tumors

Question 1

CNS tumors epidemiology

Answer 1

Overall: intracranial brain tumors: more common, intraspinal tumors less common

In kids- 20% of all kid cancers are brain tumors (second to leukemia)

Location- CNS tumors occur most 75% in posterior fossa
Adult- CNS tumors are most often supratentorial (localization of adult CNS tumors follows a mass distribution- most occur in the cerebral hemispheres, frontal lobes most often because they are the biggest), Tumors met to brain aare more common than primary brain tumors

Question 2

Primary brain tumors

Answer 2

meningiomas 35%, gliomas 29% (glioblastoma 15, lower grade asrtocytomas)

Question 3

General principles of primary CNS tumors

Answer 3

Both low and high grade neoplasms have significant morbidity and mortality- diffusely infiltrative, involvement of critical anatomic areas, inability to resect critical anatomic areas, most of the time do not spread outside of brain (met is extremely uncommon- may spread through subarachnoid space

Question 4

Astrocytomas

Answer 4

the most common glial tumor, (glioblastoma is a high grade astrocytoma)

Diffuse astrocytomas have an inherent tendency to progress to higher grades (anaplastic astrocytoma and glioblastoma) over time
Annual incidence 3-4/100k, at least 8-% are glioblastomas, –> seizures, focal neurodeficits (gradual not abrupt), headaches

Question 5

Diffuse cerebral astrocytic neoplasms

Answer 5

Astrocytoma- age at diagnosis- 35yrs, survival of 80 months

Anaplastic astrocytoma- age at 40 yrs and survive 30 mos

Glioblastoma multiform- 62/48 survival of 14 mos

Question 6

Grading of astrocytomas

Answer 6

Grade 1 (not diffuse)- pilocytic astrocytoma
Grade 2- Astrocytoma (diffuse)- cellularity is moderately increased and occassional nuclear atypia
Grade 3- Anaplastic astrocytoma- increased cellularity, nuclear atypai and MITOTIC ACTIVITY
Grade 4- glioblastoma multiform- pleomorphic astrocytic cells, brisk mitotic activity, prominent microvasculat proliferation and necrosis

Question 7

pilocytic astrocytoma WHO grade 1

Answer 7

most common glioma in children, typically present in 1st 2 decades, clinical features- most commonly occur in cerebellum, may also occur in optic nerve 3rd ventricle, hypothalamus, brainstem, and cerebral hemispheres
Presentation with focal neurologic deficit, seizures, or s/s of increased intracranial pressure

Imaging- well demarcated, cystic contrast enhancing tumor

Prognosis- slow growing, overall excellent prognosis, surgery is often curative

Question 8

Oligodendroglioma

Answer 8

adults in 5th and 6th decade, clinical SS- long history progressive neurological symptoms (seizures, headache focal signs), imaging- well defined hypodense /hypointense mass, may see calcification)

Prognosis- Median survival 5-10yrs for grade 2, better survival than astrocytomas

2 WHO grades (oligodendroglioma, anaplastic oligodendroglioma)

Allelic loss of chromosome 1p and 19q are predictors of prolonged survival and susceptibility to chemo in anaplastic oligodendrogliomas

Fried egg appearance

Question 9

Ependymoma

Answer 9

typically occurs in kids and young adults, occurs along ventricular system, usually posterior fossa 4th ventricle, clinical SS- hydrocephalus, occasionally seizures

Imaging- well circumscribed mass

2 grades- 2 ependymoma, anaplastic epedymoma

Prognonis- 4 yrs

Rosette appearance, look like mini ventricles

Question 10

Etiology of gliomas

Answer 10

No cause identified in most common types, Familial tumor(rare <5%)

Li-fraumeni syndrome (TP53 germline mutations)- predominantly astrocytoma

Turcot syndrome (APC and DNA mismatch repair genes)- glioblastoma or medulloblastoma

Cowden syndrome (PTEN gene mutation)- cerebellar gangliocytoma)

NF1, NF2, Tuberous sclerosis, von Hippel Lindau

Only environmental factor definitively associated with increased risk of brain tumors is therapeutic radiation

Question 11

Genetic analyses of gliomas

Answer 11

astrocytomas and oligodendrogliomas (WHO grades 2 and 3), Mutation in the isocitrate dehydrogenas (IDH) genes (IDH1 an d2), Common in both low grade astrocytomas and oligodendrogliomas- leads to increased production of 2 hydroxyglutarate which interferes with gene expression, not found in pilocytic astrocytomas

Deletions of 1 p and 19q- diagnostic of oligodendroglioma, not found in astrocytomas

Gliobastoma- WHO grade 4, no mutation in IDH 1/2 a variety of other mutations present

Question 12

medulloblastoma

Answer 12

embryonal neuroepithelial neoplasm of posterior fossa tumor in children

Clinical features- cerebellar dysfunction Ataxia and increased intracranial pressure

Tendency to spread through CSF pathways
Surgery and radiation,

Craniospinal invasion,

Question 13

meningioma

Answer 13

Most common extraparenchymal neoplasm of CNS, Clinical features- Occurs in middle to late adult life, W>M, symptoms dependent on location may lead to increased intracranial pressure, focal signs, seizures
Dural based usually well defined, contrast- enhancing

Pathogenesis- unknown, significance of presense of progesterone receptors on cells and increased occurrence in women is not understood

Associations- previous radiotherapy and NF2, Genetic abnormalities- monosomy of chromosome 22 or mutation of NF2 gene

psammoma bodies and Whorls (look like tornadoes)

Question 14

Met tumors to the CNS

Answer 14

1st presentation of malignancy, most origiinate in the lung or breast, distinct contrast enhancing mass
Prognosis- poor most die within a few months

Question 15

Peripheral nerve sheath tumors- schwannomas

Answer 15

Benign tumor composed schwann cells, most common 4th to 6th decades

Involve peripheral nerves, usually in head and neck and flexor surfaces of extremities, Asymptomatic masses, spinal tumors- radicular pain

Intracranial tumors most often in cerebellopontine angle and attached to 8th nerve, symptoms of hearing loss, tinnitis, facial numbness, Scans show well defined contrast enhancing mass, associated with neurofibromatosis type 2

Question 16

Peripheral nerve sheath tumor Neurofibromas

Answer 16

benign tumor composed of schwann cells, fibroblasts, and perineural cells, Associated with neurofibromatosis type 1, Multiple forms
Cutaneous (localized) neurofibroma most common, in dermis or subdermal, usually solitary (not associated with NF1)
Peripheral nerve- Solitary, plexifrom usually in NF1, transformation of multiple fascicles of nerves into neurofibroma with preservation of anatomic configuration, typically affects larger nerves or a plexus, increased likelihood of malignant transformation

Question 17

NF1 (vonrecklinghausen disease)

Answer 17

autosomal dominant, almost complete penetrance, however 50% represent new mutations

much more common than NF2
Criteria include: neurofibromas, cafeaulait spots, lisch nodules, optic glioma, osseous lesions, axillary freckling, family history

Associated tumors- NF (most important is neurofibromas that undergo transformation to malignant peripheral nerve sheath tumors)

Optic nerve gliomas and other astrocytomas, rhabdomyosarcomas, pheochromocytoma, carcinoid tumors)

Germline mutation in NF1 gene (a tumor suppressor gene) on chr 17, gene product- neurofibromin, mutation results in decreased neurofibromin protein levels

Question 18

von hippe. lindau disease

Answer 18

Autosomal dominant, hemangioblastomas of CNS and retina (cerebellar hemangioblastomas), renal cell carcinoma, pheochromocytoma, visceral cysts (pancreas, liver, and kidneys), retinal angiomas)

VHL gene on chr 3, VHL protein functions as a tumor suppressor protein which is inactivated with mutation

Question 19

Hemangioblastoma

Answer 19

Most commonly occurs in cerebellum (occasionally in cerebrum or spinal cord), symptoms usually secondary to increased intracranial pressure due to obstruction

MRI shows well-defined contrast enhancing cystic mass with mural nodule
Treatment- surgical resection WHO grade 1 rare reports of recurrence cell of origin not known

Question 20

Tuberous sclerosis

Answer 20

Autosomal dominant, seizures, autism, cognitive dysfunction

Development of hamartomas (tubers) and benign neoplasms, a hamartoma- a benign tumor like nodule composed of an overgrowth of mature cells and tissue normally present in the affected part, but with disorganiztion and often with one element predominating, subependymal giant cell astrocytomas, cutaneous angiofibromas, subungual fibromas, cardiac rhabdomyomas, renal angiomyolipomas, retinal hamartomas

TSC1 (chr 9- codes hartin), TSC2 (chr 16- codes protein tuberin), these proteins formdimers and regulate protein synthesis and cell proliferation inhibit mTOR)