Pathology Flashcards
What percent of primary intracranial tumors are accounted for by meningiomas?
~30% of all primary intracranial tumors are meningiomas
Meningiomas are probably derived from ____ cells
Arachnoidal cap cells which form the outer layer of the arachnoid mater and arachnoid villi
What is the annual incidence of meningiomas per 100,000?
4-5 per 100,000 individuals
In what decade of life are meningiomas most comon?
What is the sex ratio?
7th decade of life
More common in women with female to male ratio 2:1.
(One theory is that there is a role of sex hormones (particularly progesterone receptor))
What autosomal dominant disorder is strongly associated with meningioma development? What is the associated mutation?
Neurofibromatosis type 2
Associated with mutation in NF2 gene on chromosome 22q12
NF2 mutations lead to LOSS of merlin expression which is a cytoskeleton protein associated with CD44 and important for growth arrest signal
Describe the WHO grading system of meningiomas
WHO grade I - benign - low risk of recurrence and aggressive growth
atypical - WHO grade II - atypical - greather likelihood of recurrence and/or agressive behavior
WHO grade III - anaplastic/malignant - high likelihood of recurrence and/or aggressive behavior
What are the criteria for meningioma WHO grade I?
Benign meningioma (WHO grade I)
- Histological variant OTHER than clear-cell, chordoid, papillary, or rhabdoid
- Lacks criteria of atypical and anaplastic meningioma
What are the criteria for meningioma WHO grade II?
Atypical meningioma (WHO grade II) - any of the three criteria
1. Mitotic index >/= 4 mitoses/10 HPF
2. At least 3/5 parameters:
- Increased cellularity
- High nuclear/cytoplasmic ratio (small cells)
- Prominent nucleioli
- Uninterupted patternless or sheet-like growth
- Foci of spontaneous necrosis (ie not induced by embolisation or radiation)
3. Brain invasion
Certain variants such as clear-cell and choroidal meningioma variants are associated with higher recurrence rates even in the absence of other criteria and thus are always graded II by definition (unless additional features for III)
What are the criteria for WHO grade III?
Anaplastic (malignant) meningioma (WHO grade III) is defined of EITHER of two criteria:
1. Mitotic index >/= 20 mitoses/10HPF
2. Anaplasia (sarcoma, carcinoma, or melanoma-like histology)
Name and describe the following found on biopsy of meningioma
Psammoa (“sand-like”) bodies so called because of gritty gross appearance which are formed by concentric calcifications (tumor cells wrap around one another, hylanize, and calcify)
Associated with psammomatous meningiomas (WHO grade I)
If a meningioma invades the dural sinuses, skull, or orbit, soft tissue, skin, is the tumor considered malignant?
No, not necessarily, the meningioma could still be classified as WHO grade I
Only if a meningioma is associated with brain invasion is the recurrence/mortality rate lead to a higher who designation (even if the tumor seems completely benign otherwise)
Following gross total resection, what is the recurrence rate at 5 years for….
Benign meningiomas
Atypical meningiomas
Malignant meningiomas
- Benign meningiomas - 5%
- Atypical meningiomas - 40% at 5 years and increases after that
- Malignant meningiomas - 50-80% and median survival less than 2 years (2006 paper)
What is the most reliable histological correlate of recurrence risk?
Increased mitotic activity
How common are each WHO grade of meningioma (% of all meningiomas)?
Benign WHO grade I
Atypical WHO grade II
Malignant WHO grade III
Benign WHO grade I - 80%
Atypical WHO grade II - 15-20%
Malignant WHO grade III - 1-3%
What meningioma variants are consistently associated with malignant behavior and classified as WHO grade III?
Papillary meningiomas which usually occur in cihldren and can have pseudopapillary pattern and even pseudorosette-like structures similar to ependymoma
(papillary = cells sticking together to form “finger like” projections)
Rhabdoid meningioma
What is the major mutation in meningioma to be aware of? What is the function of its product?
Chromosome 22q, the NF2 gene, and its product merlin. Obvi present in virtually all NF2 meningiomas but also about 50% of sporadic meningiomas.
This causes a loss of merlin function which has important role in cytoskeleton and interaction with CD44 to provide growth arrest signal
Mutations in NF2 are considered to be involved in meningioma INITIATION rather than progression
What are a few deletions/mutations commonly associated with anaplastic meningiomas? What chromosome are they on?
CDKN2A (encoding p16)
ARF
CDKN2B (encoding p15)
all located on chromosome 9p21
which lead to inactivation of G1/S phase cell-cycle checkpoint
