Brain tumors

Brain tumors

Brain tumors are generally classified into primary and secondary brain tumors.
Primary brain tumors are a heterogeneous collection of neoplasms arising from the brain tissue or meninges, and vary from benign to highly malignant.
The most common benign brain tumor is a meningioma.
Primary malignant brain tumors account for 1% of all adult tumors but a higher proportion in children.
Primary brain tumors do not metastasize due to the absence of lymphatic drainage in the brain.
There are rare pathological subtypes such as medulloblastoma, which do have a propensity to metastasize; the reasons for this are not clear.


Most cerebral tumors are sporadic but may be associated with genetic syndromes such as neurofibromatosis or tuberous sclerosis.
Brain tumors are not classified by the usual TNM system but by the World Health Organization (WHO) grading I–IV; this is based on histology (e.g. nuclear pleomorphism, presence of mitoses and presence of necrosis), with grade I the most benign and grade IV the most malignant.
Although the lower-grade brain tumors (I and II) may be very indolent, with prognosis measured in terms of many years, these may transform to higher-grade disease at any time, with a resultant sharp decline in life expectancy.

The most common primary brain tumors in order of descending frequency:

Gliomas
60%
pituitary tumors
meningiomas
20%
10%


the most common glioma is aggressive glioblastoma multiforme (WHO grade IV)

Secondary brain tumors

Most malignant brain tumours are due to metastases, The rate is higher with primaries in the bronchus, breast and gastrointestinal tract.
Metastases usually occur in the white matter of the cerebral or cerebellar hemispheres but there are diffuse leptomeningeal types.
Contrast-enhanced CT showing a large metastasis within the left hemisphere (large arrow). There is surrounding cerebral edema, and a smaller metastasis (small arrow) within the wall of the right lateral ventricle. The primary lesion was a lung carcinoma.

Clinical features

The presentation is variable and usually influenced by the rate of growth. High-grade disease (WHO grades III and IV) tends to present with a short (weeks) history of mass effect (headache, nausea secondary to RICP), while more indolent tumors can present with slowly progressive focal neurological deficits, depending on their location
generalized or focal seizures are common in either.
Isolated stable headache is almost never due to intracranial tumor.

The size of the primary tumor is less prognostic significance than its location within the brain. Tumors within the brainstem will result in early neurological deficits, while those in the frontal region may be quite large before symptoms occur.
Magnetic resonance image showing a meningioma in the frontal lobe (arrow A) with associated edema (arrow B).
Magnetic resonance image of an acoustic neuroma (arrows) in the posterior fossa compressing the brainstem.

Investigations

Diagnosis is by neuroimaging and pathological grading following biopsy or resection where possible.
The more malignant tumors are more likely to demonstrate contrast enhancement on imaging.
If the tumor appears metastatic, further investigation to find the primary is required.

Management

Brain tumors are treated with a combination of surgery, radiotherapy and chemotherapy, depending on the type of tumor and the patient.
Advancing age is the most powerful negative prognostic factor in CNS tumors, so best supportive care (including glucocorticoid therapy) may be most appropriate in older patients with metastases or high-grade disease.
Treatment may not always be indicated in low-grade gliomas and watchful waiting may be appropriate, although a more aggressive approach is increasingly favored.
Dexamethasone given orally (or intravenously where RICP is acutely or severely raised) may reduce the vasogenic edema typically associated with metastases and high-grade gliomas.


Prolactin- or growth hormone-secreting pituitary adenomas may respond well to treatment with dopamine agonists (such as bromocriptine, cabergoline or quinagolide); in this situation, imaging and hormone levels may be all that is required to establish a formal diagnosis, precluding the need for surgery.
Surgical
The mainstay of primary treatment is surgery, either resection (full or partial debulking) or biopsy, depending on the site and likely radiological diagnosis.
In general, maximal safe resection is the optimal surgical management.
Meningiomas and acoustic neuromas offer the best prospects for complete removal and thus cure.


Pituitary adenomas may be removed by a trans-sphenoidal route, avoiding the need for a craniotomy.
Unfortunately, glioma, which account for the majority of brain tumors, cannot be completely excised, since infiltration spreads well beyond the apparent radiological boundaries of the intracranial mass. Recurrence is therefore the rule, even if the mass of the tumor is apparently removed completely.

Prognosis

The WHO histological grading system is a powerful predictor of prognosis in primary CNS tumors, though it does not yet take account of individual biomarkers. For each tumor type and grade, advancing age and deteriorating functional status are the next most important negative prognostic features. The overall 5-year survival rate of about 14% in adults masks a wide variation that depends on tumor type.


CEREBELLOPONTINE ANGLE TUMOR
CP angle is a triangular region in the posterior fossa bordered by the cerebellum, lateral pons, and petrous ridge
The most common cerebellopontine angle tumors is Acoustic neuromas (schwannoma),accounting for 80–90%.
Less common tumors at this site include meningiomas and primary cholesteatomas (epidermoid cysts).
Acoustic neuromas usually occur as isolated lesions in patients 30 to 60 years old, but may also be a manifestation of neurofibromatosis.

Investigations

MRI is the investigation of choice.
Management
Surgery is the treatment of choice. If the tumor can be completely removed, the prognosis is excellent, although deafness is a common complication of surgery. radiotherapy may be appropriate for some lesions.

Neurofibromatosis

Neurofibromatosis encompasses two clinically and genetically separate conditions, with an autosomal dominant pattern of inheritance. The more common neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene on chromosome 17.
NF1 is characterized by neurofibromas (benign peripheral nerve sheath tumors) and skin involvement and may affect numerous systems.
Neurofibromatosis type 2 (NF2) is caused by mutations of the NF2 gene on chromosome 22, and is characterized by schwannomas (benign peripheral nerve sheath tumors comprising Schwann cells only) with little skin involvement; the clinical manifestations are more restricted to the eye and nervous system.
Malignant change may occur in NF1 neurofibromas but is rare in NF2 schwannomas.


Neurofibromatosis 1 (von Recklinghausen disease) is a common autosomal dominant disorder related to mutations in neurofibromin 1 (NF1) on Ch.17.
In addition to unilateral acoustic neuromas, neurofibromatosis 1 is associated with
• cafe-au-lait spots on the skin( more than 6),
• cutaneous neurofibromas,
• axillary or inguinal freckles,
• optic gliomas,
• Lisch nodules (iris hamartomas),
• and dysplastic bony lesions.
Neurofibromatosis 2 is a rare autosomal dominant disorder caused by mutations in neurofibromin 2 (NF2) on Ch.22.
Its hallmark is bilateral acoustic neuromas, which may be accompanied by
• cafe-au-lait spots on the skin(less than 6),
• other central or peripheral nervous system tumors, including neurofibromas, meningiomas, gliomas, and schwannomas.

A café au lait spot (arrow A)

and subcutaneous nodules
(arrows B) on the forearm of a patient with neurofibromatosis type 1.
Axillary freckle
Iris hamatoma

CLINICAL FINDINGS

Insidious hearing loss is usually the initial symptom. Less often, patients present with facial weakness, facial pain. headache, vertigo, gait ataxia.
Unilateral sensorineural hearing loss is the most common finding on examination. Other frequent findings are ipsilateral facial palsy, depressed or absent corneal reflex, and sensory loss over the face. Ataxia, spontaneous nystagmus.
DIFFERENTIAL DIAGNOSIS
Acoustic neuroma must be distinguished from other cerebellopontine angle tumors. Meningioma should be considered in patients whose initial symptoms indicate more than isolated vestibulocochlear (VIII) nerve disease.
Cholesteatoma is suggested by conductive hearing loss, early facial weakness, or facial twitching.

Treatment

is complete surgical excision. Patients with acoustic neuroma and neurofibromatosis 2 may benefit from bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGFA).
In untreated cases, severe complications can result from brainstem compression or hydrocephalus.