Neuropathology Questions

Question 1

1.	What primary CNS neoplasm is associated with eosinophilic
granular bodies?
A.	Anaplastic astrocytoma
B.	Oligodendroglioma
C.	Gemistocytic astrocytoma
D.	Pilocytic astrocytoma
E.	Germinoma

Answer 1

1. D. Pilocytic astrocytomas typically have a biphasic ap­
   pearance. They usually consist of regions of elongated cells
   arranged in compact fascicles intermixed with regions of
   stellate cells that encompass microcysts. Pilocytic astrocy­
   tomas can exhibit some nuclear pleomorphism and hyperchromasia,
   but
   mitoses
   and
   necrosis
   are
   absent.
   These

tumors
are
classically
associated
with
Rosenthal
fibers

and
intracellular
eosinophilic
globules
(granular
bodies).

Intracellular
eosinophilic
conglomerations
can
also
be
ob­
served
in
pleomorphic
xanthoastrocytoma
but
not
anaplastic

astrocytoma
or
oligodendroglioma.
Gemistocytic
astrocy­
toma
is
characterized
by
large,
plump
astrocytes
with

diffuse,
glassy
cytoplasm
(Ellison,
pp.
630-634;
WHO,
pp.
25,

45-54,
56-64).

Question 2

2.	Which of the following is associated with deposition of
phosphorylated tau protein?
A.	Hirano bodies
B.	Neurofibrillary tangles
C.	Diffuse amyloid plaques
D.	Lewy  bodies
E.	Granulovacuolar degeneration

Answer 2

2. B. Neurofibrillary tangles (NFTs) are cytoplasmic, baso­
   philic structures that are prevalent in neurons in patients
   with Alzheimer’s disease (AD). NFTs contain large amounts
   of paired helical filament protein, which largely consists of
   hyperphosphorylated tau. Tau protein is also phosphorylated
   in
   normal
   brain;
   however,
   these
   phosphate
   groups
   are

easily
removed
by
phosphatases.
The
hyperphosphorylated

tau
of
NFTs
is
largely
resistant
to
phosphatases,
which
may

be
a
key
feature
in
its
deposition
in
AD.
Other
key
features
of

AD
include
Hirano
bodies
(which
are
composed
of
actin),

amyloid
plaques,
and
granulovacuolar
degeneration
(which

primarily
affects
hippocampal
neurons).
Amyloid
plaques

are
extracellular
deposits
of
amyloid
and
preamyloid
mate­
rial,
which
are
easily
demonstrated
with
silver
stains
and

immunohistochemical
stains
for
Ap
peptide.
Diffuse
plaques

contain
normal
neuronal
processes
and
lack
tau
protein.

Classic
(mature)
plaques
often
consist
of
dense
core
regions

with
a
peripheral
halo
and
may
stain
positive
for
tau
protein

(Ellison,
pp.
550-565).

Question 3

3.	What neoplasm is depicted in the following photomicro-
graph (H&E section) (Figure 4.3QJ?
A.	Lymphoma
B.	Fibrillary astrocytoma
C.	Glioblastoma
D.	Medulloblastoma
E.	Meningioma

Answer 3

3. C. Glioblastoma multiforme (GBM) is characterized by
   cellular pleomorphism and a diversity of histologic appear­
   ances. Regardless of the predominant histologic pattern of
   a particular GBM, cytologic pleomorphism, nuclear hyper-
   chromasia, and frequent mitoses are often observed. By
   definition, tumor necrosis and/or microvascular prolifera­
   tion is present. Pseudopalisading of neoplastic cells around a
   central necrotic region (pseudopalisading necrosis), as de­
   picted here, is characteristic of GBMs. These features easily
   distinguish GBM from low-grade astrocytomas: medulloblastomas
   exhibit
   a
   more
   homogenous
   population
   of
   small
   blue cells that lack pseudopalisading necrosis. Lymphomas are
   characterized by sheets of neoplastic lymphocytes that often
   surround blood vessels and occasionally exhibit necrosis
   (Ellison, pp. 628-630; WHO, pp. 27-28, 29-39, 129-132,
   199-201).

Question 4

4.	Wliat chromosome abnormality is associated with neuro-
fibromatosis type 1?
A.	5
B.	7
C.	10
D.	17
E.	20

Answer 4

4. D. Neurofibromatosis type 1 is associated with abnormali­
   ties of the neurofibromin gene, which is located on chromo­
   some 17qll. NF1 exhibits autosomal inheritance with almost
   complete penetrance; however, approximately 50% of all cases
   are secondary to spontaneous mutations. Neurofibromin
   is a guanosine triphosphatase-activating protein that is
   important for cell proliferation and differentiation (Ellison,
   pp. 695-696; WHO, pp. 216-218).

Question 5

5.	Congenital CMY infection is characterized by all of the
following EXCEPT?
A.	Periventricular calcifications
B.	Microglial nodules
C.	Chorioretinitis
D.	Megalencephaly
E.	Hydrocephalus

Answer 5

5. D. Congenital CMV infection represents the most com­
   mon intrauterine viral infection, affecting 0.5 to 2.0% of all
   births. Macroscopically, CMV infection is characterized by
   microcephaly, periventricular and basal ganglial calcifica­
   tions, and hydrocephalus. Microscopically, CMV infections
   exhibit microglial nodules, cytomegalic inclusion cells, ventriculoencephalitis,
   and
   gliosis.
   Infants
   with
   congenital
   CMV

infections
can
also
exhibit
mental
retardation,
seizures,

chorioretinitis,
optic
atrophy,
sensorineural
hearing
loss,

and
death
in
30%
of
acute
infections
(Ellison,
pp.
284-286).

Question 6

6. Which of the following disorders is associated with
   Opalski cells on microscopic examination?
   A. Hallervorden-Spatz disease
   B. Werdnig-Hoffman disease
   C. Wilson’s disease
   D. Tay-Sachs disease
   E. Gaucher’s disease

Answer 6

6. C. Opalski cells are round, with a small central nucleus
   and prominent granular eosinophilic cytoplasm. These cells
   are most commonly observed in the globus pallidus in pa­
   tients with Wilson’s disease (hepatolenticular degeneration)
   and acquired hepatic encephalopathy (Ellison, pp. 429-432).

Question 7

7.	Which of the following proteins compose the Lewy body?
A.	Ubiquitin
B.	Neurofilaments
C.	a-Synuclein
D.	Both A and G
E.	All of the above

Answer 7

7. E. Lewy bodies are associated with Parkinson's disease
and are composed of neurofilament proteins (form the cytoskeleton
of
the
inclusion),
ubiquitin
(involved
in
cytosolic

proteolysis),
ccB
crystallin
(neurofilament
chaperone
pro­
tein),
and
a-synuclein
(catalyze
phosphorylation
of
neuro­
filaments).
Immunohistochemical
stains
for
ubiquitin
are

among
the
most
sensitive
methods
of
identifying
Lewy

bodies
(Ellison,
pp.
511-513).

Question 8

8.	Ganavan's disease results from deficiencies of which of
the following enzymes?
A.	Aspartoacylase
B.	Aryl sulfatase A
C.	Glucocerebrosidase
D.	Hexosaminidase A
E.	Iduronidase

Answer 8

8. A. Canavan’s disease (spongiform leukodystrophy) is an
   autosomal recessive disorder characterized by extensive
   vacuolation of the white matter due to the widespread loss of
   myelin at the gray-white junction. Although cortical neurons
   are normal, there are numerous Alzheimer type II astrocytes within the gray matter. Cortical changes include enlarged
   pale astrocytes in the deeper cortical layers that contain
   abnormally long mitochondria with ladder-like cristae, an
   abnormality unique to Ganavan’s disease. Ganavan’s disease
   does not spare the subcortical U fibers and is a result of
   deficiencies of the enzyme aspartoacylase (Ellison, pp.
   121-122, 125).

Question 9

9. What is depicted in the following photomicrograph (Figure 4.9QJ?
FIGURE 4.9Q
A.	Fibrillary astrocytoma
B.	Reactive astrocytosis
C.	Anaplastic astrocytoma
D.	Clear cell meningioma
E.	Yolk sac tumor

Answer 9

9. A. Fibrillary astrocytoma is characterized by atypical
   astrocytes in a loose fibrillary matrix. The neoplastic cells
   lack visible cytoplasm and show features of mild nuclear
   atypia, such as hyperchromasia, elongation, or angulation.
   As in this case, microcysts are often prominent. Mitoses,
   necrosis, and endothelial proliferation are not observed.
   Reactive astrocytosis can occasionally be confused with a
   fibrillary astrocytoma; however, astrocytosis is character­
   ized by an even distribution of slightly enlarged astrocytic
   nuclei with abundant cytoplasm and long, tapering pro­
   cesses. There is usually no significant hypercellularity in
   reactive astrocytosis. Microcysts are also not observed with
   reactive astrocytosis (Ellison, pp. 623-628; WHO, pp. 2425).

Question 10

10.	Which of the following neoplasms is not associated with
neurofibromatosis type 2?
A.	Ependymoma
B.	Schwannoma
C.	Meningioma
D.	Glioma
E.	Plexiform neurofibroma

Answer 10

10. E. NF-2 is an autosomal dominant condition that is most
    commonly associated with bilateral schwannomas of the
    eighth cranial nerve and multiple intracranial meningiomas.
    NF-2 is also associated with schwannomas of other cranial
    nerves, spinal meningiomas, astrocytomas (spinal, brain­
    stem, and cerebellar), and spinal ependymomas. Spinal
    schwannomas are occasionally observed with NF-2, although
    spinal neurofibromas and plexiform neurofibromas are not
    (WHO, pp. 219-222; Ellison, pp. 696-699; Kaye and Laws,
    pp. 71-76).

Question 11

11. What is the most likely clinical history associated with
    the following photomicrograph (Figure 4.HQ,)?
    A. Seizures and progressive hypotonia in infancy
    B. Rapidly progressing dementing illness of an adult
    C. Gradually progressive focal neurologic deficit
    D. Asymptomatic lesion that can often be treated with
    antibiotics alone
    E. Asymptomatic lesion that typically responds favorably
    to surgery alone

Answer 11

11. B. The photomicrograph illustrates the classic spongi­
    form change that is associated with Greutzfeldt-Jakob dis­
    ease (CJD). CJD usually affects adults in the sixth to eighth
    decades of life. Approximately 85% of all cases of CJD are
    sporadic and 10% are familial. Microscopically, CJD is char­
    acterized by neuronal loss, astrocytosis, spongiform change
    (fine vacuolation of the neuropil), and a lack of inflam­
    mation. Clinically, CJD is characterized initially by subtle
    motor signs and ataxia, followed by a rapidly progressive
    dementing illness that culminates in severe myoclonus,
    akinetic mutism, and death within 1 year from initial symp­
    tom onset. The prion diseases, including CJD, GerstmannStraussler-Scheinker
    disease,
    fatal
    familial
    insomnia,
    and

kuru,
are
believed
to
have
a
common
molecular
pathology

that
involves
the
conversion
of
a
normal
cellular
protein

(encoded
on
human
chromosome
20),
called
prion
protein

(PrP),
into
an
abnormal
isoform
that
is
resistant
to
protease

degradation
(PrPres).
This
abnormal
isoform
is
believed
to

accumulate
within
cells,
and
also
outside
of
cells
in
the
form

of
amyloid.
Although
immunostaining
for
PrPres
is
diagnostic

for
CJD.
the
CSF
immunoassay
for
protein
14-3-3
has
96%

sensitivity and specificity for detecting CJD among patients
with dementia. The characteristic EEG findings include
bilateral, symmetric, and periodic bi- or triphasic syn­
chronous sharp-wave complexes (periodic spikes, 0.5 to 2/s),
which have 70% sensitivity and 86% specificity for CJD. Fully
effective and recommended operating room procedures for
instrument sterilization includes steam autoclaving for
1 hour at 132°C or immersion in IN sodium hydroxide
(NaOH) for 1 hour at room temperature. Partially effective
procedures include steam autoclaving at either 121 or 132°C
for 15 to 30 minutes, immersion in IN NaOH for 15 minutes,
or immersion in sodium hypochlorite (household bleach)
undiluted or up to 1:10 dilution (0.5%) for 1 hour. Ineffec­
tive sterilization procedures include boiling, UV light,
ionizing radiation, ethylene oxide, ethanol, formalin, betapropiolactone,
ammonium
compounds,
iodine,
or
acetone

(Ellison,
pp.
585-598;
Greenberg,
pp.
228-231).

Question 12

QUESTIONS   12-16
Directions: Match the following items with their appropriate inclusion body. Some letters may be used more than once.
A.	Actin
B.	Ubiquitin
C.	Polyglucosans
D.	Amyotrophic lateral sclerosis
E.	oc-Synuclein
12.	Marinesco bodies

13. Lafora bodies
14. Bunina bodies
15. Hirano bodies
16. Pick bodies End of set

Answer 12

12-B; 13-C; 14-D; 15-A; 16-B. Marinesco bodies are small
eosinophilic intranuclear inclusions that are prominent in
neurons of the substantia nigra and are composed largely
of ubiquitin and intermediate filaments. Lafora bodies
are composed of polysaccharide polymers (polyglucosans)
and have a round core that is strongly PAS-positive. Bunina
bodies are small eosinophilic inclusions that are observed in
motor neuron diseases such as amyotrophic lateral sclerosis.
Hirano bodies are brightly eosinophilic cytoplasmic inclusions
that are prominent in hippocampal neurons in Alzheimer’s
disease. Hirano bodies are composed of actin and actinassociated
proteins.
Pick
bodies
are
slightly
basophilic

neuronal
cytoplasmic
inclusions
that
are
observed
in
all

layers
of
the
cerebral
cortex
and
some
subcortical
nuclei
in

patients
with
Pick's
disease.
Pick
bodies
consist
of
ubiquitin,

tubulin,
tau,
and
chromogranin-A
(Ellison,
pp.
7-10,
504505,
552,
566-567,
570-572).

Question 13

17.	What pathologic condition is depicted in the following photomicrograph (Figure 4.17Q)?
A.	Capillary telangiectasia
B.	Cavernous malformation
C.	Venous angioma
D.	Arteriovenous malformation
E.	Angiomatous meningioma

Answer 13

17. D. Arteriovenous malformations (AVMs) are character­
    ized by clusters of dilated vessels of varying diameters with
    abnormally thick or thin walls and occasional intervening
    brain parenchyma. AVMs often contain calcification, and
    the surrounding brain parenchyma may exhibit prominent
    astrocytosis. Capillary telangiectasias consist of much smaller,
    uniformly thin-walled vascular channels without evidence
    of hemorrhage or surrounding astrocytosis. Cavernous mal­
    formations are characterized by tightly packed hyalinized
    vascular channels without elastic tissue. There is usually no
    intervening brain parenchyma. Venous angiomas are com­
    posed of thin-walled, dilated vascular channels interspersed
    among normal brain parenchyma (Ellison, pp. 226-233).

Question 14

18. What feature of chronic subdural hematomas is most
    likely to lead to progressive expansion in size over time?
    A. Reinjury of bridging veins
    B. Osmotic migration across the dura into the subdural
    space
    C. Hemorrhage in the granulation tissue of the pseu-
    domembrane
    D. Breakdown of the blood-brain barrier in adjacent brain
    parenchyma
    E. None of the above

Answer 14

18. C. Chronic subdural hematomas (SDH) are usually
    initiated from the tearing of bridging veins, which can
    often be precipitated by minimal trauma in patients with
    significant cerebral atrophy. After the initial hemorrhagic
    event, a pseudomembrane organizes immediately beneath
    the fibrous dura along the surface of the hematoma. This
    pseudomembrane develops dense granulation tissue with
    prominent neovascularization. Large-caliber vessels in this
    granulation tissue are initially unstable and tend to bleed
    spontaneously, which leads to progressive, stepwise enlarge­
    ment of the SDH (Ellison, pp. 210-211).

Question 15

19. What is the most likely etiology of the lesion depicted
    below in this gross specimen (Figure 4.19Q.)?
    A. Direct contusion
    B. Shearing injury
    C. Herniation
    D. Arterial dissection
    E. Arterial rupture

Answer 15

19. C. This specimen exhibits a prominent pontine hemor­
    rhage, known as a Duret hemorrhage. Duret hemorrhages
    occur when internal herniation (usually transtentorial
    herniation) results in compression or stretching of pontine
    perforating vessels. This leads to ischemic damage in the
    pons, which then undergoes secondary hemorrhagic conver­
    sion. This type of hemorrhage is not a direct result of trauma
    and occurs only after prolonged elevations in intracranial
    pressure with concomitant herniation (Ellison, pp. 257-259).

Question 16

20. What is the most common organism isolated from intracranial  abscesses?
A.	Staphylococcus	aureus
B.	Pseudomonas	aeruginosa
C.	Streptococcus	pneumoniae
D.	Streptococcus	milleri
E.	Mycobacterium	tuberculosis

Answer 16

20. D. Streptococcus milleri is the most common isolate
    from intracranial abscesses. Many intracranial abscesses are
    polymicrobial, however. Infants are particularly susceptible
    to developing abscesses in association with the development
    of meningitis from infections by Citrobacter diversus
    or Proteus mirabilis. Brain abscesses often result from
    hematogenous seeding in a septic patient (2596), or direct
    spread from infections of the middle ear, paranasal sinuses,
    or dental roots (50%) (Ellison, pp. 330-335; Greenberg,
    p. 218).

Question 17

21. What neoplasm is depicted in the following photomicro¬graph (Figure 4.21Q)?
A.	Choriocarcinoma
B.	Yolk sac tumor
C.	Secretory meningoma
D.	Germinoma
E.	Ependymoma

Answer 17

21. D. Germinomas are characterized by groups of round
    neoplastic cells that contain clear cytoplasm with inter­
    spersed regions of lymphocytic infiltrates. It is the presence
    of chronic inflammation in this specimen that distinguishes
    this tumor from the other choices and is characteristic of
    germinomas. Choriocarcinoma exhibits a bilaminar pattern
    of syncytiotrophoblastic giant cells interspersed among smaller
    neoplastic cells, which is often associated with necrosis
    and hemorrhage. Yolk sac tumor is characterized by a loose
    arrangement of clear cells and occasional Schiller-Duval
    bodies. Secretory meningiomas exhibit typical meningothelial
    or
    transitional
    patterns
    with
    occasional
    intracellular

eosinophilic
globules.
Ependymomas
are
characterized
by

uniform
neoplastic
cells
with
higher
nuclear-cytoplasmic

ratios
arranged
in
pseudorosettes.
with
the
rare
observance

of
true
rosettes
(Ellison,
pp.
645-647,
667-670,
680-683,

710;
WHO,
pp.
72-77,129-137,
179,
208-214).

Question 18

22.	What is the most common cranial nerve affected by
neurosarcoidosis?
A.	Optic
B.	Oculomotor
C.	Trigeminal
D.	Abducens
E.	Facial

Answer 18

22. E. The facial nerve is by far the most commonly involved
    cranial nerve with neurosarcoidosis. In fact, the most com­
    mon clinical presentation of neurosarcoidosis is unilateral
    facial nerve palsy. Other neurologic manifestations may
    include deafness, vertigo, aseptic meningitis, hydrocephalus,
    diabetes insipidus, or hypothyroidism. Intracranial disease is
    quite commonly associated with peripheral nervous system
    and muscle involvement (Ellison, pp. 346-348; Greenberg,
    pp. 79-80).

Question 19

23.	Which of the following regions of the brain exhibit
prominent atrophy with Alzheimer's disease?
1.	Hippocampus
2.	Occipital lobe
3.	Frontal lobe
4.	Primarv motor cortex
A. 1,2, and 3 are correct
B.	1 and 3 are correct
C.	2 and 4 are correct
D.	Only 4 is correct
E.	All of the above are correct

Answer 19

23. B. The gross brain of patients with Alzheimer’s disease
    usually exhibits prominent atrophy of the medial temporal
    lobes, anterior frontal lobes, and the parietal lobes. The hip­
    pocampus is particularly affected, whereas the motor cortex
    and occipital lobes are usually spared (Ellison, pp. 550-565).

Question 20

24. Bilirubin deposition in the brain of a neonate with kernicterus is commonly observed in which of the following regions?
25. Subthalamic nucleus
26. Globus pallidus
27. Dentate nucleus
28. Red nucleus
    A. 1,2, and 3 are correct
    B. 1 and 3 are correct
    C. 2 and 4 are correct
    D. Only 4 is correct
    E. All of the above are correct

Answer 20

24. A. Bilirubin deposition with kernicterus is evidenced by
    yellow staining of several deep gray structures in the gross
    specimen. The most commonly involved regions include the
    lateral thalamus, globus pallidus, and subthalamic nucleus.
    The hippocampus, colliculi, substantia nigra pars reticulata,
    dentate nucleus, inferior olives, brainstem reticular forma­
    tion, and cranial nerve nuclei are also affected. It is the un­
    conjugated form of bilirubin that is toxic, and its accumulation
    leads to neuronal necrosis with subsequent gliosis (Ellison,
    pp. 50-52).

Question 21

25. A 58-year-old male presents with focal seizures and is
    found to have a large frontal lobe mass originating from
    the gray-white junction on MRI. The patient underwent a
    diagnostic biopsy of this lesion, and the specimen was CD45-
    negative, vimentin-positive, cytokeratin-AEl/3 positive, and
    EMA-negative. This is most consistent with which of the
    following neoplasms?
    A. Lymphoma
    B. Metastatic carcinoma
    C. Glioblastoma
    D. Hemangiopericytoma
    E. Meningioma

Answer 21

25. C. Glioblastoma multiforme exhibits staining for both
    vimentin and S-100. GBMs are usually focally positive for
    GFAP as well. With small tissue biopsies, it can be difficult to
    distinguish GBM from metastatic carcinoma and lymphoma.
    Metastatic carcinoma exhibits staining for epithelial mem­
    brane antigen (EMA) and cytokeratins, while lymphoma is
    CD45-positive, which distinguishes these neoplasms from
    GBM. GBM, however, occasionally exhibits cross reactivity
    with some keratin stains (e.g., AE1/3). Hemangiopericytoma
    is vimentin-positive and EMA-negative; however, it does
    not exhibit AE1/3 cross-reactivity (Ellison, pp. 628-632,
    689-694, 732-735, 745-750; WHO, pp. 29-39, 190,
    198-203, 250-253).

Question 22

26.	Which of the following meningioma variants is depicted
in this photomicrograph (Figure 4.26Q)?
A.	Meningothelial
B.	Fibrous
C.	Transitional
D.	Secretory
E.	Ghordoid

Answer 22

26. C. Meningothelial meningiomas exhibit sheets or lobules
    of cells with oval nuclei and indistinct cell borders.
    Rudimentary whorls are often present. Fibrous meningiomas
    exhibit streaming of elongated (spindle-shaped) nuclei with
    prominent surrounding collagen deposition. Transitional
    meningiomas contain elements of both meningothelial and
    fibrous variants. Transitional variants exhibit whorls or
    lobules as well as a fascicular (streaming) pattern of neo­
    plastic cells, as depicted here. Secretory meningiomas can
    exhibit a transitional or meningothelial pattern; however,
    many cells contain prominent eosinophilic (PAS-positive)
    globules. Ghordoid meningiomas exhibit columns of cells
    surrounded by a mucoid matrix, thus resembling a chor­
    doma (WHO, pp. 176-184; Ellison, pp. 703-716).

Question 23

27. Which of the following meningioma variants is associ-
    ated with more aggressive clinical behavior?
    A. Papillary
    B. Angiomatous
    C. Chordoid
    D. Clear cell
    E. Metaplastic

Answer 23

27. A. Papillary meningiomas are unique variants that ex­
    hibit a high nuclear-cytoplasmic ratio, prominent mitoses,
    metastasis throughout the CNS via CSF pathways, and
    occasional metastasis outside the CNS. Other meningioma
    variants are considered atypical if they exhibit prominent
    mitoses, increased cellularity, sheet-like growth patterns,
    and necrosis. Anaplastic meningiomas are frankly malignant
    lesions that exhibit prominent cellular pleomorphism and
    necrosis. Atypical and anaplastic meningiomas are more
    108 Intensive Neurosurgery Board Review
    likely to exhibit local invasion and recur after resection;
    however, distant metastasis is usually confined to papillary
    meningiomas (Ellison, pp. 711-715; WHO, pp. 179-180).

Question 24

28.	Which of the following disorders can be inherited in an
autosomal dominant fashion via mutations in the superoxide
dismutase (SOD1) gene?
A.	Refsum's disease
B.	Sanfilippo syndrome
C.	Zellweger syndrome
D.	Amyotrophic lateral sclerosis
E.	None of the above

Answer 24

28. D. Amyotrophic lateral sclerosis (ALS) is a neurodegen­
    erative disorder that results in the loss of upper and lower
    motor neurons. Although the cause of ALS is unknown, 5 to
    10% of all cases of ALS are inherited in an autosomal domi­
    nant fashion. Approximately 25% of these familial cases of
    ALS are secondary to mutations of the copper/zinc super­
    oxide dismutase (SOD1) gene located on chromosome 21q.
    Refsum’s disease results from deficiencies of the enzyme
    phytanoyl GoA hydroxylase, which results in the accumula­
    tion of phytanic acid. Clinical manifestations of Refsum’s
    disease include ataxia, peripheral neuropathy, and retinitis
    pigmentosa. Sanfilippo syndrome is one of the mucopolysac­
    charidoses and results from defective glycosaminoglycan
    (heparan sulfate) metabolism. Zellweger syndrome is a
    peroxisomal disorder that is associated with pachygyria,
    polymicrogyria, and various heterotopias (Ellison, pp. 93,
    445-447, 452-454, 501-507; Merritt, pp. 539-540).

Question 25

``` 29. Which of the following major histocompatibility com- plexes is associated with the development of multiple sclerosis? 1. HLA-DR15 A. 1,2, and 3 are correct 2. HLA-DR2 B. 1 and 3 are correct 3. HLA-B7 C. 2 and 4 are correct 4. HLA-DR4 D. Only 4 is correct E. All of the above are correct ```

Answer 25

29. A. Multiple sclerosis (MS) is classically associated with the HLA-DR2 allele, and HLA-DR15 is common in Northern Europeans with MS. The HLA alleles A3, B7, and DR3 are also overrepresented in the MS population. The incidence and prevalence of MS vary with latitude, increasing with greater distance from the equator. If, however, an individual migrates to a higher-risk latitude after the teen years, that individual's risk of developing MS is no greater than the risk associated with the original region (Ellison, pp. 389-404).

Question 26

``` QUESTIONS 30-34 Directions: Match the following neoplasms with the most common protein/stain using each answer once, more than once, or not at all. A. Vimentin B. CD 45 C. CD34 D. S-100 E. Synaptophysin 30. Lymphoma 31. Hemangiopericytoma 32. Sustentacular cell of paraganglioma 33. Meningioma 34. Central neurocytoma End of set ```

Answer 26

``` 30-B; 31-C; 32-D; 33-A; 34-E. Hemangiopericytoma is vimentinpositive, with focal reactivity to GD34 as well. The sustentacular cell of paragangliomas exhibits immunoreactivity for ``` ``` S-100, while chief cells exhibit chromogranin-A and synaptophysin positivity. Meningiomas are vimentin-positive, with ``` ``` occasional focal reactivity for EMA, S-100, and cytokeratins. ``` ``` Notably, meningiomas are GFAP-negative. Central neurocy­ toma exhibits immunoreactivity for synaptophysin, GFAP, ``` ``` and neurofilament proteins. Primary CNS T-cell lymphomas ``` ``` are CD 45- and CD 3-positive, while B-cell lymphomas usu­ ally show immunoreactivity to CD 79a and CD 20 (Ellison, ``` ``` pp. 656-659, 691-692, 703-716, 732-735). ```

Question 27

``` 35. What neoplasm is depicted in the following photomicro¬graph (Figure 4.35QJ? A. Clear cell meningioma B. Medulloblastoma C. Fibrillary astrocytoma D. Oligodendroglioma E. Hemangiopericytoma ```

Answer 27

35. D. Oligodendrogliomas are characterized by uniform cells, arranged back to back, and interspersed prominent branching capillaries ("chicken-wire" vasculature). Artifactual clearing of the cytoplasm ("fried-egg" appearance), as de­ picted here, results from delayed formalin fixation and is not always observed. The neoplastic cells of oligodendrogliomas contain monomorphic round nuclei. Oligodendrogliomas frequently exhibit loss of heterozygosity on chromosome lp and 19q and rarely contain p53 mutations. Very few cells in these neoplasms exhibit immunoreactivity for GFAP. Clear cell meningiomas resemble oligodendrogliomas microscopi­ cally, but like other meningiomas, clear cell meningiomas contain bands of collagen. They also lack the chicken-wire vasculature of oligodendrogliomas (Ellison, pp. 641-644; WHO, pp. 56-64).

Question 28

``` 36. What abnormality is depicted in the following photo¬micrograph (Figure 4.36Q)? A. Gemistocytic astrocytoma B. Reactive astrocytosis C. Acute infarction D. Viral encephalitis E. Bacterial meningitis ```

Answer 28

36. C. Microscopically, acute cerebral infarcts (after 8 to 12 hours) exhibit neuronal eosinophilia, pyknosis, and vacuolation of the neuropil. Subacute infarcts (2 to 4 days) also ex­ hibit neuronal eosinophilia; however, they may also contain ``` neutrophil infiltrates, occasional necrotic microvessels, ``` ``` and scattered foamy histiocytes. Chronic infarcts exhibit ``` ``` foamy macrophages, reactive astrocytosis, thin-walled blood ``` ``` vessels (neovascularization), and ferrugination of residual ``` ``` neurons surrounding a cystic (acellular) cavity. Gemistocytic astrocytomas exhibit large plump eosinophilic cells ``` ``` with glassy cytoplasm and are hypercellular. Viral encephali­ tis can exhibit neuronal eosinophilia, especially in the early ``` ``` stages; however, inclusion bodies are usually observed in ``` ``` conjunction with prominent lymphocytic infiltrates. Bacterial ``` ``` meningitis exhibits prominent infiltrates of neutrophils and ``` ``` lymphocytes, often with infiltration of leptomeningeal and ``` ``` cortical vessels. The above photomicrograph illustrates ``` ``` neuronal eosinophilia and pyknosis with vacuolation of the ``` ``` surrounding neuropil and a paucity of inflammation. This ``` ``` is most consistent with an acute cerebral infarction (Ellison, ``` ``` pp. 197-203, 627; WHO, p. 25). ```

Question 29

``` 37. Which of the following is not observed with acute spinal cord injury microscopically? A. Axonal spheroids B. Hemorrhagic necrosis C. Cavitation. D. Inflammatory infiltrates E. Edema ```

Answer 29

37. C. Acute spinal cord injury is characterized by axonal swellings (spheroids), hemorrhagic necrosis of gray and white matter, and variable amounts of surrounding edema. Over the following weeks there is infiltration of macrophages and a gradual removal of myelin and neuronal debris. Posttraumatic syrinx formation, or cavitation, is a relatively late feature of spinal cord injury, often occurring months to years after the original injury. The gray matter often shows prominent fibroblastic proliferation and associated collage­ nous fibrosis, as well as hyaline thickening of small blood vessels (Ellison, pp. 262-269).

Question 30

``` 38. What is the most common chromosomal abnormality associated with meningiomas? A. Allelic loss of lp B. Monosomy 22 C. Allelic loss of 10 D. Allelic loss of 22q E. Monosomy 2 ```

Answer 30

38. B. Monosomy 22 is by far the most common cytogenetic abnormality of meningiomas, and greater than 75% of all meningiomas exhibit loss of heterozygosity for chromosome 22q markers. Allelic losses of chromosomes lp, 10, and 14q are associated with progression to more aggressive menin­ giomas (atypical and anaplastic). Despite the occurrence of (multiple) meningiomas with NF-2, which also localizes to chromosome 22, the tumor suppressor gene that is respon­ sible for tumorigenesis with meningiomas in patients with­ out neurofibromatosis is separate from the NF-2 gene locus (Ellison, p. 715; Kaye and Laws, p. 78).

Question 31

``` 39. What is the inheritance pattern of Sturge-Weber syn- drome? A. Autosomal recessive B. Autosomal dominant C. X-linked recessive D. Mitochondrial E. Sporadic ```

Answer 31

39. E. Sturge-Weber syndrome (encephalotrigeminal angio­ matosis) is a neurocutaneous disorder that occurs sporad­ ically. The disorder is characterized by port wine stains in the distribution of the sensory fibers of the trigeminal nerve, with associated ocular angiomas and leptomeningeal venous angiomas of the ipsilateral cerebral hemisphere. Occasion­ ally the cerebral hemispheres are involved bilaterally. Most patients with Sturge-Weber syndrome develop epilepsy over time, and many exhibit progressive neurologic deficits such as hemiparesis, hemisensory loss, and homonymous hemianopsia. On microscopic analysis, there is widespread gliosis and dystrophic calcification of the involved brain parenchyma, with iron and calcium deposition in large, tor­ tuous meningeal vessels. The treatment of this disorder is largely symptomatic (Ellison, pp. 107-108).

Question 32

40. Which of the following disorders is associated with the lesion depicted in this photomicrograph (Figure 4.40QJ? 1. HIV encephalitis 2. Toxoplasmosis 3. CAR'encephalitis 4. Neurosyphilis A. 1,2, and 3 are correct B. 1 and 3 are correct C. 2 and 4 are correct D. Only 4 is correct E. All of the above are correct

Answer 32

``` 40. E. This photomicrograph depicts a microglial nodule. Microglia typically have rod-shaped nuclei and are GD68positive. Microglia proliferate in many chronic CNS infec­ tions and viral encephalitides. Microglial nodules sometimes ``` ``` contain neurons with viral inclusion bodies, and they are ``` ``` commonly observed with neurosyphilis, toxoplasmosis, and ``` ``` many different viral infections of the CNS (e.g., GMV, HIV, ``` ``` arboviruses, polioviruses). The aggregation of microglia and ``` ``` macrophages around dying neurons is called "neuronophagia" (Ellison, pp. 273-275, 277, 303-304, 319, 324). ```

Question 33

41. Which of the following characteristics is not associated with Hunter syndrome (mucopolysaccharidosis type II)? A. Lysosomal disorder B. X-linked recessive inheritance C. Hepatosplenomegaly D. Corneal clouding E. Mental retardation

Answer 33

41. D. Hunter syndrome is a lysosomal disorder that results from deficiencies of the enzyme iduronate sulfatase. It is in­ herited in an X-linked recessive fashion and usually presents in the first 2 to 4 years of life. Clinical findings of Hunter syn­ drome include delayed growth (short stature), coarse facial features, joint stiffness, macrocephaly, progressive hearing loss, hepatosplenomegaly, and various degrees of mental retardation. Hurler syndrome (MPS I), not Hunter syndrome, is associated with corneal clouding (Ellison, pp. 445-446).

Question 34

``` 42. What is depicted in the following photomicrograph (Figure 4.42Q)? A. Intracranial abscess B. Intracranial metastases C. Multiple sclerosis plaque D. Acute infarction E. Fungal infection ```

Answer 34

42. B. CNS metastatic lesions can occur anywhere but are typically located at the gray-white junction of the cerebral hemispheres. This H&E photomicrograph depicts a malig­ nant metastatic melanoma characterized by areas of hemor­ rhage, prominent nucleoli (dark spot inside nucleus), and some tumor cells containing melanin pigment (brown). Grossly, metastases can be firm, or they can exhibit a soft, necrotic central region. Hemorrhage is often associated with metastatic melanoma, renal cell carcinoma, or choriocarci­ noma. Metastases rarely involve the brainstem or spinal cord. Intracranial abscesses can also occur at the gray-white junction as a result of hematogenous spread, and they usu­ ally occur in the MCA distribution. Grossly, abscesses usually exhibit a well-defined capsule that is thicker toward the cortical surface and thinner toward the deep surface. The center of a brain abscess contains purulent, necrotic debris. MS plaques are well-demarcated gray areas of discoloration that commonly occur at the lateral angles of the lateral ven­ tricles. Foci of cavitation are rare with MS plaques but can be observed with fulminant, acute plaques. Acute infarcts exhibit only slight blurring of the gray-white junction with CHAPTER 4 Neuropathology Answers 109 dusky discoloration, often in major vascular territories (Ellison, pp. 197-202, 327-334, 389-398, 743-750).

Question 35

43. Which of the following disorders is associated with accommodation (ciliary) paralysis, facial paralysis, pre- servation of extraocular movements, and an ascending sensorimotor polyneuropathy? A. Neurosarcoidosis B. Neurosyphilis C. Diphtheria D. Lyme disease E. Guillain-Barre syndrome

Answer 35

43. C. Diphtheria infections can result in paralysis of accommodation (ciliary ganglion), followed by facial and oropharyngeal paralysis with preservation of extraocular movements. The fifth to eighth week of the illness is associ­ ated with an ascending sensorimotor polyneuropathy in approximately 20% of all cases; this results in a mild to severe paralysis. The disease course is shortened by early treatment with antitoxin and antibiotics, and the majority of patients eventually make a full recovery. Symptoms of neurosarcoidosis include cranial nerve palsies (facial weakness, ``` hearing loss, vertigo, optic atrophy), hypopituitarism, hydro­ cephalus, and ataxia. Neurosyphilis is associated with cranial ``` ``` nerve palsies, hydrocephalus, arteritis, seizures, and eventu­ ally psychosis and cognitive decline. Lyme disease results ``` ``` in an enlarging maculopapular rash with central clearing ``` ``` (erythema chronicum migrans), followed by the develop­ ment of axonal neuropathies, lymphocytic meningitis, ``` ``` encephalopathy, polyradiculitis, and cranial nerve palsies. ``` ``` Lyme disease can also affect the joints and cardiovascular ``` ``` system. Guillain-Barre syndrome (GBS) is an acute ascend­ ing monophasic motor polyneuropathy that can involve the ``` ``` face, limbs, and even respiratory musculature. GBS is not ``` ``` typically associated with any sensory loss or ciliary paralysis, ``` ``` however (Ellison, pp. 342-349; Merritt, pp. 613-615). ```

Question 36

QUESTIONS 44-45 The following responses are in reference to questions 44 and 45: A. Subependymal germinal matrix hemorrhage B. Choroid plexus hemorrhage C. Both A and B D. Neither A nor B 44. The most common cause of intraventricular hemorrhage in term infants 45. The most common cause of intraventricular hemorrhage in premature infants End of set

Answer 36

44-B; 45-A. Subependymal germinal matrix hemorrhage is usually observed in low-birth-weight premature infants and can result in intraventricular hemorrhage. The microcircula­ tion of the periventricular matrix zone is extremely fragile and persists in the neonate until 34 weeks of gestation. This microcirculation is prone to hemorrhage, with hypoxia and secondary failures of autoregulation. Choroid plexus hemorrhage is the most common cause of intraventricular hemorrhage in the term infant and can result in anything from minimal (asymptomatic) hemorrhage to massive intra­ ventricular hemorrhage (Ellison, pp. 34-37).

Question 37

``` 46. Which of the following disorders are secondaiy to defec- tive neuronal migration? 1. Polymicrogyria 2. Schizencephaly 3. Focal nodular heterotopia 4. Holoprosencephaly A. 1, 2, and 3 are correct B. 1 and 3 are correct C. 2 and 4 are correct D. Only 4 is correct E. All of the above are correct ```

Answer 37

46. B. Disorders of abnormal neuronal migration include agyria, pachygyria, polymicrogyria, cortical dysplasia, and focal and diffuse heterotopias. Schizencephaly and poren­ cephaly are fetal hypoxic-ischemic lesions, and holoprosencephaly results from a failure of the normal growth and ``` cleavage of the prosencephalic vesicles (Ellison, pp. 29-32, ``` 62-68, 71-80, 82-85, 87-89).

Question 38

``` QUESTIONS 47-51 Directions: Match the following meningitis-causative organ¬isms with the age group most likely to be afflicted. A. Streptococcus pneumoniae B. Haemophilus influenzae C. Liste7-ia monocytogenes D. Proteus mirabilis E. S. epidermidis 47. Children 1 to 5 years of age 48. Adults 49. Unique to the elderly population 50. Associated with ventriculoperitoneal shunt infections 51. Associated with coexistent cerebral abscesses in neonates End of set ```

Answer 38

47-B; 48-A; 49-C; 50-E; 51-D. Pediatric patients with bacterial meningitis are usually due to infection by Streptococcus pneumoniae, Neisseria meningitidis, or Haemophilus influenzae. The incidence of H. influenzae meningitis in the pediatric population has decreased significantly in the past decade because of the widespread use of the H. influenzae B vaccination. Bacterial meningitis in the adult population 110 Intensive Neurosurgery Board Review is usually secondary to infection by S. pneumoniae or N. meningitidis. Meningitis in the elderly commonly results from S. pneumoniae and gram-negative rods. Listeria mono­ cytogenes can also afflict this older population. Neonatal bacterial meningitis is usually a result of infection by group B streptococci and Escherichia coli; however, Citrobacter diversus and Proteus mirabilis-related meningitis are asso­ ciated with the development of concomitant cerebral abscesses in this population (Ellison, pp. 327-330; Merritt, pp. 103-107).

Question 39

``` 52. What neoplasm is depicted in the following photomicro- graph (Figure 4.5 2 Q)? A. Medulloblastoma B. Ganglion cell tumor C. Central neurocytoma D. Ependymoma E. Anaplastic astrocytoma ```

Answer 39

``` 52. B. Ganglion cell tumors (gangliocytomas and gangliogliomas) are characterized by neoplastic ganglion cells, ``` ``` with or without a component of neoplastic glial tissue (usu­ ally with an astrocytic morphology). Neoplastic ganglion ``` ``` cells resemble normal neurons but are abnormally large ``` ``` and round, arranged in clusters, and contain an eccentric ``` ``` nucleus with a prominent nucleolus. The classic finding is ``` ``` binucleation, seen in one of the ganglion cells here, which ``` ``` never occurs in normal neurons. Gangliogliomas occasion­ ally exhibit nuclear pleomorphism, but mitoses are absent. ``` ``` Ganglion cells exhibit immunoreactivity for synaptophysin ``` ``` and neurofilaments. Medulloblastomas are characterized by ``` ``` a uniform population of small blue cells with hyperchromatic ``` ``` nuclei, minimal cytoplasm, mitoses, and occasional foci of ``` ``` necrosis. Central neurocytoma consists of uniform round ``` ``` cells with few mitoses. Ependymomas also contain uniform ``` ``` cells with round nuclei that often form pseudorosettes and ``` ``` rarely form true (ependymal) rosettes (Ellison, pp. 645-647, ``` ``` 653-657, 667-672; WHO, pp. 72-77, 96-98,129-137). ```

Question 40

``` 53. What neoplasm is depicted in the following photomicro¬graph (Figure 4.53Q)? A. Neurofibroma B. Schwannoma C. Fibrous meningioma D. Malignant nerve sheath tumor E. None of the above ```

Answer 40

53. B. Schwannomas are characterized by compact arrange­ ments of interwoven fascicles of cells (Antoni A areas) and spindle-shaped cells arranged in a loose myxoid stroma (Antoni B areas). The Antoni A areas often exhibit sequential palisading nuclei (Verocay bodies), shown here. Thickened blood vessels with hyaline walls may be seen. Neurofibromas are characterized by spindle-shaped cells with wavy nuclei arranged haphazardly within a mucoid matrix with inter­ spersed bundles of collagen ("shredded carrots" appear­ ance). Fibrous meningiomas consist of spindle-shaped cells with intermixed collagen and lack a mucoid matrix and Verocay bodies. Malignant nerve sheath tumors can also exhibit a fascicular pattern; however, this tumor is highly cellular and contains frequent mitoses and necrosis. The presence of Verocay bodies in this specimen is consistent with a schwannoma (Ellison, pp. 695-702, 707, 715; WHO, pp. 164-166,172-174,176-184).

Question 41

``` 54. What neoplasm is depicted in the following photomicro¬graph (Figure 4.54QJ? A. Dermoid cyst (mature teratoma) B. Craniopharyngioma C. Ependymoma D. Yolk sac tumor E. None of the above ```

Answer 41

54. D. Mature teratomas, the most common of which is the dermoid cyst depicted here, exhibit a mixture of ectodermal, mesodermal, and endodermal components. These neoplasms are well circumscribed and rarely associated with malignant transformation into carcinomas or sarcomas. Dermoid cysts are lined by squamous epithelium and contain adnexal struc­ tures such as sebaceous glands (shown in this example). Craniopharyngiomas (adamantinomatous) are character­ ized by collections of squamous cells with intermingled clusters of keratinized ghost cells, calcification, and choles­ terol clefts (Ellison, pp. 683-684, 724-727, 737-739).

Question 42

``` 55. Which of the following conditions is associated with Sprengel's deformity? A. Hallervorden-Spatz disease B. Leigh's disease C. Niemann-Pick disease D. Tuberous sclerosis E. Klippel-Feil anomaly ```

Answer 42

55. E. Klippel-Feil anomaly results from the failure of cervi­ cal vertebral (somite) segmentation. Klippel-Feil anomaly is classically associated with the triad of short neck, low pos­ terior hairline, and limited cervical motion. Approximately one-third of all Klippel-Feil cases are associated with congen­ ital elevation of the scapula, which is known as Sprengel's deformity. Klippel-Feil is also associated with diastematomyelia, Chiari I malformations, basilar impression, and ``` genitourinary abnormalities (Merritt, p. 490). ```

Question 43

``` 56. Which of the following lesions is thought to develop as a consequence of premature disjunction? A. Rathke's cleft cyst B. Diastematomyelia C. Neurenteric cyst D. Spinal lipoma E. Dandy-Walker malformation ```

Answer 43

56. D. Disjunction refers to the separation of superficial ectoderm from neural ectoderm during development. It is thought that premature disjunction allows cells of meso­ dermal origin to migrate between these two layers of ectoderm, which can lead to the formation of lipomas (Wilkins, pp. 3497-3499).

Question 44

``` 57. Which of the following neoplasms is/are associated with von Hippel-Lindau syndrome? 1. Pheochromocytomas 2. Renal cell carcinoma 3. Cerebellar hemangioblastomas 4. Endolymphatic sac tumors A. 1, 2, and 3 are correct B. 1 and 3 are correct C. 2 and 4 are correct D. Only 4 is correct E. All of the above are correct ```

Answer 44

57. E. Von Hippel-Lindau syndrome (VHL) is an autosomal dominant neurocutaneous disorder that is associated with chromosome 3p. VHL patients develop hemangioblastomas of the brainstem, cerebellum, and spinal cord. VHL is also associated with the development of retinal angiomas, paragangliomas, endolymphatic sac tumors, pheochromocytoma, epididymal cystadenoma, renal and pancreatic cysts, ``` and renal cell carcinoma. The production of erythropoietin ``` ``` by hemangioblastomas can occur with VHL and result in ``` ``` polycythemia (Ellison, pp. 736-738; WHO, pp. 223-226; ``` ``` Kaye and Laws, pp. 75-76) ```

Question 45

``` 58. What disorder is associated with the following photo-micrograph (Figure 4.58QJ? A. Parkinson's disease B. Gorticobasal degeneration C. Rabies encephalitis D. Alzheimer's disease E. None of the above ```

Answer 45

58. A. The Lewy body is an intracellular neuronal inclusion characterized by the presence of a hyaline eosinophilic core and a pale halo. Lewy bodies are observed within the sub­ stantia nigra in Parkinson's disease and within the cerebral cortex in certain forms of dementia (e.g., "dementia with Lewy bodies"). Rabies encephalitis is characterized by the presence of Negri bodies, which are intracellular inclusions resembling red blood cells, and Babes' nodules, which are clusters of microglia. Corticobasal degeneration is character­ ized by the presence of swollen cortical neurons (ballooned neurons), gliosis, and microvacuolation (Ellison, pp. 287289, 512-514).

Question 46

59. What neoplasm is depicted in the following photomicro-graph (Figure 4.59Q)? A. Pilocytic astrocytoma B. Subependymoma C. Myxopapillary ependymoma D. Dysembryoplastic neuroepithelial tumor E. None of the above

Answer 46

59. B. Subependymomas are characterized by the presence of clusters of cells with round nuclei and interspersed regions of very low cellularity ("islands of blue in a sea of pink"). Subependymomas often exhibit microcysts; how­ ever, nuclear pleomorphism and mitoses are universally absent. Myxopapillary ependymomas classically exhibit col­ lars of epithelioid cells surrounding pools of mucin with central blood vessels. Dysembryoplastic neuroepithelial tumor (DNET) is a supratentorial cortical neoplasm of chil­ dren and young adults that is usually located in the temporal lobe and presents with seizures. Microscopically, DNETs exhibit nodules of oligodendrocyte-like cells, mucinous cysts, and neurons that appear to "float" in the mucinous cysts (Ellison, pp. 651, 659-661; WHO, pp. 78-81,103-106).

Question 47

``` 60. Which of the following lesions is depicted in these two photomicrographs (two areas of the same lesion) (Fig¬ure 4.60Q)? A. Malignant nerve sheath tumor B. Fibrous meningioma C. Gliosarcoma D. Embryonal carcinoma E. None of the above ```

Answer 47

60. C. Gliosarcoma is a variant of glioblastoma multiforme. The presenting features, demographic characteristics, cyto­ genetic changes, and prognosis of the gliosarcoma (Feigin tumor) are all similar to that of the glioblastoma. Microsco­ pically, the gliosarcoma consists of two distinct cell popu­ lations: sarcomatous areas containing spindle-shaped cells arranged in a streaming fashion (left photomicrograph) and areas of conventional glioblastoma (right photomicrograph). Malignant nerve sheath tumors also contain spindle-shaped neoplastic cells; however, areas of conventional glioblastoma are not observed. Embryonal carcinoma exhibits large cells with slight pleomorphism arranged in solid, glandular, papil­ lary7, or cribriform patterns. Spindle-shaped cells are absent in embryonal carcinoma (Ellison, pp. 628-632, 682, 700702; WHO, pp. 42-44).

Question 48

``` 54. What neoplasm is depicted in the following photomicro¬graph (Figure 4.54QJ? A. Dermoid cyst (mature teratoma) B. Craniopharyngioma C. Ependymoma D. Yolk sac tumor E. None of the above ```

Answer 48

54. D. Mature teratomas, the most common of which is the dermoid cyst depicted here, exhibit a mixture of ectodermal, mesodermal, and endodermal components. These neoplasms are well circumscribed and rarely associated with malignant transformation into carcinomas or sarcomas. Dermoid cysts are lined by squamous epithelium and contain adnexal struc­ tures such as sebaceous glands (shown in this example). Craniopharyngiomas (adamantinomatous) are character­ ized by collections of squamous cells with intermingled clusters of keratinized ghost cells, calcification, and choles­ terol clefts (Ellison, pp. 683-684, 724-727, 737-739).

Question 49

``` 55. Which of the following conditions is associated with Sprengel's deformity? A. Hallervorden-Spatz disease B. Leigh's disease C. Niemann-Pick disease D. Tuberous sclerosis E. Klippel-Feil anomaly ```

Answer 49

55. E. Klippel-Feil anomaly results from the failure of cervi­ cal vertebral (somite) segmentation. Klippel-Feil anomaly is classically associated with the triad of short neck, low pos­ terior hairline, and limited cervical motion. Approximately one-third of all Klippel-Feil cases are associated with congen­ ital elevation of the scapula, which is known as Sprengel's deformity. Klippel-Feil is also associated with diastematomyelia, Chiari I malformations, basilar impression, and ``` genitourinary abnormalities (Merritt, p. 490). ```

Question 50

``` 56. Which of the following lesions is thought to develop as a consequence of premature disjunction? A. Rathke's cleft cyst B. Diastematomyelia C. Neurenteric cyst D. Spinal lipoma E. Dandy-Walker malformation ```

Answer 50

56. D. Disjunction refers to the separation of superficial ectoderm from neural ectoderm during development. It is thought that premature disjunction allows cells of meso­ dermal origin to migrate between these two layers of ectoderm, which can lead to the formation of lipomas (Wilkins, pp. 3497-3499).

Question 51

``` 57. Which of the following neoplasms is/are associated with von Hippel-Lindau syndrome? 1. Pheochromocytomas 2. Renal cell carcinoma 3. Cerebellar hemangioblastomas 4. Endolymphatic sac tumors A. 1, 2, and 3 are correct B. 1 and 3 are correct C. 2 and 4 are correct D. Only 4 is correct E. All of the above are correct ```

Answer 51

57. E. Von Hippel-Lindau syndrome (VHL) is an autosomal dominant neurocutaneous disorder that is associated with chromosome 3p. VHL patients develop hemangioblastomas of the brainstem, cerebellum, and spinal cord. VHL is also associated with the development of retinal angiomas, paragangliomas, endolymphatic sac tumors, pheochromocytoma, epididymal cystadenoma, renal and pancreatic cysts, ``` and renal cell carcinoma. The production of erythropoietin ``` ``` by hemangioblastomas can occur with VHL and result in ``` ``` polycythemia (Ellison, pp. 736-738; WHO, pp. 223-226; ``` ``` Kaye and Laws, pp. 75-76) ```

Question 52

``` 58. What disorder is associated with the following photo-micrograph (Figure 4.58QJ? A. Parkinson's disease B. Gorticobasal degeneration C. Rabies encephalitis D. Alzheimer's disease E. None of the above ```

Answer 52

58. A. The Lewy body is an intracellular neuronal inclusion characterized by the presence of a hyaline eosinophilic core and a pale halo. Lewy bodies are observed within the sub­ stantia nigra in Parkinson's disease and within the cerebral cortex in certain forms of dementia (e.g., "dementia with Lewy bodies"). Rabies encephalitis is characterized by the presence of Negri bodies, which are intracellular inclusions resembling red blood cells, and Babes' nodules, which are clusters of microglia. Corticobasal degeneration is character­ ized by the presence of swollen cortical neurons (ballooned neurons), gliosis, and microvacuolation (Ellison, pp. 287289, 512-514).

Question 53

59. What neoplasm is depicted in the following photomicro-graph (Figure 4.59Q)? A. Pilocytic astrocytoma B. Subependymoma C. Myxopapillary ependymoma D. Dysembryoplastic neuroepithelial tumor E. None of the above

Answer 53

59. B. Subependymomas are characterized by the presence of clusters of cells with round nuclei and interspersed regions of very low cellularity ("islands of blue in a sea of pink"). Subependymomas often exhibit microcysts; how­ ever, nuclear pleomorphism and mitoses are universally absent. Myxopapillary ependymomas classically exhibit col­ lars of epithelioid cells surrounding pools of mucin with central blood vessels. Dysembryoplastic neuroepithelial tumor (DNET) is a supratentorial cortical neoplasm of chil­ dren and young adults that is usually located in the temporal lobe and presents with seizures. Microscopically, DNETs exhibit nodules of oligodendrocyte-like cells, mucinous cysts, and neurons that appear to "float" in the mucinous cysts (Ellison, pp. 651, 659-661; WHO, pp. 78-81,103-106).

Question 54

``` 60. Which of the following lesions is depicted in these two photomicrographs (two areas of the same lesion) (Fig¬ure 4.60Q)? A. Malignant nerve sheath tumor B. Fibrous meningioma C. Gliosarcoma D. Embryonal carcinoma E. None of the above ```

Answer 54

60. C. Gliosarcoma is a variant of glioblastoma multiforme. The presenting features, demographic characteristics, cyto­ genetic changes, and prognosis of the gliosarcoma (Feigin tumor) are all similar to that of the glioblastoma. Microsco­ pically, the gliosarcoma consists of two distinct cell popu­ lations: sarcomatous areas containing spindle-shaped cells arranged in a streaming fashion (left photomicrograph) and areas of conventional glioblastoma (right photomicrograph). Malignant nerve sheath tumors also contain spindle-shaped neoplastic cells; however, areas of conventional glioblastoma are not observed. Embryonal carcinoma exhibits large cells with slight pleomorphism arranged in solid, glandular, papil­ lary7, or cribriform patterns. Spindle-shaped cells are absent in embryonal carcinoma (Ellison, pp. 628-632, 682, 700702; WHO, pp. 42-44).

Question 55

``` 1. What primary CNS neoplasm is associated with eosinophilic granular bodies? A. Anaplastic astrocytoma B. Oligodendroglioma C. Gemistocytic astrocytoma D. Pilocytic astrocytoma E. Germinoma ```

Answer 55

1. D. Pilocytic astrocytomas typically have a biphasic ap­ pearance. They usually consist of regions of elongated cells arranged in compact fascicles intermixed with regions of stellate cells that encompass microcysts. Pilocytic astrocy­ tomas can exhibit some nuclear pleomorphism and hyperchromasia, but mitoses and necrosis are absent. These ``` tumors are classically associated with Rosenthal fibers ``` ``` and intracellular eosinophilic globules (granular bodies). ``` ``` Intracellular eosinophilic conglomerations can also be ob­ served in pleomorphic xanthoastrocytoma but not anaplastic ``` ``` astrocytoma or oligodendroglioma. Gemistocytic astrocy­ toma is characterized by large, plump astrocytes with ``` ``` diffuse, glassy cytoplasm (Ellison, pp. 630-634; WHO, pp. 25, ``` 45-54, 56-64).

Question 56

``` 1. What primary CNS neoplasm is associated with eosinophilic granular bodies? A. Anaplastic astrocytoma B. Oligodendroglioma C. Gemistocytic astrocytoma D. Pilocytic astrocytoma E. Germinoma ```

Answer 56

1. D. Pilocytic astrocytomas typically have a biphasic ap­ pearance. They usually consist of regions of elongated cells arranged in compact fascicles intermixed with regions of stellate cells that encompass microcysts. Pilocytic astrocy­ tomas can exhibit some nuclear pleomorphism and hyperchromasia, but mitoses and necrosis are absent. These ``` tumors are classically associated with Rosenthal fibers ``` ``` and intracellular eosinophilic globules (granular bodies). ``` ``` Intracellular eosinophilic conglomerations can also be ob­ served in pleomorphic xanthoastrocytoma but not anaplastic ``` ``` astrocytoma or oligodendroglioma. Gemistocytic astrocy­ toma is characterized by large, plump astrocytes with ``` ``` diffuse, glassy cytoplasm (Ellison, pp. 630-634; WHO, pp. 25, ``` 45-54, 56-64).

Question 57

61. What is the most likely presentation of the following neo¬plasm (Figure 4.61QJ? A. Supratentorial mass in a 55-year-old male with a lung mass B. Complex partial epilepsy in a 12-year-old male C. Hypopituitarism in a 19-year-old female D. Nausea, vomiting, and ataxia in a 5-year-old male E. Hearing loss in a patient with neurofibromatosis type 2

Answer 57

61. D. This photomicrograph illustrates a medulloblastoma, which is characterized by a population of undifferentiated cells with hyperchromatic nuclei and minimal cytoplasm. Medulloblastomas exhibit prominent mitoses, with focal re­ gions of necrosis and apoptosis. Occasionally cells may form rosettes that lack a central canal or blood vessel (HomerWright rosettes). Medulloblastomas often spread throughout ``` the GNS via GSF pathways. Approximately 50% of all medul­ loblastomas present in children less than 10 years of age; ``` ``` they are usually located in the cerebellar vermis in children. ``` ``` Therefore this tumor could lead to ataxia and hydro­ cephalus, which is consistent with answer D (Ellison, ``` ``` pp. 667-672; WHO, pp. 129-137). ```

Question 58

``` QUESTIONS 62-63 The following answers are in reference to questions 62 and 63. A. Neurofibromatosis type 1 B. Tuberous sclerosis C. Both of the above D. Neither of the above 62. Complete penetrance 63. Incomplete penetrance ```

Answer 58

62-A; 63-B. Neurofibromatosis type 1 (NF-1) is an autosomal dominant neurocutaneous disorder that localizes to chromo­ some 17. The NF-1 gene is very large and associated with a high spontaneous mutation rate. Approximately 50% of all NF-1 cases are secondary to spontaneous mutations. NF-1 is associated with 100% penetrance and variable expressivity. Tuberous sclerosis (TS) is also an autosomal dominant neurocutaneous disorder that is associated with a high spon­ taneous mutation rate. TS can result from mutations at two different loci, one located on chromosome 9 and the other on chromosome 11. Tuberous sclerosis is associated with approximately 80% penetrance and variable expressivity (Kaye and Laws, pp. 69-72, 75; WHO, pp. 216-222; Ellison, pp. 695-697).

Question 59

64. Which of the following scenarios is the most likely pre¬sentation of the disorder depicted below in this gross speci¬men (Figure 4.64QJ? A. Optic neuritis and Uhthoff's sign in a 32-year-old female B. Ataxia, confusion, and lateral gaze palsy in a 48-year- old male alcoholic C. Headache, nausea, and vomiting in a 62-year-old female with a systemic malignancy D. Right hemiparesis in a 75-year-old man with a history of hypertension E. None of the above

Answer 59

64. B. This gross specimen exhibits bilateral petechial hemorrhages within the mamillary bodies, which is associated with Wernicke's encephalopathy. Wernicke's encephalopathy is associated with thiamine deficiency and is commonly observed in chronic alcoholics and some patients with gastrointestinal disorders. Patients with Wernicke's encephalopathy exhibit ataxia, gaze palsies, confusion, and apathy, which is often reversible with the administration of thiamine. The chronic form of the disease is known as Korsakoff's psychosis and is associated with retrograde and anterograde amnesia, with concomitant confabulation, usually irreversible (Ellison, pp. 415-418).

Question 60

QUESTIONS 65-67 Directions: Match the following questions with the appropri¬ate syndrome using each answer once, more than once, or not at all. A. Crouzon's disease B. Apert's syndrome C. Both of the above D. Neither of the above 65. Autosomal dominant inheritance 66. Uniformly associated with mental retardation 67. Associated with frontoethmoid synostosis QUESTIONS 65-67 Directions: Match the following questions with the appropri¬ate syndrome using each answer once, more than once, or not at all. A. Crouzon's disease B. Apert's syndrome C. Both of the above D. Neither of the above 65. Autosomal dominant inheritance 66. Uniformly associated with mental retardation 67. Associated with frontoethmoid synostosis

Answer 60

65-C; 66-B; 67-C. Grouzon's disease is an autosomal dominant condition that results in bilateral coronal, frontosphenoid, and frontoethmoid synostosis. Patients with Grouzon's disease have a high incidence of hydrocephalus; however, the vast majority achieve normal IQ's with adequate treatment of the hydrocephalus. Facial features of Grouzon's disease include proptosis, maxillary hypoplasia, and a "parrot's beak" nose. Apert's syndrome is an autosomal dominant condition that involves premature closure of all cranial sutures. These patients have facies that resemble those of Grouzon's disease and also have a high incidence of hydrocephalus. Apert's syndrome is associated with syndactyly, short thumbs, and a uniformly decreased IQ even with adequate treatment of the hydrocephalus (Wilkins, pp. 3693-3694)

Question 61

68. Craniosynostosis is associated with mutations in which of the following genes? A. p53 B. Fibroblast growth factor receptor (FGF-R) C. Interleukin 6 (IL-6) D. Epidermal growth factor receptor (EGFR) E. None of the above

Answer 61

68. B. Craniosynostosis refers to the premature closure of cranial sutures; this condition is often associated with Crouzon's disease and Apert's syndrome, although many cases are isolated and sporadic as well. Many cases of craniosynostosis are associated with mutations of the fibroblast growth factor receptor gene. Craniosynostosis is more common in males, and isolated sagittal synostosis (scaphocephaly) accounts for approximately 50% of all cases (most common type of synostosis) (Wilkins, pp. 3673-3676).

Question 62

69. Which of the following clinical presentations is most con¬sistent with the lesion depicted below in this gross specimen (Figure 4.69QJ? A. Bilateral facial and abducens palsies in the neonate B. Ipsilateral port wine stain in the distribution of Vj in a 5-year-old C. Developmental delay in a 1-year-old D. Sepsis in the preterm infant E. Epilepsy in a 6-month-old

Answer 62

69. E. Tuberous sclerosis (TS) often presents in children between the ages of 1 and 6 months with seizures, which usually consists of infantile spasms. Approximately 90% of all patients with TS experience seizures, and the vast majority also exhibit various degrees of mental retardation. TS is associated with the development of cortical tubers, which are firm, pale nodules that project from the cortical surface, as depicted in this gross specimen. TS is also associated with subependymal nodules and the development of subependymal giant cell astrocytoma (Ellison, pp. 108-110; WHO, pp. 227-230).

Question 63

``` 70. What is the most likely etiology of the abnormality depicted below (Figure 4.70QJ? A. Elevated intracranial pressure B. Atherosclerotic disease C. CNS infection D. Neurodegenerative disorder E. None of the above ```

Answer 63

70. A. Prolonged elevations in intracranial pressure can result in various herniation syndromes. Transtentorial herniation of the uncus through the tentorial incisura can result in compression of the ipsilateral oculomotor nerve, midbrain, and ipsilateral posterior cerebral artery, with subsequent infarction. Prolonged herniation can result in the development of hemorrhagic necrosis within the pons and 112 Intensive Neurosurgery Board Review midbrain (Duret hemorrhages) as a consequence of penetrating arteriolar compression and ischemia. This gross specimen illustrates transtentorial herniation of the uncus, with notable indentation of the surrounding cerebrum by the tentorium cerebelli (Ellison, pp. 257-259).

Question 64

``` 71. Which of the following structures are often involved with diffuse axonal injuries? 1 . Parasagittal deep white matter 2. Superior cerebellar peduncles 3. Corpus callosum 4. Rostral brainstem A. 1,2, and 3 are correct B. 1 and 3 are correct C. 2 and 4 are correct D. Only 4 is correct E. All of the above are correct ```

Answer 64

71. E. Diffuse axonal injury (DAI) results from acceleration/ deceleration injuries of the brain. DAI can exhibit prominent petechial hemorrhages within the corpus callosum, interventricular septum, dorsolateral brainstem, superior cerebellar peduncles, and parasagittal deep white matter on gross specimens. Microscopically, DAI specimens exhibit prominent axonal spheroids, especially with silver stains. DAI varies in severity from minimal disturbances in level of consciousness to vegetative states with subsequent death (Ellison, pp. 249- 253).

Question 65

``` 72. What infection is depicted in the following photomicro- graph (Figure 4.72QJ? A. Aspergillosis B. Mucormycosis C. Cryptococcosis D. Candidiasis E. None of the above ```

Answer 65

72. A. Cerebral aspergillosis is usually secondary to hematogenous dissemination from the lungs or local spread from the paranasal sinuses of Aspergillus fianigatus or Aspergillus flwcus. Symptoms of cerebral aspergillosis are variable and include headache, seizures, cranial nerve palsies, hemiparesis, and elevated intracranial pressure. Aspergillus has a tendency to exhibit prominent vascular invasion, with subsequent vascular thrombosis, infarction, and hemorrhage. Aspergillus is characterized by septate hyphae that are readily demonstrated on silver stains. In contrast, mucormycosis exhibits broad nonseptate hyphae, candidiasis exhibits budding yeasts and pseudohyphae, and cryptococcosis exhibits only a yeast form with CNS infections (Ellison, pp. 351-355, 357-362).

Question 66

``` 73. What disorder is depicted in the following low-power photomicrograph (Figure 4.73Q) of a section stained for myelin? A. Subacute combined degeneration B. Multiple sclerosis C. Tabes dorsalis D. Amyotrophic lateral sclerosis E. Friedreich's ataxia ```

Answer 66

73. D. Amyotrophic lateral sclerosis (ALS) affects primarily the anterior and lateral corticospinal tracts of the spinal cord, as evidenced by the loss of myelinated axons (as depicted in the specimen). Subacute combined degeneration (SACD) results from vitamin B1 2 (cobalamin) deficiency and exhibits symmetric demyelination in the posterior and lateral columns of the spinal cord. In severe cases of SACD, the anterior columns can also be involved. Tabes dorsalis results from chronic inflammation of the dorsal roots and dorsal root ganglia and is usually observed 15 to 20 years after initial infection with syphilis. The posterior columns are primarily affected in tabes dorsalis. Friedreich's ataxia (FA) is an autosomal recessive disorder that localizes to chromosome 9 and results in deterioration of the posterior columns, spinocerebellar tracts, Clarke's nucleus, and distal (thoracolumbar) corticospinal tracts (Ellison, pp. 344-345, 417-420, 501-508, 533-534).

Question 67

QUESTIONS 74-77 Directions: Match the following questions with the appropri¬ate demyelinating disease using each answer either once, more than once, or not at all. A. Multiple sclerosis B. Acute disseminated encephalomyelitis C. Both of the above D. Neither of the above 74. Monophasic 75. Experimental allergic encephalomyelitis represents the animal model of this disorder 76. Symptoms usually improve with administration of IV steroids 77. Is associated with perivenular inflammation on micro¬scopic examination

Answer 67

basic protein and usually presents with fever, headache, nuchal rigidity, and focal neurologic deficits. ADEM is characterized by perivenular inflammation and demyelination on microscopic analysis. Patients with ADEM usually exhibit a full recovery (10 to 20% have permanent neurologic deficits), and the disease course is generally shorter with the administration of IV steroids. Experimental allergic encephalomyelitis (EAE) is a monophasic autoimmune response that occurs in genetically susceptible animals after immunization with myelin basic protein. EAE is actually the animal model of ADEM, although there is a chronic relapsing form of the disease that resembles MS and has provided much of the immunologic information that there is about MS in humans. MS is typically a chronic relapsing/remitting demyelinating disorder that affects adults between the third to fifth decades of life and is more common in women than men. Approximately 85% of acute MS exacerbations improve with the administration of IV methylprednisolone. Acute MS plaques can exhibit perivascular inflammation; however, arterioles are involved (as well as venules). Interferon P-lb Betaserone), interferon (3-la (Avonex), and Copaxone are generally utilized to decrease the frequency of MS attacks (Ellison, pp. 389-404, 405-407; Merritt, pp. 151-153, 773-791; Greenberg, pp. 69-71).

Question 68

``` 78. What disorder is depicted in the photomicrograph below (Figure 4.78QJ? A. Acute disseminated encephalomyelitis B. GNS lymphoma C. Viral encephalitis D. Active MS plaque E. None of the above ```

Answer 68

78. B. CNS lymphoma is characterized by numerous malignant lymphocytes that tend to invade the walls of blood vessels. Lymphoma cells are prominent in the perivascular spaces, and they diffusely invade brain parenchyma toward the periphery of the lesion. More than 80% of these tumors are diffuse large B-cell lymphomas. The surrounding brain often exhibits reactive astrocytosis, which can resemble other inflammatory disorders. Interspersed small reactive (nonneoplastic) lymphocytes are usually observed as well and provide contrast to the larger, polymorphous malignant lymphocytes, which facilitates distinguishing lymphoma from other inflammatory conditions. B-cell lymphomas are positive for CD20 (Ellison, pp. 689-694; WHO, pp. 198- 203).

Question 69

``` 79. What neoplasm is depicted in the following photomicro¬graph (Figure 4.79Q)? A. Papillary craniopharyngioma B. Papillary meningioma C. Colloid cyst D. Choroid plexus papilloma E. Pineocytoma ```

Answer 69

79. D. Choroid plexus papillomas (CPPs) exhibit a columnar epithelium with an underlying fibrovascular network and prominent papillary projections. CPPs exhibit slight nuclear crowding and loss of the normal "cobblestone" surface, which differentiates them from normal choroid plexus. CPPs are generally positive for S-100, transthyretin, and cytokeratin. Papillary meningiomas are aggressive tumors that exhibit prominent mitoses, a high nuclear-cytoplasmic ratio, and poorly defined papillary structures. Papillary craniopharyngiomas are composed of papillae of squamous cells without fibrovascular cores. Colloid cysts are lined by a single layer of columnar cells. Many of the cells of a colloid cyst wall are ciliated, and mucin-containing goblet cells may also be located within the epithelial layer (WHO, pp. 84-86, 180, 244-246; Ellison, pp. 685-688, 713, 724-727, 738-740).

Question 70

80. All of the following are features of paragangliomas EXCEPT? A. Contain synaptophysin positive chief cells B. Contain GFAP positive sustentacular cells • C. Arise from the Cauda equina or glomus jugulare D. WHO grade I lesion E. Dense core granules on ultrastructural examination

Answer 70

80. B. Paragangliomas usually arise from the cauda equina or jugular bulb (glomus jugulare tumors) and consist of lobules of chief cells (Zellballen) surrounded by a single layer of sustentacular cells. Chief cells are labeled with synaptophysin, neurofilament, and chromogranin immunostains. Sustentacular cells are S-100-positive. Myxopapillary ependymomas can also originate from the cauda equina region; however, they are GFAP-positive, whereas paragangliomas are GFAP-negative. Paragangliomas are WHO grade I lesions (Ellison, pp. 651, 658-659; WHO, pp. 78-79, 1 1 2 - 114).

Question 71

81. What abnormality is depicted in the following gross speci- men (Figure 4.81QJ? A. Subacute infarct B. Progressive multifocal leukoencephalopathy C. Adrenoleukodystrophy D. Fat embolism E. Multiple sclerosis plaques

Answer 71

81. D. Fat embolism is usually observed in trauma patients with multisystem injuries and is often associated with long bone fractures. Grossly, fat embolism is characterized by multiple petechial hemorrhages that affect both the gray and white matter of the cerebral hemispheres diffusely, with concomitant regions of perivascular (gray) discoloration. Microscopically, fat embolism exhibits hemorrhagic lesions surrounding capillaries with signs of fibrinoid necrosis. Lipid globules can be demonstrated in necrotic regions with oil red O stains. Progressive multifocal leukoencephalopathy (PML) results from JC virus (polyomavirus) reactivation in the CNS of immunocompromised patients. PML exhibits foci of gray discoloration with regions of necrosis and cavitation, primarily in the deep white matter. Adrenoleukodystrophy is characterized by extensive white matter demyelination with sparing of the subcortical U fibers, and involves the parietooccipital regions more extensively than the frontotemporal region. This specimen exhibits multiple petechial hemorrhages in both the cortical gray and deep white matter, which is most consistent with fat embolism (Ellison, pp. 254-256, 298-300, 454-456).

Question 72

82. Which of the following are useful myelin stains? 1. Weigert 2. Sudan 3. March i 4. Phosphotungstic acid/hematoxylin (PTAH) A. 1, 2, and 3 are correct B. 1 and 3 are correct C. 2 and 4 are correct D. Only 4 E. All of the above

Answer 72

82. A. PTAH stains for collagen, while the Sudan, Weigert, and Marchi are useful myelin stains (Wheater, pp. 102, 149, 309).

Question 73

```

83. What neoplasm is depicted in the following photomicro- graph (Figure 4.83Q)? A. Ependymoma B. Neuroblastoma C. Central neurocytoma D. Subependymoma E. Pilocytic astrocytoma

```

Answer 73

83. A. Ependymomas are characterized by the presence of uniform cells with round nuclei, mild nuclear pleomorphism, and indistinct cytoplasmic borders. Pseudorosettes (with a central blood vessel) are commonly observed in ependymo­ mas; however, true rosettes with a central lumen (shown in the mid-upper portion of the picture) are less frequent. Some ependymomas exhibit epithelial differentiation and the presence of true gland-like canals. Ependymomas are GFAPpositive. The presence of numerous perivascular pseu­ dorosettes in the above specimen is most consistent with an ``` ependymoma (Ellison, pp. 645-651; WHO, pp. 72-77).

```

Question 74

```

84. Which of the following CNS neoplasms can exhibit prominent melanin? 1. Schwannomas 2. Embryonal neoplasms 3. Primary malignant melanoma 4. Ependymomas A. 1, 2, and 3 are correct B. 1 and 3 are correct C. 2 and 4 are correct D. Only 4 is correct E. All of the above are correct

```

Answer 74

84. E. Melanocytes are present within the leptomeninges of the CNS and can lead to the formation of malignant melanoma, diffuse melanosis, and melanocytomas. All of these neoplasms exhibit prominent melanin. Occasion­ ally, schwannomas, ependymomas, pineal neoplasms, and CHAPTER 4 Neuropathology Answers 113 embryonal neoplasms can also exhibit prominent melanin (Ellison, pp. 734-737).

Question 75

```

85. Which of the following disorders is associated with prominent iron deposition within the globus pallidus? A. Wilson's disease B. Hallervorden-Spatz disease C. Wernicke's encephalopathy D. Pick's disease E. Ataxia-telangiectasia

```

Answer 75

85. B. Hallervorden-Spatz disease (HSD) is an autosomal recessive disorder that presents with progressive gait distur­ bance, dystonia, dysarthria, and choreoathetosis in children and young adults. An adult variant of HSD presents with progressive cognitive decline and extrapyramidal signs. T2weighted MPJ exhibits prominent hypointensity within the ``` globus pallidus in patients with HSD ("eye of the tiger" sign), ``` ``` which is secondary to the accumulation of iron pigment. ``` ``` Microscopically, HSD is characterized by the presence of ``` ``` gliosis, axonal spheroids, and occasional Lewy bodies and ``` ``` neurofibrillary tangles within the globus pallidus and sub­ stantia nigra (pars reticulata). Wilson's disease (hepatolen­ ticular degeneration) is also characterized by abnormalities ``` ``` of the pallidum; however, prominent iron deposition is not ``` ``` observed (Ellison, pp. 134-136, 603-605)

```

Question 76

86. What abnormality is depicted in the following gross speci¬men (Figure 4.86Q)?

A. Metastatic lesion B. Intracerebral abscess C. Cysticercus D. Arachnoid cyst E. Cortical tuber

Answer 76

86. C. Neurocysticercosis results from ingestion of the larval form of Taenia solium. These larvae migrate throughout the body and can involve the eyes, liver, brain, lung, and skeletal muscle. Grossly, neurocysticercosis exhibits the presence of a variable number of cysts that usually involve the cortical gray matter. Viable cysts are often 1 to 2 cm in diameter; they become fibrotic and calcified with degeneration. Occasionally a prominent scolex is observed within the viable cysts (Ellison, pp. 377-381).

Question 77

87. Which of the following neurologic complications is asso¬ciated with Paget's disease? 1. Trigeminal neuralgia 2. Peripheral neuropathy 3. Development of osteogenic sarcoma 4. Hypopituitarism A. 1,2, and 3 are correct B. 1 and 3 are correct C. 2 and 4 are correct D. Only 4 is correct E. All of the above are correct

Answer 77

87. E. Paget's disease is characterized by initial excessive bone resorption by osteoclasts, followed by the progressive deposition of disorganized vascular bone. Paget's disease can involve any bone in the body and can exhibit neurologic symptoms by neural compression, fracture/dislocations, hemorrhage, vascular insufficiency ("steal" phenomena), and malignant degeneration into osteogenic sarcoma or fibrosarcoma with local invasion. Common neurologic symp­ toms associated with Paget's disease include cranial nerve palsies (optic atrophy, trigeminal neuralgia, facial paralysis, hearing loss), entrapment neuropathies, hypopituitarism, myeloradiculopathy, and brainstem compression (Wilkins, pp. 3887-3889).

Question 78

``` 88. Which of the following disorders exhibits the abnormality depicted in the following photomicrograph (Figure 4.88Q.)? A. Gaucher's disease B. Niemann-Pick disease C. Alzheimer's disease D. Hepatic encephalopathy E. Pyridoxine deficiency ```

Answer 78

88. D. Alzheimer type II astrocytes exhibit an enlarged vesicular nucleus with peripheral chromatin and minimal cytoplasm. Alzheimer type II astrocytes can be observed in the caudate, putamen, thalamus, hypothalamus, and brain­ stem of patients with Wilson's disease and acquired hepatic encephalopathy (Ellison, pp. 430-432).

Question 79

``` 83. What neoplasm is depicted in the following photomicro- graph (Figure 4.83Q)? A. Ependymoma B. Neuroblastoma C. Central neurocytoma D. Subependymoma E. Pilocytic astrocytoma ```

Answer 79

83. A. Ependymomas are characterized by the presence of uniform cells with round nuclei, mild nuclear pleomorphism, and indistinct cytoplasmic borders. Pseudorosettes (with a central blood vessel) are commonly observed in ependymo­ mas; however, true rosettes with a central lumen (shown in the mid-upper portion of the picture) are less frequent. Some ependymomas exhibit epithelial differentiation and the presence of true gland-like canals. Ependymomas are GFAPpositive. The presence of numerous perivascular pseu­ dorosettes in the above specimen is most consistent with an ``` ependymoma (Ellison, pp. 645-651; WHO, pp. 72-77). ```

Question 80

``` 84. Which of the following CNS neoplasms can exhibit prominent melanin? 1. Schwannomas 2. Embryonal neoplasms 3. Primary malignant melanoma 4. Ependymomas A. 1, 2, and 3 are correct B. 1 and 3 are correct C. 2 and 4 are correct D. Only 4 is correct E. All of the above are correct ```

Answer 80

84. E. Melanocytes are present within the leptomeninges of the CNS and can lead to the formation of malignant melanoma, diffuse melanosis, and melanocytomas. All of these neoplasms exhibit prominent melanin. Occasion­ ally, schwannomas, ependymomas, pineal neoplasms, and CHAPTER 4 Neuropathology Answers 113 embryonal neoplasms can also exhibit prominent melanin (Ellison, pp. 734-737).

Question 81

85. Which of the following disorders is associated with prominent iron deposition within the globus pallidus? A. Wilson's disease B. Hallervorden-Spatz disease C. Wernicke's encephalopathy D. Pick's disease E. Ataxia-telangiectasia

Answer 81

85. B. Hallervorden-Spatz disease (HSD) is an autosomal recessive disorder that presents with progressive gait distur­ bance, dystonia, dysarthria, and choreoathetosis in children and young adults. An adult variant of HSD presents with progressive cognitive decline and extrapyramidal signs. T2weighted MPJ exhibits prominent hypointensity within the ``` globus pallidus in patients with HSD ("eye of the tiger" sign), ``` ``` which is secondary to the accumulation of iron pigment. ``` ``` Microscopically, HSD is characterized by the presence of ``` ``` gliosis, axonal spheroids, and occasional Lewy bodies and ``` ``` neurofibrillary tangles within the globus pallidus and sub­ stantia nigra (pars reticulata). Wilson's disease (hepatolen­ ticular degeneration) is also characterized by abnormalities ``` ``` of the pallidum; however, prominent iron deposition is not ``` ``` observed (Ellison, pp. 134-136, 603-605) ```