• Clinical science

Brain tumors

Abstract

Brain tumors are masses of abnormal cells within the brain. They can be primary or metastatic, benign or malignant. Common tumors in children are pilocytic astrocytomas, meningiomas, medulloblastomas, ependymomas, and craniopharyngiomas. Adults most often develop glioblastoma multiforme, meningiomas, hemangioblastomas, schwannomas, oligodendrogliomas, and pituitary adenomas. Clinical features and radiological findings vary according to the type, location, and onset of the tumor. Magnetic resonance imaging (MRI) is the primary diagnostic method. Removal of the entire tumor is a prerequisite for remission. The histological grade of the tumor, which is determined postoperatively, is an important factor in determining the prognosis. Malignant tumors usually require additional treatment with radiotherapy and/or chemotherapy.

Astrocytomas (e.g., pilocytic astrocytoma, glioblastoma multiforme), meningiomas, pituitary adenomas, and schwannomas are discussed in separate learning cards.

Epidemiology

  • Sex: > (except meningiomas)
  • Age
    • Children
      • Brain tumors account for ∼ 20% of cancer cases and are the primary cause of cancer deaths in children in the US.
      • Most common primary brain tumors: astrocytoma, medulloblastoma
    • Adults
  • ∼ 70% of brain tumors are metastases, while ∼ 30% are primary brain tumors.
  • ∼ 40% of primary brain tumors are benign.

References:[1][1][2][3][4][5][6][7]

Epidemiological data refers to the US, unless otherwise specified.

Classification

2016 World Health Organization classification of CNS tumors

General clinical features of brain tumors

Symptoms depend on the type and location of the tumor (see “Differential diagnoses of brain tumors” below). Onset is usually insidious.

References:[1][8][9]

General radiological findings of brain tumors

Intracranial tumors have different radiological features, depending on whether they derive from brain parenchyma (intra‑axial) or associated structures (extra‑axial).

General Intra-axial lesions Extra-axial lesions
  • Strong contrast enhancement
  • Necrotic areas within the tumor
  • Irregular border
  • Perifocal edema
  • Infiltration of the ventricles → Consecutive CSF circulatory dysfunction with hydrocephalus is possible.
  • Claw sign: unaffected brain parenchyma “embracing” the lesion at sharp angles
  • The lesion connects directly to grey matter.
  • Perifocal edema more distinct

References:[1][10][11][12][13][14]

Primary brain tumors

  • Primary brain tumors arise within the CNS
  • Metastasis

Pediatric primary brain tumors

Pilocytic astrocytoma

Medulloblastoma Ependymoma Craniopharyngioma Pinealoma
Precursor
  • Primitive, neuroectodermal tissue
  • Rathke pouch
  • Pineal gland
Typical location
  • Posterior cranial fossa (infratentorial)
  • Cerebellar vermis (infratentorial)
  • Suprasellar region (supratentorial)
Typical histology
  • Perivascular pseudorosettes
  • Large vacuolated cells with round nuclei (fried egg cells)
  • Lymphoid stroma

In children, most primary brain tumors arise infratentorially, craniopharyngiomas being an important exception!

Adult primary brain tumors

Glioblastoma multiforme

Meningioma

Hemangioblastoma

Schwannoma

Oligodendroglioma

Pituitary adenoma

Precursor
  • Arachnoid cap cells
  • Uncertain origin
  • Pituitary adenotrophic cells (typically lactotrophs)
Typical locations
  • Cerebral hemispheres (supratentorial)
    • May cross the midline (butterfly glioma)
  • Extra-parenchymal tumor that can occur in supratentorial or infratentorial regions
  • Cerebellopontine angle (infratentorial)
  • Frontal lobes (supratentorial)
  • Sella turcica (supratentorial)
Typical histology
  • Densely packed thin-walled capillaries
  • Spindle cells in palisades (Antoni A tissue) alternating with myxoid areas (Antoni B tissue)
  • S-100 positive
  • Large vacuolated cells with round nuclei (fried egg cells)
  • Chicken-wire pattern of capillary anastomoses
  • Monomorphic, acidophilic or basophilic, polygonal cells arranged in sheets or cords

In adults, most primary brain tumors arise supratentorially, hemangioblastomas and schwannomas being important exceptions!

References:[1][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]

Pilocytic astrocytoma

Medulloblastoma

  • Description:: a highly malignant tumor derived from primitive, neuroectodermal tissue
  • Epidemiology
    • Peak incidence: 1st decade
    • Most common malignant pediatric brain tumor (approx. 20–25% of all cases)
  • Associated conditions
    • Turcot syndrome
  • Clinical features
  • Diagnostics
    • Imaging
      • Intraparenchymal contrast-enhancing mass
        • CT: hyperdense mass
        • MRI
          • T1: hypointense
          • T2: iso or hyperintense
    • Biopsy: anaplastic small round blue cells that surround a central neuropil (Homer-Wright rosettes)
  • Treatment
    • Resection
    • Adjuvant therapy
  • Prognosis
    • Poor prognostic factors
      • Inadequate resection
      • Presence of drop metastases
      • HER2/neu mutation

Ependymoma

Craniopharyngioma

Glioblastoma multiforme

Meningioma

Hemangioblastoma

  • Description: : a benign, highly vascularized neoplasm
  • Epidemiology
    • Rare
    • Peak incidence: 20–50 years
  • Associated conditions
  • Clinical features
  • Diagnostics
    • Imaging
      • Sharply demarcated intra-parenchymal mass
        • 60% are cystic with a non-enhancing wall and an enhancing mural nodule
        • 40% are solid
      • MRI
        • T1: hypointense or isointense
        • T2: hyperintense
    • Biopsy: thin-walled capillary vessels, densely packed together with scarce parenchyma
  • Treatment
    • Resection
    • Antiangiogenic therapy
  • Prognosis
    • Risk of recurrence is generally < 25 %

Schwannoma

Oligodendroglioma

  • Description: : a tumor that arises from oligodendrocytes
  • Epidemiology
    • Median age: 40–50 years
  • Clinical features
    • The most common location is the cerebral hemisphere (typically the frontal lobe) → seizures, focal neurological deficits, personality changes
  • Diagnostics
    • Molecular testing: assessment of 1p/19q codeletion
    • Imaging
      • Intra-parenchymal tumor with calcifications
      • CT
        • Hypodense lesion
      • MRI
        • T1: hypointense or mixed lesions
        • T2: hyperintense lesions
    • Biopsy
      • Cells with a clear cytoplasm and round nucleus (fried egg cells)
      • Chicken-wire pattern of capillary anastomoses
  • Treatment
  • Prognosis
    • Almost 100% recurrence rate
    • 5-year survival rate ∼ 50–60%
    • Good prognostic indicator
      • Presence or absence of 1p/19q codeletion → better response to chemotherapy and radiotherapy

Pituitary adenoma

Treatment

Prognosis

WHO grade

Mean survival time

Most common tumors
I > 5 years
II 3–5 years
III 2–3 years
IV 6–15 months

The WHO grading assesses the malignancy of the tumor based on the mean survival time!

Brain metastases

  • Epidemiology: most common cause of brain tumors in adults
  • Etiology
  • Clinical features
    • Acute or subacute onset of symptoms due to rapid tumor growth
      • Headaches
      • Cognitive deficits
      • Focal neurological deficits
      • Seizures
  • Diagnostics
    • Neuroimaging findings
      • Well-circumscribed tumors at the junction of gray and white matter; and/or watershed areas of the arterial system
    • Work-up if the primary tumor is unknown
      • Whole body contrast CT and/or PET scan
  • Treatment
  • Prognosis
    • Without treatment: mean survival ∼1 month
    • With treatment: mean survival < 1 year