofibroma and Schwannoma of the Sciatic Nerve
    Simultaneous Neurofibroma and Schwannoma of the Sciatic Nerve 1 4 1 1 2 3 1 S. A. Sintzoff, Jr.,I.5 W . 0. Bank, · P. A. Gevenois, C. Matos, J. Noterman, J. Flament-Durand, and J. Struyven Summary: The authors report a case of simultaneously occur­ MR imaging was performed on a 0.5-T system (Gyro­ ring neurofibroma and schwannoma of the sciatic nerve and scan T5, Philips Medical Systems, Eindhoven, The Neth­ discuss the complementary aspects of MR and OS. The Schwan­ erlands) using a wrap-around knee surface coil in order to norna was well-defined and showed distal enhancement on better define the relationships between the tumors and the sonographic evaluation, whereas the neurofibroma was ill-de­ nerve. Each tumor was isointense to the normal nerve on fined; both tumors were hypoechoic. Tl- and T2-weighted MR T1-weighted images and hyperintense to it on proton Images revealed similar signal characteristics of the two tumors, density and T2-weighted images (Fig. 2A-2C). After intra­ but Intense enhancement following administration of gadolin­ venous gadolinium-DTPA injection, the distal mass showed ium-DTPA distinguished the schwannoma from the neurofi­ intense enhancement, conserving a thin hypointense border broma. (Fig. 2D). Physical and neurologic examination, MR of the central nervous system and skeletal radiographs failed to Index terms: Nerves, sciatic; Neuroma; Schwannoma demonstrate any additional lesions, permitting the reason­ able exclusion of neurofibromatosis types 1 and 2. Schwannomas and neurofibromas are com­ Surgical exposure demonstrated the two tumors on the external popliteal nerve (Fig. 3). The distal tumor could be (1, mon peripheral nerve neoplasms 2).
    [Show full text]
  • Central Nervous System Tumors General ~1% of Tumors in Adults, but ~25% of Malignancies in Children (Only 2Nd to Leukemia)
    Last updated: 3/4/2021 Prepared by Kurt Schaberg Central Nervous System Tumors General ~1% of tumors in adults, but ~25% of malignancies in children (only 2nd to leukemia). Significant increase in incidence in primary brain tumors in elderly. Metastases to the brain far outnumber primary CNS tumors→ multiple cerebral tumors. One can develop a very good DDX by just location, age, and imaging. Differential Diagnosis by clinical information: Location Pediatric/Young Adult Older Adult Cerebral/ Ganglioglioma, DNET, PXA, Glioblastoma Multiforme (GBM) Supratentorial Ependymoma, AT/RT Infiltrating Astrocytoma (grades II-III), CNS Embryonal Neoplasms Oligodendroglioma, Metastases, Lymphoma, Infection Cerebellar/ PA, Medulloblastoma, Ependymoma, Metastases, Hemangioblastoma, Infratentorial/ Choroid plexus papilloma, AT/RT Choroid plexus papilloma, Subependymoma Fourth ventricle Brainstem PA, DMG Astrocytoma, Glioblastoma, DMG, Metastases Spinal cord Ependymoma, PA, DMG, MPE, Drop Ependymoma, Astrocytoma, DMG, MPE (filum), (intramedullary) metastases Paraganglioma (filum), Spinal cord Meningioma, Schwannoma, Schwannoma, Meningioma, (extramedullary) Metastases, Melanocytoma/melanoma Melanocytoma/melanoma, MPNST Spinal cord Bone tumor, Meningioma, Abscess, Herniated disk, Lymphoma, Abscess, (extradural) Vascular malformation, Metastases, Extra-axial/Dural/ Leukemia/lymphoma, Ewing Sarcoma, Meningioma, SFT, Metastases, Lymphoma, Leptomeningeal Rhabdomyosarcoma, Disseminated medulloblastoma, DLGNT, Sellar/infundibular Pituitary adenoma, Pituitary adenoma,
    [Show full text]
  • A Case of Cerebral Astroblastoma with Rhabdoid Features : a Cytological, Histological, and Immunohistochemical Study
    Title A case of cerebral astroblastoma with rhabdoid features : a cytological, histological, and immunohistochemical study Yuzawa, Sayaka; Nishihara, Hiroshi; Tanino, Mishie; Kimura, Taichi; Moriya, Jun; Kamoshima, Yuuta; Nagashima, Author(s) Kazuo; Tanaka, Shinya Brain tumor pathology, 33(1), 63-70 Citation https://doi.org/10.1007/s10014-015-0241-5 Issue Date 2016-01 Doc URL http://hdl.handle.net/2115/63975 Rights The final publication is available at link.springer.com Type article (author version) File Information Astroblastoma_yuzawa_HUSCAP.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Case report A case of cerebral astroblastoma with rhabdoid features: a cytological, histological, and immunohistochemical study Sayaka Yuzawa1, Hiroshi Nishihara2, 3, Mishie Tanino1, Taichi Kimura2, 3, Jun Moriya1, Yuuta Kamoshima4, 5, Kazuo Nagashima6, and Shinya Tanaka1, 2. 1Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan. 2Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 3Translational Research Laboratory, Hokkaido University Hospital, Clinical Research and Medical Innovation Center, Sapporo, Japan. 4Sapporo Azabu Neurosurgical Hospital, Sapporo, Japan. 5Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 6Higashi Tokushukai Hospital, Sapporo, Japan. Correspondence: Shinya Tanaka Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan. Tel: +81-11-706-5053 Fax: +81-11-706-5902 E-mail: [email protected] 1 Abstract Astroblastoma is a rare neuroepithelial neoplasm of unknown origin, usually occurring in children and young adults. Here we report a case of astroblastoma with uncommon features in an 18-year-old female.
    [Show full text]
  • Multiple Inherited Schwannomas, Meningiomas, and Ependymomas Syndrome in an Adult Patient
    Published online: 2021-05-23 Practitioner Section Multiple Inherited Schwannomas, Meningiomas, and Ependymomas Syndrome in an Adult Patient Abstract Vijay Parshuram Neurofibromatosis type 2 (NF2) is also known as multiple inherited schwannomas, meningiomas, Raturi, and ependymomas (MISME) syndrome. Mutation in NF2 gene is the cause for MISME syndrome. Rahul Singh We are reporting here a case of MISME syndrome with triple tumor in a 30‑year‑old male patient Department of Radiotherapy, who presented with the chief complaints of spastic paraparesis, bowel and bladder incontinence, and King George Medical decreased vision in the right eye. University, Lucknow, Uttar Pradesh, India Keywords: Ependymoma, meningioma, multiple inherited schwannomas, and neurofibromatosis Introduction system shows tone to be normal in the upper limb and power grade 5/5 in the bilateral Neurofibromatosis type 2 (NF2) incidence is upper limb. Tone reduced in bilateral 1 in 33,000 and prevalence is 1 in 60,000.[1,2] lower limbs. Deep tendon reflex was It has no predilection for sex, race, and absent in bilateral lower limbs. Pure‑tone ethnicity, and it is most commonly seen in audiometry showed bilateral sensory neural the second and third decades of life that too deafness, which was more on the right side. most commonly between 16 and 24 years Ophthalmic evaluation was done and was of age.[3] Approximately 50% of cases are suggestive of macular corneal opacity of familial and remaining 50% are sporadic in the left eye and central serous retinopathy nature.[4] NF2 is caused by the mutation in with nystagmus in the right eye. MRI merlin gene, which is located on the long brain with contrast showed a well‑defined arm of chromosome 22 (22q12.2).[5] The enhancing extra‑axial space‑occupying hallmark for the diagnosis of NF2 is bilateral lesion (SOL) at left cerebellopontine (CP) vestibular schwannomas on magnetic angle largest measuring 1.4 cm × 1.2 cm.
    [Show full text]
  • Hemorrhagic Vestibular Schwannoma: an Unusual Clinical Entity Case Report
    Neurosurg Focus 5 (3):Article 9, 1998 Hemorrhagic vestibular schwannoma: an unusual clinical entity Case report Dean Chou, M.D., Prakash Sampath, M.D., and Henry Brem, M.D. Departments of Neurological Surgery and Neuro-Oncology, The Johns Hopkins Hospital, Baltimore, Maryland Hemorrhagic vestibular schwannomas are rare entities, with only a few case reports in the literature during the last 25 years. The authors review the literature on vestibular schwannoma hemorrhage and the presenting symptoms of this entity, which include headache, nausea, vomiting, sudden cranial nerve dysfunction, and ataxia. A very unusual case is presented of a 36-year-old man, who unlike most of the patients reported in the literature, had clinically silent vestibular schwannoma hemorrhage. The authors also discuss the management issues involved in more than 1000 vestibular schwannomas treated at their institution during a 25-year period. Key Words * acoustic tumor * schwannoma * neuroma * hemorrhage * hemorrhagic vestibular tumor Vestibular schwannomas are the most common tumors found in the cerebellopontine angle (CPA), comprising approximately 80% of all tumors arising in this region. They are usually slow-growing, benign tumors that manifest clinically by directly compressing the neural elements traversing the CPA, including the pons, cerebellum, and the lower cranial nerves. Hemorrhage into a vestibular schwannoma is rare and has been shown to present with acute neurological changes and deterioration. We review the literature on the presenting symptoms of hemorrhagic vestibular schwannomas and describe the case of a man with a large hemorrhagic vestibular schwannoma who presented with signs and symptoms of a slow-growing, insidious compressive lesion. In doing so, we hope to shed light on this unusual clinical entity and discuss management issues.
    [Show full text]
  • Cervical Intramedullary Schwannoma with Syrinx: Case Report and Review of the Literature
    THIEME Case Report 239 Cervical Intramedullary Schwannoma with Syrinx: Case Report and Review of the Literature Abdulaziz AlQarni1 A. AlArifi1 Ali H. Alassiri1 Amjed Kouli1 M. T. Abbas1 1Department of Neurosurgery, King Abdulaziz Medical City, Address for correspondence Abdulaziz AlQarni, MBBS, Department Saudi Arabia, Riyadh of Surgery, King Abdulaziz Medical City, Ministry of National Guard, P.O. Box: 22490, Riyadh 11426, Saudi Arabia, Riyadh (e-mail: [email protected]). Indian J Neurosurg 2018;7:239–248 Abstract Schwannoma is a nerve sheath tumor originating from the Schwann cell. It is be- nign in nature and it arises from anywhere where Schwann cells can be found. It is rarely found in the parenchyma of the spinal cord. Intramedullary schwannomas (or neurilemmomas) without evidence of neurofibromatosis are rare spinal cord tumors. Intramedullary schwannoma was first reported in 1932 by Penfield. Our patient pre- sented with neck pain, gradually worsening, weakness in the right upper and lower limbs, numbness in both shoulders, and a decrease in the grasping strength of both hands over a 4-year period. A magnetic resonance imaging of the spine showed a heterogeneously enhancing mass in the cervical spinal cord extending from the C2 to T1 levels with associated hemorrhagic changes. Histologically, the tumor was found Keywords to be composed of bland spindle cells with blunt-ended and sometimes wavy nuclei ► intramedullary admixed with hyalinized vasculature. Surrounding reactive spinal cord parenchyma schwannomas with frequent Rosenthal fibers was also observed. Focal Verocay bodies were evident, ► syrinx and with immunohistochemistry, there was diffuse and strong positivity for S100, ► spinal cord tumor which is confirmatory for the diagnosis of schwannoma.
    [Show full text]
  • Current Understanding of Neurofibromatosis Type 1, 2, And
    International Journal of Molecular Sciences Review Current Understanding of Neurofibromatosis Type 1, 2, and Schwannomatosis Ryota Tamura Department of Neurosurgery, Kawasaki Municipal Hospital, Shinkawadori, Kanagawa, Kawasaki-ku 210-0013, Japan; [email protected] Abstract: Neurofibromatosis (NF) is a neurocutaneous syndrome characterized by the development of tumors of the central or peripheral nervous system including the brain, spinal cord, organs, skin, and bones. There are three types of NF: NF1 accounting for 96% of all cases, NF2 in 3%, and schwannomatosis (SWN) in <1%. The NF1 gene is located on chromosome 17q11.2, which encodes for a tumor suppressor protein, neurofibromin, that functions as a negative regulator of Ras/MAPK and PI3K/mTOR signaling pathways. The NF2 gene is identified on chromosome 22q12, which encodes for merlin, a tumor suppressor protein related to ezrin-radixin-moesin that modulates the activity of PI3K/AKT, Raf/MEK/ERK, and mTOR signaling pathways. In contrast, molecular insights on the different forms of SWN remain unclear. Inactivating mutations in the tumor suppressor genes SMARCB1 and LZTR1 are considered responsible for a majority of cases. Recently, treatment strategies to target specific genetic or molecular events involved in their tumorigenesis are developed. This study discusses molecular pathways and related targeted therapies for NF1, NF2, and SWN and reviews recent clinical trials which involve NF patients. Keywords: neurofibromatosis type 1; neurofibromatosis type 2; schwannomatosis; molecular tar- geted therapy; clinical trial Citation: Tamura, R. Current Understanding of Neurofibromatosis Int. Type 1, 2, and Schwannomatosis. 1. Introduction J. Mol. Sci. 2021, 22, 5850. https:// doi.org/10.3390/ijms22115850 Neurofibromatosis (NF) is a genetic disorder that causes multiple tumors on nerve tissues, including brain, spinal cord, and peripheral nerves [1–3].
    [Show full text]
  • Genetic Testing for Neurofibromatosis and Related Disorders
    Corporate Medical Policy Genetic Testing for Neurofibromatosis and Related Disorders AHS – M2134 File Name: genetic_testing_for_neurofibromatosis_and_related_disorders Origination: 01/2019 Last CAPReview: 07/2021 Next CAP Review: 07/2022 Last Review: 07/2021 Description of Procedure or Service Neurofibromatoses are a group of three clinically and genetically distinct disorders that cause tumors to form on nerve tissue. Neurofibromatosis type 1 (NF1) is caused by autosomal dominant mutations in the neurofibromin (NF1) gene and is characterized by multiple café-au-lait macules and neurofibromas (Korf, 2021). Neurofibromatosis type (NF2) is caused by autosomal dominant mutations in the merlin, also known as schwannomin, (NF2) gene, and is characterized by multiple tumors of the nervous system, including the more common bilateral vestibular schwannomas as well as intracranial and spinal meningiomas, intrinsic ependymomas, and other spine tumors (Evans, 2020). Schwannomatosis is caused by inactivating mutations in SMARCB1 and LZTR and is characterized by multiple schwannomas and pain arising in adulthood (Yohay & Bergner, 2019). Legius syndrome is an NF1-like disorder caused by autosomal dominant mutations in the sprout-related EVH1 [enabled/vasodilator-stimulated phosphoprotein homology 1] domain-containing protein 1 (SPRED1) gene, resulting in café-au-lait macules. Constitutional mismatch repair-deficiency syndrome (CMMR-D), caused by mutations in mismatch repair genes, can also result in café-au-lait macules, axillary freckling, and Lisch nodules similar to NF1; however, unlike NF1, CMMR-D can also result in a variety of different malignancies, including glioblastoma and colorectal cancer (Korf, 2021). Related Policies Prenatal Screening AHS-G2035 ***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician.
    [Show full text]
  • Use of Calretinin, CD56, and CD34 for Differential Diagnosis of Schwannoma and Neurofibroma
    The Korean Journal of Pathology 2011; 45: 30-35 DOI: 10.4132/KoreanJPathol.2011.45.1.30 Use of Calretinin, CD56, and CD34 for Differential Diagnosis of Schwannoma and Neurofibroma Ji Young Park ∙ Hoon Park1 Background: It is important to differentiate between schwannomas and neurofibromas for the Nam Jo Park ∙ June Sik Park2 cases in which the histopathologic features overlap. Depending on the tumor type, surgeons can Hyun-Jung Sung3 ∙ Sang Sook Lee decide on a treatment method and whether to preserve or sacrifice the nerve; the possibility of malignant transformation in the case of neurofibromas also needs to be considered. Methods: We studied 101 cases of schwannoma and 103 cases of neurofibroma. All the hematoxylin and Department of Pathology, Keimyung University School of Medicine, Daegu; 1Department of eosin slides for these cases were reviewed, and tissue microarrays were prepared from the repre- Otolaryngology, Korea Cancer Center Hospital, sentative areas. Immunohistochemical analysis was performed using antibodies for S-100 pro- Seoul; 2Department of Otolaryngology, tein, calretinin, CD56 and CD34. Results: All the tumors except 3 neurofibromas were positive for Kyungpook National University School of the S-100 protein. Calretinin was found in 26.7% of the schwannomas (27/101), but it was not Medicine; 3Department of Pathology, Catholic found in any of the neurofibromas. CD56 was positive in 77.2% of the schwannomas (78/101) University of Daegu School of Medicine, Daegu, and in 9.8% of the neurofibromas (10/102). CD34 was positive in 42.5% of the schwannomas Korea (43/101) and in 80.2% of the neurofibromas (81/101).
    [Show full text]
  • Supraclavicular Solitary Hybrid Schwannoma/Neurofibroma: a Case Report
    Open Access Case Report DOI: 10.7759/cureus.8531 Supraclavicular Solitary Hybrid Schwannoma/Neurofibroma: A Case Report Alanoud Alomair 1 , Mohammad Dababo 2 , Suresh Velagapudi 1 1. Otolaryngology, King Faisal Specialist Hospital and Research Centre, Riyadh, SAU 2. Anatomic Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, SAU Corresponding author: Alanoud Alomair, [email protected] Abstract Peripheral nerve sheath tumors (PNSTs) are benign lesions arising from the connective tissue sheath surrounding the neurons and are labeled schwannoma, perineurioma, or neurofibroma according to their histopathological characteristics. Lesions with a mixture of two or more of the aforementioned tumors are known as hybrid peripheral nerve sheath tumors (HPNSTs). These hybrid tumors have been described as rare entities. In this report, we present a case of a solitary hybrid schwannoma/neurofibroma in an unusual location. Categories: Otolaryngology, Pathology, Neurosurgery Keywords: schwannoma, neurofibroma, hybrid Introduction Peripheral nerve sheath tumors (PNST) are benign lesions arising from the connective tissue sheath surrounding the neurons. Most of these tumors present as focal soft tissue swelling with symptoms attributable to mass effect to adjacent structures. Diagnostic classifications based on the histopathology of PNST have been published previously [1]. The most common of these are schwannoma, perineurioma, and neurofibroma. A lesion with histopathological evidence of a nerve sheath tumor not specific to one of the aforementioned tumors is classified as a hybrid peripheral nerve sheath tumor (HPNST). These tumors are a benign combination with shared characteristics of the previously mentioned tumors. HPNSTs were officially introduced in the fourth edition of the World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone published in 2013, with the revised edition being released in 2016 [2,3].
    [Show full text]