CNS Brain Tumors

CNS Brain Tumors

By Jarvis Williams

A 51-year-old woman presented to her GP with a 6-week history of increasingly severe headaches. A neurological exam was unremarkable. An MRI was performed and based on the presumptive diagnosis, an attempt at embolization of the mass was made. While she was in recovery, she experienced a massive myocardial infarction and died. An autopsy was performed.

​Case 540

​MRI T1

Hotspot

Point to the lesion.

Multiple Choice

Which of the following is the best description of this lesion?

• circumscribed, contrast enhancing, extra-axial mass

• infiltrative, contrast enhancing, extra-axial mass

• circumscribed lesion with irregular peripheral rim enhancement with central necrosis

• infiltrative, lesion with irregular peripheral rim enhancement with central necrosis

Word Cloud

What is in your differential?

Diagnoses to consider:

• Meningioma

• Solitary fibrous tumor

• Metastatic disease

• Hematolymphoid neoplasms

• Infection

• Glioma

• ​From which structure is the lesion arising?

• Do you think it is growing quickly or slowly?

​​Identify and describe the lesion?

Multiple Choice

What do we expect to see microscopically?

• An aggressive, infiltrating, astrocytic glioma

• A small, blue, round cell tumor

• A spindle cell tumor composed of compact hypercellular areas showing nuclear palisading and loose microcystic areas

• A cellular proliferation, with ovoid to spindle cells among numerous psammoma bodies

​Go to Digital scope (540).

Multiple Choice

Which of the following is the MOST COMMONLY mutated gene in patients with this tumor?

• IDH1

• MYC

• NF2

• TSC2

• VHL

• Nearly 50% of meningiomas when seen in patients without the neurofibromatosis type 2 syndrome, show NF2 mutations on chromosome 22q.

• IDH1 mutations are seen in low grade gliomas.

• MYC mutations are associated with medulloblastomas.

• TSC2 mutations are associated with tuberous sclerosis complex.

• VHL or Von hippel lindau mutations are seen in renal cell carcinoma.

Multiple Choice

Which of the following is a histologic feature FREQUENTLY seen in this type of tumor?

• Brisk mitotic activity

• Cytoplasmic halo

• Homer Wright rosettes

• Necrosis

• Psammoma bodies

• Meningiomas can have variable patterns including meningothelial, or whorled, architectural pattern which shows ovoid to spindled cells in clusters and indistinct cell membranes, fibroblastic patterns, transitional patterns (with both meningothelial and fibroblastic patterns), psammomatous (large numbers of psammoma bodies), and secretory patterns (gland like, PAS positive material). The point is, there are numerous different growth patterns, but they are all called meningiomas!

• Atypical meningiomas have increased mitoses, cellularity, necrosis, and increased cytologic atypia and are typically associated with more aggressive growth and recurrence.

• The other answers describe various other tumors including oligodendrogliomas (clear halo, fried egg appearance), Homer Wright rosettes (medulloblastoma), and necrosis (associated with glioblastoma, see later).

​Next case (541).

Case 541

A 34-year-old woman with no prior history of disease presents to the emergency department after her spouse noticed her having a seizure. An MRI revealed a 3 x 4 x 4.2 cm mass in the right temporal lobe. A biopsy was performed.

​MRI, T2 sequence (left), T1 sequence, with gadolinium (right)

Hotspot

Identify the lesion.

Multiple Choice

Describe the lesion?

• The right shows peritumor edema. The left shows areas of necrosis and a thickened ring that demonstrates pooling of gadolinium

• The left shows peritumor edema. The right shows areas of necrosis and a thickened ring that demonstrates pooling of gadolinium

• Heterogeneous hypointense to isointense mass at the foramen of Monro

• Homogenous hypointense to isointense mass at the foramen of Monro

Q: What does the pattern of gadolinium reveal about the lesion?

It's a Jigglypuff, seen from above.

A: Breakdown of the blood-brain barrier.

Word Cloud

What is in your differential?

Diagnoses to consider:

• Astrocytoma, IDH-mutant

• Glioblastoma, IDH-wildtype

• Lymphoma

• Infection

• Abscess

• Metastatic disease

  What do we expect to see microscopically?
  

​Go to DigitalScope (541).

Identify necrosis, vascular proliferation, pleomorphic cells.

Multiple Choice

Which of the following genes is MOST COMMONLY mutated in this tumor?

• TP53

• MYC

• IDH2

• TSC

• VHL

Explanation

• 1p/19q codeletion would be seen in an oligodendroglioma which are typically grade 2 or 3 and have different morphologic features.

• EGFR amplification can be seen in IDH-wildtype glioblastoma which is progrowth; loss-of-function wouldn’t be seen in either tumor.

• TP53 can be mutated in both IDH-wildtype glioblastoma or IDH-mutant astrocytoma so wildtype TP53 would be a bit less likely.

• VHL is associated with von Hippel-Lindau syndrome which is characterized by cerebellar hemangioblastomas, not high grade gliomas.

• IDH-wildtype glioblastoma is the most common malignant glioma and the other answers are less likely. There are two IDH genes that can be mutated: IDH1 and IDH2, IDH1 is the gene that is typically mutated in gliomas (about 95% of cases!). The standard protocol is to perform immunohistochemistry for IDH1. If positive, we report the tumor as positive for IDH mutation. If negative, we reflex molecular test for both IDH1 and IDH2 (there is not an immunostain yet for IDH2).  

Multiple Choice

Which of the following is true regarding this disease?

• Median survival is less than 2 years

• In situ stages are detectable up to 5 years before diagnosis

• Metastases to lung and liver are common

• Posterior fossa is the most common site of origin

• Psammoma bodies are commonly found histologically.

Explanation

Glioblastomas have a poor prognosis, with a median survival of less than 2 years. While some glioblastomas arise from lower grade gliomas, there is no "in situ" precursor lesion as seen in other organ systems.