Neuropathology of CNS Tumors Flashcards
I didn't give the herniation syndromes exhaustive treatment, since that's mostly review.
What are the 7 major histopathological categories of CNS tumors?
Tumors of neuroepithelial tissue Tumors of cranial and spinal nerves Tumors of the meninges Lymphomas and hematopoietic neoplasms Germ cell tumors Tumors of the sellar region Metastatic tumors
What are the 3 types of glial cells and the names of the tumors that arise from them?
Astrocytes -> astrocytomas
Oligodendrocytes -> oligodendrocytomas
Ependymal cells -> ependymomas
Of the 7 main histopathological categories of CNS tumors, which is most common?
Tumors of neuroepithelial tissue.
What are the two broad categories of astrocytomas?
Diffuse, infiltrating
Well-circumscribed
What are the 3 grades of diffuse, infiltrating astrocytoma? What’s the WHO grade level for each?
Diffuse Astrocytoma (WHO Grade II) Anaplastic Astrocytoma (WHO Grade III) Glioblastoma (WHO Grade IV)
What are the 3 relatively circumscribed astrocytomas?
Pilocytic astrocytoma
Pleomorphic xanthroastrocytoma (PXA)
Subependymal giant cells astrocytoma
What are the pathological features that define astrocytoma (WHO Grade II)?
Atypia, no mitoses
What are the pathological features that define anaplastic astrocytoma (WHO Grade III)?
Atypia with mitoses.
What are the pathological features that define glioblastoma (WHO Grade IV)?
Atypia, mitoses, and vascular proliferation and/or necrosis
What’s the purpose of grading CNS tumors? (2 points)
Predicting biological behavior (i.e. prognosis).
Guiding therapy.
Do any tumors of the CNS have a capsule?
Nope. Some are “well-circumscribed,” but no capsule.
What will you see in low power histology of white matter in diffuse fibrillary astrocytoma (WHO Grade II)? (3 things)
Increased cellularity
Elongated, irregular hypochromatic nuclei
Meshwork of fibrillary processes
What will you see in high power histology of white matter diffuse fibrillary astrocytoma (WHO grade II)? What won’t you see?
Irregular, pleomorphic angulated nuclei. Won’t see mitoses.
contrast with the regular, round nuclei of oligodendrocytes that should usually dominate the white matter
What are the characteristics of gemistocystic variant diffuse astrocytoma (WHO grade II)?
Plump cells with glassy pink cytoplasm.
What histological feature distinguishes anaplastic astrocytoma (WHO grade III) from diffuse astrocytoma (WHO grade II)?
mitoses will be present in anaplastic astrocytoma
What’s GBM?
glioblastoma
it’s an old abbreviation…
What’s a serious, acute complication of a brain tumor?
Hemorrhage -> increased ICP -> herniation
What will you see on histology of glioblastoma (WHO grade IV)?
Areas of necrosis
Neoangiogenesis (glomeruloid tufts)
What are glomeruloid tufts?
Areas of neoangiogenesis. (They resemble glomeruli, histologically).
What’s the difference between primary and secondary GBM?
Primary arises de novo.
Secondary has evolved from a grade II astrocytoma.
(the genetic mutations driving these cancers are different)
What’s the major genetic change in primary glioblastoma?
EGFR overexpression.
What are the 2 major genetic changes in secondary glioblastoma?
p53 (aka TP53) mutation
IDH1 / IDH2 mutation
What grade are relatively circumscribed astrocytomas?
I or II
If you’re going to have a brain tumor, which one would you most want?
Pilocytic astrocytomas - they have the best prognoses
What’s the most common genetic mutation that drives pilocytic astrocytoma?
BRAF-KIAA1549 fusion oncogene
What does a low power view of pilocytic astrocytoma histology look like?
Biphasic architecture: compact and cystic/spongey areas
What’s special about the histology of the cystic/spongey areas of pilocytic astrocytoma?
Eosinophilic granular bodies.
What’s special about the histology of compact areas of pilocytic astrocytoma?
Spindle-shaped / "hair-like" / pilloid cells, which are elongated fibrillary astrocytes. Rosenthal fibers (eosinophilic, corkscrew shaped things)
What does the histology of an oligodendroglioma look like?
Oligodendrocytes everywhere. Too many. Too closely packed.
What grade can’t oligodendrogliomas be? Why?
Grade I. They’re too infiltrative.
What’s a common presentation of oligodendroglioma in a young person?
Sudden onset of seizures.
What does oligodendroglioma look like histologically? (2 things)
Cells with small, centrally located nucleus and scant, clear cytoplasm.
Branching capillaries.
Why is oligodendroglioma called the “chicken” tumor?
The cells look like fried eggs, and the branching capillaries look like chicken wire (…sort of).
Most common genetic changes in oligodendroglioma? Do these changes have prognostic value?
Loss of heterozygosity in 1p and 19q. These genetic changes seem to actually be associated with better outcomes…
What’s an ependymal rosette? Are they typically found in ependymomas?
A cluster of ependymal cells surrounding a central lumen. Found in a “minority” of ependymomas.
What are pseudorosettes?
Perivascular clusters of neoplastic ependymoma cells.
Who gets embryonic CNS tumors?
Children. They’re rare in adults.
What grade are all embryonic CNS tumors?
IV - high grade.
What’s the most common embryonic CNS tumor?
Medulloblastoma.
From what area of the CNS do medulloblastomas arise?
The vermis of the cerebellum.
Why do medulloblastomas produce headache and vomiting?
Invasion of 4th ventricle -> obstructive hydrocephalus -> increased ICP.
Macroscopic features of medulloblastoma? (Name 5… color, texture, etc.)
Well circumscribed. Solid, but sometimes cystic or nodular. Gray / pink. Soft/gelatinous or firm, depending on connective tissue. Small foci of necrosis, if present.
From what embryological origin are medulloblastomas thought to arise?
Granular neuron precursor cells, which produce the external granular layer of the cerebellum, and usually disappear within the first postnatal year.
What does medulloblastoma look like histologically?
Densely packed, small cells with round nuclei and high N/C ratio.
Lots of mitosis.
Sometimes Homer Wright rosettes are present.
What are Homer Wright rosettes?
Clusters of tumor cells encircling neuropil. Suggestive of neuronal differentiation.
What’s a way to detect neuronal differentiation in medulloblastoma?
Immunostain for neurofilament protein.
Are medulloblastomas genetically homogenous?
nope.
What are 3 main tumors of cranial and spinal nerves?
Schwannomas (neurilemmomas), neurofibromas, and malignant peripheral nerve sheath tumors.
If you see a patient with bilateral acoustic / vestibular Schwannoma, what should be at the top of your DDx?
NF2 - neurofibromatosis type II (a hereditary condition)
What are neurofibromas? What are the 2 variants?
Tumors of the nerve sheath (really, non-myelinating Schwann cells, says Wikipedia)
- Dermal (nodular skin lesion)
- Intraneural / solitary / plexiform
If you see multiple neurofibromas, what should be at the top of your DDx?
NF1 - neurofibromatosis type I
Would a meningioma arise from the dura or arachnoid mater?
Arachnoid. Meningiomas are from the leptomeninges.
What are 3 risk factors for meningioma?
Increased age, being female, having NF2
What’s the typical histological pattern of transitional meningioma?
“Whirls and cords” (see slide 56)
What immunostain can be used to identify meningioma?
EMA
3 histological variants of meningioma? Histological buzzwords?
Transitional - whirls and cords
Psammomatous - compact cords with psammoma bodies…
Fibrous - …fibrous…
Do adults or kids have more metastatic cancers in the CNS? Why?
Adults, as these come from tumors that affect adults more, such as carcinomas.
How common is it to get a solitary metastasis in the CNS?
Only happens 50% of the time. Often there are multiple mets.
In the general population, what percentage of cancers are primary CNS neoplasms?
2%
In children, what percentage of cancers are primary CNS neoplasms?
20% (2nd most common, after leukemias)
When you include secondary (metastatic) CNS neoplasms, what does the age distribution look like?
Bimodal. Peak in childen < 5 years. Peak at 45-70 years.
What are the 2 most common CNS tumors of childhood?
Embryonal/medulloblastoma (predominates in 0-4 yrs). Pilocytic astrocytoma (predominates in 5-19 yrs old)
Which primary CNS tumors have sex-based differences in frequency?
Gliomas and embryonic tumors - more in males.
Meningiomas - more in females
What types of CNS neoplasm does Neufibromatosis type 1 (NF1) predispose people to? (name 4)
Neurofibroma.
Malignant nerve sheath tumor.
Optic nerve astrocytoma.
Meningioma.
What types of CNS neoplasm does Neufibromatosis type 2 (NF2) predispose people to? (name 2)
Schwannoma
Meningioma
Ependymoma
What types of CNS neoplasm does tuberous sclerosis predispose people to? What else does it cause?
Subependymal giant cell astrocytomas (which often causes hydrocephalus).
Mental retardation and seizures.
What’s the one really well-proven environmental risk factor for brain tumors? Which brain tumors does it predispose to?
X-irradiation (i.e. for cancer treatment, not diagnostic X rays).
Predisposes to a) meningiomas and b) astrocytomas/neuroepithelial tumors in children treated for ALL.
What are some risk factors for primary CNS lymphoma?
Acquired or congenital immunodeficiency.
4 signs/symptoms that can help you localize a tumor?
Epilepsy (focal or generalized), focal neuro deficits, mental changes, obstructive hydrocephalus (headache)
Review: Signs/symptoms of raised ICP? (name 4)
Headache (postural / morning headache)
Vomiting (esp. children)
Papilledema
Clouding of consciousness and coma
What are Duret hemorrhages?
Pons hemorrhages secondary to transtentorial herniation causing stretching/tearing of brainstem vasculature.
3 nerves/tracts that can be compressed in herniation? Associated sign?
Abducens -> lateral gaze palsy
Occulomotor -> blow pupil / “down and out” eye
Cerebral peduncle -> hemiparesis ipsilateral to lesion (at first, then may become bilateral).
Bilateral acoustic-vestibular Schwannoma is characteristic of which familial syndrome?
NF2
Oligodendroglioma in left frontal lobe with cortex infiltration. Most likely symptom is... A. Ataxia & dysmetria B. Mental status changes + shizophrenia C. Epileptiform fits D. Loss of vision
C. Epileptiform fits - due to cortical involvement.
