Brain Tumors I

Question 1

Spectrum of pilocystic astrocytoma morphology

Answer 1

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.

Question 1

Four main histologic criteria for grading a brain tumor

Answer 1

1. Nuclear pleomorphism
2. Mitoses
3. Microvascular proliferation
4. Necrosis

Question 2

Diffuse type astrocytoma molecular genetics

Answer 2

Most have the following:
1. IDH1 or IDH2 mutation (most commonly IDH1 R132H)
2. TP53 mutation
3. ATRX mutation

Question 3

When you encounter an IDH WT diffuse type astrocytoma, it is important to ensure it does not represent. . .

Answer 3

. . . an under-sampled GBM

Question 4

IDH WT GBM alternative molecular features

Answer 4

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

Question 5

Diffuse midline glioma

Answer 5

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

Question 6

Classical microscopic features of GBM

Answer 6

Cellular anaplasia, necrosis with pseudopallisading, microvascular proliferation with glomeruloid structures

Question 7

Giant cell GBM

Answer 7

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.

Question 8

What is the origin of pallisading necrosis in GBM?

Answer 8

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.

Question 9

Common IDH WT GBM mutations

Answer 9

TERT promoter mutation (most common)
EGFR mutation or amplification
PTEN, PIK3CA, or PIK3R1 mutations

Question 10

Evaluating IDH status by immunostain

Answer 10

Two ways to go about this:

1. There is an antibody against IDH1 R132H, the most common variant
2. You can stain for nuclear ATRX. Loss of nuclear ATRX indicates IDH mutation pathway progression in GBM.

Question 11

Genetic features of oligodendroglioma

Answer 11

1. IDH mutation
2. TERT promoter mutation
3. Deletion of 1p and 19q

Question 12

Chicken-wire vessels

Answer 12

Very fine capillary blood vessels which branch at wide angles.

Hallmark histologic feature of oligodendrogliomas

Question 13

Pilocytic astrocytoma molecular genetics

Answer 13

Involve some mutation of the MAPK pathway

Note that they are very common in NF1, since NF1 loss is one way this is achieved

Question 14

Ependymoma defining histologic features

Answer 14

Lots of perivascular pseudorosettes (“Ependymomas like to line things”)

Formation of true lumens lined by cilia

Question 15

GFAP is positive in. . .

Answer 15

. . . all gliomas:

1. Astrocytomas
2. Oligodendrocytomas
3. Ependymomas

Question 16

Best stains for a suspected ependymoma

Answer 16

1. GFAP (ensure it is a glioma)
2. EMA (epithelial membrane antigen – in normal ependymal lining it is neat and straight, however in free ependymoma cells it forms perinuclear granules)

Question 17

Meningiomas are thought to arise from cells of the __ layer

Answer 17

Arachnoid

Question 18

Meningiomas are __-responsive tumors

Answer 18

Progesterone

So, many will grow during pregnancy and may present during pregnancy

Question 19

Meningioma nuclear pseudoinclusions

Answer 19

Not true nuclear inclusions, but invaginations of the cytoplasm overlying the nucleus

Nonspecific, but very common in meningiomas

Question 20

A meningioma with lots of psammoma bodies is a. . .

Answer 20

psammomatous meningioma

Question 21

Microcystic meningioma

Answer 21

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.

Question 22

Sclerosed angiomatous meningioma

Answer 22

Many slow-growing angiomatous meningiomas will hyalinize over time, sometimes leaving only pockets of tumor.

Question 23

Secretory meningioma

Answer 23

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.

Question 24

Ways that a meningioma can be upgraded to grade 2

Answer 24

1. Clear cell morphology 2. Chordoid meningioma 3. Brain invasion (really just a functional definition -- if it invades it is higher grade) 4. >/= 4 mitoses/10 high power fields 5. At least 3 out of 5 of the following: - Hypercellularity - Small cell change - Prominent nucleoli - Necrosis - Sheeting architecture

Question 25

Clear cell meningioma

Answer 25

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.

Question 26

Chordoid meningioma

Answer 26

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.

Question 27

Features of an anaplastic meningioma

Answer 27

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.

Question 28

Rhabdoid meningioma

Answer 28

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).

Question 29

Papillary meningioma

Answer 29

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).

Question 30

Sarcomatous meningioma

Answer 30

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,

Question 31

Best stains for meningioma

Answer 31

EMA Vimentin Somatostatin receptor 2A

Question 32

Most common cytogenetic aberrations in meningioma

Answer 32

Deletions of 22q including the NF2 locus

Question 33

Poor prognostic cytogenetic aberrations in meningioma

Answer 33

TERT promoter mutations and homozygous CDKN2A mutations.

Question 34

Ganglioglioma

Answer 34

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.

Question 35

Most common genetic mutation in ganglioglioma

Answer 35

BRAF V600E If not this, it is often anther MAPK gene mutation

Question 36

Dysembryoplastic neuroepithelial tumor

Answer 36

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!

Question 37

Most common genetic mutation in dysemryoplastic neuroepithelial tumor

Answer 37

BRAF V600E

Question 38

Myxopapillary Ependymoma

Answer 38

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!

Question 39

Subependymoma

Answer 39

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.