Lecture 3: Tumors of the CNS Flashcards
What are the 7 major histopathological categories of CNS tumors?
- tumors of the neuroepithelial tissue
- tumors of cranial and spinal nerves
- tumors of the meninges
- lymphomas and hematopoietic neoplasms
- germ cell tumors
- Tumors of the sellar (sella turcica) region
- Metastatic tumors
What are the different types of neuroepithelial tissue tumors?
i. Glial cells
i. astrocytes
ii. oligodendrocytes
iii. ependymal cells
ii. Primitive cells
-embryonal tumors
iii. nerve cells/neurons
-neurocytoma
iv. glial AND nerve cells
-mixed neuronal-glial tumors
No need to know iii and iv
What are the different types of glial cell neuroepithelial tissue tumors?
i. Astrocytoma
ii. Oligodendrogliomas
iii. Ependymomas
What are the different types of Astrocytomas?
i. Diffuse, infiltrating
ii. Relatively circumscribed
What are the different types of diffuse, infiltrating astrocytomas?
i. Diffuse Astrocytomas (grade II)
ii. Anaplastic astrocytoma (grade III)
iii. glioblastoma (grade IV)
What are the different types of relatively circumscribed astrocytomas?
i. Pilocytic astrocytoma
ii. Pleomorphic xanthoastrocytoma
iii. Subependymal giant cell astrocytoma
- common in tuberous sclerosis
What are the key histologic characteristics of diffuse astrocytomas?
Cell atypia
NO mitoses
Nuclei = ANGULATED, pleomorphic, hyperchromatic
What is the gemistocytic variant? Significance?
A variant of a diffuse astrocytoma
Characterized by plump cells with pink cytoplasm
ECCENTRIC nucleus
Seen in nervous tissue affected by edema, demyelination, infarction
What are the key histological characteristics of anaplastic astrocytoma?
Cell atypia
YES mitosis
What are the key histological characteristics of Glioblastoma?
Cell atypia
YES mitosis
Vascular proliferation (looks like glomeruli)
Necrosis
What does the formation of “glomeruloid” tufts in neuroepithelium suggest?
Glioblastoma
Neovascularization is characteristic of glioblastoma
-looks like glomeruli
How does astrocytoma progress? What is the course?
Progresses from diffuse astrocytoma to anaplastic astrocytoma to glioblastoma (Grade II Grade III grade IV)
What are the delineating features of pilocytic astrocytoma?
Rosenthal fibers (pilo = hair-like) Well-circumscribed (no infiltration) -biphasic architecture with eosinophilic granular bodies (half of slide looks different from other) -better prognosis CALCIFICATIONS
What is the most common genetic alteration that leads to pilocytic astrocytoma?
Mutation in 7q34 between BRAF and KIAA1549
What are the mean age of presentation/survival for astrocytomas?
The youngest presentation with the LONGEST median survival = diffuse astrocytoma
The oldest presentation with the SHORTEST median survival = glioblastoma
Example: Ted Kennedy has a glioblastoma
An astrocytoma demonstrates atypia and mitoses. What additional histological features are required for it to be a glioblastoma?
Microvascular proliferation and/or necrosis
What astrocytoma has best prognosis?
Pilocytic astrocytoma (grade I) aka PA
What is a key feature of normal oligodendrocytes (glial cells in general)?
They don’t like each other (in that you never see glial cells bunched up together…the lilke their space)
Significance: tumors like each other and invade each other’s personal space
What is the histological differentiating factor of oligodendrogliomas?
Called the “chicken tumor” because they look like lots of fried eggs
- only grade II because it is intrinsically infiltrative
- frequently expands the gyri/deep white matter
- cells are well-differentiated
What is the significance of a “fried egg” or a “chicken-wire” appearance in histological slides?
Fried-egg = oligodendrocytoma Chicken-wire = branching capillary = oligodendrocytoma
What are the most common genetic alterations in oligodendroglioma?
Loss of heterozygosity in chromosomes 1p and 19q
Prognosis is FAVORABLE with this genetic variation
What are the key histological differentiating elements of ependymomas?
Pseudorosettes (when neoplastic cells tend to cluster around blood vessels)
-looks like glandular tumors
What types of neoplasms arise from primitive cells?
Embryonal Tumors
Example: Medulloblastoma
What are the key characteristics of embryonal tumors
Grade IV
Predominance in children
Includes medulloblastoma, supratentorial primitive neuroectodermal tumor, etc.
What are the key characteristics of medulloblastoma?
20% of childhood CNS neoplasms
90% of childhood embryonal tumors
Can present at any age
What are the gross features of medulloblastoma?
Presents and arises from cerebellum at midline/vermis
- extension into 4th ventricle, from subarachnoid space
- gray/pink
- soft or firm
- necrosis is limited to small foci
Where do medulloblastomas originate from?
External granular layer in CEREBELLUM
Originate from granule neurons of precursor cells that produce the external granule layer that DISAPPEARS within the first postnatal year
What are the delineating histological features of medulloblastomas?
DENSELY packed
Mitoses frequent
Homer Wright rosettes are present
-neuronal differentiation
Where are rosettes present?
Ependymoma (pseudorosettes)
Medulloblastomas
How can you detect neuronal differentiation in a medulloblastoma?
With an antibody to neurofilament protein
Neuroblastic rosettes
What are the different types of tumors of cranial/spinal nerves
- Schwannomas (neurilemmomas)
- Neurofibromas
- Malignant peripheral nerve sheath
What do patients with neurofibromatosis 1 usually present with?
Presence of multiple neurofibromas
Presence of multiple neurofibromas suggest the presence of?
NF-1
What do patients with neurofibromatosis 2 usually present with?
Bilateral acoustic/vestibular schwannoma
Loss of hearing loss
Meningiomas
Presence of acoustic/vestibular schwannoma suggests the presence of?
NF-2
Meningiomas present
What are the key features of Schwannomas?
-slowly growing neoplasms composed of Schwann cells
-solitary schwannoma will occur on cranial and spinal nerve roots
Most common nerve is CN 8 (acoustic/vestibular)
What are the key features of neurofibromas?
- DERMAL, producing nodular lesion of skin
- Intraneural peripheral nerves, solitary or plexiform
- presence of multiple neurofibromas = NF1
What is the relationship of neurofibroma to associated nerve?
Neurofibroma incorporates the axons
What is the relationship of schwannoma to associated nerve?
Schwannoma displaces normal elements of the nerve to one side
What is the difference between schwannoma and neurfibroma?
Schwannomas go around axons
Neurofibromas incorporate axons
What are the key characteristics of meningiomas?
Most frequent in female adults
- occurs in half of the patients with neurofibromatosis 2 (NF2)
- hard to resect if from the base of the brain
- arise from meningothelial cells from leptomeninges
Where do the meningiomas usually form?
- cerebral hemispheres (convexity)
- para-sagittal from falx cerebri
- sphenoid ridge
- olfactory groove
- diaphragm of sella
- tentorium
- foramen magnum
What are the different types of meningioma?
- Transitional meningioma
2. Psammomatous meningioma
What are the key characteristics of transitional meningioma?
Composed of WHORLS and cords of neoplastic cell
-is able to stain for EMA in immunohistochemistry
What are the delineating histological features of psammomatous meningiomas?
Consist of numerous compact whorls that contain psammoma bodies
Psammoma body = collection of calcium
What are the delineating factors of metastatic tumors?
Seocndary CNS neoplasms
-most common primary site is lung, breast, skin, kidney, colon
Frequent in adults and not in children
Solitary in approximately 50% of patients
The medulloblastoma is a
tumor of the cerebellum (embryonal)
Ependymomas are
Tumors of the neuroepithelial tissue
What gene is implicated in primary glioblastoma (GBM) De novo?
EGFR (Epidermal growth factor) overexpression
What genes are implicated in secondary GBM evolving from Grade II?
TP53 (tumor suppressor gene)
IDH1/IDH2
-isocitrate dehydrogenase 1
