Neuropathology Questions Flashcards
1
Q
1. What primary CNS neoplasm is associated with eosinophilic granular bodies? A. Anaplastic astrocytoma B. Oligodendroglioma C. Gemistocytic astrocytoma D. Pilocytic astrocytoma E. Germinoma
A
- 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).
2
Q
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
A
- 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).
3
Q
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
A
- 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).
4
Q
4. Wliat chromosome abnormality is associated with neuro- fibromatosis type 1? A. 5 B. 7 C. 10 D. 17 E. 20
A
- 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).
5
Q
5. Congenital CMY infection is characterized by all of the following EXCEPT? A. Periventricular calcifications B. Microglial nodules C. Chorioretinitis D. Megalencephaly E. Hydrocephalus
A
- 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).
6
Q
- 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
A
- 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).
7
Q
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
A
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).
8
Q
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
A
- 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).
9
Q
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
A
- 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).
10
Q
10. Which of the following neoplasms is not associated with neurofibromatosis type 2? A. Ependymoma B. Schwannoma C. Meningioma D. Glioma E. Plexiform neurofibroma
A
- 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).
11
Q
- 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
A
- 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).
12
Q
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
- Lafora bodies
- Bunina bodies
- Hirano bodies
- Pick bodies End of set
A
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).
13
Q
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
A
- 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).
14
Q
- 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
A
- 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).
15
Q
- 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
A
- 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).
16
Q
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
A
- 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).
17
Q
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
A
- 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).
18
Q
22. What is the most common cranial nerve affected by neurosarcoidosis? A. Optic B. Oculomotor C. Trigeminal D. Abducens E. Facial
A
- 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).
19
Q
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
A
- 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).
20
Q
- Bilirubin deposition in the brain of a neonate with kernicterus is commonly observed in which of the following regions?
- Subthalamic nucleus
- Globus pallidus
- Dentate nucleus
- 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
A
- 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).
21
Q
- 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
A
- 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).
22
Q
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
A
- 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).
23
Q
- 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
A
- 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).
24
Q
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
A
- 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).
25
Q
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
A
- 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).
26
Q
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
A
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).
27
Q
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
A
- 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).
28
Q
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
A
- 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).
29
Q
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
A
- 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).
30
Q
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
A
- 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).
31
Q
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
A
- 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).
32
Q
- Which of the following disorders is associated with the lesion depicted in this photomicrograph (Figure 4.40QJ?
- HIV encephalitis
- Toxoplasmosis
- CAR’encephalitis
- 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
A
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).
