Case Study 9

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Case Study 9

• Craig Horbinski, M.D., Ph.D.

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Question 1

• The patient is a 26 year-old female.  MRI with
  contrast was done.  What do you see?

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T1 with contrast
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T1 with contrast
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T1 with contrast
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T1 with contrast
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T1 with contrast
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Answer

• Multiple extra-axial dural-based tumors (note the
  dural tails), right cerebellopontine angle tumor,
  C1 intraspinal canal tumor.

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Question 2

• What are the extra-axial dural-based tumors most
  likely?  What about the CPA tumor?  The C1
  intraspinal canal tumor?

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Answer

• The location of all these tumors dictates the
  most likely diagnoses.  The extra-axial
  dural-based tumors are most likely meningiomas. 
  The more intensely enhancing CPA tumor is
  probably a schwannoma.  The intraspinal canal
  tumor is an ependymoma, which tend to be
  sausage-shaped and like to occupy the central
  canal or one of the ventricles.

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Question 3

• What is the overall diagnosis in this patient
  (i.e. what disease produces all the
  aforementioned tumors)?

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Answer

• Neurofibromatosis type 2.  The diagnosis had
  already been confirmed years ago via molecular
  genetic testing, but this single MRI study is
  pathognomonic even if you knew nothing at all
  about the patient.

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Question 4

• No intraoperative consultation was requested. 
  Several tumors were resected, including a left
  frontal mass.  The permanent slides of this tumor
  arrived.  What do you see?
• Click here to view slide.

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Answer

• Hypercellular spindle cells organized into vague
  whorls, fascicles, and sheets psammoma bodies
  rare mitoses generally bland oval nuclei with
  intranuclear pseudoinclusions and inconspicuous
  nucleoli.

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Question 5

• What is the diagnosis?  What stains would you do
  to confirm the diagnosis?

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Answer

• Meningioma.  Routine immunostains include EMA
  (80 are focally positive, 100 of schwannomas
  are negative) and Ki67 (assesses proliferation
  index).

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Question 6

• What WHO grade would you assign it?

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Answer

• WHO grade 1.  Despite the cellularity and
  presence of a few mitoses, it's not enough to
  call this an atypical meningioma, WHO grade 2. 
  To do that, you need to see either 4 or more
  mitoses per 10 high power fields OR 3 of the
  following hypercellularity, small cell change,
  prominent nucleoli, sheet-like growth pattern,
  necrosis, brain invasion.  In this tumor there is
  only about 1 mitosis per 10 high power fields
  with hypercellularity and a sheet-like growth
  pattern.  It's close to being a grade 2, but not
  quite there.

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Question 7

• The immunostains you ordered have arrived
  (assuming these were the ones you ordered,
  anyway).  Does the Ki67 immunostain help "push"
  this tumor to a higher grade?  If so, how high
  does the index have to be?  If not, why bother
  doing the stain?
• Click the following links to view slides EMA,
  Ki67

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Answer

• No.  Even though the estimated proliferation
  index is around 10-15, which is pretty high for
  a meningioma, the criteria for upgrading it to
  "atypical" status does not include Ki67
  proliferation index (at least, not yet).  Even
  so, quite frequently the surgeons will ask what
  the proliferation index is a proliferation index
  this high might very well influence the
  management of this patient.  Moreover, sometimes
  a "hot spot" of Ki67 immunoreactivity will call
  attention to a focus of high mitotic activity
  that otherwise might have been missed on HE. 
  Thus it is part of the routine workup of all
  meningiomas, as well as many other brain tumors.

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Question 8

• What does grade mean in this setting, anyway? 
  What does it imply for a typical patient?  For
  this patient?

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Answer

• For meningiomas, grade predicts the likelihood of
  recurrence.  (The main predictor is, of course,
  extent of surgical resection, but grade
  nonetheless is important.)  Grade 1 meningiomas
  recur around 10-15 of the time, whereas grade 2
  recurs up to 40 of the time.  Grade 3
  meningiomas recur up to 80 of the time. 
  However, these numbers are for sporadic tumors. 
  In this particular patient it's a little
  different because she has a germline genetic
  disease that will undoubtedly come back.

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Question 9

• What are the official criteria for NF2?  (Yes,
  this is fair game for the general pathology
  boards.)

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Answer

• The diagnostic criteria for NF2 can be met in 1
  of 3 ways
• Bilateral vestibular schwannomas
• In a patient with a first-degree relative already
  diagnosed with NF2, either one vestibular
  schwannoma or 2 of the following meningioma,
  schwannoma of another nerve, glioma (e.g. diffuse
  astrocytoma or ependymoma), cerebral
  calcification, lens cataracts.
• 2 of the following 1 vestibular schwannoma,
  multiple meningiomas, glioma (e.g. diffuse
  astrocytoma or ependymoma), schwannoma of another
  nerve, cerebral calcification, lens cataracts.
• This patient has a vestibular schwannoma plus
  multiple meningiomas, so she meets the diagnostic
  criteria for NF2.

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Question 10

• What is the most common deletion seen in this
  tumor? (Another high-yield boards question.)

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Answer

• Deletion on chromosome 22q (del 22q).

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Question 11

• What key gene is on this region of deleted DNA? 
  What does it do?

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Answer

• Merlin (a.k.a. schwannomin or neurofibromin 2),
  located on 22q12.  It's a tumor suppressor
  protein that inhibits Rac-dependent signaling and
  STAT activation.