HNS41 Pathology Of Intracranial Tumours Flashcards
Intracranial tumours diagnosis consideration
Primary (>100 types) vs Metastatic
Metastatic cranial tumour: 20-25% of all intracranial tumours
—> common primary sites (lung, breast, kidney, malignant melanoma, choriocarcinoma (Chinese female) etc.)
—> sometimes primary site symptoms may NOT be obvious
Revision: Glial cells in CNS + PNS
CNS:
- Astrocytes —> metabolic support, phagocytosis (fibrosis)
- Oligodendrocytes —> form myelin sheath
- Microglia —> APC, phagocytosis
- Ependymal cells —> form choroid plexus for CSF production
PNS:
- Schwann cells —> form myelin sheath
- Perineuronal satellite cells —> ~ Schwann cells but not form myelin
***2 major groups of Primary intracranial tumours
- Neuroectodermal (brain substance) tumours (50%)
- Glial cells (Gliomas) —> ***Astrocytoma —> ***Glioblastoma multiforme —> ***Oligodendroglioma —> ***Ependymoma
- Neurons and primitive cells
—> ***Medulloblastoma
—> Neuroblastoma
- Other structures within cranial cavity
—> **Meningioma
—> **Schwannoma (Schwann cells in peripheral nerve)
—> Vascular tumour
—> Differ in types of tumour, treatment, behaviour
General behaviour of CNS tumours
- Recurrence
- difficulty in total resection of tumour - Extracranial tumour extensions
- Skull bone
- Craniotomy - Metastasis
- via CSF
- blood (rare)
Prognosis depend on:
Nature of growth site
- benign tumour in critical sites can still have bad prognosis
- deep brain tumours —> impossible to resect
Good prognosis:
- Meningioma
- Schwannoma
Investigation and Diagnosis
- Radiology:
- Plain skull X-ray (NOT helpful since behind thick skull bone)
- CT
- MRI
- Angiography
- Myelogram (detect spinal cord pathology) - Cerebral biopsy (definitive surgery and diagnosis have to occur at the same time):
- **Smear (usually tumours are soft —> good smear)
- **Frozen section (intraoperative)
- Paraffin section
- Special stain
- ***Immunohistochemistry (e.g. GFAP, NF)
- Electron microscopy
Biologic malignancy vs Histologic maglinancy
Histologic malignancy:
- Histological features e.g. rapidly dividing
Biologic malignancy
- How likely the tumour is to kill the patient
- Reasons:
- Diffusely infiltrative
- ***Unencapsulated / not confined by BM
- e.g. well-differentiated neuroectodermal tumours like Astrocytoma, Oligodendroglioma, Ependymoma) —> Diffusely infiltrate surrounding tissue
- well-differentiated tumour can also become poor-differentiated (malignant) after years - Inoperable sites
- medulla, pons, midbrain, deep in hemisphere
Biological properties of CNS primary tumours
- Malignancy transformation of well differentiated tumours may occur
- Extracranial metastasis ***RARE
- Spread:
1. Direct infiltrative —> Carcinomatous meningitis (diffuse meningeal infiltration)
2. Via CSF - Brain tumours may be part of a syndrome (affect other parts as well) e.g. von Recklinghausen’s Neurofibromatosis, von Hippel Lindau syndrome
Anaplasia
- Increased cellularity
- Nuclear pleomorphism
- Mitosis
- Vascular endothelial proliferation
- Necrosis
***Deleterous effects of CNS tumours
- Destruction of normal tissue
- Distortion of intracranial contents
- Space-occupying effect
- obstruction of CSF flow —> Hydrocephalus - Oedema
- ↑ ICP
Astrocytoma
Common sites:
- Children (Posterior cranial fossa):
—> Brainstem —> Diffuse enlargement of region
—> Cerebellum —> ***Cystic tumours containing proteinaceous fluid
- Adult: Cerebral hemisphere —> Diffuse enlargement of region
Gross appearance:
1. Solitary
2. ***Diffuse (gliomatosis cerebri) (mostly)
—> ∵ no confinement (vs basement membrane)
—> difficult to cure
3. Cystic
Types (Mostly mixed):
- Protoplasmic
- ***Fibrillary —> Prototype
- ***Pilocytic
- Gemistocytic
Grading: - Based on histological features - Grade 1-4 —> increasing anaplasia - Low grade vs High grade (no benign vs malignant classification)
Histological features:
- Nuclear pleomorphism —> Grade 2 (hard to distinguish from reactive astrocytosis / fibrotic healing process)
- Mitotic activity —> Grade 3
- Necrosis —> Grade 4 (very aggressive ∵ outgrow extensive vascularisation of brain)
- Vascular endothelial hyperplasia (blood vessel proliferation) —> Grade 4
Naming:
Grade 2: Astrocytoma grade 2 (Low grade)
Grade 3: Anaplastic astrocytoma (Intermediate)
Grade 4: ***Glioblastoma multiforme (High grade)
Prognosis:
- ***Incomplete resection
- May undergo malignant change after 5 / 10 years
Glioblastoma multiforme
***Very poor prognosis (most deadly primary CNS tumour)
Origin of tumour cell:
- Undifferentiated glial cells (de novo)
- Pre-existing astrocytomas (by progressive malignant transformation)
Site:
- ***Cerebral hemisphere
Pattern of growth:
- Infiltrative (follow white matter tracts e.g. fornix, corpus callosum to other hemisphere)
- Ventricular system + Subarachnoid space spread
- **Histology:
1. ***Pseudo-palisades (characteristic)
- ***Necrosis and haemorrhage
—> surrounded by viable but degenerate tumour -
**Endothelial proliferation / hyperplasia (Glomeruloid body)
—> tumours cell send angiogenic growth factor to promote vessel development
—> leaky blood vessels —> contrast-enhancing —> **edema —> aggravate space-occupying effect by tumour - Extensive nuclear + cytoplasmic pleomorphism, Multinucleate cell, Hyperchromasia
—> abnormal mitoses - Variable (∴ multiforme)
Oligodendroglioma
Common sites:
- Cerebral hemisphere (adults)
Gross appearance:
- ***Well-circumscribed
- Little necrosis
Histology:
- ***Box-like cells (high cell density) with clear halo
- ***Calcification within tumour common (may be visible on skull X-ray)
Prognosis:
- Good (for well-differentiated)
(Gene:
1p/19q codeletion)
Genetic pathways to primary and secondary Glioblastoma
Glioblastoma = Glioblastoma multiforme
Primary glioblastoma (de novo pathway): Glial progenitor cells —> (TERT / EGFR / PTEN mutation) —> Primary glioblastoma (very short clinical course, 1-2 years)
Secondary glioblastoma pathway:
Glial progenitor cells
—> IDH1/2 mutation —>
- Diffuse astrocytoma
—> Anaplastic (more malignant) astrocytoma
—> Secondary glioblastoma
(over course of many years, tumour become progressively more malignant) - Oligodendroglioma
—> Anaplastic oligodendroglioma
Ependymoma
Origin:
- Ependymal cells (lining ventricles producing CSF)
Sites:
- Brainstem, Cerebellum (difficult to surgical resection)
Signs and symptoms:
- ***Hydrocephalus (CSF flow blocked)
- Spinal cord signs and symptoms (sensory / motor symptoms)
Gross appearance: - Masses protruding into ventricles (***4th ventricle, Aqueduct of Sylvius) —> blockage of ventricular system —> ***Hydrocephalus —> ↑ ICP
Histology:
- ***Rosettes (cuboidal tumour cells surrounding central true lumen)
- ***Pseudo-rosettes (tumour cells around blood vessels —> pink fibrillation halo around vessels) (characteristic)
- Spindle cells
- Blepharoplasts
Prognosis: - ***Poor - ***Slow growing / not aggressive —> Poor response to chemotherapy —> only possible by Surgical resection but difficult to resect due to critical sites
