Ch34 Primary tumours - classification and tumour markers Flashcards
What WHO grade is a pleomorphic xanthoastrocytoma?
2
What WHO grade is a SEGA?
1
What WHO grade is an anaplastic oligodendroglioma?
3
Which meningiomas are grade 2?
Atypical Clear cell Choroid
Which meningiomas are grade 3?
Anaplastic Rhabdoid Papillary
What proportion of brain tumours present with seizures?
26%
What proportion of brain tumours are infratentorial in children?
0-6months 27% 6-12months 53% 12-24months 74% 2-16 years 42%
Would you give prophylactic anticonvulsants to brain tumour patients?
Level I evidence : prophylactic AEDs should not be used routinely in patients with newly diagnosed brain tumors Level II evidence : in patients with brain tumors undergoing craniotomy, prophylactic AEDs may be used, and if there has been no seizure, it is appropriate to taper off AEDs starting 1 week post-op Glantz et al. 2000 Practice parameter (American Academy of Neurology)
How does avastin work?
Bevacizumab - anti VEGF antibody, may be useful in vestibular schwannomas due to NF2
How does Tamoxifen work?
Oestrogen receptor inhibitor - used in premenopausal women with ER+ breast ca. (Protein kinase C inhibitor at high doses)
How do Carmustine and lomustine work?
DNA crosslinks, carbamoylation of amino groups
How do Temozolomide and procarbazine work?
Alkylating agent The active metabolite is monomethyl triazenoimidazole carboxamide (MTIC). The mutagenic/cytotoxic effect of MTIC is associated with alkylation (methylation) to DNA at various sites primarily at the O6 and N7 positions on guanine. Most cells can repair this damage via MGMT. Temozolomide is more effective against tumors with low MGMT activity i.e. when there is MGMT promoter methylation (which includes many glioblastomas).
In what percentage of cases is the intraoperative pathological diagnosis different from the definitive?
3-10%
What does a +ve GFAP stain indicate?
Likely glial tumour (astrocytes>oligodendrogliomas)
What immunohistochemical stain would you use to confirm malignant melanoma?
S-100
Which tumours are +ve with EMA?
Meningiomas Renal cell Ca mets Ependymomas
A useful marker of cell proliferation
Ki-67 / MIB-1
What is serum S-100 useful for?
Raised levels in brain injury (trauma) and CJD (confirme with high 14-3-3)
What do raised CSF CEA levels indicate?
Metastatic lung Ca>Breast Ca>melanoma>bladder
What are the 3 types of IDH wildtype GBM?
Giant cell glioblastoma Epitheloid glioblastoma Gliosarcoma
What mutation is seen in diffuse midline gliomas?
H3 M27K-mutant
What molecular features are found in oligodendroglioma?
1p 19q co-deletion
What are the different histological subtypes of epiendymoma?
Myxopapillary Papillary Clear cell Tanycytic RELA fusion positive
What is Lhermitte-Duclos disease?
Dysplastic cerebellar gangliocytoma
How are medulloblastomas defined Genetically?
Wnt-activated SHH-activated (TP53 mutant or WT) Group 3 Group 4
How are medulloblastomas defined Histologically?
Classic Nodular / desmoplastic Extensive nodularity Large cell / anaplastic All are WHO 4!
What tumours arise directly from the pineal gland?
Pineocytoma WHO 1 Pineal parenchymal tumour of intermediate differentiation WHO 2/3 Pineoblastoma WHO 4 Papillary tumour of the pineal gland WHO 2/3
What WHO grade are ATRTs?
Atypical teratoid / rhabdoid tumour = WHO grade 4
What are the different subtypes of germ cell tumour?
Mnemonic: G E T - M Y - C T Germinoma Embryonal carcinoma Teratoma (immature and mature) Mixed germ cell tumours Yolk sac tumour Choriocarcioma Teratoma with malignant transformation
What are the subtypes of craniopharyngioma?
Adamantinomatous (paediatrics) Papillary (adults)
What symptoms are related to frontal lobe tumours?
Hemiparesis (m1) Personality change Abulia / Dementia Expressive dysphasia (IFG) Frontal eye field (MFG) Apraxia (Premotor area)
What symptoms are related to temporal tumours?
Olfactory / auditory hallucinations Deja-vu Memory impairment Visual field deficit Seizures
What symptoms are related to parietal tumours?
Sensory/motor impairment Homonymous hemianopsia Agnosias (inability to interpret sensory inputs) Apraxia (inability to construct movements)
What are the causes of headache in brain tumour?
Raised ICP (mass effect / hydrocephalus / haemorrhage) Dural / periosteal invasion Diplopia from cranial neuropathy or raised ICP
What clinical features are suggestive of a cerebellar hemisphere lesion?
Limb ataxia, dysmetria and intention tremor
What clinical features are suggestive of a cerebellar vermis lesion?
Truncal ataxia Broad based gait Titubation
What imaging should be requested in a patient with a suspected posterior fossa lesion?
MRI brain and spine (for drop mets)
How do you treat a patient with a p-fossa lesion and hydrocephalus?
- CSF diversion and delayed surgery if in extremis 2. Dexamethasone and surgery within 24 hours If neurologically stable
What are the concerns in placing a VP shunt in a patient with a p-fossa tumour?
- Seeding malignant cells 2. Infection 3. Lifelong shunt 4. Prolonged hospital stay 5. Upward transtentorial herniation
What is the most common tumour in a neonate?
Teratoma
What are the most common presenting features for tumours in a child?
Vomiting Arrest Regression of development Macrocrania Failure to thrive / poor feeding Seizures
What dexamethasone dose is used in paediatrics?
0.5-1 mg/kg loading 0.25-0.5 mg /kg / day divide QDS or TDS
Which tumours are most common in the first year of life?
Pilocytic astrocytoma Diffuse midline glioma Choroid plexus tumour Ependymoma Craniopharyngioma Medulloblastoma
What are the histological features of a LGG?
Increased cellularity Nuclear atypia Increased perineuronal and perivascular cells Subpial neoplastic cell accumulation
What are the classical features of meningiomas?
Keratinous whorls Psammoma bodies Intranuclear pseudoinclusions
What des luxol fast blue stain?
Myelin
What does reticulin stain tell you about pituitary lesion?
Reticulin stains connective tissue in the normal pituitary gland which is lost in pituitary adenomas
What is trichrome stain used for?
Delineates the sarcomatous component of gliosarcomas
What stains are suggestive of melanoma?
S100
What stain is positive with meningiomas, ependymomas and chordomas?
EMA (epithelial membrane antigen)
Which CNS tumour is positive for cytokeratin CAM5.2, KIR7.1 and synaptophysin?
Choroid plexus papilloma.
Also used to diagnose metastatic carcinomas
What is GFAP?
Glial fibrillary acid protein - positive in glial cell tumours such as oligodendrogliomas
What is S100?
A calcium binding protein. Used to diagnose metastatic melanoma and also to confirm the diagnosis of schwannoma or neurofibroma (less staining with neurofibromas)
How can hemangioblastoma be differentiated from renal cell ca histologically?
EMA is positive with renal cell ca but negative with haemangioblastoma
What is Ki-67 antibody?
A monoclonal mouse antibody to human Ki67 which is expressed in all phases of the cell cycle except G0. It is a marker of cell proliferation and correlates with the degree of malignancy
What do chromogranin and synaptophysin stain?
Synaptic vesicles.
What do CD3 and CD5 stain?
T-cells
What do CD20 and CD30 / 138 stain?
B-cells and plasma cells
What does CD56 stain?
Neuroendocrine cells (small cell lung ca, pheochromocytoma, merkel cell tumour etc and NK-cells
What do high beta-HCG level suggest?
Released from syncitiotrophoblasts it is raised in Pregnancy and with Choriocarcinoma. If plasma:CSF beta-HCG is >2% then diagnostic of cerebral choriocarcinoma or embryonal cell ca.
Who do high AFP levels suggest?
Open neural tube defect Hepatic tumour Teratoma Testicular tumours
What does high CSF Carcinoembryonic antigen suggest?
Colorectal adenoCa Lung and breast Ca with leptomeningeal spread
What conditions cause a rise in serum S100?
Head injury CJD (also check for CSF 14-3-3)
What are the driving rules for brain tumour surgery?
Craniotomy for low grade = 1 year Craniotomy for high grade = 2 years if no evidence of progression TSH no restriction Craniotomy for pituitary 6 months SRS no driving for one month Post-fossa surgery - no restrictions If single seizure and no abnormality on EEG/Scan then 6 months If epilepsy then 12 months
Which brain tumours are the most common?
Meningioma 36% > pituitary 15.5% > GBM 15.1% > Nerve sheath tumour 8% > Diffuse astrocytoma 2.3% > CNS lymphoma 2%
What tumours are most likely to cause brain metastases?
Lung > Breast > Melanoma > Colon > Prostate > Liver & pancreas
Where are metastases found?
80% cerebral hemispheres 15% posterior fossa 5% brainstem
What are the indications for stereotactic biopsy of a tumour?
Deep lesions, eloquent cortex, infiltrative and not curable with surgery (e.g. lymphoma). Do not perform if risk of haemorrhage!
How do you perform a stereotactic biopsy of a lesion in the lower pons?
Contralateral frontal extraventricular approach
How do you biopsy a lesion int he Midrain and upper pons?
Ipsilateral transfrontal. Requires an intraventricular approach through the anterior thalamus and cerebral peduncle.
What stereotactic approach do you use for medial pontine, lower midbrain or rostral medulla biopsy?
Suboccipital trans middle cerebellar peduncle approach
What are the open approaches to the brainstem?
Midbrain = Lateral mesencephalic sulcus, supracollicular, infracollicular, perioculomotor zone
Pons: ventral = peritrigeminal
dorsal = floor of 4th ventricle = suprafacial, infrafacial, acoustic area (lateral)
Medulla: ventral = pre- or post-olivary sulcus
dorsal = median sulcus, intermediate sulcus or lateral sulcus
Do you do stereotactic biopsies through an occipital transtentorial approach?
NO - risk to CN4 as well as large veins
What is the prognosis of a patient with a GBM and KPS<70?
2 months (will have conservative management as KPS is too low for surgical intervention)
What are the features of tumefactive necrosis on MR spectroscopy?
High glutamate peak with reduced NAA
Choline, lipid and lactate are high.
No change in rCBF
What are the features of GBM on MR spectroscopy?
High Chol:Cr ratio
Low NAA
Low myoinositol
Lipid choline and lactate are raised
Perfusion imaging shows marked increase in rCBF
What are the features of lymphoma on MR spectroscopy?
Very high choline peak and very low NAA. rCBF is only modestly elevated.
What is the dose of 5-ALA?
20 mg/Kg
What does 5-ALA signal correlate with?
Cell density
How does 5-ALA work?
Converted to Protoporphyrin IX which fluoresces under UV light (405 nm wavelength filter)
What proportion of craniopharyngioma patients have endocrine dysfunction at presentation?
75%
Most frequently GH deficiency!
What is the prevalence of DI in craniopharyngioma at diagnosis?
Up to 1/3
What is the risk of DI and panhypopituitarism post-op craniopharyngioma resection?
75%
What is the consequence of hypothalamic injury with craniopharyngioma?
Hyperphagia
Obesity
Agressive behaviour
Altered neuropsychology
What proportion of patients are obese post-op craniopharyngioma resection?
80%
Between 5-50% are obese pre-operatively
What is the main cause of morbidity following craniopharngioma resection?
Hypothalamic injury
What is the treatment strategy for craniopharyngiomas presenting with raised ICP or visual loss?
Acute treatment of hydrocephalus and cyst aspiration
MRI post cyst aspiration is then needed to plan definitive treatment
How are purely cystic craniopharyngiomas managed?
Catheter with Ommaya reservoir insertion to allow repeated aspiration. Intracystic INF-alpha if recurrent.
Intracystic Yttrium-90 and Phosphorus-30 or Bleomycin not effective
What proportion of patients with craniopharyngioma and visual dysfunction with improve with treatment of raised ICP?
2/3
What is the only independent risk factor for severe obesity in patients with craniopharyngioma?
Degree of hypothalamic involvement pre-operatively
What is the Paris grading for craniopharyngiomas (pre-op)?
0 = No involvement
1 = Distortion / elevation of floor of 3rd ventricle
2 = Floor of 3rd ventricle not visible due to invasion
Puget et al 2007
What is the Paris grading for craniopharyngiomas (post-op)?
0 = Intact
1 = Breech or residue on the infundibulum / floor of 3rd ventricle
2 = Severe injury to floor of 3rd ventricle
How does the pre-op Paris grading of craniopharyngiomas guide treatment strategy?
0 = Complete resection suitable
1 = Total resection but spare infundibulum
2 = Subtotal resection sparing the hypothalamus and local irradiation to residual
What is the effectiveness of radiotherapy for paediatric craniopharyngiomas?
80% disease control at 10 years
What are the risks of radiotherapy for craniopharyngioma?
Late onset Moya-Moya syndrome
Tumour genesis
Cognitive dysfunction
Proton beam reduces irradiation of the optic pathway and hypothalamus
Where should radiotherapy be targeted when treating craniopharyngioma?
The solid portion
Cystic components should be aspiration pre-radiation
What is the effectiveness of radiotherapy following subtotal resection?
Risk of progression falls to 15-20% with radiotherapy compared to 80% with surgery alone
What mutation has been found in craniopharyngioma?
Beta-catenin (CTNNB1) mutations are found in a subset of adamantinomatous craniopharyngiomas suggesting Wnt signalling abnormalities are associated
What WHO grade are craniopharyngiomas?
WHO grade 1
How should patients with craniopharyngioma be worked up?
Radiology (MRI + CT)
Endocrinology
Opthalmology - papilloedema / visual fields
Neuropsychology
