Case Study 32
Henry Armah, M.D., M.Phil.
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?
T1
T1+C
T2
T2
Answer
1. Multifocal decreased T2 signal throughout the cerebral
hemispheres bilaterally.
2. No abnormal contrast enhancement other than some
vague enhancement surrounding some of the foci of
abnormal T2 signal.
3. Extensive multifocal white matter signal seen with
aging.
4. Moderately extensive microvascular disease changes
and age-appropriate symmetrical brain volume loss.
Question 2
What are your differential diagnoses from these
radiographs?
Answer
1. Multiple cavernous angiomata.
2. Extensive amyloid angiopathic changes.
T2
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?
Answer
Multiple bilateral coalescent hemorrhagic foci in cerebral
white matter especially centrum semiovale and corpus
callosum, cerebellar white matter, pons, and medulla.
Question 4
Sections of the brain lesions were processed for histology.
Describe the microscopic findings on this slide?
Click here to view slide.
Answer
Multiple foci of coalescent cavernous angiomas with
minimal intervening perivascular gliosis, foamy and
hemosiderin-laden macrophages, and mineralization.
Question 5
What additional stain would you need to rule out an
important differential diagnosis in this case?
Answer
Beta-A4 amyloid immunostain to rule out amyloid
angiopathy.
Question 6
Describe the microscopic findings on this additional stain?
Click here to view slide.
Answer
Beta-A4 amyloid immunostain is negative in wall of
vessels.
Question 7
What is your final diagnosis in this case?
Answer
Multiple Cerebral Cavernous Angiomas.
Question 8
Is the likely pathogenesis of lesion sporadic or
familial/congenital in this case? Give reason for your
choice.
Answer
Familial/Congenital on account of multiple lesions.
Question 9
Based on cranial MRI and necropsy studies of large
cohorts of patients, the estimated population prevalence
of this lesion is?
A.0.1%
B.0.5%
C.5%
D.10%
E.25%
Answer
B. 0.5%
Question 10
In what percentage of individuals is lesion clinically
symptomatic?
A.2-4%
B.5-10%
C.20-30%
D.40-50%
E.None of the above
Answer
C. 20-30%
Question 11
What is the mode of inheritance of the familial/congenital
form of this lesion?
Answer
Autosomal Dominant
Question 12
Familial/congenital forms of this lesion have been
associated with loss of function gene mutations at all the
following chromosomal loci, except?
A.KRIT1/CCM1 (7q21-22)
B.NF2 (22q12)
C.MGC4607/CCM2 (7p13-15)
D.PDCD10/CCM3 (3q25.2-27)
Answer
B. NF2 (22q12)
Question 13
What follow-up studies may be warranted in symptomatic
and/or at-risk relatives of this patient?
Answer
1. Cerebral magnetic resonance imaging.
2. DNA-based genetic screening for CCM1, CCM2, and
CCM3 mutations.