brain-surgery.us
homepage
site contents
What's New
Feedback
About the Author
Mission
Disclaimer
Contact
 
 

Khurana - Neurosurgery - Brain Tumor Education Resource



This Brain Tumor Education Resource is at present comprised of two modules (a third module with intraoperative videos will be added later this year):

  • MODULE 1: INTRODUCTION TO BRAIN TUMOURS/BRAIN TUMORS
    • Classification
    • Pathophysiology
    • Incidence
    • Clinical presentation
    • Investigation
    • Immediate management
    • Treatment
  • MODULE 2: LINKS TO BRAIN TUMOR/BRAIN TUMOUR CASE HISTORIES
    • Meningioma
    • Glioma (including information on AWAKE BRAIN SURGERY/AWAKE CRANIOTOMY)
    • Metastasis
    • Schwannoma


MODULE 1: INTRODUCTION TO BRAIN TUMOURS/TUMORS:

Only the essential points are summarized here. For more information, follow the brain tumour links on the Home Page.

1. Classification of brain tumors/brain tumours:

  • There are many brain tumors to classify and many different ways to classify them! For example, by the cell-type of origin, the degree of malignancy, their location, and so forth. Pathological classification means that the microscopic cell features of the tumor and its cell type of origin were used to classify it. Radiological classification means that the location of the tumor was used to classify it.
  • The World Health Organization (WHO) classifies brain tumours according to their cell of origin as follows:
    • Tumors of neuroepithelial tissue - e.g., astrocytoma, oligodendroglioma, mixed glioma, ependymoma, choroid plexus papilloma or carcinoma, and other more rare tumours such as DNET (dysembryoplastic neuroepithelial tumor), PNET (neuroblastoma, medulloblastoma, olfactory neuroblastoma or esthesioneuroblastoma), pineocytoma, pineoblastoma, and ATRT (atyplical teratoid/rhabdoid tumor)
    • Tumors of peripheral nerves - e.g., Schwannoma (neurilemmoma), neurofibroma, malignant peripheral nerve sheath tumor (MPNST)
    • Tumors of the meninges - meningioma
    • Blood cell tumors - e.g., lymphoma (primary CNS lymphoma versus secondary non-Hodgkin's lymphoma versus Hodgkin's lymphoma) and plasmacytoma (solitary or as part of multiple myeloma)
    • Germ cell tumors - e.g., germinoma, embryonal carcinoma, yolk sac tumor, teratoma, or a mixture
    • Miscellaneous tumors - e.g., paraganglioma (glomus), craniopharyngioma, pituitary adenoma, lipoma, liposarcoma, fibrosarcoma, hemangiopericytoma, hemangioblastoma, angiosarcoma, osteoma, osteosarcoma, chondroma, chondrosarcoma, chordoma, hemangioma, rhabdomyoma, rhabdomyosarcoma, melanoma,...
  • Some of the above tumors (e.g., glioma, meningioma) are subclassified according to the degree of atypia (bizarre or worrisome microscopic features) and malignancy, and are therefore "graded". For examples of this type of subclassification (or "tumor grading"), see the glioma and meningioma case series. As a rule of thumb, by WHO classification methods, a higher grade of tumor implies more atypia and a greater tendency to recur and/or invade the brain and therefore a worse prognosis. This is where the concept of "benign" versus "malignant" brain tumor arises.
  • Tumors in the brain may have arisen from "native" brain cell types themselves ("primary" brain tumors), or from "foreign" cell types, i.e., outside of the central nervous system ("secondary" or "metastatic" brain tumors). Primary brain tumors include gliomas, meningiomas, Schwannomas; secondary ones (metastases) include lung, breast, bowel, kidney, and melanoma (but melanoma can also occur as a primary brain tumor).
  • Tumors in the brain can be classified according to their location. Broadly, they may be "intraaxial" (arising in the substance of the brain itself; "intraparenchymal") or "extraaxial" (arising in the coverings of the brain or skull/skull base). Examples of the former include astrocytoma, ependymoma, germ cell tumor, most metastases, and medulloblastoma; examples of the latter include meningioma, Schwannoma, osteoma, angiofibroma, esthesioneuroblastoma, plasmacytoma and dural-based metastases.
    • Cerebellopontine angle (CPA) tumors such as meningioma or vestibular Schwannoma/acoustic neuroma
    • Sellar and parasellar region tumors such as pituitary adenoma, germ cell tumor, optic glioma, meningioma, chondrosarcoma, and craniopharyngioma
    • Pineal region tumors such as pineocytoma, pineoblastoma, astrocytoma, germ cell tumor
    • Intraventricular tumors such as choroid plexus papilloma or carcinoma, central neurocytoma, ependymoma, and (rarely) meningioma
    • Nasal region tumors such as juvenile angiofibroma and esthesioneuroblastoma
    • Periventricular tumors such as subependymoma, subependymal giant cell astrocytoma (SEGA), lymphoma
    • Tentorial region tumors such as meningiomas and dural-based metastases
    • Clival region tumors such as chordoma, chondrosarcoma
    • Cerebellar tumors such as epedymoma, pilocytic astrocytoma, medulloblastoma, astrocytoma, choroid plexus papilloma or carcinoma, subependymoma,...
  • Note that there are many conditions that mimic brain tumors and by definition are not brain tumors themselves:
    • A variety of cysts - colloid cyst, dermoid cyst, arachnoid cyst, epidermoid cyst, Rathke's cleft cyst, neuroenteric cyst, pineal cyst
    • Radiation necrosis
    • Brain abscess - bacterial (Staph, Strep) or fungal infection (toxoplasmosis, TB, etc.), or a parasite infection such as cysticercosis
    • A giant aneurysm or a venous varix or a cavernous malformation (cavernoma)
    • Neurosarcoidosis
    • Paget's disease of bone and fibrous dysplasia
    • Tumefactive multiple sclerosis (MS)
  • CONSULT THE NATIONAL CANCER INSTITUTE BRAIN TUMOR WEB PAGE FOR MORE INFORMATION

2. Pathophysiology of brain tumors/brain tumours:

  • A number of genetic abberations associated with CNS tumors are hereditary, but the vast majority appear to be acquired
  • Hereditary conditions associated with CNS tumors include:
    • Neurofibromatosis Type 1 (NF1; aka von Reckinghausen's disease)
      • Mutation on chrom 17 q11
      • Autosomal dominant inheritance
      • Associated with defect in "neurofibromin" protein -- this protein is encoded by a tumor suppressor gene)
      • Tumors in NF1 include neurofibroma and optic glioma, but NF1 is also associated with astrocytoma, meningioma, and Schwannoma (but NOT bilateral vestibular Schwannoma which is a hallmark of NF2; see below).
    • Neurofibromatosis Type 2 (NF2)
      • Mutation on chrom 22 q12
      • Autosomal dominant inheritance
      • Leads to inactivation of "Schwannomin" (aka "Merlin")
      • Tumors in NF2 include bilateral vestibular Schwannoma (i.e., bilateral "acoustic neuroma"), neurofibroma, astrocytoma, meningioma, and ependymoma
    • Von Hippel Lindau (VHL)
      • Mutation on chrom 3 p (encoding pVHL)
      • Tumors in VHL include hemangioblastoma (freq. multiple) and phaeochromocytoma
    • Tuberous sclerosis (TS)
      • Mutation on 9 q (encoding hamartin, a TSG) and 16 p (encoding tuberin)
      • 50% autosomal dominant; many also sporadic (noninherited) cases
      • Astrocytoma (SEGA; subependymal giant cell astrocytoma)
  • Loss of tumor suppressor gene (TSG) function ("loss of heterozygosity" at TSG chromosome loci) is thought to be fundamental in tumor development and progression. Classic TSGs include p53 and retinoblastoma susceptibility (Rb) genes; others include p16 and p19. These genes play key roles at cell cycle "checkpoints", i.e., points in the cell cycle at which cells with unrepaired DNA damage are removed from the cell cycle (i.e., undergo apoptosis). Therefore, loss of function of TSGs is associated with unregulated cell cycle activity (unchecked mitotic activity) and therefore tumorigenesis.
  • Gain of oncogene function is also associated with CNS tumors. For example, amplification and overexpression of the epidermal growth factor receptor (EGFR) oncogene on chromosome 7 is seen in many GBM. Another example is platelet-derived growth receptor alpha (PDGFRa) oncogene on chromosome 22, found to be overexpressed in especially low grade astrocytoma.
  • Possible risk factors for acquired CNS tumors include oncogenic viruses and ionizing radiation. Emerging evidence for a link between brain tumors and mobile phones (emitting low but persistent levels of electromagnetic radiation at close proximity to the brain) is presented elsewhere.

3. Incidence of brain tumors/brain tumours:

  • The incidence of a primary brain tumor is about 3 times less than that of a brain metastasis
  • The incidence of primary brain tumors has been reported by a number of sources to be increasing. Reasons for this may be related to better and earlier diagnosis, or may in part be related to other factors including increasing exposure to electromagnetic radiation (EMR) in our "Wireless Age" (see elsewhere for more details).
  • In the United States, the following statistics apply:
    • Incidence of a primary tumor of the central nervous system (CNS) is approximately 18.2 per 100,000 persons (i.e., each year, for every 100,000 people in the US, approximately 18 people will be diagnosed with a primary CNS tumor. This data is from the 2007/2008 Statistical Report of the Central Brain Tumor Registry of the United States. That report only has data as recent as 2004, owing to the delay in data collection and reporting.
    • The yearly incidence of new primary CNS tumors in the US is somewhere between 40,000 to 50,000 people
    • The lifetime chance of developing a primary CNS tumor is approximately 1 in 200 (slightly higher in men than women)
    • CNS tumors are the leading cause of cancer-related deaths in children and teenagers, and the second leading cause of cancer-related deaths in males aged 20-40 years
    • 40% of primary CNS tumors are "gliomas" (e.g., astrocytoma, oligodendroglioma, ependymoma, mixed glioma)
    • 80% of malignant CNS tumors are gliomas
  • For every 100 persons diagnosed with a new CNS glioma, approximately 50 (i.e., 50%) will have the most malignant form (glioblastoma multiforme or GBM) at the time of diagnosis. More specifically, the spread is something like this: 50 with GBM, 9 with oligodendroglioma, 8 with anaplastic astrocytoma, 6 with pilocytic astrocytoma, 6 with ependymoma, 2 with gliomatosis cerebri, and 19 with a variety of other types of gliomas.

4. Clinical presentation of brain tumors/brain tumours:

  • Headache (especially regular morning headache), with or without nausea, vomiting, blurred vision, diplopia (double vision) -- one or more of these may be indicative of raised intracranial pressure
  • Seizure (motor or sensory)
  • Progressive sensory or motor deficit
  • Language dysfunction (aphasia)

5. Investigation of brain tumors/brain tumours:

  • The most common radiological investigations are:
    • Computerized tomography (CT or CAT) scan of the head, with and without contrast
    • Magnetic resonance imaging (MRI) of the head, with and without contrast
  • Other special investigations depend on the tumor and may include one or more of:
    • Positron emission spectroscopy (PET) scanning or contrast-CT chest/abdomen/pelvis (for patients with suspected metastatic disease)
    • Cerebral angiography for patients with highly vascular tumors such as paraganglioma, hemangiopericytoma or angiofibroma
    • Functional MRI (fMRI) to determine spatial relationship of tumor to eloquent regions of the brain such as speech and motor centres, and MR spectroscopy (MRS) to determine the biochemical nature of the tumor (or differentiate it from a non-tumor lesion such as an abscess or radiation necrosis.
  • Do NOT carry out a lumbar puncture (typically nondiagnostic, and there may be significant risk of downward "herniation" or "coning")

6. Immediate management of brain tumors/brain tumours:

  • Routine lab studies: CBC, EUC, coags (INR/PT, APTT), type & screen or group & hold
  • Steroids (IV or po dexamethasone/Decadron) to control vasogenic edema
  • Proton pump inhibitor (PPI; e.g. omeprazole, pentoprazole) while on steroids
  • Anticonvulstant (phenytoin or Dilantin) - "load" if seizure; check serum phenytoin levels after 48 hrs and again at 6-7 days post-load
  • Neurosurgery consult
  • In extremis from raised ICP: IV mannitol or hypertonic saline if threatened-herniation; will therefore also need intubation, hyperventilation, and emergency surgery
  • If obstructive hydrocephalus is the critical presenting issue, neurosurgical preoperative external ventricular drain (EVD) placement for CSF diversion is typically appropriate
  • Appropriate imaging (see above) - CT scan with and without contrast is often the rapid first step

7. Treatment of brain tumors/brain tumours:

  • Surgery
    • Usually the first-line of treatment
      • Stereotactic biopsy to obtain diagnostic tissue
      • Craniotomy for tumor burden reduction, aiming for gross-total resection whenever feasible
    • For salvage in the setting of recurrent or persistent tumor whenever feasible
  • Endovascular therapy
    • Preoperative embolization of highly vascular tumors (e.g., large hemangiopericytoma, glomus/paraganglioma, juvenile angiofibroma, angiosarcoma)
  • Radiation therapy
    • Whole-brain radiotherapy (WBRT; especially for metastatic disease or astrocytoma); typically adminstered over 4-6 weeks as part of a "fractioned" treatment plan
    • Stereotactic radiosurgery (SRS); typically fully administered in part of one day only!
      • Mini-linear accelerator (Linac)-based systems such as Cyberknife and Novalis (high-energy X-ray photons)
      • Gamma irradiation-based systems such as Gammaknife (lower energy gamma ray photons)
      • Proton-beam irradiation (protons)
    • Brachytherapy (implanted radiopharmaceutical such as P32) e.g., for craniopharyngioma
  • Chemotherapy
    • Systemic
      • Especially for high-grade gliomas (e.g., can use temozolamide) or lymphoma
      • Bromocriptine or cabergoline (dopamine receptor agonists) for prolactinoma
    • Brachy
      • Implantation of BCNU (Gliadel) wafers in glioblastoma multiforme (GBM) resection cavities
    • Intraventricular
      • Chemodelivery via an Ommaya-type reservoir
  • Palliative therapy
    • For when the above is not appropriate or has failed
    • Ventriculoperitoneal shunt placement (for obstructive hydrocephalus in the setting of a refractory or "inoperable" tumor)
    • Consult a Palliative Care Service


MODULE 2: LINKS TO BRAIN TUMOR/BRAIN TUMOUR CASE HISTORIES:

Four brain tumor/brain tumour series, containing a total of 19 individual case examples, are presented here for patient, medical student and neurosurgical trainee comprehensive learning purposes.

Each series has the following information:

  1. Brain tumor/brain tumour background: An introduction to the type of brain tumor/brain tumour being case-presented. For example: How is the tumor defined? What cells make up the tumor? Who is susceptible to get such tumors? Where do they occur in the brain?
  2. Brain tumor/brain tumour clinical presentation: What were the brain tumor/brain tumour's symptoms and signs? That is: What did the patient experience? What did the physician detect during the physical examination of the patient?
  3. Brain tumor/brain tumour diagnostic workup: What investigations were used to diagnose the brain tumor/brain tumour? That is: What scans were ordered? Were any other special tests ordered as part of the diagnostic workup?
  4. Brain tumor/brain tumour treatment paradigm: What were the options and proposed treatment for the brain tumor/brain tumour? Was surgery the first-line treatment? What were the feasible alternatives? Was gross-total resection a realistic plan for this kind of tumor? Would radiation therapy or chemotherapy play a role postoperatively?
  5. Brain tumor/brain tumour operative procedure/operative approach: What specific approach did the surgeon use for the brain tumor/brain tumour? What kind of operation was carried out?
  6. Brain tumor/brain tumour technical nuances and potential surgical pitfalls: What were some of the important considerations for the brain tumor/brain tumour surgery? What would a surgeon need to consider beforehand to make the surgery safer for the patient?
  7. Where available, brain tumor/brain tumour pre- and post-operative radiological images and/or intraoperative images will be shown for the following brain tumor/brain tumour case examples.

Please note:

  1. In time, brain tumor/brain tumour intraoperative videos will be added to this Resource (as MODULE 3).
  2. Basic brain anatomy, symptoms and signs of neurosurgical lesions, step-by-step investigation and operative procedure details, operative risk counselling, potential treatment-related complications, informed consent, recovery and rehabilitation issues, follow-up and salvage recommendations for recurrent or persistent disease, FAQs and other case histories are all detailed elsewhere.

* CONTENTS OF THE BRAIN TUMOUR CASE HISTORY SERIES:

Click the following links for more information on...

Brain tumor/brain tumour series #1: Meningioma

  1. Sphenoid wing WHO grade I meningioma
  2. Parafalcine WHO grade II meningioma
  3. Intraosseous meningioma
  4. Brainstem region meningioma

[Key Learning Objectives for Brain tumor/brain tumour series #1: Meningioma: What is a meningioma and what does a meningioma look like on imaging? What are the different pathologic grades of a meningioma and how does the meningioma "grade" affect how such a brain tumor/brain tumour behaves? Where are some of the different locations that this brain tumor/brain tumour can occur at, and how does the location of the meningioma affect the surgical approach? How are these types of brain tumors/brain tumours treated and what are some of the important considerations for patients and surgeons alike in the management of a meningioma?]


Brain tumor/brain tumour series #2: Glioma

  1. Glioblastoma multiforme (GBM; WHO Grade 4 of 4 fibrillary astrocytoma)
  2. Awake craniotomy/awake brain surgery for recurrent frontal oligoastrocytoma
  3. Frontal oligodendroglioma
  4. Ependymoma
  5. Pilocytic astrocytoma (PCA; WHO Grade 1 of 4 astrocytoma)
  6. Brainstem glioma (diffuse pontine astrocytoma)
  7. Gliomatosis cerebri (diffuse multilobar astroscytoma)

[Key Learning Objectives for Brain tumor/brain tumour series #2: Glioma: What is a glioma (e.g., astrocytoma) and what does a glioma (e.g., astrocytoma) look like on imaging? What are the different pathologic grades of a glioma (e.g., astrocytoma) and how does the glioma (e.g., astrocytoma) "grade" affect how such brain tumors/brain tumours behave? Where are some of the different locations that this brain tumor/brain tumour can occur at, and how does the location of the glioma (e.g., astrocytoma) affect the surgical approach? How are these types of brain tumors/brain tumours treated and what are some of the important considerations for patients and surgeons alike in the management of a glioma (e.g., astrocytoma)? Additional information is provided in this section regarding awake brain surgery/awake craniotomy]


Brain tumor/brain tumour series #3: Metastasis

  1. Speech center esophageal cancer metastasis
  2. Bifrontal supplementary motor area lung cancer metastasis
  3. Frontal and cerebellar breast cancer metastases
  4. Metastatic melanoma

[Key Learning Objectives for Brain tumor/brain tumour series #3: Metastasis: What is a metastasis, how does a metastasis arise, and what does a metastasis look like on imaging? Where are some of the different locations that a metastasis can occur at, and how does the location of the metastasis affect the surgical approach? How are these types of brain tumors/brain tumours treated and what are some of the important considerations for patients and surgeons alike in the management of a metastasis?]


Brain tumor/brain tumour series #4: Schwannoma

  1. Trigeminal Schwannoma
  2. Foramen magnum Schwannoma
  3. Jugular foramen Schwannoma
  4. Vestibular Schwannoma (acoustic neuroma)

[Key Learning Objectives for Brain tumor/brain tumour series #4: Schwannoma: What is a Schwannoma (e.g., vestibular Schwannoma or acoustic neuroma)? What is a Schwann cell, and what does a Schwannoma (e.g., vestibular Schwannoma or acoustic neuroma) look like on imaging? Where are some of the different locations that a Schwannoma (e.g., vestibular Schwannoma or acoustic neuroma) can occur at, and how does the exact location and/or extent of the Schwannoma (e.g., vestibular Schwannoma or acoustic neuroma) affect the surgical approach? How are these types of brain tumors/brain tumours treated and what are some of the important considerations for patients and surgeons alike in the management of a Schwannoma (e.g., vestibular Schwannoma or acoustic neuroma)?]


Brain Tumor Series Inventory:

Acoustic neuroma; Anaplastic astrocytoma; Anaplastic meningioma; Astrocytoma; Awake Craniotomy; Brainstem glioma; Breast cancer metastasis; Chemotherapy; Colloid cyst; Cranioplasty for skull bone tumor; Craniotomy; CyberKnife; Diffuse glioma; Ependymoma; Fibrillary astrocytoma; GammaKnife; GBM; Glioblastoma multiforme; Glioma; Gliomatosis cerebri; High grade astrocytoma; High grade glioma; Intraosseous meningioma; Low grade astrocytoma; Low grade glioma; Lung cancer metastasis; Malignant glioma; Malignant meningioma; Meningioma; Metastasis; Metastatic melanoma; Mixed glioma; Mobile phones and brain tumors; Oligoastrocytoma; Oligodendroglioma; Pilocytic astrocytoma; Pituitary adenoma; Pituitary tumor; Primary brain tumor; Radiotherapy; Schwannoma; Secondary brain tumor; Sphenoid wing meningioma; Skull base tumors; Skull base meningioma (1); Skull base meningioma (2); Skull bone tumor cranioplasty; Stereotactic radiosurgery (SRS); Trigeminal Schwannoma; Vestibular Schwannoma; WHO astrocytoma grade; WHO meningioma grade
 
 
Home | Contents | What's New | Feedback | About | Mission | Disclaimer | Contact Us | Sitemap

© 2006. G. Khurana. All rights reserved.