Central Nervous System Tumors - Brain Tumors

Diagnosis

Indications for Testing

• New onset of headaches associated with focal neurologic deficits in patient without previous headaches
• Change in character of headaches in patient with previous headaches
• New onset of seizures

Laboratory Testing

• CBC, chemistry profile, erythrocyte sedimentation rate (ESR)
  • Very few abnormalities except for possible increased ESR
  • Not used to make diagnosis

Histology

• Immunohistochemistry
  • Glial tumors – Ki-67, GFAP, S-100, p53, IDH1
  • Dysgerminomas – PLAP, CD117 (c-Kit), beta-hCG, AFP
  • Capillary hemangioblastomas – inhibin, D2-40
  • Meningioma – Ki-67, claudin1
  • Medulloblastoma – synaptophysin
• Mutation testing – 1p/19q deletion by FISH
  • Presence of codeletion establishes diagnosis of oligodendroglioma
  • Gain of chromosome 19 supports diagnosis of high-grade astrocytoma

Imaging Studies

• CT, MRI – MRI is more sensitive than CT for diagnosis and for identifying tumor type
• PET – used in assessing diagnosis, grading gliomas and differentiating between tumor recurrence and radiation necrosis

Prognosis

• Differentiation of astrocytomas from oligodendrogliomas has prognostic and therapeutic importance

• FISH
  • Combined loss of short arm of chromosome 1 (1p) and long arm of chromosomes 19 (19q) is a prognostic marker of oligodendrogliomas
    • 1p/19q codeletion has a better prognosis than those with a single deletion or none
    • Loss of 1p may identify treatment-sensitive malignant gliomas, in particular subtypes of anaplastic oligodendroglioma
      • Prognostic relevance in low-grade tumors less well-characterized
    • 1p/19q codeletion is mutually exclusive for TP53 and EGFR amplification
    • 1p/19q codeletion is frequently associated with IDH1 or IDH2 mutations
  • IDH1 mutation – improved outcome in glioblastoma if present
    • Rarely occurring in primary glioblastomas
    • Higher frequency in secondary glioblastomas
  • MGMT methylation
    • Improves prognosis if treated with temozolomide and radiotherapy
    • Found in glioblastoma
  • Immunohistochemistry – p53

Differential Diagnosis

• Infections
  • Meningitis
  • Encephalitis
  • Brain abscess
• Parasites
  • Taenia solium
  • Toxocara spp
• Seizure disorders 
• Migraine headache
• Stroke
• Vasculitis

Clinical Background

Central nervous system (CNS) tumors cause either focal or generalized neurologic symptoms.

Epidemiology

• Incidence – 18/100,000 for both benign and malignant brain tumors
  • ~50% are histologically benign
• Sex – M<F (minimal)
  • Higher meningioma incidence in females
• Age – highest increased incidence in patients >70 years
  • Peak incidence for anaplastic glioma/glioblastoma is 45-55 years

Risk Factors

• High-dose ionizing radiation (gliomas)
• Familial
  • Neurofibromatosis 1 (NF1) (glioma)
  • Neurofibromatosis 2 (NF2) (schwannoma, meningioma, glioma)
  • Schwannomatosis (schwannoma, meningioma)
  • Malignant rhabdoid tumor predisposition
  • Medulloblastoma predisposition
  • Nevoid basal cell carcinoma syndrome (medulloblastoma)
  • Lhermitte-Duclos disease (cerebellar dysplastic gangliocytoma)
  • Tuberous sclerosis complex (astrocytoma)
  • von Hippel-Lindau disease (hemangioblastoma, endolymphatic sac tumor)
  • Turcot syndrome (medulloblastoma, glioblastoma)
  • Constitutional mismatch repair-deficiency syndrome (glioblastoma)
  • Li-Fraumeni syndrome (glioma, astrocytomas, choroid plexus tumors, medulloblastoma)
  • Retinoblastoma
  • Multiple endocrine neoplasia type 1 (pituitary adenoma, glioma)
  • Carney complex (pituitary adenoma, schwannoma)
  • Pituitary adenoma predisposition
  • Gorlin syndrome (medulloblastoma)
• Viral infection
  • HIV infection is associated with an increased risk of CNS lymphoma

Pathophysiology

• Histologically classified as glioma or non-glioma
  • Gliomas (about 50% of primary brain tumors) – most common
    • Astrocytomas (includes glioblastoma multiforme [GBM])
      • GBM – 50% of gliomas
      • Low-grade astrocytoma can transform into glioblastoma within 5-10 years
    • Oligodendrogliomas
    • Mixed gliomas
    • Ependymomas
  • Non-gliomas
    • Meningiomas – usually benign
    • Pituitary adenomas – often benign
    • Primary CNS lymphoma
    • Medulloblastoma – childhood cerebellar tumor
    • Brain metastases – neoplasm of lung, breast, or skin (melanoma) most common

Clinical Presentation

• Headache, nausea, vomiting, hemiparesis, aphasia, memory loss, language deficit, visual deficit
• Seizures – more common with gliomas

Pediatrics

Clinical Background

Epidemiology

• Incidence – 2-5/100,000

Risk Factors

• Irradiation
• Familial syndromes (refer to Clinical Background tab)

Clinical Presentation

• Focal neurologic deficits
• Visual field deficits
  • Paresis of upgaze (setting sun sign)
• Nausea, emesis, headaches much more common than in adults

Specific tumors

• Glioma
  • Incidence – 60% of childhood CNS tumors
  • Age – 5-10 years; peak is 6 years
  • Seizures more common with this tumor
• Medulloblastoma
  • Incidence – 6/100,000
    • Most common childhood malignant CNS tumor
  • Age – peak is 6 years
  • Sex – M>F; 1.6:1
  • Ethnicity – more common in Caucasians
• Ependymomas
  • Incidence – 10% of childhood tumors
  • Clinical presentation – predilection for 6th and 7th nerve palsies, loss of hearing and swallowing
• Craniopharyngiomas
  • Incidence – 5-10% of all childhood CNS tumors
  • Age – bimodal peaks: 6-10 years, 11-15 years
  • Clinical presentation – visual signs and symptoms and endocrine abnormalities
• Teratoma
  • Astrocytoma, primitive neuroectodermal and choroid plexus papillomas
  • Incidence – rare (1-3/1,000,000 live births)
  • Age – neonate (usually <1 year)
  • Clinical presentation
    • Often diagnosed prenatally by ultrasound
    • Bulging fontanelle, failure to thrive, apnea, emesis, abnormal head circumference
    • Benign tumors often exhibit malignant behavior in this age group

Diagnosis

• Refer to Diagnosis tab

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory