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Brain & CNS tumors

The term ” brain tumors” refers to a mixed group of neoplasms originating from intracranial tissues and the meninges with degree of malignancy ranging from benign to aggressive
( McKinney PA Journal of Neurology , Neurosurgery & Psychiatry 2004 )

Primary brain tumors are uncommon – they account for about 1 % of all newly diagnosed cancers in the US and 2 % of cancer deaths In the UK they ( brain tumors ) are responsible for about 2 % of all cancers in adults – every year about 4000 people are diagnosed with brain tumor ( compared to about 40 000 women with breast cancer & about 25 000 men with prostate cancer ) Studies have shown that between 1990 and 2016 number of incident of CNS cancers have increased along all geographic locations ( this may be attributed to advances in diagnostic technologies particularly CT , MRI and it has been also hypothesized that ionizing radiation exposure from early CTs may have contributed to this although there is no strong evidence to support this ) CNS tumors in children and young adults where they respectively account for about 30 % and 20 % of cancer deaths Incidence varies by histologic type of tumor , age at diagnosis , sex , and race / ethnicity Most papers mention that CNS tumors are more common in men

Primary brain and spinal cord tumors are collectively called CNS tumors CNS tumors include tumors of the brain , cranial nerves , spinal nerves and meninges A heterogenous group which comprises of over 100 histologic types Vast majority of CNS tumors ( > 90 % ) happen in the brain and remainder are found in the meninges , spinal cord and cranial nerves Primary brain tumors are named according to the type of cells or the anatomic location they come from The classification is complex ( provided by WHO 2016 ) but broadly they can be

Non-malignant –benign Most are non malignant of which the majority ( in the US ) are meningiomas Meningiomas Schwannomas Chordomas Craniopharyngiomas Gangliocystomas Glomus jugulare Pituitary adenomas

Malignant- Most common malignant brain tumors ( BT ) are gliomas of which glioblastoma is the most common histologic subtype Gliomas- these are subdivided into
○ astrocytomas
○ ependymomas
○ Glioblastoma multiforme
○ medulloblastomas
○ oligodendrogliomas Others as
○ hemangioblastomas
○ rhabdoid tumors

Stages- Graded from
 I to IV ( WHO )- this indicates s tumors malignancy or benignity based on histologic features under a microscope and describes them as
 most malignant rapid growth , aggressive widely infiltrative rapid recurrence necrosis prone.

It should be noted that even the benign tumors can be lethal based on their location in the brain , their ability to infiltrate locally and their propensity to transform to a malignancy

Gliomas are the most common histological subtypes of primary CNS cancer and the remainder are made up of various histologies including tumours of glial origin , medulloblastomas , CNS lymphomas and meningiomas.

few established risk factors only consistent associations have been positive association with ionizing radiations ( for e.g from atomic weapons , previous therapeutic radiation ) and negative association with atopic conditions as asthma , eczema , food allergies some genetic syndromes have been associated with low frequency alleles are associated with increased risk of CNS cancers but these are responsible for a minority of cases 
( examples of these inherited syndromes include tuberous sclerosis , neurofibromatosis 1 & 2 , nevoid basal cell carcinoma syndrome and syndromes involving adenomatous polyps ) a multitude of risk factors have been studied including cell phone radiation , aspirin use , hormonal factors , low frequency magnetic fields , pesticides , dietary factors and industrial exposure – none of these have shown consistent association with risk of CNS cancers

Problems with recognition – Brain and CNS tumors are rare compared to other cancers but account for significant morbidity and mortality Currently there is no simple , population – wide screening test available for CNS tumors which allows for early , uniform detection Symptoms as headache or seizure are often too common , non-specific to indicate neuroimaging patients are usually diagnosed when major neurological symptoms emerge Presentation is often with constellation of non-specific symptoms and signs and progress to life threatening conditions before definitive radiological diagnosis Presentation manifest when the cancer becomes significantly large or extend to eloquent areas Managing CNS tumors is expensive- patients require access to neurological services , ICU units and highly specialised radiation and neuro-oncology services.

Adults with progressive , sub-acute loss of central neurological function- Consider urgent direct access 
MRI of the brain – or CT if MRI is contraindicated to be done
 within 2 weeks.

Children and young people with newly abnormal cerebellar or other central neurological dysfunction Consider very urgent referral for suspected brain or CNS cancer

Red flags – here the probability of an underlying tumor exceeds 1 % papilloedema significant alterations in consciousness , memory , confusion or co-ordination new epileptic seizure new onset cluster headache headache in a patient with previous h/o cancer particularly breast and lung headache with corresponding abnormal neurological findings or symptoms.

Orange flags – probability of 
underlying cancer is between
 0.1 % and 1 %

( these need careful monitoring ) new headache where a diagnostic pattern has not emerged after 8 weeks from presentation headaches made worse by exertion or Valsalva manoeuvre headache associates with vomiting pre-existing headache for some time which has changed significantly , has become more frequent new headache in a patient over 50 headaches that wake the patient from sleep confusion.

Yellow flags -here the chances of cancer are less than 0.1 % but this is above the population rate of 0.01 % diagnosis of migraine or tension headache isolated weakness or motor loss memory loss.

Glioblastoma – most common primary malignant brain tumor originate from glial or neuronal precursor cells they make up up to 16 % of all primary brain and CNS tumors glioblastoma is an umbrella term that encapsulates subtypes charecterized by distinct molecular properties uncommon in children diagnosed primarily at older age with a median age of diagnosis at 64 yrs most are located in the supratentorial region ie frontal , temporal parietal and occipital lobes followed by temporal & parietal lobes GBM’s hapen mostly in brain but can also be found in the brain stem , cerebellum and spinal cord GBM with a low survival rate are defined as grade IV presentation depends upon the size , location & the anatomic structures involved presenting features include
○ symptoms of raised ICP
○ seizure.

high malignant grade mainly due to its invasiveness which arises from the signaling pathway with tyrosine receptors incurable with a median survival of only 15months classical standard treatment is safe resection followed by concurrent chemoradiotherapy with subsequent adjuvant temozolomide

Astrocytoma – low grade gliomas originate in astrocytes -glial cells in the cerebrum which are star shaped as per WHO these can range from grade 1 to grade 4 most astrocytomas affect people > 40 Grade 1 – pilocytic astrocytoma , pleomorphic xanthoastrocytoma , subependymal giant cell astrocytoma ( SEGA ) Grade 2 diffuse astrocytoma Grade 3 anaplastic astrocytoma presenting features include- headache ( usually early morning ) , nausea , vomiting , cognitive difficulties , personality changes , gait disorders . localizing symptoms include seizures , aphasia or visual field defects , seizures can occur in about 90 % of patients with low grade glioma. Treatment is multimodal which includes surgical , medical and radiation therapies.

Meningioma – benign CNS tumor arising from the meninges of the brain & the spinal cord commonest primary CNS tumors accounting for about 37.6 % of them and about 50 % of all benign tumors typically present with gradual onset of symptoms in the later decades of life classified into 3 grades and about 1 % to 3 % of them can be transformed into malignant tumors with a 5 year survival rate of 32 to 64 % presentation depends upon the location and size – some patients may be asymptomatic whereas others may present with neurological deficits
○ headache ○ focal cranial nerve deficits ○ seizure
○ cognitive changes ○ weakness ○ vertigo / dizziness ○ ataxia / gait changes mean age of presentation is 66 yrs with a female preponderance 100 % of meningiomas have somatostatin receptor 2 ( SSTR2 ) 88 % have progesterone receptors , 40 % estrogen receptors and 40 % androgen receptors metastasis is rare – most common sites are lung and pleura.

low aggressiveness and better outcomes than other CNS tumors asymptomatic small sized tumors can be followed up with close observation lesions with accelerated growth are treated with maximum gross surgical resection radiotherapy – for e.g external beam radiotherapy or brachytherapy after surgical resection adjuvant therapies may be employed to reduce the recurrence rate.

Schwannoma benign well encapsulated , slow growing nerve sheath tumors made exclusively of Schwann cells can originate from myelinated central or peripheral nerve with Schwann cells often slow growing with delayed presentations – presentation depends upon the location and can include
○ asymptomatic mass , mild pain in the area or paraesthesia due to pressure on the parent nerve ○ sciatic schwannoma can mimick disc herniation ○ on ankle and wrist can present as tarsal tunnel syndrome or carpal tunnel syndrome ○ vestibular schwannoma aka acoustic neuroma can present with reduced hearing , tinnitus and imbalance. often observation is employed with MRIs to assess the rate of tumor growth local resection – it can also be problematic as it may result in significant phsyiological deficit.


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