W2 - Primary Neoplasms of the CNS

Question 1

In which age groups are primary CNS tumours most common?

Answer 1

Two peaks:

• 1st decade (0-10yo)
• 5th-6th decades (40-60yo)

Question 2

Which primary CNS tumours are common in adults?

Which primary CNS tumours are common in children?

Answer 2

Adults:

• 70% supratentorial (located above the tentorium cerebelli)
• Glioblastoma multiforme (6th most common tumour in adults), this is a type of astrocytoma

Children:

• 70% of CNS tumours in CNS arise in posterior fossa (cerebellar lesions common)
• Most of these are astrocytomas (45%) or neuroectodermal neoplasms (45%)

Question 3

How are primary CNS tumours classified?

Answer 3

May be classified:

Based on cell of origin (histogenetic classification)

• Neural tube (glioma, astrocytoma, oligodendroglioma)
• Neural crest (schwannoma, neurofibroma, meningioma)
• Embryonic remnants (melanoma, germinoma)

Benign vs malignant (rate of growth)

Primary or secondary

Question 4

How are astrocytomas classified?

Answer 4

Astrocytomas derived from astrocytes (glial cell derived from neural tube) and are most common primary CNS neoplasms

Grade I - Well differentiated (low grade)

• Slow growing but infiltrative (death in 5-10 years)
• Neoplastic cells retain characteristics of astrocytes
• Common in children

Grade II & III - Anaplastic

• More rapidly growing (death in 1-5 years)
• Low/no level of differentiation (do not retain characteristics of astrocytes)

Grade IV - Highly undifferentiated (high grade)
- Very rapid growing and infiltrative (death usually <1 year)

Question 5

Write brief notes on “Glioblastoma multiforme”

Answer 5

• Most common type of astrocytoma (which is most common type of primary CNS neoplasm). 30% of CNS tumours in adults.
• Grade IV (high grade) neoplasm = rapid growth, infiltrative, tumour cells show little/no differentiation
• Typically grow across midline of the brain to form a “butterfly tumour”
• Neovascularisation common
• Necrosis and haemorrhage common (new blood vessels fragile, prone to rupture. Fast growth –> outgrows bloody supply –> necrosis)

Question 6

Write brief notes on “oligodendroglioma”

Answer 6

• Derived from oligodendroglia (glial cell derived from neural tube) but pure oligodendrogliomas rare (usually mixed tumour)
• Rare in children, account for 3% primary CNS neoplasms in adults
• Mainly found in cerebral hemispheres, tend to be slower growing than astrocytomas
• Can be identified by speckled calcification on X-Ray

Question 7

Define the following terms:

a) Choroid plexus papilloma

b) Medulloblastoma

Answer 7

a) Choroid plexus papilloma
A rare, benign tumour derived from ependymal cells (neural tube derivative) that commonly affects the lateral ventricles that may spread via CSF pathway and have the ability to secrete CSF, causing increased ICP and hydrocephalus

b) Medulloblastoma
Primary CNS neoplasm derived from neurons (derivative of neural tube) that commonly effects children and are usually found in the midline cerebellar vermis (spinocerebellum). Medulloblastomas have rapid growth rate (malignant) and commonly infiltrate CSF, spreading via CSF pathways. They may cause raised ICP and hydrocephalus (due to blockage/back up of CSF in ventricles)

Question 8

Write brief notes on the following primary CNS neoplasms which are derived from cells originating in the neural crest:

a) Meningioma
b) Schwannoma

Answer 8

a) Meningioma
- Origin: Derived from arachnoid cap cells that are a component of the arachnoid villi (present in arachnoid membrane)
- Frequency: 18% of intracranial neoplasms in adults (2:1 female/male ratio)
Common sites: Foramen magnum, olfactory groove and wing of sphenoid
- Biological behaviour: Usually benign (slow growing) but may be malignant, often infiltrates adjacent bone and dura (brain infiltration rare). Cause marked compression of CNS, observe small foci from calcification

b) Schwannoma
- Origin: Schwann cells (type of glial cell) in the myelin sheath of cranial & spinal nerves.
- Frequency: 10-12% of primary CNS neoplasms in adults (more common in females)
- Site: Commonly the vestibular branch of CN VIII near cerebellopontine angle (aka acoustic neuroma)
- Biological behaviour: Benign (slow growing), well encapsulated

Question 9

Briefly define the following terms:

a) Neurofibroma
b) Craniopharyngioma

Answer 9

Note: Neurofibromas and craniopharyngiomas are not neoplasms.

a) Neurofibroma
A benign tumour arising from the myelin sheath of spinal nerves that is composed of Schwann cells and fibroblasts that are usually found on the dorsal roots of spinal nerves, but may arise from a peripheral nerve in the skin or viscera. It has a hereditary component (autosomal dominant) and is also seen in neurofibromatosis (affects CN VIII). Causes compressive Ssx but may be excised, although nerve function is lost.

b) Craniopharyngioma
A benign, well encapsulated tumour derived from ectodermal cells of Rathke’s pouch (embryonic remnant cells) that is common in children and is usually located in the suprasellar region. Causes pituitary dysfunction resulting in hydrocephalus and visual disturbances. Craniopharyngiomas often calcify and there is a high recurrence rate.

Question 10

a) Define the term “neurofibromatosis”.

b) Is it a common disease?

Answer 10

a) A pair of autosomal dominant disorders with a strong familial pattern of distribution, characterised by lesions in the skin, NS, bones, endocrine glands and viscera. The two types are Peripheral (Von Recklinghausen’s disease) and Central (CN VIII).
b) 1/3000-4000 (fairly common)

Question 11

List and describe the clinical manifestations of Type I (Peripheral) neurofibromatosis

Answer 11

Skin pigmentation
- Café-au-lait spots - Brown, freckle-like spots found in axilla (Crowe’s sign - pathognomonic/specific to peripheral neurofibromatosis) and other intertriginous areas (groin, under breasts, knee and elbow creases) that appear at or shortly after birth. If a spot >1.5cm in adulthood they are indicative of Von Recklinhausen’s Disease (Peripheral neurofibromatosis) but need at least 6 spots for diagnosis.

Cutaneous tumors
- Soft, brown/purple mole-like papules found in the dermis that are tender and invaginate into the skin when pressed (button sign). They may present in different shapes and usually appear later in childhood.

Subcutaneous tumours
Multiple and have 2 types (both of which may cause hideous disfigurement:
- Neurofibromas - Firm, discrete nodules attached to a nerve
- Plexiform - An overgrowth of subcutaneous tissues, bone, skin, neurovascular fibromatous tissue

Miscellaneous manifestations

• Neurofibromas in dorsal roots of spinal & cranial nerves
• Scoliosis, bone cysts, cranial bone defects, bone hypertrophy and pathological bone fracture
• Glial tumours of CNS –> Intellectual impairment, hyperactivity, seizures
• Precocious (early onset) puberty
• Lisch nodule (Small, whitish spot on iris of eye)

Question 12

How is Type I (Peripheral) neurofibromatosis diagnosed?

Answer 12

At least 6 café-au-lait spots in one crease, with at least one being >1.5cm in diameter. Crowe’s sign (café-au-lait spots in axilla).
Neuro Ssx caused by neurofibromas, obvious physical disfigurement and other skin manifestations may also assist diagnosis.