DOCSLIB.ORG

Optic Nerve Glioma in Mice Requires Astrocyte Nf1 Gene Inactivation and Nf1 Brain Heterozygosity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Optic Nerve Glioma in Mice Requires Astrocyte Nf1 Gene Inactivation and Nf1 Brain Heterozygosity [CANCER RESEARCH 63, 8573–8577, December 15, 2003] Advances in Brief Optic Nerve Glioma in Mice Requires Astrocyte Nf1 Gene Inactivation and Nf1 Brain Heterozygosity M. Livia Bajenaru,1 M. Rosario Hernandez,2 Arie Perry,3 Yuan Zhu,6 Luis F. Parada,6 Joel R. Garbow,4,5 and David H. Gutmann1 Departments of 1Neurology, 2Ophthalmology, 3Pathology, 4Radiology, and 5Chemistry, Washington University School of Medicine, St. Louis, Missouri, and 6Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas Abstract bryonic day 14 using Cre/LoxP technology (11). Glial fibrillary acidic protein (GFAP) Cre; Nf1flox/flox mice are viable and fertile and exhibit Whereas biallelic neurofibromatosis 1 (NF1) inactivation is observed in increased numbers of brain and optic nerve astrocytes, but they do not NF1-associated gliomas, astrocyte-restricted Nf1 conditional knockout develop gliomas. The absence of glioma formation in these mice, even mice do not develop gliomas. These observations suggest that NF1 glioma formation requires additional cellular or genetic conditions. To determine after 20 months of age, suggests that additional cellular or genetic the effect of an Nf1 heterozygous brain environment on NF1 glioma events are necessary for glioma tumorigenesis in the setting of NF1. -formation, we generated Nf1؉/؊ mice lacking Nf1 expression in astro- Because patients with NF1 are heterozygous for a germ-line inacti cytes. In contrast to astrocyte-restricted Nf1 conditional knockout mice, vating NF1 mutation, and Nf1 mutant mice develop neurofibroma, Nf1؉/؊ mice lacking Nf1 in astrocytes develop optic nerve gliomas. This another NF1-associated nervous system tumor, only in the setting of mouse model demonstrates that Nf1؉/؊ cells contribute to the pathogen- constitutional Nf1 heterozygosity (12), we generated Nf1ϩ/Ϫ mice esis of gliomas in NF1 and provides a tool for the preclinical evaluation of lacking Nf1 expression in astrocytes. In this report, we describe this potential therapeutic interventions for these tumors. unique model of NF1-associated optic nerve glioma, in which Nf1ϩ/Ϫ mice with conditional Nf1 inactivation in astrocytes develop Introduction low-grade optic nerve and chiasm astrocytomas. Low-grade astrocytomas (gliomas) are common central nervous system tumors affecting children (1). Children with the inherited Materials and Methods tumor predisposition syndrome neurofibromatosis 1 (NF1) are prone Transgenic Mice. Nf1ϩ/Ϫ mice (10) were bred with Nf1flox/flox mice (13) to the development of WHO grade I pilocytic astrocytomas (PAs), to produce Nf1flox/mut mice, which were subsequently crossed with GFAPCre; which predominantly involve the optic nerve and chiasm (2). Al- Nf1flox/flox mice (11) to generate GFAPCre; Nf1flox/mut mice. Optic nerves and though these tumors are low-grade neoplasms, they can demonstrate brains from 8–12-month-old GFAPCre; Nf1flox/mut mice (n ϭ 12) and 8–18- aggressive biological features, diffusely infiltrate the optic pathway month-old GFAPCre; Nf1flox/flox mice (n ϭ 20) were analyzed. We used and neighboring hypothalamus, and culminate in visual loss and control mice of genotypes Nf1flox/flox, Nf1flox/mut, and Nf1ϩ/Ϫ at 8–12 months precocious puberty (2). Previous studies have shown that NF1-asso- of age (n ϭ 10). ciated optic pathway gliomas involve biallelic inactivation of the NF1 Histopathology and Immunohistochemistry. Control and mutant mice gene, whereas histologically similar sporadic PAs do not exhibit NF1 were perfused transcardially with 4% paraformaldehyde in 0.1 M sodium loss (3–6). In addition, PAs do not harbor genetic changes typical of phosphate buffer (pH 7.4). Eyes, optic nerves, optic chiasms, and brains were diffuse fibrillary astrocytomas, such as inactivation of CDKN2A, dissected and postfixed in 4% paraformaldehyde overnight at 4°C before TP53, or PTEN/MMAC1 or amplification of CDK4 or the epidermal examination for gross anatomical changes and photography with a digital camera (Optronics) attached to a dissection microscope (Nikon). All specimens growth factor receptor gene (7). were then processed for paraffin embedding and sectioning in the Pharmacol- Current animal models of astrocytoma have focused on oncogenic ogy Histology Core or Ophthalmology Histology Core at Washington Univer- events (e.g., constitutive RAS activation) or on combinatorial inacti- sity School of Medicine. vating events involving p53 (reviewed in Ref. 8). These mice develop Serial 4-␮m paraffin sections of the eyes and optic nerve heads, optic nerves high-grade gliomas, which are histologically and biologically distinct and chiasms, and brains were stained with H&E and examined under the from those observed in NF1 patients. Using an alternate approach, microscope for the presence of tumors or abnormal collections of cells by an heterozygous Nf1 mutant mice are cancer prone but do not develop experienced neuropathologist (A. P.). gliomas (9). Because mice lacking Nf1 expression do not survive Immunohistochemistry was performed on adjacent paraffin sections with rat embryonic development (9, 10), we developed a conditional knockout anti-GFAP (1:100; Zymed) and rabbit anti-Ki67 (1:1000; Novocastra) anti- mouse in which the Nf1 gene was inactivated in astrocytes by em- bodies. We used microwave antigen retrieval and detected the primary anti- bodies with biotinylated secondary antibodies, followed by amplification with peroxidase-conjugated avidin (Vectastain Elite ABC Kit; Vector Laboratories) Received 8/31/03; revised 10/10/03; accepted 10/17/03. and treatment with 3,3Ј-diaminobenzidine or Vector VIP substrate kits (Vector Grant support: NIH Grants NS36996 (to D. H. G.), F32-NS42428 (to M. L. B.), and 1 R24 CA83060; a grant from the Small Animal Imaging Resource Program (to J. R. G.); Laboratories), followed by counterstaining with hematoxylin or methyl green a grant from National Institutes of Neurological Disorders and Stroke (to L. F. P.); The (Vector Laboratories). Representative sections were photographed with a dig- United States Army Medical Research and Materiel Command’s Office of Congression- ital camera (Optronics) attached to an inverted microscope (Nikon). ally Directed Medical Research Programs Grant DAMD17-03-1-0215 (to D. H. G.), and a grant from The National Neurofibromatosis Foundation (to Y. Z.). Microglia cells were identified in optic nerve and chiasm sections by lectin The costs of publication of this article were defrayed in part by the payment of page histochemistry (14) using FITC-conjugated Bandeiraea (Griffonia) simplici- charges. This article must therefore be hereby marked advertisement in accordance with folia agglutinin isolectin-B4 (BSI-B4; Sigma). Briefly, optic nerve and chiasm 18 U.S.C. Section 1734 solely to indicate this fact. sections were deparaffinized and washed in PBS, followed by overnight Requests for reprints: David H. Gutmann, Department of Neurology, Box 8111, 660 ␮ South Euclid Avenue, St. Louis, Missouri 63110. Phone: (314) 362-7379; Fax: (314) 362- incubation at 4°C with FITC-conjugated BSI-B4 (10 g/ml) in PBS containing 2388; E-mail: [email protected]. 0.5% Triton X-100. After subsequent washes in PBS, fluorescence images 8573 Downloaded from cancerres.aacrjournals.org on September 26, 2021. © 2003 American Association for Cancer Research. OPTIC NERVE GLIOMA IN Nf1 MUTANT MICE were recorded by digital photomicrography (Spot Advanced; Diagnostic In- ities. Pathological examination of their brains failed to demonstrate struments, Sterling Heights, MI). astrocytoma (data not shown). These results suggest that Nf1 inacti- Proliferative indices were determined by counting the number of Ki67- vation, either alone or in combination with Nf1 heterozygosity, does labeled nuclei per 100 cell nuclei within the prechiasmatic optic nerves (areas not result in parenchymal brain tumor formation. ϫ 1 and 2) and the optic chiasm (area 3), using a 10-mm ocular grid at 400 Because gliomas in NF1 most typically involve the optic nerve, magnification. chiasm, and hypothalamus, we examined the optic nerves and chiasm Magnetic Resonance Imaging. Images were collected in an Oxford In- flox/mut ϭ struments 4.7-Tesla magnet (33 cm, clear bore) equipped with 15-cm inner in GFAPCre; Nf1 mice. All mice examined (n 12) demon- diameter, actively shielded gradient coils (maximum gradient, 18 G/cm; rise strated areas of gross optic nerve and/or chiasm enlargement, which flox/flox time, 100 ␮s). The magnet/gradients are interfaced with a Varian (Palo Alto, were not seen in either Nf1ϩ/Ϫ or GFAPCre; Nf1 mice. These CA) INOVA console, and data were collected using a 1.5-cm outer diameter gross abnormalities were seen in mice as early as 8 months of age, surface coil (receive) and a 9-cm inner diameter Helmholtz coil (transmit). although younger mice have not been systematically examined to Before the imaging experiments, the mice were anesthetized with isoflu- date. We observed multiple patterns of gross pathology, including rane/O2 [4% (v/v)], and they were maintained on isoflurane/O2 [1.5% (v/v)] unilateral as well as bilateral optic nerve enlargement, with and throughout the experiments. Diffusion tensor imaging data were acquired using without chiasmal involvement (Fig. 1). These patterns are highly a conventional spin-echo imaging sequence, modified by the addition of a reminiscent of those found in children with NF1. Stejskal-Tanner diffusion-sensitizing
Load more

Recommended publications
  • A Case of Intramedullary Spinal Cord Astrocytoma Associated with Neurofibromatosis Type 1
    KISEP J Korean Neurosurg Soc 36 : 69-71, 2004 Case Report A Case of Intramedullary Spinal Cord Astrocytoma Associated with Neurofibromatosis Type 1 Jae Taek Hong, M.D.,1 Sang Won Lee, M.D.,1 Byung Chul Son, M.D.,1 Moon Chan Kim, M.D.2 Department of Neurosurgery,1 St. Vincent Hospital, The Catholic University of Korea, Suwon, Korea Department of Neurosurgery,2 Kangnam St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea The authors report a symptomatic intramedullary spinal cord astrocytoma in the thoracolumbar area associated with neurofibromatosis type 1 (NF-1). A 38-year-old woman presented with paraparesis. Magnetic resonance imaging revealed an intramedullary lesion within the lower thoracic spinal cord and conus medullaris, which was removed surgically. Pathological investigation showed anaplastic astrocytoma. This case confirms that the diagnosis criteria set by the National Institute of Health Consensus Development Conference can be useful to differentiate ependymoma from astrocytoma when making a preoperative diagnosis of intramedullary spinal cord tumor in patients of NF-1. KEY WORDS : Astrocytoma·Intramedullary cord tumor·Neurofibromatosis. Introduction eurofibromatosis type 1 (NF-1), also known as von N Recklinghausen's disease, is one of the most common autosomal dominant inherited disorders with an incidence of 1 in 3,000 individuals and is characterized by a predisposition to tumors of the nervous system5,6,12,16). Central nervous system lesions associated with NF-1 include optic nerve glioma and low-grade gliomas of the hypothalamus, cerebellum and brain stem6,10). Since the introduction of magnetic resonance(MR) imaging, Fig. 1. Photograph of the patient's back shows multiple subcutaneous incidental lesions with uncertain pathological characteristic nodules (black arrow) and a cafe-au-lait spot (white arrow), which have been a frequent finding in the brain and spinal cord of are typical of NF-1.
    [Show full text]
  • Pediatric Orbital Tumors and Lacrimal Drainage System
    Pediatric Orbital Tumors and Lacrimal Drainage System Peter MacIntosh, MD University of Illinois • No financial disclosures Dermoid Cyst • Congenital • Keratinized epidermis • Dermal appendage • Trapped during embryogenesis • 6% of lesions • 40-50% of orbital pediatric orbital lesion • Usually discovered in the first year of life • Painless/firm/subQ mass • Rarely presents as an acute inflammatory lesion (Rupture?) • Frontozygomatic (70%) • Maxillofrontal (20%) suture Imaging - CT • Erosion/remodeling of bone • Adjacent bony changes: “smooth fossa” (85%) • Dumbell dermoid: extraorbital and intraorbital components through bony defect Imaging - MRI • Encapsulated • Enhancement of wall but not lumen Treatment Options • Observation • Risk of anesthesia • Surgical Removal • Changes to bone • Rupture of cyst can lead to acute inflammation • Irrigation • Abx • Steroids Dermoid INFANTILE/Capillary Hemangioma • Common BENIGN orbital lesion of children • F>M • Prematurity • Appears in 1st or 2nd week of life • Soft, bluish mass deep to the eyelid • Superonasal orbit • Rapidly expands over 6-12 months • Increases with valsalva (crying) • Clinical findings • Proptosis Astigmatism • Strabismus Amblyopia INFANTILE/Capillary Hemangioma • May enlarge for 1-2 years then regress • 70-80% resolve before age 7 • HIGH flow on doppler • Kasabach-Merritt Syndrome • Multiple large visceral capillary hemangiomas • Sequestration of platelets into tumor • Consumptive thrombocytopenia • Supportive therapy and treat underlying tumor • Complications • DIC • death •Homogenous
    [Show full text]
  • Neuro-Oncology 1 XX(XX), 1–12, 2016 | Doi:10.1093/Neuonc/Now267
    Neuro-Oncology 1 XX(XX), 1–12, 2016 | doi:10.1093/neuonc/now267 Defining the temporal course of murine neurofibromatosis-1 optic gliomagenesis reveals a therapeutic window to attenuate retinal dysfunction Joseph A. Toonen, Yu Ma, and David H. Gutmann Department of Neurology, Washington University School of Medicine (WUSM), St Louis, Missouri (J.A.T., Y.M., D.H.G.) Corresponding Author: David H. Gutmann, MD, PhD, Department of Neurology, Washington University, Box 8111, 660 S. Euclid Avenue, St. Louis MO 63110 ([email protected]). Abstract Background. Optic gliomas arising in the neurofibromatosis type 1 (NF1) cancer predisposition syndrome cause reduced visual acuity in 30%–50% of affected children. Since human specimens are rare, genetically engineered mouse (GEM) models have been successfully employed for preclinical therapeutic discovery and validation. However, the sequence of cellular and molecular events that culminate in retinal dysfunction and vision loss has not been fully defined relevant to potential neuroprotective treatment strategies. Methods. Nf1flox/mut GFAP-Cre (FMC) mice and age-matched Nf1flox/flox (FF) controls were euthanized at defined intervals from 2 weeks to 24 weeks of age. Optic nerve volumes were measured, and optic nerves/retinae analyzed by immunohistochemistry. Optical coherence tomography (OCT) was performed on anesthetized mice. FMC mice were treated with lovastatin from 12 to 16 weeks of age. Results. The earliest event in tumorigenesis was a persistent elevation in proliferation (4 wk), which preceded sustained microglia numbers and incremental increases in S100+ glial cells. Microglia activation, as evidenced by increased interleukin (IL)-1β expression and morphologic changes, coincided with axonal injury and retinal ganglion cell (RGC) apoptosis (6 wk).
    [Show full text]
  • Clinical Manifestations of Hypothalamic Tumors*
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 10, No. 6 Copyright © 1980, Institute for Clinical Science, Inc. Clinical Manifestations of Hypothalamic Tumors* ADOLFO D. GARNICA, M.D., MICHAEL L. NETZLOFF, M.D.,f and A. L. ROSENBLOOM, M.D. Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610 and f Department of Human Development, Michigan State University East Lansing, MI 88823 ABSTRACT The regulatory function of the central nervous system encompasses di­ verse endocrine, metabolic, and behavioral processes. Many of these origi­ nate, are integrated, or are coordinated through hypothalamic pathways or nuclei. Thus, tumors affecting areas projecting to the hypothalamus, tumors of the hypothalamus, and tumors invading or compressing the hypothalamus can produce abnormalities of hypothalamic function. Introduction tary.4,7,31 A secretory function for certain hypothalamic neurons was postulated in Until recently, no endocrine disorder 1928 and subsequently confirmed by the directly attributable to hypothalamic dys­ demonstration of hormone synthesis in function had been recognized, and the the supraoptic and paraventricular nu­ majority of endocrine-metabolic homeo­ clei.28,53 Moreover, observations on the static processes were acknowledged to be effects of environment on the menstrual under the control of the anterior pitui­ cycles of women and the study of repro­ tary.48,49 However, in 1901 Frohlich re­ ductive cycles in animals have shown a ported a patient with a suprasellar tumor, functional connection
    [Show full text]
  • Low-Grade Central Nervous System Tumors
    Neurosurg Focus 12 (2):Article 1, 2002, Click here to return to Table of Contents Low-grade central nervous system tumors M. BEATRIZ S. LOPES, M.D., AND EDWARD R. LAWS, JR., M.D. Departments of Pathology (Neuropathology) and Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia Low-grade tumors of the central nervous system constitute 15 to 35% of primary brain tumors. Although this cate- gory of tumors encompasses a number of different well-characterized entities, low-grade tumors constitute every tumor not obviously malignant at initial diagnosis. In this brief review, the authors discuss the pathological classification, diagnostic procedures, treatment, and possible pathogenic mechanisms of these tumors. Emphasis is given in the neu- roradiological and pathological features of the several entities. KEY WORDS • glioma • astrocytoma • treatment outcome Low-grade gliomas of the brain represent a large pro- toses. The pilocytic (juvenile) astrocytoma is a character- portion of primary brain tumors, ranging from 15 to 35% istic, more circumscribed lesion occurring primarily in in most reported series.1–5 They include a remarkable di- childhood and with a predilection for being located in the versity of lesions, all of which have been lumped together cerebellum. It usually appears as a cystic tumor with a under the heading of "low-grade glioma." This category mural nodule. The tumor tissue itself may have features of includes virtually every tumor of glial origin that is not microcystic degeneration and Rosenthal fibers which are overtly malignant at the time of initial diagnosis. degenerative structures in the astrocytic processes. Other reasonably common types of low-grade gliomas include CLASSIFICATION OF GLIOMAS the low-grade oligodendroglioma and the low-grade ependymoma, which is usually anatomically related to the Table 1 provides a classification of low-grade tumors of ventricular ependymal lining.
    [Show full text]
  • Cranial Nerve Disorders: Clinical Manifestations and Topographyଝ
    Radiología. 2019;61(2):99---123 www.elsevier.es/rx UPDATE IN RADIOLOGY Cranial nerve disorders: Clinical manifestations and topographyଝ a,∗ a b c M. Jorquera Moya , S. Merino Menéndez , J. Porta Etessam , J. Escribano Vera , a M. Yus Fuertes a Sección de Neurorradiología, Hospital Clínico San Carlos, Madrid, Spain b Servicio de Neurología, Hospital Clínico San Carlos, Madrid, Spain c Neurorradiología, Hospital Ruber Internacional, Madrid, Spain Received 17 November 2017; accepted 27 September 2018 KEYWORDS Abstract The detection of pathological conditions related to the twelve cranial pairs rep- Cranial pairs; resents a significant challenge for both clinicians and radiologists; imaging techniques are Cranial nerves; fundamental for the management of many patients with these conditions. In addition to knowl- Cranial neuropathies; edge about the anatomy and pathological entities that can potentially affect the cranial pairs, Neuralgia; the imaging evaluation of patients with possible cranial pair disorders requires specific exami- Cranial nerve palsy nation protocols, acquisition techniques, and image processing. This article provides a review of the most common symptoms and syndromes related with the cranial pairs that might require imaging tests, together with a brief overview of the anatomy, the most common underlying processes, and the most appropriate imaging tests for different indications. © 2018 SERAM. Published by Elsevier Espana,˜ S.L.U. All rights reserved. PALABRAS CLAVE Sintomatología derivada de los pares craneales: Clínica y topografía Pares craneales; Resumen La detección de la patología relacionada con los doce pares craneales representa Nervios craneales; un importante desafío, tanto para los clínicos como para los radiólogos. Las técnicas de imagen Neuropatía de pares craneales; son fundamentales para el manejo de muchos de los pacientes.
    [Show full text]
  • Immunohistochemical Properties of Human Optic Nerve Glioma
    Investigative Ophthalmology & Visual Science, Vol. 32, No. 9, August 1991 Copyright © Association for Research in Vision and Ophthalmology Immunohistochemical Properties of Human Optic Nerve Glioma Evidence of Type 1 Astrocyte Origin Paul E. Cutarelli,* Uros R. Roessmann,* Robert H. Miller, f Charles S. Spechr4 and Hans E. Grossniklaus§ The peroxidase-antiperoxidase method was used to study ten surgically obtained human optic nerve gliomas (pilocytic astrocytomas). All tissues were formalin fixed and paraffin embedded. Primary antisera included glial fibrillary acidic protein (GFAP), HNK-1 (type 1 astrocyte precursor marker), A2B5 (type 2 astrocyte precursor marker), S-100, vimentin, myelin basic protein (MBP), laminin, keratin, cytokeratin, epithelial membrane antigen (EMA), and neuron-specific enolase (NSE). Neo- plastic astrocytes in optic nerve gliomas stained with GFAP, HNK-1, S-100, and vimentin. Oligoden- drocytes and myelin sheaths stained for MBP, and NSE stained surviving axons in the tumors. Neo- plastic astrocytes did not stain for A2B5, keratin, cytokeratin, EMA, or laminin. These results suggest that human optic nerve gliomas (pilocytic astrocytomas) arise from type 1 astrocytes. Invest Ophthal- mol Vis Sci 32:2521-2524,1991 As a result of the variable histopathologic appear- with the identification in the rat central nervous sys- ance of optic nerve glioma, several classifications of tem of a macroglial progenitor cell capable of forming the origin of the proliferating astrocyte comprising astrocytes and oligodendrocytes.4-5 To characterize these tumors have arisen.1"3 The light microscopic ap- more fully the cellular elements present in optic nerve pearance of certain cells in optic nerve glioma encour- glioma and to identify the origin of the proliferating aged some authors to interpret these tumors as oligo- astrocyte, we immunostained ten human optic nerve dendrogliomas.1 The detection of neurofibrils in these gliomas.
    [Show full text]
  • Table S1. Summary of Studies That Include Children with Solid Tumors Treated with Antiangiogenic Drugs
    Table S1. Summary of studies that include children with solid tumors treated with antiangiogenic drugs. Tumor Patient Age Best Worst Treatment Diagnostic Reference type s (years) response response BVZ Optic nerve glioma 4 1.2-4 PR (x4) PR (x4) [56] Pilocytic astrocytoma 3 0.92-7 PR (x2) PD (x1) [56] Ganglioglioma 1 1.92 PR PR [56] Pilomyxoid astrocytoma 1 1.92 PR PD [68] Visual pathway glioma 1 2.6 PR Side effects [66] LGG 15 1-20 CR (x3) Toxicity (x1) [58] Visual pathway glioma 3 6-13 PR (x2) PD (x1) [60] Pilocytic astrocytoma 5 3.1-11.2 PR (x5) PR (x5) [65] BVZ+IRO Pilomyxoid astrocytoma 2 7.9-12.2 PR (x2) PR (x2) [65] Oligodendroglioma 1 11.1 PD PD [65] Ganglioglioma 3 4.1-16.8 PR (x2) SD (x1) [65] Optic nerve glioma 2 9-15 PR (x1) SD (x1) [63] LGG 35 0.6-17.6 PR (x2) PD (x8) [61] Pilocytic astrocytoma 10 1.8-15.3 PR (x4) PD (x1) [62] Pleomorphic 1 9.4 PD PD [62] xanthoastrocytoma LGG 5 3.9-9.2 PR (x2) SD (x3) [62] Pilocytic astrocytoma 4 4.67-12.17 PR (x2) PD (x3) [57] Pilomyxoid astrocytoma 1 3 SD PD [57] Fibrillary astrocytoma 3 1.92-11.08 CR (x1) PD (x3) [57] Other LGG 6 1-13.42 PR (x2) PD (x6) [57] Visual pathway glioma 1 11 PR SD [60] Fibrillary astrocytoma 3 1.5-11.1 CR (x1) SD (x1) [64] Pilocytic astrocytoma 2 3.75-9.8 PR (x1) MR (x1) [64] Low-grade glioma Pilomyxoid astrocytoma 1 3 SD SD [64] Brain tumor Brain tumor Other LGG 4 3-9.6 PR (x2) Side effects [64] Pleomorphic BVZ+TMZ 1 13.4 PR PR [153] xanthoastrocytoma Pilocytic astrocytoma 9 5-17 PR (x3) PD (x3) [59] BVZ+CHEM Pleomorphic 1 18 SD PD [59] xanthoastrocytoma Ganglioglioma
    [Show full text]
  • Differential Diagnosis of Sellar Masses
    ~~ ~~ ~ ADVANCES IN PITUITARY TUMOR THERAPY 0889-8529/99 $8.00 + .OO DIFFERENTIAL DIAGNOSIS OF SELLAR MASSES Pamela U. Freda, MD, and Kalmon D. Post, MD Pituitary adenomas are the most common cause of a mass in the sella. In as many as 9% of cases, other etiologies are responsible for mass lesions in the sellar regions4,13' (Table 1). The differential diagnosis of nonpituitary sellar masses is broad and includes cell rest tumors, germ cell tumors, gliomas, menin- giomas, metastatic tumors, vascular lesions, and granulomatous, infectious, and inflammatory processes (Table 2). Differentiating among these potential etiolo- gies may not always be straightforward because many of these lesions, tumorous and nontumorous, may mimic the clinical, endocrinologic, and radiographic presentations of pituitary adenomas. In some cases, there are no features that clearly distinguish the unusual etiologies from the clinically nonfunctioning pituitary adenoma. In others, certain endocrine, neurologic, and radiographic findings that are more characteristic of patients with a nonpituitary sellar mass may be present and can help in their differentiation. Correct preoperative diag- nosis is clinically important because the treatment of choice for many of these nonpituitary sellar masses differs from that of a pituitary tumor. This article provides an overview of the clinical and radiographic characteristics of both pituitary tumors and the nonpituitary lesions found in the sellar/parasellar region and discusses in detail the specific nonpituitary etiologies of the sellar mass. SIGNS AND SYMPTOMS OF PITUITARY TUMORS Pituitary tumors vary in presentation. Clinical findings depend largely on whether the tumor is hormone secreting or clinically nonfunctioning, on the size and pattern of tumor growth, and on whether normal pituitary gland function is disrupted.
    [Show full text]
  • Optic Nerve: Developmental Anomalies and Common Tumors
    DOI: 10.5772/intechopen.80326 ProvisionalChapter chapter 3 Optic Nerve: Developmental Anomalies and Common Tumors HindHind Alkatan, Alkatan, Daniah AlshowaeirDaniah Alshowaeir and TariqTariq Alzahem Alzahem Additional information is available at the end of the chapter http://dx.doi.org/10.5772/intechopen.80326 Abstract The optic nerve, also known as the second cranial nerve, is composed of axons that trans- mit visual information from the neurosensory retina to the visual cortex. There are mul- tiple pathologies that can affect the human optic nerve. Congenital anomalies of the optic nerve include myelinated nerve fibers, morning glory syndrome, optic nerve choristoma, optic nerve coloboma, optic nerve hypoplasia and aplasia, and others. Tumors that can affect the optic nerve (ON) may occur primarily from within the nerve itself, from the sur- rounding optic nerve sheath (ONS), or secondarily spreading to the nerve from a distant site. They include optic pathway glioma, medulloepithelioma, oligodendroglioma, optic nerve sheath meningioma, and others. Here in this chapter, we will review the optic nerve anatomy, embryology, and physiology in addition to assessment of optic nerve function. Moreover, the clinical features, imaging findings, pathology, and treatment options of the most common and some rare congenital anomalies and primary tumors of the ON and sheath will be reviewed. Keywords: myelinated nerve fibers, morning glory syndrome, optic nerve choristoma, optic nerve coloboma, optic nerve hypoplasia, aplasia, optic nerve tumor, glioma, meningioma, ganglioglioma, medulloepithelioma, hemangioblastoma, oligodendroglioma 1. Introduction Visual perception occurs when light stimulus in the surrounding environment converts to nerve impulses at the level of photoreceptors, which then reach the brain to be processed.
    [Show full text]
  • CT-Scan Findings of Orbital Mass Among Pediatric Patients at a Tertiary Care Hospital in Bangladesh
    ORIGINAL ARTICLE CT-Scan Findings of Orbital Mass Among Pediatric Patients at a Tertiary Care Hospital in Bangladesh *M A Rahman1, SA Azad2, N Islam3, S Amin4, MZ Haque5, MHM Kamal6, Mukhdira7 1*Dr Meher Angez Rahman. Consultant, Department of Radiology and Imaging Anwar Khan Modern Medical College and Hospital 2Prof Salauddin Al Azad, Professor, Department of Radiology & Imaging, BSMMU 3Dr. Nazrul Islam, Associate Professor, Department of Radiology & Imaging, BSMMU 4Dr. Prof Sadrul Amin, Associate Professor, Department of Radiology & Imaging, BSMMU 5Dr. Md ziaul Haque, ex-Associate Professor, Department of Radiology & Imaging, BSMMU 6Dr. Mahmud Hasan Mostofa Kamal, ex-Assistant Professor, Department of Radiology & Imaging, BSMMU 7Dr. Mukhdira, Lecturer, Department of Physiology, Community Based Medical College *Corresponding Author Date of submission: 08.05.2016 Date of acceptance:12.11.2016 ABSTRACT Background: CT-Scan for the detection of orbital mass among pediatric patients is very important noninvasive radiological modality. The purpose of the study was to find out CT-Scan findings of orbital mass among pediatric patients in a tertiary care hospital. Methodology: This is a cross sectional study was carried out in Ophthalmology and Radiology and Imaging department of National Institute of Ophthalmology (NIO) from January 2012 to December 2013. All the patient below 18 years of age presented with suspected orbital mass at Ophthalmology and Radiology and Imaging department of NIO and performed CT- Scan of orbit for diagnosis of the disease and also done histopathology after operation was enrolled in this study. Results: In this study it was observed that a total of 29 cases identified as malignant evaluated by CT, among them 27 cases were true positive and 2 cases were false positive.
    [Show full text]
  • Orbital Mass in a Child
    Orbital Mass in a Child Edward G. Buckley, MD Banks Anderson Professor of Ophthalmology Duke University Orbital Tumors/Lesions in Children • Malformations • Choristomas - Hemangioma, Lymphangioma, Varix, Neurofibroma • Primary Neoplasms - Glioma, Rhabdomyosarcoma, fibrous dysplasia • Secondary tumors – Astrocytoma, medulloepithelioma • Metastatic tumors – Neuroblastoma, Wilm’s , Ewing’s sarcoma • Leukemias / Lymphoma – Burkitt’s • Histiocytoses/Xanthogranuloma- esosinophilic granuloma • Inflammations- Pseudotumor, myositis • Infections – orbital cellulitis How to evaluate a child with orbital mass? Neuro-imaging ! Which neuro-imaging test is best ? CT scans are superior in most cases MRI may be desirable in certain cases when optic nerve dysfunction is present How to evaluate an orbital mass in a child? Ways to: How to determine: Classify ? Seriousness ? Categorize ? Urgency ? Compartmentalize ? Morbidity ? Is it Rapidly Expanding ?….. • Cellulitis/abscess • Pseudotumor/myositis • Hemangioma • Rhabdomyosarcoma • Neuroblastoma • Lymphoma • Eosinophilic granuloma Bilateral ?….. • Optic nerve glioma • Neuroblastoma • Leukemia • Lymphoma • Pseudotumor/myositis • Eosinophilic granuloma Eyelid echymosis ?…. • Neuroblastoma • Ewing’s sarcoma • Leukemia • Eosinophilic granuloma • Lymphanigoma Present at birth ?...... Microphthalmos with cyst Varix Teratoma Optic nerve glioma Capillary hemangioma Retinoblastoma Lymphangioma Neuroblastoma Dermoid cyst Neurofibroma Meningoencephalocele Juvrnile xanthogranuloma Intermittent ?.... Lympangioma Dermoid
    [Show full text]