Neuro-oncology Flashcards
How do you investigate a patient with multiple intracranial lesions and a history of breast cancer?
The patient will need a full metastatic work up with CT chest abdomen and pelvis, tumour markers if indicated and an MRI brain with and without contrast to further delineate the lesion.
What is the differential diagnosis of multiple intracranial lesions?
Metastasis – lung, breast, melanoma and leukaemia; Abscess – bacterial, toxoplasmosis, Cryptococcus, aspergillus, herpes encephalitis; Glioma – Multicentric GBM, tuberous sclerosis – giant cell astrocytomas, multiple meningiomas, lymphoma, PNET and multiple neuromas (NF); Inflammatory – tuberculosis, granuloma, amyloidosis, sarcoidosis, vasculitis; Demyelination – MS; Radiation necrosis; Vascular – haemorrhages, venous infarct, strokes and moya moya disease.
What are the indications for biopsy?
If no primary disease can be found (10%), to rule out radiation necrosis if previously had brain radiation or unusual presentation where infection or malignancy cannot be differentiated.
What are the indications for surgery on an intracranial metastasis?
Primary disease is controlled, expected disease free survival, good prognosis, KPS >70, young age, fewer than 4 lesions and absence of leptomeningeal enhancement.
What factors favour surgery over radiotherapy?
Surgical accessibility, undiagnosed primary allows histological diagnosis, rapid deterioration due to mass effect, lesion causing hydrocephalus, rapid weaning of steroids, cystic lesions, lesions >3cm and radioresistant tumours.
Which metastases are radioresistant?
Thyroid, renal and melanoma.
What factors favour radiotherapy over surgery?
Avoids multiple craniotomies, lesions which are radiosensitive (small cell lung ca, germ cell tumours, multiple myelomas and leukaemia) and patients not fit enough for surgery.
Should WBRT follow resection of the metastasis?
Yes – it significantly improves the control of intracranial disease.
What is the prognosis of multiple brain metastases?
8 weeks with steroids, 6 months with WBRT and 14 months with surgery and WBRT. Patients with more than 4 metastases are not treated surgically.
What is the differential diagnosis of leptomeningeal enhancement?
Neurogenic – high or low ICP; Inflammatory – sarcoid; Infection – meningitis including TB meningitis, fungal infection or granulomatous cell infiltration; Vascular – ischaemia, venous thrombosis, SAH, Trauma; Malignancy – local tumour infiltration, primary meningeal glioma, PNET, Primary meningeal melanoma and rhadomyosarcoma of the meninges.
What is the most common cause of meningeal carcinomatosis?
5% of all patients with cancer get meningeal carcinomatosis – mainly breast, lung, head and neck cancers, melanoma and gastric malignancies.
How would you investigate a patient with meningeal carcinomatosis?
CSF cytology, cranial and spine MRI, CT CAP for primary and meningeal biopsy from a region of meninges that enhances on the MRI if CSF cytology is non-diagnostic.
What is the diagnostic yield of an LP in meningeal carcinomatosis?
40-50% - but improves to 90% on the third LP if >10ml of CSF is taken every time.
What is the mechanism of invasion with meningeal carcinomatosis?
Haematogenous spread via dural arterial circulation and also in the spine retrograde venous circulation from Batson’s venous plexus and perneural lymphatic spread. These malignant cells then enter the CSF and are seeded throughout the meninges.
Which areas are mostly affected by meningeal carcinomatosis?
Basal cisterns, posterior fossa and cauda equina.
What are the classical features of meningeal carcinomatosis?
Enhancement and enlargement of the cranial nerves, superficial linear dural enhancement, irregular tentorial or ependymal enhancement, cisternal / sulcal obliteration, communicating hydrocephalus, multiple superficial brain nodules, spinal cord enlargement and asymmetry of the root with clumping of the cauda equina.
What are the treatment options for meningeal carcinomatosis?
Analgesia, focal radiotherapy, seizure management and treatment of hydrocephalus.
What are the pros and cons of Ommaya reservoir placement?
Pros - CSF sampling or drug administration is easier, better drug distribution in the cranial CSF spaces, reduces neurotoxicity a drug doses are less, avoids complications of LPs and ensures drug administration in to the CSF. Cons – Infection risk, seizures – if drug extravasates into brain, small ventricles are technically challenging and catheter obstruction.
What is the treatment of meningeal carcinomatosis?
Palliative radiotherapy may provide symptom relief. Chemotherapy is given intrathecally (methotrexate).
What is the prognosis of meningeal carcinomatosis?
Palliative with survival around 2 months, although those with lymphoma / leukaemia have a better prognosis with some remaining in remission for years.
What are the MRI findings with primary CNS lymphoma?
Multiple enhancing lesions that are dispersed throughout the brain with some abutting the ventricular system.
What the differential diagnosis of a periventricular enhancing lesion?
Primary CNS lymphoma, ependymoma, metastases, multifocal GBM, toxoplasmosis, brain abscess, MS and vasculopathy.
How would you investigate a patient with ?primary CNS lymphoma?
Metastatic work up with CT-CAP, blood tumour markers, HIV and CSF sampling.
Should steroids be given if the patient is suspected of having lymphoma?
No as this will make the biopsy less successful as the lesion vanishes.
How is primary CNS lymphoma treated?
High dose methotrexate systemic and intrathecal. Radiotherapy to the neuroaxis is only given if the patient is
What is the role of surgery in Primary CNS Lymphoma?
Diagnostic for biopsy only.
What is the prognosis of primary CNS lymphoma?
Without any treatment
What is the differential diagnosis of a single posterior fossa mass in a young patient?
Medulloblastoma, Haemangioblastoma, pilocystic astrocytoma, ependymoma and metastasis. Less likely causes are tuberculoma, cavernous haemangioma, abscess, glioma, lymphoma, dermoid and haemorrhage.
What are the locations of medulloblastomas?
In children they tend to be midline whilst in adults they are more laterally placed.
How would you manage a patient with tumour of the vermis obstructing the 4th ventricle?
Initial management would be treatment of the hydrocephalus as a result of the 4th ventricular obstruction. Steroids will reduce local mass effect. Then a metastatic work up is needed with MRI+/- contast of the brain and spine (for drop mets). Definitive surgical treatment is needed.
What is the approach to a vermian / 4th ventricular lesion?
Concorde position with midline incision and posterior fossa craniectomy. A frazier burr hole may be places (6cm above and 3 cm lateral to the inion).
What is the treatment of medulloblastoma?
Resection followed by radiotherapy to the whole neuroaxis even when no residual or other lesion is seen on imaging.
What is the treatment of a haemangioblastoma/cavernoma/ pilocystic astrocytoma?
Full surgical resection is curative and adjuvant radiotherapy is debated.
What is the management of a tuberculoma?
Full surgical resection is not required with a tuberculoma but the patient needs prolonged treatment with anti-tubercular medications.
What are the differences between medulloblastomas in childhood and adults?
Peak incidence in children is 3-5 years, midline location and show contrast enhancement as they are mostly solid with well defined margins. In adults they occur between 20-40 years, laterally placed and enhance less with contrast due to the cystic and necrotic nature. The margins are usually poorly defined.
Which familial conditions are associated with medulloblastomas?
Gorlin syndrome, rubinstein-taybi syndrome, ataxia telangiectasia, turcot’s syndrome, Li-fraumeni syndrome, Neurofibromatosis and tuberous sclerosis.
What is the prognosis of a medulloblastoma?
Larger tumours with invasion of the brainstem and dissemination mean complete resection is unlikely and is associated with a poorer outcome. Children have better outcomes as the lesions are less invasive. 5 year disease free survival can be up to 80%. Undifferentiated histological subtypes have a better prognosis than the differentiated subtype.
What is the differential diagnosis of a young patient with an enhancing hyperostotic lesion of the skull base?
Fibrous dysplasia, Ossifying fibroma, primary bone tumour, bone metastasis, lymphoma, paget’s disease, osteomyelitis or meningioma.
In a patient with fibrous dyplasia what pre-op investigations are needed?
Fine cut CT of the skull base, ophthalmology assessement, angiography for ?embolisation and lab studies for Ca and ALP (Paget’s).
What are the indications for surgery in fibrous dysplasia?
Cosmetic deformity, compromise of vision / ocular mobility, intractable headaches, rapid or aggressive growth.
What is the pathology of fibrous dysplasia?
This is not a true neoplasia but is a result of the arrest of the bone maturation in the woven lamellar stage. Growth usually slows after puberty.
What are the surgical goals in fibrous dysplasia?
Decompression of vital structures. Due to its polyostotic structure and poor demarcation complete resection may not be possible and carries the risk of future growth. Patients should also be on a bisphosphonate or calcitonin in non-operative cases.
Should radiotherapy be given to fibrous dysplasic bone?
No evidence for its use and could result in malignant transformation.
What is McCune-Albright syndrome?
Characterised by fibrous dysplasia, precocious puberty with endocrinopathies and cafe au lait spots.
What the classification of intra-orbital tumours?
Excluding primary ocular tumours the intraorbital tumours are classified based on where they arise from: Intraconal lesion are within the muscle cone and result in visual loss and mobility restriction (diplopia), Extraconal lesion are outside the muscle cone and cause proptosis / orbital displacement as well as visual loss and impaired mobility and Intracanalicular are within the optic canal and cause loss of vision with optic disc swelling and loss of vision but rarely proptosis.
What is the annulus of Zinn?
The aperture formed by the cone of muscles.
Which structures are within the annulus of Zinn?
Optic nerve, ophthalmic artery, orbital branch of the meningeal artery, sympathetics from the ICA, superior and inferior divisions of the oculomotor nerve, the nasociliary nerve and the abducent nerve.
What is the differential diagnosis of an extra-axial intra-conal lesion that does not affect the globe?
Hemangioma, optic sheath meningioma, neurofibroma, melanoma, lymphoma, vascular, endocrine, infectious or inflammatory disease.
What is the initially management of a patient with an intraorbital tumour?
Urgent ophthalmology assessment, CT and MRI and metastatic work up with CT-CAP. Present the options of resection or conservative management.
What is the prognosis following intra-orbital haemangioma resection?
Complete resection is curative.
What are the risk factors for intra-cerebral abscess formation that can be sought from the history?
Weight loss, night sweats, IV drug use, cardiac or pulmonary abnormalities, HIV, recent chemotherapy, lymphoma etc
What is the differential diagnosis of multiple intracerebral ring enhancing lesions?
Multiple bacterial abscesses, neurocystercosis, toxoplasmosis, tuberculomas, metastasis or multifocal GBM.
What are the initial investigations for a patient with multiple intracranial ring enhancing lesions?
Markers of infection (FBC / CRP / ESR etc), Immune status (HIV / HepB / HepC), CT-CAP, blood cultures, Anti-toxoplasma titres, western blot to detect taenial solium antigens, ECG and abdominal USS.
How can an abscess be differentiated from a tumour on MRI?
Diffusion weighted imaging where abscesses show restricted diffusion and GBMs or cystic mets do not.
What are the histological stages of cerebral abscess formation?
1- Early cerebritis (14 days) with central necrosis, thin wall with collagen capsule and CT shows a thin enhancing wall. Note the capsule wall is thinner along the ventricles so is prone to rupture into the ventricles.
What are the main sources of bacterial abscesses?
Haematogenous (25%) with the most common organism being strep viridians, then from the middle ear or paranasal sinuses with strep milleri and then third route is trauma or post-surgical with staphylococcus aureus or epidermidis.
What is the treatment of intracerebral abscesses?
Antibiotics based on cultures so a brain biopsy may be needed or surgical resection of a lesion if there is significant mass effect. Steroids for symptom relief.
A patient with speech difficulty, shoulder weakness and tongue wasting has lesion in which location?
Jugular foramen (CN 9 / 10 / 11). The tongue wasting shows CN12 involvement which would then suggest extracranial disease (Collet-Sicard).
What is the most common cause of a tumour at the jugular foramen?
Glomus jugulare (paraganglioma). The differential diagnosis also includes schwannoma, meningioma, chordoma, endolymphatic sac tumour, temporal bone carcinoma and metastases.
How would you investigate a patient with a jugular foramen tumour?
CT-CAP and CT-angiogram / formal DSA, serum and urine catecholamines and urine VMAs.
Which other tumours are associated with glomus tumours?
Glomus tumours are neuroendocrine tumours and patients should be investigated for a concurrent phaeochromocytoma.
Why are serum catecholamines sent in the investigation of phaeochromocytoma?
The conversion of NAdr to Adr requires phenylethanolamine-N-methyl transferase (PNMT) in the medulla. A high level of Adr therefore signifies a phaeochromocytoma whereas high NAdr can be produced by chemically active glomus tumours.
How should hypertensive crisis in a patient with a phaeochromocytoma be managed?
With both alpha (phenoxybenzamine) and beta (propanolol) blockade. Alpha blockade must be given first to prevent worsening of the hypertension.
What is the most common vessel to supply a glomus tumour?
The ascending pharyngeal artery. Other feeders include the occipital and maxillary arteries from the ECA as well as the vertebrobasilar system.
What are the treatment options for glomus tumours?
Surgery / radiosurgery / radiotherapy.
What are the outcomes following radiotherapy for a glomus tumour?
94% 20 year survival and 75% 20 year disease free survival.
What is the aim of radiosurgery for glomus tumours?
Tumour control with a 2.1% recurrence rate and no mortality. The tumour gets smaller in only 1/3 of cases.
What are the outcomes following surgery for glomus tumours?
1% mortality, 3% recurrence and 90% gross resection.
What pre-operative steps should be taken prior to operating on a glomus jugulare tumour?
Angiogram + embolisation, alpha and betablocker therapy to control BP if the tumour is hormonally active, intraoperative cranial nerve monitoring along with brainstem auditory evoked responses and SSEPs.
Which nerves are most at risk during surgery on a glomus tumour?
The lower cranial nerves (10/11) are usually pushed medially by the tumour so are at less risk than the 7 and 9.
What is the management of patients with bilateral glomus tumours?
Resect one at a time and only resect the second tumour if there was no cranial nerve deficit from the first resection. Alternatives include radiosurgery.
What are the key features in the pathology staining for a glomus tumour?
Sustentacular cell density and staining of the sustentacular cells with S100 is inversely proportional to the aggressiveness of the tumour. Low staining means very aggressive therefore.
What is the embryological origin of a glomus tumour?
They are of neuroectodermal origin.
Where are the genes for glomus tumour development found?
On chromosome 11 resulting in a germline mutation in succinate dehydrogenase subunits (mitochondrial enzyme) in an autosomal dominant fashion with variable penetrance from the father.
What is the classification system for jugular foramen syndromes?
Vernet = 9/10/11 due to an intracranial lesion at the jugular foramen, Collet sicard = 9/10/11/12 due to an extracranial skull base lesion, Schmit 10/11, Jackson = 10/11/12 vascular infarction of the medullary tegmentus , Tapia 10 to larynx only/ 11/12/sympathetic and Villaret 9/10/12 and sympathetic due to a high cervical lesion
How are glomus tumours classified?
Fisch classification: A – limited to the middle ear cleft; B – limited to the tympanomastoid; C – involvement of the infralabyrinthine segment and along the carotid canal to the petrous apex; D – Intracranial extension. Glassock-Jackson classification: A – small involving jugular bulb, middle ear and mastoid; B – extends into the IAC; C – extends to the petrous apex +/- intracranial extension; D – Beyond the petrous apex to the clivus or infratemporal fossa +/- intracranial extension.
What are the jugular foramen syndromes?
Vernet – CN9, 10 & 11 – intracranial lesion; Collet-sicard - CN9, 10, 11 & 12 – skull base lesion; Schmidt – CN10 & 11 ; Jackson – CN 10, 11 & 12 – vascular infarction of the medullary tegmentum; Tapia – CN Laryngeal 10, 11, 12 & sympathetics – high cervical lesion; Villaret – CN 9, 10, 11, 12 & sympathetic.
What are the features of a colloid cyst on MRI?
Circular homogenous lesion with thin rim enhancement that is hypointense on T1 and T2 sequences.
What is the differential diagnosis of a 3rd ventricular lesion?
Most likely is a colloid cyst; Differential diagnosis is MATCH-O-GRAM: Meningioma, AVM, Aneurysm, Teratoma, Colloid cyst, Craniopharyngioma, Choroid plexus papilloma, Hypothalamic hamartoma, histiocytosis, Optic glioma, Germinoma, Rathke’s cyst, Abscess and metastasis.
What is this midline lesion?
Skull dermoids
What is this lesion?
Langerhans cell histiocytosis
Appears as a punched out lytic lesion skull xray
What are the MRI features of a chordoma?
Bright on T2, dark on T1 and no enhancement.
Diagnosis?
Hyperostosis frontalis interna
Diagnosis?
Paget’s disease
Diagnosis?
Osteopetrosis
What is the classical feature of hyperostosis frontalis interna?
The midline bone at the insertion of the falx is spared.
More common in Females (9:1)
Associated with acromegaly, hyperprolactinaemia, hyperphosphataemia and DISH.
What is this X-ray finding?
Shepherd’s crook deformity, associated with fibrous dysplasia of the prox femur
What is Meckel’s cave?
A CSF filled cavity containing the trigeminal ganglion that lies between the periosteal and meningeal layers of dura that sits posterio-lateral to the cavernous sinus with the cavernous carotid medial and petrous carotid inferior.
What is Bill’s bar?
Vertical crest separating the Facial nerve anteriorly from the superior vestibular nerve posteriorly.
(7up, Coke down)
What are the features on this histological slide?
The ovoid cells with a prominent nucleolus = neurons.
The arrow head is pointing at a mitotic figure.
The remaining cells are astrocytes on the background of the normal neuropil.
The presence of diffusely infiltrating astrocytes that are pleomorphic, as well as the mitotic figure, suggests a diffuse astrocytoma.
What are the features on this histological slide?
There is evidence of pseudopalisading surrounding central necrosis suggesting IDH-WT. There is a marked increase in cell density. There is vascular proliferation and the bottom arrow represents a thrombus within the vessel. This is in keeping with a high-grade astrocytoma (GBM).
What are the features on this histological slide?
There are Rosenthal fibres (eosinophilic intracystoplasmic inclusion) with bipolar astrocytes that have hair-like projections. There are no mitotic fibres visible. This is in keeping with a WHO grade 1 pilocytic astrocytoma. I would stain for mucin to differentiate between a pilomyxoid tumour.
