Brain Tumors I Flashcards
Spectrum of pilocystic astrocytoma morphology
Pilocytic astrocytomas may have varied histologic appearances.
Classically, they have hairy projections in the background and contain eosinophilic granule bodies with Rosenthal fibers.
Hairy pseudorosettes may also be seen, and towards the edge of the tumor you may find invading cells with an oligodendrocytic morphology.
Four main histologic criteria for grading a brain tumor
- Nuclear pleomorphism
- Mitoses
- Microvascular proliferation
- Necrosis
Diffuse type astrocytoma molecular genetics
Most have the following:
1. IDH1 or IDH2 mutation (most commonly IDH1 R132H)
2. TP53 mutation
3. ATRX mutation
When you encounter an IDH WT diffuse type astrocytoma, it is important to ensure it does not represent. . .
. . . an under-sampled GBM
IDH WT GBM alternative molecular features
CDKN2A/p16/ARF loss
RB loss
CDK4/6 amplification
Chromosome 10 loss (PTEN is on chromosome 10)
Polysomy 7 (EGFR is on chromosome 7)
EGFR amplification
Diffuse midline glioma
Integrated diagnosis:
- H3.3 K27M mutation (evaluated by immunostain, either against K27M variant or as loss of K27 trimethylation)
- Midline location
- Infiltrative growth pattern on histology
Classical microscopic features of GBM
Cellular anaplasia, necrosis with pseudopallisading, microvascular proliferation with glomeruloid structures
Giant cell GBM
Characterized by giant, multinucleate cells with GFAP positivity.
The major differential for this diagnosis is anaplastic pleomorphic xanthoastrocytoma, a similar appearing malignancy which often demonstrates a reticulin fibrotic background.
High frequency of TP53 and PTEN mutations.
What is the origin of pallisading necrosis in GBM?
The mobile, discohesive cells flee from hypoxic necrosis and in doing so result in a gradient on the edges of the necrosis, giving a pallisading appearance.
Common IDH WT GBM mutations
TERT promoter mutation (most common)
EGFR mutation or amplification
PTEN, PIK3CA, or PIK3R1 mutations
Evaluating IDH status by immunostain
Two ways to go about this:
- There is an antibody against IDH1 R132H, the most common variant
- You can stain for nuclear ATRX. Loss of nuclear ATRX indicates IDH mutation pathway progression in GBM.
Genetic features of oligodendroglioma
- IDH mutation
- TERT promoter mutation
- Deletion of 1p and 19q
Chicken-wire vessels
Very fine capillary blood vessels which branch at wide angles.
Hallmark histologic feature of oligodendrogliomas
Pilocytic astrocytoma molecular genetics
Involve some mutation of the MAPK pathway
Note that they are very common in NF1, since NF1 loss is one way this is achieved
Ependymoma defining histologic features
Lots of perivascular pseudorosettes (“Ependymomas like to line things”)
Formation of true lumens lined by cilia
GFAP is positive in. . .
. . . all gliomas:
- Astrocytomas
- Oligodendrocytomas
- Ependymomas
Best stains for a suspected ependymoma
- GFAP (ensure it is a glioma)
- EMA (epithelial membrane antigen – in normal ependymal lining it is neat and straight, however in free ependymoma cells it forms perinuclear granules)
Meningiomas are thought to arise from cells of the __ layer
Arachnoid
Meningiomas are __-responsive tumors
Progesterone
So, many will grow during pregnancy and may present during pregnancy
Meningioma nuclear pseudoinclusions
Not true nuclear inclusions, but invaginations of the cytoplasm overlying the nucleus
Nonspecific, but very common in meningiomas
A meningioma with lots of psammoma bodies is a. . .
psammomatous meningioma
Microcystic meningioma
These tumors are also commonly angiomatous with many blood vessels (sometimes called angiomatous/microcystic meningiomas)
Does not portend a different prognosis, still grade 1, however it looks quite different from your run of the mill whorling streams of nuclei.
These will often sclerose over time.
Sclerosed angiomatous meningioma
Many slow-growing angiomatous meningiomas will hyalinize over time, sometimes leaving only pockets of tumor.
Secretory meningioma
Pink, hyaline-like secretions in globules are interspersed between whorls of cells.
They can be brought out with an EMA stain or a CEA stain.
Ways that a meningioma can be upgraded to grade 2
- Clear cell morphology
- Chordoid meningioma
- Brain invasion (really just a functional definition – if it invades it is higher grade)
- > /= 4 mitoses/10 high power fields
- At least 3 out of 5 of the following:
- Hypercellularity
- Small cell change
- Prominent nucleoli
- Necrosis
- Sheeting architecture
Clear cell meningioma
Grade 2
Characterized by cleared-out, glycogen-rich cytoplasm with a preserved whorling structure, but also with thick collagen bands interwoven between streams of cells.
PAS brings out the glycogen in these cells.
Chordoid meningioma
Grade 2
Characterized by a myxoid background with “cords” of cells weaving through the guck.
To make this diagnosis, chordoid morphology should really be a prominent feature of the tumor and not just present in a small subsection of the field.
Features of an anaplastic meningioma
WHO grade 3
May have rhabdoid or papillary architecture, or be overtly malignant with truly anaplastic features. May have features of a carcinoma, melanoma, or high grade sarcoma. (ie, if histology looks sarcomatous but stains say meningioma, think anaplastic meningioma)
20 or more mitoses per 10 HPF.
Rhabdoid meningioma
WHO grade 3, type of anaplastic meningioma
Cells are enlarged with eosinophilic cytoplasm, eccentricly placed nuclei, and cell borders are distinct (unlike low grade meningiomas).
Papillary meningioma
WHO grade 3, type of anaplastic meningioma
Cells are arranged in a papillary architecture and are EMA and vimentin positive. Pretty atypical appearance for a meningioma, but you have to be on the lookout due to its poor prognosis.
Also on the ddx are metastatic adenocarcinoma, chemodectoma, and papillary variants of the gliomas (astroblastoma and ependymoma).
Sarcomatous meningioma
WHO grade 3, type of anaplastic meningioma
As the name suggests, sarcomatoid appearance with spindle cells. Often there will be focal areas of more typical meningioma appearance, or areas that give a distinct impression of whorling.
EMA, GFAP,
Best stains for meningioma
EMA
Vimentin
Somatostatin receptor 2A
Most common cytogenetic aberrations in meningioma
Deletions of 22q including the NF2 locus
Poor prognostic cytogenetic aberrations in meningioma
TERT promoter mutations and homozygous CDKN2A mutations.
Ganglioglioma
Rare glial neoplasm. Most common in patients under 30 years of age. Often demonstrates a cystic structure in the temporal lobe on imaging.
Mixture of mature neurons and glial tissue on biopsy. “Nodular” on low power, but this may be difficult to appreciate in larger tumors.
Neural and glial components are the hallmark of this type of tumor.
Most common genetic mutation in ganglioglioma
BRAF V600E
If not this, it is often anther MAPK gene mutation
Dysembryoplastic neuroepithelial tumor
Rare glial tumors that tend to occur in teenagers or young adults.
On imaging these tumors most often appear as a nodular cortical lesion in the frontal or temporal lobes.
Microscopically, these tumors are composed of small, round, oligodendrocytoid cells in clusters on a myxoid, mucosy background. Neurons are often mixed in with these cells as well.
“Neurons floating in pools of mucin”
Good prognosis with gross resection!
Most common genetic mutation in dysemryoplastic neuroepithelial tumor
BRAF V600E
Myxopapillary Ependymoma
Occurs in the “filum terminale” of the spinal cord – a modification of the pia mater which extends downward from the conus medullaris.
Microscopically, characterized by papillary features on an abundant myxoid background. Nuclei are characteristically ependymomal with round, ovular shape, bland, monotonous.
Good prognosis if surgically resected!
Subependymoma
Tumor of middle aged to elderly patients.
Classic location is the roof of the 4th ventricle, but can happen in any ventricle or the spinal cord. Classically presents with hydrocephalus (like classic ependymomas). May calcify and display consistent imaging features.
Microscopically, the tumor is classically hypocellular and arranged in vague nodules, often easier to appreciate on low magnification. Nuclei are characteristically ependymomal with round, ovular shape, bland, monotonous.
