eMedicine Specialties > Neurology > Neuro-oncology

Primitive Neuroectodermal Tumors of the Central Nervous System

Author: Subrata Ghosh, MD, MBBS, MS, Staff Physician, Assistant Professor of Neurosurgery, Baylor College of Medicine, Houston, Division of Neurosurgery, St. Luke's Episcopal Hospital, Texas Medical Center, Houston, TX
Coauthor(s): Draga Jichici, BSc, MD, FRCP, Associate Clinical Professor, Department of Medicine, Division of Neurology and Critical Care Medicine, McMaster University, Canada
Contributor Information and Disclosures

Updated: Jun 30, 2009

Introduction

Background

Primitive neuroectodermal tumors (PNET) are neoplasms of which medulloblastoma is the prototype. These are small cell, malignant embryonal tumors showing divergent differentiation of variable degree along neuronal, glial, or rarely mesenchymal lines. Only tumors of the CNS are discussed here. Peripheral primitive neuroectodermal tumors are regarded as distinct entities.

Pathophysiology

PNET of the CNS can be divided grossly into infratentorial tumors (medulloblastoma or iPNET) and supratentorial tumors (sPNET).

Considerable controversy exists regarding the histogenesis of these tumors. Initially, these dense, cellular, embryonal tumors were thought to have a common origin from primitive neuroectodermal cells and to differ only in their location, type, and degree of differentiation. In the revised World Health Organization (WHO) classification, however, many of these tumors are given a separate niche on the basis of the assumption that these embryonal tumors also could arise from cells already committed to differentiation.1

Regardless of the controversy, these tumors are discussed as infratentorial (medulloblastoma) and supratentorial. The latter occur rarely (25:1) and are more common in young adults than infratentorial tumors.

Spinal dissemination via the cerebrospinal fluid (CSF) is the most common form of metastatic spread of PNETs.

Frequency

United States

Medulloblastoma represents the most common type of primary solid malignant brain tumor in children (as many as 30% of all solid brain tumors). In contrast, only 1% of brain tumors in adults are medulloblastomas. The overall annual incidence is approximately 0.5 case per 100,000 children. Seventy-five percent arise in the midline (vermis), while 25% occur in the lateral cerebellum.

International

The Swedish Cancer Registry reported, as part of a population-based study, that medulloblastomas represented 21% of all primary brain tumors in children. Similar figures were provided by the British Tumor Registry and from the United States (Surveillance, Epidemiology and End Results Program).

Mortality/Morbidity

Risk of sudden death secondary to obstructive hydrocephalus has been hypothesized; however, it is not often observed clinically.

Race

National Cancer Survey suggests a slightly higher incidence in white than in blacks.

Sex

A slight male preponderance is observed (male-to-female ratio 1.8:1).

Age

Three fourths of these tumors appear in children younger than 15 years, and 50% are seen in the first decade of life. A second, smaller peak occurs in young adults (aged 21-40 y).

Clinical

History

  • No pathognomonic signs or symptoms exist. The onset at presentation is insidious.
  • The observed symptoms are due to the neuroanatomical location of the tumor or are a consequence of increased intracranial pressure. They include the following:
    • Irritability, lethargy, and decreased social interaction (60%)
    • Intermittent vomiting (40%)
    • Headache (40%) (usually worse in the morning)
    • Visual blurring/change (30%)
    • Nausea - Unusual as a distinct symptom, unless the tumor infiltrates the floor of the fourth ventricle (5%)
    • Imbalance (40%)

Physical

  • Papilledema (60%)
  • Ataxia (50%)
  • Nystagmus with or without gaze palsy (40%)
  • Lower cranial nerve palsy (20%)
  • Dysdiadochokinesia, hypotonia, dysmetria, particularly in lateralized lesions of the cerebellum (20%)
  • Increased head circumference in children younger than 2 years (30%)

Causes

  • Isolated PNET is sporadic in nature, and only 14 familial cases have been reported in the literature.
  • Loss of the short arm of chromosome 17 (17p13.3) is the most frequent abnormality (particularly with medulloblastoma, in which it is found in 30-40% of cases), the presence of which also affects prognosis. This site is, however, distinct from the common tumor suppressor gene, TP53. Other genetic loci of interest in the pathogenesis of medulloblastoma include PAX genes and sonic hedgehog (SHH) genes, the roles of which are under intense investigation.
  • Certain conditions have increased associations with PNETs.
    • Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is an autosomal dominant disorder with mutations of the PTCH gene. It is characterized by a combination of neoplastic and malformative disorders including nevoid basal cell carcinoma, jaw keratocysts, skeletal abnormalities, ovarian fibromas, and ectopic calcifications. Approximately 5% of mutation carriers develop medulloblastoma at an early age.
    • Turcot syndrome is a heterogenous group of autosomal dominant disorders with occurrence of multiple colorectal neoplasms and medulloblastomas or glioblastomas.
    • Li-Fraumeni syndrome is an autosomal dominant disorder characterized by multiple tumors in children, including soft-tissue sarcomas, osteosarcomas, breast cancer, leukemias, and a higher incidence of brain tumors than in the general population.
  • Other reported genetic abnormalities include isochromosome 17q (i17q), loss of segments of chromosome arms 10q and 9q, and amplification of the c-myc gene.
  • Karyotypically, almost all PNETs are abnormal.

More on Primitive Neuroectodermal Tumors of the Central Nervous System

Overview: Primitive Neuroectodermal Tumors of the Central Nervous System
Differential Diagnoses & Workup: Primitive Neuroectodermal Tumors of the Central Nervous System
Treatment & Medication: Primitive Neuroectodermal Tumors of the Central Nervous System
Follow-up: Primitive Neuroectodermal Tumors of the Central Nervous System
Multimedia: Primitive Neuroectodermal Tumors of the Central Nervous System
References
[ CLOSE WINDOW ]

References

  1. Kleihues P, Burger PC, Scheithauer BW. The new WHO classification of brain tumours. Brain Pathol. Jul 1993;3(3):255-68. [Medline].

  2. Allen JC, Donahue B, DaRosso R, Nirenberg A. Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for children with newly diagnosed medulloblastoma and other primitive neuroectodermal tumors. Int J Radiat Oncol Biol Phys. Dec 1 1996;36(5):1155-61. [Medline].

  3. Albright AL, Pollack IF, Adelson PD. Principles and Practice of Pediatric Neurosurgery. 1st ed. New York: Thieme;1999: 591-608.

  4. Goldwein JW, Radcliffe J, Johnson J, et al. Updated results of a pilot study of low dose craniospinal irradiation plus chemotherapy for children under five with cerebellar primitive neuroectodermal tumors (medulloblastoma). Int J Radiat Oncol Biol Phys. Mar 1 1996;34(4):899-904. [Medline].

  5. Graham DI, Lantos PL. Greenfield's Neuropathology. Vol 2. 6th ed. New York: Oxford University Press; 1997:698-710.

  6. Kay A, et al. Brain tumors. First ed. New York: Churchill Livingstone; 1997:561-574.

  7. Kleihues P, Cavanee WK. Pathology and genetics of tumours of the nervous system. Lyon, France: International Agency for Research on Cancer (IARC); 1997:49-55.

  8. Kun LE. Brain tumors. Challenges and directions. Pediatr Clin North Am. Aug 1997;44(4):907-17. [Medline].

  9. Prados MD, Wara W, Edwards MS, et al. Treatment of high-risk medulloblastoma and other primitive neuroectodermal tumors with reduced dose craniospinal radiation therapy and multi-agent nitrosourea-based chemotherapy. Pediatr Neurosurg. Oct 1996;25(4):174-81. [Medline].

  10. Rood BR, Macdonald TJ, Packer RJ. Current treatment of medulloblastoma: recent advances and future challenges. Semin Oncol. Oct 2004;31(5):666-75. [Medline].

  11. Russell DS, et al. Pathology of Tumors of the Nervous System. 4th ed. Baltimore: Williams & Wilkins; 1977:203-26.

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

PNET, central neuroblastoma, ependymoblastoma, medulloblastoma, infratentorial tumor, iPNET, supratentorial tumors, sPNET, primary solid malignant brain tumor, Gorlin syndrome, nevoid basal cell carcinoma syndrome, PAX genes, sonic hedgehog genes, SHH genes, PTCH gene mutation, Turcot syndrome, glioblastomas, Li-Fraumeni syndrome, amplification of the c-myc gene

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Subrata Ghosh, MD, MBBS, MS, Staff Physician, Assistant Professor of Neurosurgery, Baylor College of Medicine, Houston, Division of Neurosurgery, St. Luke's Episcopal Hospital, Texas Medical Center, Houston, TX
Subrata Ghosh, MD, MBBS, MS is a member of the following medical societies: American Association of Neurological Surgeons, American Medical Association, Congress of Neurological Surgeons, and Texas Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Draga Jichici, BSc, MD, FRCP, Associate Clinical Professor, Department of Medicine, Division of Neurology and Critical Care Medicine, McMaster University, Canada
Disclosure: Nothing to disclose.

Medical Editor

Roberta J Seidman, MD, Associate Professor of Clinical Pathology, Stony Brook University; Director of Neuropathology, Department of Pathology, Stony Brook University Medical Center
Roberta J Seidman, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuropathologists, New York Association of Neuropathologists (The Neuroplex), and Suffolk County Society of Pathologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Jorge Kattah, MD, Head, Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria
Jorge Kattah, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, and New York Academy of Sciences
Disclosure: Biogen Honoraria Consulting; Bayer Corporation Honoraria Consulting

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, FRCP(C), FACP, Professor of Neurology, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Chair, Department of Neurology, Crouse Irving Memorial Hospital
Tarakad S Ramachandran, MBBS, FRCP(C), FACP is a member of the following medical societies: American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners, American College of International Physicians, American College of Managed Care Medicine, American College of Physicians, American Heart Association, American Stroke Association, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, and Royal Society of Medicine
Disclosure: Abbott Labs  Honoraria Consulting; Teva Marion Honoraria Consulting; Boeringer-Ingelheim Honoraria Speaking and teaching

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.