Case Study 32

1
Case Study 32

• Henry Armah, M.D., M.Phil.

2
Question 1

• Clinical history 78-year-old white female with
  history of morbid obesity, hypertension,
  hypercholesterolemia, hypothyroidism, left knee
  replacement surgery, and partial colectomy for a
  6.2 cm villous adenoma. She had a 35 pack-year
  history of smoking ending approximately 15 years
  prior. She occasionally used alcohol socially and
  did not use illicit drugs. She also had a recent
  history of bilateral pulmonary embolism following
  a motor vehicle accident and she was then started
  on Coumadin. The findings of a subsequent cranial
  MRI performed for complaints of vertigo and
  bilateral tinnitus resulted in the
  discontinuation of Coumadin. Describe the
  abnormal MRI findings?

3
T1
4
T1C
5
T2
6
T2
7
Answer

• Multifocal decreased T2 signal throughout the
  cerebral hemispheres bilaterally.
• No abnormal contrast enhancement other than some
  vague enhancement surrounding some of the foci of
  abnormal T2 signal.
• Extensive multifocal white matter signal seen
  with aging.
• Moderately extensive microvascular disease
  changes and age-appropriate symmetrical brain
  volume loss.

8
Question 2

• What are your differential diagnoses from these
  radiographs?

9
Answer

• Multiple cavernous angiomata.
• Extensive amyloid angiopathic changes.

T2

10
Question 3

• Ultimately she died from a combination of
  pulmonary thromboembolism due to presumptive deep
  venous thrombosis morbid obesity which is a
  predisposing factor in the development of deep
  venous thrombosis severe atherosclerotic
  coronary artery disease due to hypertension and
  hypercholesterolemia and mild cardiac
  amyloidosis. An autopsy was performed. Describe
  the abnormal gross brain findings?

11
(No Transcript)
12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15
Answer

• Multiple bilateral coalescent hemorrhagic foci in
  cerebral white matter especially centrum
  semiovale and corpus callosum, cerebellar white
  matter, pons, and medulla.

16
Question 4

• Sections of the brain lesions were processed for
  histology. Describe the microscopic findings on
  this slide?
• Click here to view slide.

17
Answer

• Multiple foci of coalescent cavernous angiomas
  with minimal intervening perivascular gliosis,
  foamy and hemosiderin-laden macrophages, and
  mineralization.

18
Question 5

• What additional stain would you need to rule out
  an important differential diagnosis in this case?
•  

19
Answer

• Beta-A4 amyloid immunostain to rule out amyloid
  angiopathy.

20
Question 6

• Describe the microscopic findings on this
  additional stain?
• Click here to view slide.

21
Answer

• Beta-A4 amyloid immunostain is negative in wall
  of vessels.

22
Question 7

• What is your final diagnosis in this case?

23
Answer

• Multiple Cerebral Cavernous Angiomas.

24
Question 8

• Is the likely pathogenesis of lesion sporadic or
  familial/congenital in this case? Give reason for
  your choice.

25
Answer

• Familial/Congenital on account of multiple
  lesions.

26
Question 9

• Based on cranial MRI and necropsy studies of
  large cohorts of patients, the estimated
  population prevalence of this lesion is?
• 0.1
• 0.5
• 5
• 10
• 25

27
Answer

• B. 0.5

28
Question 10

• In what percentage of individuals is lesion
  clinically symptomatic?
• 2-4
• 5-10
• 20-30
• 40-50
• None of the above

29
Answer

• C. 20-30

30
Question 11

• What is the mode of inheritance of the
  familial/congenital form of this lesion?

31
Answer

• Autosomal Dominant

32
Question 12

• Familial/congenital forms of this lesion have
  been associated with loss of function gene
  mutations at all the following chromosomal loci,
  except?
• KRIT1/CCM1 (7q21-22)
• NF2 (22q12)
• MGC4607/CCM2 (7p13-15)
• PDCD10/CCM3 (3q25.2-27)

33
Answer

• B. NF2 (22q12)

34
Question 13

• What follow-up studies may be warranted in
  symptomatic and/or at-risk relatives of this
  patient?

35
Answer

• Cerebral magnetic resonance imaging.
• DNA-based genetic screening for CCM1, CCM2, and
  CCM3 mutations.