Neuropathology Flashcards
What primary CNS neoplasm is associated with eosinophilic
granular bodies ?
A. Anaplastic astrocytoma
B. Oligodendroglioma
C. Gemistocytic astrocytoma
D. Pilocytic astrocytoma
E. Germinoma
A. Anaplastic astrocytoma
B. Oligodendroglioma
C. Gemistocytic astrocytoma
**D. Pilocytic astrocytoma **
E. Germinoma
Pilocytic astrocytomas typically have a biphasic appearance. They usually consist of regions of elongated cells
arranged in compact fascicles intermixed with regions of
stellate cells that encompass microcysts. Pilocytic astrocytomas 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 observed in pleomorphic xanthoastrocytoma but not anaplastic
astrocytoma or oligodendroglioma. Gemistocytic astrocytoma is characterized by large, plump astrocytes with
diffuse , glassy cytoplasm (Ellison, pp. 630- 634; WHO, pp. 25,
45-54,56- 64).
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. Hirano bodies
**B. Neurofibrillary tangles **
C. Diffuse amyloid plaques
D. Lewy bodies
E. Granulovacuolar degeneration
Neurofibrillary tangles (NFTs) are cytoplasmic, basophilic 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 material, which are easily demonstrated with silver stains and
immunohistochemical stains for A~ 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).
What neoplasm is depicted in the following photomicrograph (H&E section)
A. Lymphoma
B. Fibrillary astrocytoma
C. Glioblastoma
D. Medulloblastoma
E. Meningioma
A. Lymphoma
B. Fibrillary astrocytoma
**C. Glioblastoma **
D. Medulloblastoma
E. Meningioma
Glioblastoma multiforme (GBM) is characterized by
cellular pleomorphism and a diversity of histologic appearances. Regardless of the predominant histologic pattern of
a particular GBi'I, cytologic pleomorphism, nuclear hyperchromasia, and frequent mitoses are often observed. By
definition, tumor necrosis and/or microvascular proliferation is present. Pseudopalisading of neoplastic cells around a
central necrotic region (pseudopalisading necrosis), as depicted here, is characteristic of GBMs. These features easily
distinguish GEM 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).
What chromosome abnormality is associated with neurofibromatosis type I?
A. 5
B. 7
C. 10
D. 17
E. 20
A. 5
B. 7
C. 10
D.17
E. 20
Neurofibromatosis type 1 is associated with abnormalities of the neurofibromin gene, which is located on chromosome l7qll. NFl exhibits autosoma l 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).
Congenital CMV infection is characterized by all of the
following EXCEPT?
A. Peri ventricular calcifications
B. Microglialnodules
C. Chorioretinitis
D. Mega lencephaly
E. I-Iydrocephalus
A. Peri ventricular calcifications
B. Microglialnodules
C. Chorioretinitis
**D. Mega lencephaly **
E. I-Iydrocephalus
Congenital CMV infection represents the most common intrauterine viral infection, affecting 0.5 to 2.0% of all
births. Macroscopically, CMV infection is characterized by
microcephaly, periventricular and basal ganglial calcifications, 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).
Which of the following disorders is associated with
Opalski cells on microscopic examination?
A. I-Iallervorden-Spatz disease
B. We rdnig-HoffmHn disease
C. Wilson’s disease
D. Tay-Sachs disease
E. Gaucher’s disease
A. I-Iallervorden-Spatz disease
B. We rdnig-HoffmHn disease
**C. Wilson’s disease **
D. Tay-Sachs disease
E. Gaucher’s disease
Opalsld cells are round, with a small central nucleus
and prominent granular eosinophilic cytoplasm. These cells
are most commonly observed in the globus pallidus in patients with Wilson’s disease (hepatolenticular degeneration)
and acquired hepatic encephalopathy (Ellison, pp. 429- 432).
Which of the following proteins compose the Lewy body?
A. Ubiquitin
B. Neu rofilamen ts
C. (Y,- Synuclein
D. Both A and C
E. All of the above
A. Ubiquitin
B. Neu rofilamen ts
C. (Y,- Synuclein
D. Both A and C
E. All of the above
Lewy bodies are associated with Parkinson’s disease
and are composed of neurofiJament proteins (form the cytoskeleton of the inclUSion), ubiquitin (involved in cytosolic
proteolYSiS), o:B crystallin (neurofilament chaperone protein), and o:-synuclein (catalyze phosphorylation of neurofilaments). Immunohistochemical stains for ubiquitin are
among the most sensitive methods of identifying Lewy
bodies (Ellison, pp. 511- 513).
Canavan’s disease results from deficiencies of which of
the following enzymes?
A. Aspartoacylase
B. Aryl sulfatase A
C. Glucocerebrosidase
D. I-Iexosaminidase A
E. Iduronidase
**A. Aspartoacylase **
B. Aryl sulfatase A
C. Glucocerebrosidase
D. I-Iexosaminidase A
E. Iduronidase
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 Canavan’s disease. Canavan’s disease
does not spare the subcortical U fibers and is a result of
deficiencies of the enzyme aspartoacylase (Ellison, pp.
121-122,125).
What is depicted in the following photomicrograph?
A. Fibrillary astrocytoma
B. Reactive astrocytosis
C. Anaplastic astrocytoma
D. Clear cell meningioma
E. Yolk sac tumor
**A. Fibrillary astrocytoma **
B. Reactive astrocytosis
C. Anaplastic astrocytoma
D. Clear cell meningioma
E. Yolk sac tumor
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. J\Htoses,
necrosis, and endothelial proliferation are not observed.
Reactive astrocytosis can occasionally be confused with a
fibrillary astrocytoma; however, astrocytosis is characterized by an even distribution of slightly enlarged astrocytic
nuclei with abundant cytoplasm and long, tapering processes. There is usually no significant hypercellularity in
reactive astrocytosis. Microcysts are also not observed with
reactive astrocytosis (Ellison, pp. 623-628; WHO, pp. 24-
25).
Which of the following neoplasms is not associated with
neurofibromatosis type 2?
A. Ependymoma
B. SchwalUloma
C. Meningioma
D. Glioma
E. Plexiform neurofibroma
A. Ependymoma
B. SchwalUloma
C. Meningioma
D. Glioma
E. Plexiform neurofibroma
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, brainstem, and cerebellar), and spinal ependymomas. Spinal
schwannomas are occasionally observed with l\TF-2, although
spinal neurofibromas and plexiform neurofibromas are not
(WHO, pp. 219- 222; Ellison, pp. 696-699; Kaye and Laws,
pp. 71- 76).
What is the most likely clinical history associated with
the following photomicrograph?
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
C
D
E
The photomicrograph illustrates the classic spongiform change that is associated with Creutzfeldt-Jakob disease (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 characterized by neuronal loss, astrocytosis, spongiform change
(fine vacuolation of the neuropil), and a lack of inflammation. 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 symptom onset. The prion diseases, including CJD, GerstmannStraussler-Scheinker disease , fatal famili al 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 (Prpre,). This abnormal isoform is believed to
accumulate within cells, and also outside of cells in the form
of amyloid . Although inul1unostaining for Prpre, 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 synchronous 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. Ineffective 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).
i'Iatch the following items with their appropriate
inclusion body: Marinesco bodies
A. Actin
B. Ubiquitin
C. Polyglucosans
D. Amyotrophic lateral sclerosis
E. a-Synuclein
A
B
C
D
E
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. Lafont bodies
are composed of polysaccharide polyme rs (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, 504-
505,552,566-567,570- 572).
i'Iatch the following items with their appropriate
inclusion body: Lafora bodies
A. Actin
B. Ubiquitin
C. Polyglucosans
D. Amyotrophic lateral sclerosis
E. a-Synuclein
A. Actin
B. Ubiquitin
**C. Polyglucosans **
D. Amyotrophic lateral sclerosis
E. a-Synuclein
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. Lafont bodies
are composed of polysaccharide polyme rs (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, 504-
505,552,566-567,570- 572).
i'Iatch the following items with their appropriate
inclusion body: Bunina bodies
A. Actin
B. Ubiquitin
C. Polyglucosans
D. Amyotrophic lateral sclerosis
E. a-Synuclein
A. Actin
B. Ubiquitin
C. Polyglucosans
D. Amyotrophic lateral sclerosis
E. a-Synuclein
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. Lafont bodies
are composed of polysaccharide polyme rs (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, 504-
505,552,566-567,570- 572).
i'Iatch the following items with their appropriate
inclusion body: Hirano bodies
A. Actin
B. Ubiquitin
C. Polyglucosans
D. Amyotrophic lateral sclerosis
E. a-Synuclein
A. Actin
B. Ubiquitin
C. Polyglucosans
D. Amyotrophic lateral sclerosis
E. a-Synuclein
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. Lafont bodies
are composed of polysaccharide polyme rs (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, 504-
505,552,566-567,570- 572).
i'Iatch the following items with their appropriate
inclusion body: Pick bodies
A. Actin
B. Ubiquitin
C. Polyglucosans
D. Amyotrophic lateral sclerosis
E. a-Synuclein
**A. Actin **
B. Ubiquitin
C. Polyglucosans
D. Amyotrophic lateral sclerosis
E. a-SynucleinA. Actin
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. Lafont bodies
are composed of polysaccharide polyme rs (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, 504-
505,552,566-567,570- 572).
What pathologic condition is depicted in the following
photomicrograph?
A. Capillary telangiectasia
B. Cavernous malformation
C. Venous angioma
D. Arteriovenous malformation
E. Angiomatous meningioma
A. Capillary telangiectasia
B. Cavernous malformation
C. Venous angioma
D. Arteriovenous malformation
E. Angiomatous meningioma
Arteriovenous malformations (AVMs) are characterized 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 malformations are characterized by tightly packed hyalinized
vascular channels without elastic tissue . There is usually no
intervening brain parenchyma. Venous angiomas are composed of thin-walled , dilated vascular channels interspersed
among normal brain parenchyma (Ellison, pp. 226- 233)
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 pseudomembrane
D. Breakdown of the blood-brain barrier in adjacent brain parenchyma
E. None of the above
A. Reinjury of bridging veins
B. Osmotic migration across the dura into the subdural space
C. Hemorrhage in the granulation tissue of the pseudomembrane
D. Breakdown of the blood-brain barrier in adjacent brain parenchyma
E. None of the above
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 initiaIJy unstable and tend to bleed
spontaneously, which leads to progressive, stepwise enlargement of the SDH (Ellison, pp. 210-211).
\Vhat is the most likely etiology of the lesion depicted
below in this gross specimen?
A. Direct contusion
B. Shearing injury
C. Herniation
D. Arterial dissection
E. .Arterial rupture
A. Direct contusion
B. Shearing injury
**C. Herniation **
D. Arterial dissection
E. .Arterial rupture
This specimen exhibits a prominent pontine hemorrhage , 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 conversion. 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).
What is the most cOl11mon organism isolated from
intracranial abscesses?
A. Staphylococcus au-reus
B. Pseudomonas aeruginosa
C. Streptococcus pneu/11oniae
D. Streptococcus m’illeri
E. Mycobacterium tuberculosis
A. Staphylococcus au-reus
B. Pseudomonas aeruginosa
C. Streptococcus pneu/11oniae
D. Streptococcus m’illeri
E. Mycobacterium tuberculosis
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 CitrobClcter diversus
or Proteus mi:ra.bilis. Brain abscesses often result from
hematogenous seeding in a septic pati ent (25%), or direct
spread from infections of the middle ear, paranasal sinuses,
or dental roots (50%) (Ellison, pp. 330-335; Greenberg,
p.218).
What neoplasm is depicted in the following photomicrograph?
A. Choriocarcinoma
B. Yolk sac tumor
C. Secretory meningoma
D. Germinoma
E. Ependymoma
A. Choriocarcinoma
B. Yolk sac tumor
C. Secretory meningoma
D. Germinoma
E. Ependymoma
Germinomas are characterized by groups of round
neoplastic cells that contain clear cytoplasm with interspersed 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 ceIJs interspersed among smaller
neoplastic cells, which is often associated with necrosis
and hemorrhage. Yoll, sac tumor is characterized by a loose
arrangement of clea r cells and occasional Schiller-Duval
bodies. Secretory meningiomas exh ibit typical meningothelia I 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).
What is the most common cranial nerve affected by
neurosarcoidosis?
A. Optic
B. Oculomotor
C. Trigeminal
D. Abducens
E. Facial
A. Optic
B. Oculomotor
C. Trigeminal
D. Abducens
E. Facial
The facial nerve is by far the most commonly involved
cranial nerve with neurosarcoidosis. In fact, the most common 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).
Which of the following regions of the brain exhibit
prominent atrophy with Alzheimer’s disease?
1. Hippocampus
2. Occipital lobe
3. Frontal lobe
4. Primary motor cortex
A. 1,2, and3 are correct
B. 1 and3 are correct
C. 2 and 4 are correct
D. Only 4 is correct
E. All of the above are correct
A. 1,2, and3 are correct
**B. 1 and3 are correct **
C. 2 and 4 are correct
D. Only 4 is correct
E. All of the above are correct
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 hippocampus is particularly affected, whereas the motor cortex
and oCcipital lobes are usually spared (Ellison, pp. 550- 565).
Bilirubin deposition in the brain of a neonate with
kernicterus is commonly observed in which of the following
regions ?
1. Subthalamic nucleus
2. Globus pallidus
3. Dentate nucleus
4. Red nucleus
A. 1,2, and3 are correct
B. 1 and3 are correct
C. 2 and 4 are correct
D. Only 4 is correct
E. All of the above are correct
A
B
C
D
E
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 formation, and cranial nerve nuclei are also affected. It is the unconjugated form of bilirubin that is toxic, and its accumulation
leads to neuronal necrosis with subsequent gliosis (Ellison,
pp.50-52).
A 58-year-old male presents with focal seizures anel is
founel 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-
nega tive, vimentin-positive, cytokeratin-AE1I3 positive, and
ElvIA-negative. This is most consistent with which of the
following neoplasms?
A. Lymphoma
B. Metastatic carcinoma
C. Glioblastoma
D. I-Iemangiopericytoma
E. J’I’Ieningioma
A
B
C
D
E
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 exh ibits staining for epithelial membrane 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., AE1I3). IIemangiopericytoma
is vimentin-positive and ElvIA-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).
Which of the following meningioma variants is depicted
in this photomicrograph?
A. Meningothelial
B. Fibrous
C. Transitional
D. Secretory
E. Choreloid
A
B
C
D
E
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 colJagen 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 neoplastic cells, as depicted here. Secretory meningiomas can
exhibit a transitional or meningothelial pattern; however,
many cells contain prominent eosinophilic (PAS-positive)
globules. Chordoid meningiomas exhibit columns of cells
surrounded by a mucoid matrix, thus resembling a chordonut (WHO, pp. 176-184; Ellison , pp. 703- 716).
Which of the following meningioma variants is associated with more aggressive clinical behavior?
A. Papillary
B. Angioma tous
C. Chordoid
D. Clear cell
E. Metaplastic
A
B
C
D
E
Papillary meningiomas are unique variants that exhibit 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
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).
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
B
C
D
E
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative 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 dominant fashion. Approximately 25% of these familial cases of
ALS are secondary to mutations of the copper/zinc superoxide dismutase (SOD1) gene located on chromosome 21q .
Refsum’s disease results from deficiencies of the enzyme
phytanoyl CoA hydroxylase, which results in the accumulation of phytanic acid. Clinical manifestations of Refsum’s
disease include ataxia, peripheral neuropathy, and retinitis
pigmentosa. Sanfilippo syndrome is one of the mucopolysacchari doses 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;Me~tt,pp.539 540).
Which of the following major histocompatibility complexes is associated with the development of multiple
sclerosis?
1. I-ILA-DR15
2. I-ILA-DR2
3. I-ILA-B7
4. I-ILA-DR4
A. 1,2, anel3 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
C
D
E
Multiple sclerosis (MS) is classically associated with
the I-ILA-DR2 allele, and I-ILA-DR15 is common in Northern
Europeans with MS . The I-ILA 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).
Match the following neoplasms with the most
common prote in/stain llsing each answer once, more than
once, or not at all:
Lymphoma
A. Vimentin
B. CD45
C. CD34
D. S-100
E. Synaptophysin
A
B
C
D
E
I-Iemangiopericytoma is vimentinpositive, with focal reactivity to CD34 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 neurocytoma exhibits immunoreactivity for synaptophysin, GFAP,
and neurofilament proteins. Primary CNS T -cell lymphomas
are CD 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison,
pp. 656-659, 691- 692,703- 716,732-735).
Match the following neoplasms with the most
common prote in/stain llsing each answer once, more than
once, or not at all:
I-Iemangiopericytoma
A. Vimentin
B. CD45
C. CD34
D. S-100
E. Synaptophysin
A
B
C
D
E
I-Iemangiopericytoma is vimentinpositive, with focal reactivity to CD34 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 neurocytoma exhibits immunoreactivity for synaptophysin, GFAP,
and neurofilament proteins. Primary CNS T -cell lymphomas
are CD 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison,
pp. 656-659, 691- 692,703- 716,732-735).
Match the following neoplasms with the most
common prote in/stain llsing each answer once, more than
once, or not at all:
Sustentacular cell of paraganglioma
A. Vimentin
B. CD45
C. CD34
D. S-100
E. Synaptophysin
A
B
C
D
E
I-Iemangiopericytoma is vimentinpositive, with focal reactivity to CD34 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 neurocytoma exhibits immunoreactivity for synaptophysin, GFAP,
and neurofilament proteins. Primary CNS T -cell lymphomas
are CD 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison,
pp. 656-659, 691- 692,703- 716,732-735).
Match the following neoplasms with the most
common prote in/stain llsing each answer once, more than
once, or not at all:
Meningioma
A. Vimentin
B. CD45
C. CD34
D. S-100
E. Synaptophysin
A
B
C
D
E
I-Iemangiopericytoma is vimentinpositive, with focal reactivity to CD34 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 neurocytoma exhibits immunoreactivity for synaptophysin, GFAP,
and neurofilament proteins. Primary CNS T -cell lymphomas
are CD 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison,
pp. 656-659, 691- 692,703- 716,732-735).
Match the following neoplasms with the most
common prote in/stain llsing each answer once, more than
once, or not at all:
Central neurocytoma
A. Vimentin
B. CD45
C. CD34
D. S-100
E. Synaptophysin
A
B
C
D
E
I-Iemangiopericytoma is vimentinpositive, with focal reactivity to CD34 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 neurocytoma exhibits immunoreactivity for synaptophysin, GFAP,
and neurofilament proteins. Primary CNS T -cell lymphomas
are CD 45- and CD 3-positive, while B-celllymphomas usually show immunoreactivity to CD 79a and CD 20 (Ellison,
pp. 656-659, 691- 692,703- 716,732-735).
What neoplasm is depicted in the following photomicrograph?
A. Clear cell meningioma
B. Medulloblastoma
C. Fibrillary astrocytoma
D. Oligodendroglioma
E. I-Iemangiopericytoma
A
B
C
D
E
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 depicted 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 hete rozygosity on chromosome 1p
and 19q and rarely contain ])53 mutations. Very few cells in
these neoplasms exhibit immunoreactivity for GFAP. Clear
cell meningiomas resemble oligodendrogliomas microscopically, 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).
What abnormality is depicted in the following photo micrograph?
A. Gemistocytic astrocytoma
B. Reactive astrocytosis
C. Acute infarction
D. Viral encephalitis
E. Bacterial meningitis
A
B
C
D
E
Microscopically, acute cerebral infarcts (after 8 to 12
hours) exhibit neuronal eosinophilia, pylmosis, and vacuolation of the neuropil. Subacute infarcts (2 to 4 days) also exhibit 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 encephalitis 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 pylmosis 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).
Which of the following is not observed with acute spinal
cord injury microscopically?
A. A.:onal spheroids
B. Hemorrhagic necrosis
C. Cavitation
D. Inflammatory infiltrates
E. Edema
A
B
C
D
E
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 collagenous fibrosis, as well as hyaline thickening of small blood
vessels (Ellison, pp. 262-269).
What is the most common chromosomal abnormality
associated with meningiomas?
A. Allelic loss of 1p
B. Monosomy 22
C. Allelic loss of 10
D. Allelic loss of 22q
E. Monosomy 2
A
B
C
D
E
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 1p, 10, and 14q
are associated with progression to more aggressive meningiomas (atypical and anaplastic). Despite the occurrence of
(multiple) meningiomas with NF-2, which also localizes to
chromosome 22, the tumor suppressor gene that is responsible for tumorigenesis with meningiomas in patients without neurofibromatosis is separate from the NF-2 gene locus
(Ellison, p. 715; Kaye and Laws, p. 78).
What is the inheritance pattern of Sturge-Weber syndrome?
A. Autosomal recessive
B. Autosomal dominant
C. X-linked recessive
D. Mitochondrial
E. Sporadic
A
B
C
D
E
Sturge-Weber syndrome (encephalotrigeminal angiomatosis) is a neurocutaneous disorder that occurs sporadically. The disorder is characterized by port wine stains i the distribution of the sensory fibers of the trigeminal nerve,
with associated ocular angiomas and leptomeningeal venous
angiomas of the ipsilateral cerebral hemisphere. Occasionally the cerebral hemispheres are involved bilaterally. Most
patients with Sturge-\Veber 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, tortuous meningeal vessels. The treatment of this disorder is
largely symptomatic (Ellison, pp. 107-108).
Which of the following disorders is associated with the
lesion depicted in this photomicrograph?
1. I-IIV encephalitis
2. Toxoplasmosis
3. ClvIVencephalitis
4. Neurosyphilis
A. 1, 2, and3 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
C
D
E
This photomicrograph depicts a microglial nodule.
Microglia typically have rod-shaped nuclei and are CD68-
positive. Microglia proliferate in many chronic CNS infections 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., CMV, HIV,
arboviruses, polioviruses). The aggregation of microglia and
macrophages around dying neurons is called “neuronophagia” (Ellison, pp. 273- 275, 277, 303-304, 319, 324).
Which of the following characteristics is not associated
with HlIllter syndrome (mucopolysaccharidosis type II)?
A. Lysosomal disorder
B. X-linked recessive inheritance
C. Hepatosplenomegaly
D. Corneal clouding
E. Mental retardation
A
B
C
D
E
Hunter syndrome is a lysosomal disorder that results
from deficiencies of the enzyme iduronate sulfatase . It is inherited in an X-linked recessive fashion and usually presents
in the first 2 to 4 years of life . Clinical findings of Hunter syndrome 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)
What is depicted in the following photomicrograph?
A. Intracranial abscess
B. Intracranial metastases
C. Multiple sclerosis plaque
D. Acute infarction
E. Fungal infection
A
B
C
D
E
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 malignant metastatic melanoma characterized by areas of hemorrhage, 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 choriocarcinoma. 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 usually 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 ventricles. Foci of cavitation are rare with ~vIS plaques but can
be observed with fulminant, acute plaques. Acute infarcts
exhibit only slight blurring of the gray-white junction with dusky discoloration , often in major vascular territories
(Ellison, pp. 197- 202,327- 334,389- 398,743- 750).
Which of the following disorders is associated with
accommodation (ciliary) paralysis, facial paralysis, preservation of extraocular movements, and an ascending
sensorimotor polyneuropathy?
A. Neurosarcoidosis
B. Neurosyphilis
C. Diphtheria
D. Lyme disease
E. Guillain-Barre syndrome
A
B
C
D
E
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 associated 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, hydrocephalus, and ataxia . Neurosyphilis is associated with cranial
nerve palsies, hydrocephalus, arteritis, seizures, and eventually psychosis and cognitive decline. Lyme disease results
in an enlarging maculopapular rash with central clearing
(erythema chronicum migrans) , followed by the development of axonal neuropathies, lymphocytic meningitis,
encephalopathy, polyradiculitis, and cranial nerve palsies.
Lyme disease can also affect the joints and cardiovascular
system. Ouillain-Barre syndrome (OBS) is an acute ascending monophasic motor polyneuropathy that can involve the
face , limbs, and even respiratory musculature. OBS is not
typically associated with any sensory loss or ciliary paralYSiS,
however (Ellison, pp. 342- 349; Merritt, pp. 613- 615)
The most common cause of intraventricular hemorrhage
in term infants
A. 8ubependymal germinal matrL’( hemorrhage
B. Choroid plexus hemorrhage
C. Both A and B
D. Neither A nor B
A
B
C
D
Subependymal germinal matrix hemorrhage is
usually observed in low-birth-weight premature infants and
can result in intraventricular hemorrhage. The microcirculation of the peri ventricular matrix zone is extremely fragile
and persists in the neonate until 34 weel(s 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 intraventricular hemorrhage (Ellison, pp. 34-37).
The most common cause of intraventricular hemorrhage
in premature infants
A. 8ubependymal germinal matrL’( hemorrhage
B. Choroid plexus hemorrhage
C. Both A and B
D. Neither A nor B
A
B
C
D
Subependymal germinal matrix hemorrhage is
usually observed in low-birth-weight premature infants and
can result in intraventricular hemorrhage. The microcirculation of the peri ventricular matrix zone is extremely fragile
and persists in the neonate until 34 weel(s 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 intraventricular hemorrhage (Ellison, pp. 34-37).
Which of the following disorders are secondary to defective neuronal migration?
1. Polymicrogyria
2. 8chizencephaly
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
A
B
C
D
E
Disorders of abnormal neuronal migration include
agyria, pachygyria, polymicrogyria, cortical dysplasia, and
focal and diffuse heterotopias. Schizencephaly and porencephaly 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).
lvIatch the following meningitis-causative organisms with the age group most likely to be afflicted:
Children 1 to 5 years of age
A. Streptococcus ]Jneu’I7loniae
B. Haemophiltls’irifluenzae
C. Listeria monocytogenes
D. Proteus mimbilis
E. S. epidennidis
A
B
C
D
E
Pediatric patients with bacterial
meningitis are usually due to infection by StreptococCllS
pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS
il1fhlellzae. The incidence of I-I . j’11fl’llellzae meningitis in the
pediatric population has decreased significantly in the past
decade because of the widespread use of the H. injl’llenzae B
vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. ‘Pnell11loniae or N.
11leningitidis. Meningitis in the elderly commonly results
from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal
bacterial meningitis is usually a result of infection by group B
streptococci and Escherichia coli; however, Citrobacter
(liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral
abscesses in this population (Ellison, pp. 327- 330; Merritt,
pp. 103-107)
lvIatch the following meningitis-causative organisms with the age group most likely to be afflicted:
Adults
A. Streptococcus pneumoniae
B. Haemophiltls’irifluenzae
C. Listeria monocytogenes
D. Proteus mimbilis
E. S. epidennidis
A
B
C
D
E
Pediatric patients with bacterial
meningitis are usually due to infection by StreptococCllS
pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS
il1fhlellzae. The incidence of I-I . j’11fl’llellzae meningitis in the
pediatric population has decreased significantly in the past
decade because of the widespread use of the H. injl’llenzae B
vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. ‘Pnell11loniae or N.
11leningitidis. Meningitis in the elderly commonly results
from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal
bacterial meningitis is usually a result of infection by group B
streptococci and Escherichia coli; however, Citrobacter
(liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral
abscesses in this population (Ellison, pp. 327- 330; Merritt,
pp. 103-107)
lvIatch the following meningitis-causative organisms with the age group most likely to be afflicted:
Unique to the elderly population
A. Streptococcus ]Jneu’I7loniae
B. Haemophiltls’irifluenzae
C. Listeria monocytogenes
D. Proteus mimbilis
E. S. epidennidis
A
B
C
D
E
Pediatric patients with bacterial
meningitis are usually due to infection by StreptococCllS
pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS
il1fhlellzae. The incidence of I-I . j’11fl’llellzae meningitis in the
pediatric population has decreased significantly in the past
decade because of the widespread use of the H. injl’llenzae B
vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. ‘Pnell11loniae or N.
11leningitidis. Meningitis in the elderly commonly results
from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal
bacterial meningitis is usually a result of infection by group B
streptococci and Escherichia coli; however, Citrobacter
(liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral
abscesses in this population (Ellison, pp. 327- 330; Merritt,
pp. 103-107)
lvIatch the following meningitis-causative organisms with the age group most likely to be afflicted:
Associated with ventriculoperitoneal shunt infections
A. Streptococcus ]Jneu’I7loniae
B. Haemophiltls’irifluenzae
C. Listeria monocytogenes
D. Proteus mimbilis
E. S. epidennidis
A
B
C
D
E
Pediatric patients with bacterial
meningitis are usually due to infection by StreptococCllS
pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS
il1fhlellzae. The incidence of I-I . j’11fl’llellzae meningitis in the
pediatric population has decreased significantly in the past
decade because of the widespread use of the H. injl’llenzae B
vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. ‘Pnell11loniae or N.
11leningitidis. Meningitis in the elderly commonly results
from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal
bacterial meningitis is usually a result of infection by group B
streptococci and Escherichia coli; however, Citrobacter
(liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral
abscesses in this population (Ellison, pp. 327- 330; Merritt,
pp. 103-107)
lvIatch the following meningitis-causative organisms with the age group most likely to be afflicted:
Associated with coexistent cerebral abscesses in
neonates
A. Streptococcus ]Jneu’I7loniae
B. Haemophiltls’irifluenzae
C. Listeria monocytogenes
D. Proteus mimbilis
E. S. epidennidis
A
B
C
D
E
Pediatric patients with bacterial
meningitis are usually due to infection by StreptococCllS
pneu.moniC/e, Neisseria meningiticiis, or Hael7lophilllS
il1fhlellzae. The incidence of I-I . j’11fl’llellzae meningitis in the
pediatric population has decreased significantly in the past
decade because of the widespread use of the H. injl’llenzae B
vaccination. Bacterial meningitis in the adult population is usually secondary to infection by S. ‘Pnell11loniae or N.
11leningitidis. Meningitis in the elderly commonly results
from S. pne ll11loniae and gram-negative rods. Listeria 11l01Wcytogenes can also afflict this older population. Neonatal
bacterial meningitis is usually a result of infection by group B
streptococci and Escherichia coli; however, Citrobacter
(liVerSlls and Protells mIrabilis-relatedmeningitis are associated with the development of concomitant cerebral
abscesses in this population (Ellison, pp. 327- 330; Merritt,
pp. 103-107)
What neoplasm is depicted in the following photomicrograph?
A. lvIedulloblastoma
B. Ganglion cell tumor
C. Central neurocytoma
D. Ependymoma
E. Anaplastic astrocytoma
A
B
C
D
E
Ganglion cell tumors (gangliocytomas and gangliogliomas) are characterized by neoplastic ganglion cells,
with or without a component of neoplastic glial tissue (usually 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
binuclea tion, seen in one of the ganglion cells here, which
never occurs in normal neurons. Gangliogliomas occasionally exhibit nuclear pleomorphism, but mitoses are absent.
Ganglion cells exhibit immunoreactivity for synaptophysin
and neurofilaments. J'ledulloblastomas 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)
What neoplasm is depicted in the following photomicrograph?
A. Neurofibroma
B. Schwannoma
C. Fibrous meningioma
D. MaUgnant nerve sheath tumor
E. None of the above
A
B
C
D
E
Schwanllomas are characterized by compact arrangements of interwoven fascicl es 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 matrLx with interspersed bundles of collagen (“shredded carrots” appearance). Fibrous meningiomas consist of spindle-shaped cells
with inte rmixed collagen and lack a mucoid matrLx 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).
What neoplasm is depicted in the following photomicrograph?
A. Dermoid cyst (mature teratoma)
B. Craniopharyngioma
C. Ependymoma
D. Yolk sac tumor
E. None of the above
A
B
C
D
E
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 epitheliu111 and contain adnexal structures such as sebaceous glands (shown in this example).
Craniopharyngiomas (adamantinomatous) are characterized by collections of squamous cells with intermingled
clusters of keratini zed ghost cells, calCification, and cholesterol clefts (Ellison, pp. 683-684,724- 727,737- 739).
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. IGippel-Feil anomaly
A
B
C
D
E
Klippel-Feil anomaly results from the failure of cervical vertebral (somite) segmentation. Klippel-Feil anomaly is
classically associated with the triad of short neck, low posterior hairline, and limited cervical motion. Approximately
one-third of all Klippel-Feil cases are associated with congenital elevation of the scapula, which is known as Sprengel’s
deformity. IGippel-Feil is also associated with diastema tomyelia, Chiari I malformations, basilar impression, and
genitourinary abnormalities (Merritt, p. 490).
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
A
B
C
D
E
Disjll.llction refers to the separation of superfiCial
ectodenll from neural ectoderm during development. It
is thought that premature disjunction allows cells of mesodermal origin to migrate between these two layers of
ectoderm, which can lead to the formation of lipomas
(Will<ins, pp. 3497-3499).
Which of the following neoplasms is/are associated with
von Hippel-Linclau syndrome?
1. Pheochromocytomas
2. Renal cell carcinoma
3. Cerebellar hemangioblastomas
4. Enclolymphatic 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
A
B
C
D
E
Von Hippel-Lindau syndrome (VEL) is an autosomal
dominant neurocutaneous disorder that is associated with
chromosome 3p. VHL patients deve lop 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)
What disorder is associated with the following photomicrograph?
A. Parkinson’s disease
B. Corticobasal degeneration
C. Rabies encephalitis
D. Alzheimer’s disease
E. None of the above
A
B
C
D
E
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 substantia 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 characterized by the presence of swollen cortical neurons (ballooned
neurons), gliosiS, and microvacuolation (Ellison, pp. 287-
289,512- 514).
What neoplasm is depicted in the following photomicrograph?
A. Pilocytic astrocytoma
B. Subependymoma
C. Myxopapillaryependymoma
D. Dysembryoplastic neuroepithelial tumor
E. None of the above
A
B
C
D
E
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”). Sllbependymomas often exhibit microcysts; however, nuclear pleomorphism and mitoses are universally
absent. Myxopapillary ependymomas claSSically exhibit collars of epithelioid cells surrounding pools of mucin with central blood vessels. Dysembryoplastic neuroepithelial
tumor (D~TET) is a supratentorial cortical neoplasm of children and young adults that is usually located in the temporal
lobe and presents with seizures. ;vIicroscopically, 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).
Which of the following lesions is depicted in these
two photomicrographs (two areas of the same lesion)?
A. Malignant nerve sheath tumor
B. Fibrous meningioma
C. Gliosarcoma
D. Embryonal carcinoma
E. None of the above
A
B
C
D
E
Gliosarcoma is a variant of glioblastoma multifonne.
The presenting features, demographic characteristics, cytogenetic changes, and prognosis of the gliosarcoma (Feigin
tumor) are all similar to that of the glioblastoma. Microscopically, the gliosarcoma consists of two distinct cell populations: 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, papillary, or cribriform patterns. Spindle-shaped cells are absent
in embryonal carcinoma (Ellison, pp. 628-632, 682, 700-
702; WHO, pp. 42- 44)
What is the most likely presentation of the following neoplasm?
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
A
B
C
D
E
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 regions of necrosis and apoptosis. Occasionally cells may form
rosettes that lack a central canal or blood vessel (HomerWright rosettes). Medulloblastomas often spread throughout
the CNS via CSF pathways. Approximately 50% of all medulloblastomas 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 hydrocephalus, which is consistent with answer D (Ellison,
pp. 667-672; WHO, pp. 129-137)
The following answers are in reference to:
Complete penetrance
A. Neurofibromatosis type 1
B. Tuberous sclerosis
C. Both of the above
D. Neither of the above
A
B
C
D
Neurofibromatosis type 1 (NF·l) is an autosomal
dominant neurocutaneous disorder that localizes to chromo·
some 17. The NF·l gene is very large and associated with a
high spontaneous mutation rate. Approximately 50% of all
NF·l cases are secondary to spontaneous mutations. NF·l 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).
Which of the following clinical presentations is most consistent with the lesion depicted below in this gross specimen?
A. Bilateral facial and abducens palsies in the neonate
B. Ipsilateral port wine stain in the distribution of V1 in a S-yea r-old
C. Developmental delay in a 1-year-old
D. Sepsis in the preterm infant
E. Epilepsy in a 6-month-old
A
B
C
D
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).
What is the most likely etiology of the abnormality depicted below?
A. Elevated intracranial pressure
B. Atherosclerotic disease
C. CNS infection
D. Neurodegenerative disorder
E. None of the above
A
B
C
D
E
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 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).
What infection is depicted in the following photomicrograph?
A. Aspergillosis
B. Mucormycosis
C. Cryptococcosis
D. Candidiasis
E. None of the above
A
B
C
D
E
Cerebral aspergillosis is usually secondary to hematogenous dissemination from the lungs or local spread from the
paranasal sinuses of Aspergillus fum:igatus or Aspergillus
f/avus. Symptoms of cerebral aspergillosis are variable and
include headache, seizures, cranial nerve palsies, hemiparesis, and elevated intracranial pressure. Aspergilltls has a
tendency to exhibit prominent vascular invasion, with subsequent vascular thrombosis, infarction, and hemorrhage.
Aspergilltls 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).
What disorder is depicted in the photomicrograph below?
A. Acute disseminated encephalomyelitis
B. CNS lymphoma
C. Viral encephalitis
D. Active MS plaque
E. None of the above
A
B
C
D
E
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-celllymphomas are
positive for CD20 (Ellison, pp. 689-694; WHO, pp. 198-
203).
What neoplasm is depicted in the following photomicrograph?
A. Papilla ry craniopharyngioma
B. Papillary meningioma
C. Colloid cyst
D. Choroid plexus papilloma
E. Pineocytoma
A
B
C
D
E
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).
What abnormality is depicted in the following gross specimen?
A. Subacute infarct
B. Progressive multifocal leukoencephalopathy
C. Adrenoleukodystrophy
D. Fat embolism
E. Multiple sclerosis plaques
A
B
C
D
E
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.
J\Hcroscopically, 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 multifocalleukoencephalopathy (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 exJ1ibits 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).
lvlatch the hormone production with the associated germ cell neoplasm (numbered items), using each answer once [(+) = immunoreactive; (- ) =
not immunoreac tive ; (+/-) = may be immunoreactive].
Teratoma
A.A
B.B
C.C
D.D
E.E
A
B
C
D
E
lvlatch the hormone production with the associated germ cell neoplasm (numbered items), using each answer once [(+) = immunoreactive; (- ) =
not immunoreac tive ; (+/-) = may be immunoreactive].
Yolk sac tumor
A.A
B.B
C.C
D.D
E.E
A
B
C
D
E
lvlatch the hormone production with the associated germ cell neoplasm (numbered items), using each answer once [(+) = immunoreactive; (- ) =
not immunoreac tive ; (+/-) = may be immunoreactive].
Embryonal carcinoma
A.A
B.B
C.C
D.D
E.E
A
B
C
D
E
lvlatch the hormone production with the associated germ cell neoplasm (numbered items), using each answer once [(+) = immunoreactive; (- ) =
not immunoreac tive ; (+/-) = may be immunoreactive].
Germinoma
A.A
B.B
C.C
D.D
E.E
A
B
C
D
E
lvlatch the hormone production with the associated germ cell neoplasm (numbered items), using each answer once [(+) = immunoreactive; (- ) =
not immunoreac tive ; (+/-) = may be immunoreactive].
Choriocarcinoma
A.A
B.B
C.C
D.D
E.E
A
B
C
D
E
What neoplasm is depicted in the photomicrograph below?
A. Psammomatous meningioma
B. Microcystic meningioma
C. PUocytic astrocytoma
D. Craniopharyngioma
E. Ependymoma
A
B
C
D
E
Note the presence of psammoma bodies intermingled with whorling meningothelial cells in this photomiCrograph, depicting a psammomatous meningioma (Ellison,
pp.708-709).
What neoplasm is depicted in the photomicrograph
below?
A. Pleomorphic xanthoastrocytoma
B. Choroid plexus papilloma
C. Dermoid tumor
D. Papillary meningioma
E. Myxopapillaryependymoma
A
B
C
D
E
This photomicrograph depic ts a myxopapillary
ependymoma with markedly thickened blood vessel walls
and cells with a delicate fibrillary cytoplasm surrounding
mucin-rich areas (Ellison, pp. 646-651).
A photomicrograph from a patient with AIDS is depicted below (Figure 4.116Q). What is the diagnosis?
A. Lymphoma
B. Cryptococcal infection
C. HIVencephalopathy
D. Progressive multifocalleukoencephalopathy
E. Toxoplasmosis
A
B
C
D
E
Note the prominent pleomorphic astrocyte and
oligodendrocytes with viral inclusions in this immunocompromised patient with PML. Patients with this disease
present with focal neurologic deficits including dysarthria,
limb weakness, visual disturbances, ataxia, personality
changes, and occasionally seizures. PML usually progresses
rapidly over the course of weeks to months, resulting in
increasing neurologic impairment, coma, and death. Treatment of the underlying immunocompromised state can lead
to remission (Ellison, pp. 298-300).
What is depicted in the photomicrograph below?
A. Neurofibroma
B. Pilocytic astrocytoma
C. Skeletal muscle
D. Schwannoma
E. Malignant peripheral nerve sheath tumor
A
B
C
D
E
Note the haphazardly arranged spindle cells with
wavy nuclei and a prominent matrL’( of mucin and collagen
in this photomicrograph depicting a neurofibroma (Ellison,
pp.699- 701).
The neoplasm depicted in the photomicrograph below is typically positive for which imll1unostains?
1. Synaptophysin
2. S-100
3. Chromogranin
4. GFAP
A. 1,2, and 3 are correct
B. 1 and 3 are correct
C. 2 and4 are correct
D. Only 4 is correct
E. All of the above
A
B
C
D
E
Note the nests of chief cells (Zellballen) surrounded by a fibrovascular stroma and sustentacular cells in this photomicrograph depicting a paraganglioma of the
tilum terminale. These neoplasms show immunoreactivity to
synaptophysin and chrolllograninj ultrastructural examination reveals dense-core granules. Sustentacular cells are
immunoreactive to S-100 protein (Ellison, pp. 658-659).
For the neoplasm depicted in the photomicrograph below, what is the diagnosis?
A. Pituitary adenoma
B. Paraganglioma of the filum terminale
C. Ganglioglioma
D. Germinoma
E. Astrocytoma
A
B
C
D
E
Note the nests of chief cells (Zellballen) surrounded by a fibrovascular stroma and sustentacular cells in this photomicrograph depicting a paraganglioma of the
tilum terminale. These neoplasms show immunoreactivity to
synaptophysin and chrolllograninj ultrastructural examination reveals dense-core granules. Sustentacular cells are
immunoreactive to S-100 protein (Ellison, pp. 658-659).
What neoplasm is depicted in the photomicrograph
below?
A. Lymphoma
B. SubependymomH
C. Melanoma
D. Medulloblastoma
E. Central neurocytom
A
B
C
D
E
Note the sheets of cells with uniform round nuclei,
which is characteristic of central neurocytomas. These neoplasms most often show synaptophysin immunoreactivity,
although a small astrocytic component is often present that
is GFAP-positive. Ultrastructural features include dense-core
and clear vesicles, microtubules, and intermediate filaments
(Ellison, pp. 656-658; WHO, pp. 107-109).
What is depicted by the gross specimen below
(Figure 4.122Q)?
A. lvlultiple sclerosis
B. Kernicterus
C. Laminar necrosis
D. Heterotopic gray matter
E. Fat emboli
A
B
C
D
E
Laminar necrosis can be related to intrapartum
difficulties, congenital heart disease, and vascular collapse in
an infant. It often involves the depths of the sulci (as depicted
here), and the necrosis can be in a laminar or pseudolaminar
pattern (Ellison, pp. 37- 43).
What is depicted by the gross specimen below?
A. Tuberous sclerosis
B. Sturge-Weber syndrome
C. Occipital encephalocele
D. Agyria
E. Subdural empyema
A
B
C
D
E
Note the absence of sulci and gyri along the
cerebral convexities of this specimen depicting agyria, which
results from abnormal cellular migration during embryologic
development (Ellison, pp. 71- 76).
What is depicted by the gross specimen below? This abnormality often results from faulty
A. Primary neurulation
B. Secondary neurulation
C. Diverticulation and cleavage
D. Cellular migration
E. Myelination
A
B
C
D
E
Note the absence of sulci and gyri along the
cerebral convexities of this specimen depicting agyria, which
results from abnormal cellular migration during embryologic
development (Ellison, pp. 71- 76).
What is depicted in the photomicrograph below?
A. Pick bodies
B. Chronic multiple sclerosis plaque
C. Cortical dysplasia
D. Siderocalcinosis
E. Neurofibrillary tangles
A
B
C
D
E
Note the prominent calcifications of residual
neurons adjacent to a chronic infarct in this photomicrograph depicting siderocalcinosis (Ellison, pp. 190- 191)
The finding in this photomicrograph may have resulted
from what pathologic event?
A. An autoimmune disorder
B. Neurodegeneration
C. Viral infection
D. Developmental anomaly
E. Chronic infarct
A
B
C
D
E
Note the prominent calcifications of residual
neurons adjacent to a chronic infarct in this photomicrograph depicting siderocalcinosis (Ellison, pp. 190- 191)
What is depicted in the photomicrograph below?
A. Bacterial meningitis
B. Ependymoma
C. Anaplastic astrocytoma
D. Amyloid angiopathy
E. None of the above
A
B
C
D
E
Note the presence of a prominent inflammatory
infiltrate within the lumen of this blood vessel with concomitant vascular thrombosis in this photomicrograph depicting
bacterial meningitis (Ellison, pp. 327-331).
What neoplasm is depicted in the photomicrograph
below?
A. Pilocytic astrocytoma
B. Transitionalmeningioma
C. Malignant nerve sheath tumor
D. Acoustic neuroma
E. Pituitary adenoma
A
B
C
D
E
Note the fascicular arrangement of these neoplastic cells that exhibit a high nuclear-cytoplasmic r and prominent mitosis in this photomicrograph depicting
a malignant nerve sheath tumor (MNST). This neoplasm
usually involves the trigeminal nerve intracranially but
most often originates from the cervical or brachial plexi.
MNST carries a poor prognosis, and approximately SO% of
patients harboring this lesion have NFl (Ellison, pp. 700-
702).
This neoplasm most often involves which cranial
nerve?
A. Oculomotor (CN III)
B. Trigeminal nerve (CNV)
C. Facial nerve (CN VII)
D. Vestibulocochlear nerve (CN VIII)
E. Spinal accessory nerve (Xl)
A
B
C
D
E
Note the fascicular arrangement of these neoplastic cells that exhibit a high nuclear-cytoplasmic r and prominent mitosis in this photomicrograph depicting
a malignant nerve sheath tumor (MNST). This neoplasm
usually involves the trigeminal nerve intracranially but
most often originates from the cervical or brachial plexi.
MNST carries a poor prognosis, and approximately SO% of
patients harboring this lesion have NFl (Ellison, pp. 700-
702).
Match the metastatic neoplasm with the corresponding photomicrograph
depicted below, using each answer once: Renal cell carcinoma
A.A
B.B
C.C
A
B
C
The most common metastatic brain
tumors originate from the lung, breast, skin, and kidney.
Photomicrograph A depicts a lesion with an area of necrosis
and branching as well as sharply angulated lobules, which
is most consistent with metastatic breast carcinoma.
Photomicrograph B depicts metastatic lung adenocarcinoma, which is thyroid transcription factor-l (TTF-l)
positive, and thyroglobulin negative. Photomicrograph C
shows a hypervascular tumor with lobules of clear cells,
which is most consistent with renal cell carcinoma [EMA
(+), CAM S.2 (+), CD 10 (+)] (Ellison, pp. 743-749; WHO,
pp. 250-253).
Match the metastatic neoplasm with the corresponding photomicrograph
depicted below, using each answer once: Breast cancer
A.A
B.B
C.C
A
B
C
The most common metastatic brain
tumors originate from the lung, breast, skin, and kidney.
Photomicrograph A depicts a lesion with an area of necrosis
and branching as well as sharply angulated lobules, which
is most consistent with metastatic breast carcinoma.
Photomicrograph B depicts metastatic lung adenocarcinoma, which is thyroid transcription factor-l (TTF-l)
positive, and thyroglobulin negative. Photomicrograph C
shows a hypervascular tumor with lobules of clear cells,
which is most consistent with renal cell carcinoma [EMA
(+), CAM S.2 (+), CD 10 (+)] (Ellison, pp. 743-749; WHO,
pp. 250-253).
Match the metastatic neoplasm with the corresponding photomicrograph
depicted below, using each answer once: Lung adenocarcinoma
A.A
B.B
C.C
A
B
C
The most common metastatic brain
tumors originate from the lung, breast, skin, and kidney.
Photomicrograph A depicts a lesion with an area of necrosis
and branching as well as sharply angulated lobules, which
is most consistent with metastatic breast carcinoma.
Photomicrograph B depicts metastatic lung adenocarcinoma, which is thyroid transcription factor-l (TTF-l)
positive, and thyroglobulin negative. Photomicrograph C
shows a hypervascular tumor with lobules of clear cells,
which is most consistent with renal cell carcinoma [EMA
(+), CAM S.2 (+), CD 10 (+)] (Ellison, pp. 743-749; WHO,
pp. 250-253).
What is depicted in the photomicrograph below?
A. Central pontine myelinosis
B. Low-grade astrocytoma
c. Subependymoma
D. Radiation necrosis
E. Microglial nodule
A
B
C
D
E
Note the areas of necrosis without intact cells or
nuclei and the hyalinized, necrotic vessel in this photomicrograph depicting radiation necrosis (Ellison , p. 632;
Berger, pp. 471-474; Greenberg, pp. 507-515).
Wha t is depicted on this gross section?
A. Multiple sclerosis plaque
B. Pilocytic astrocytoma
C. Lymphoma
D. Cerebral abscess
E. Embolic infarct
A
B
C
D
E
Note the prominent capsule and central purulent
region in this gross section depicting a brain abscess. The
central area of necrosis and surrounding capsule formation
are characteristic features of the fourth stage of abscess
formation (capsular stage). Refer to Table S.97-S.100A for
a sumnulry of the stages of abscess formation (Ellison,
pp. 330-336).
What is depicted in the photomicrograph below?
A. Amputation neuroma
B. Noncaseating granuloma
C. Acoustic neuroma
D. Paraganglioma
E. Chronic multiple sclerosis plaqu
A
B
C
D
E
Note the noncaseating sarcoid granuloma containing prominent epithelioid cells and multinucleated giant
cells. Tuberculosis is associated with caseating granulomas,
whereas MS plaques, paragangliomas, amputation neuromas,
and acoustic neuromas are not associated with granuloma
formation (Ellison, pp. 346-348).
This finding would be most consistent with what
diagnosis ?
A. Acollstic neuroma
B. Trauma
C. Neurosarcoidosis
D. Tuberculosis
E. Leigh’s disease
A
B
C
D
E
Note the noncaseating sarcoid granuloma containing prominent epithelioid cells and multinucleated giant
cells. Tuberculosis is associated with caseating granulomas,
whereas MS plaques, paragangliomas, amputation neuromas,
and acoustic neuromas are not associated with granuloma
formation (Ellison, pp. 346-348).
What is depicted in the photomicrograph below?
A. Acute infarct
B. Chronic infarct
C. Progressive l11ultifocalleukoencephalopathy
D. Amyloid angiopathy
E. Neurofibrillary tangles
A
B
C
D
E
Note the presence of hypocellularity, gliosis, demyelination, and a lack of inflammation in this photomicrograph depicting a chronic infarct (Ellison, pp. 197- 201)
Match the inclusion body with the associated
photomicrograph using each answer once: Negri body
A.A
B.B
C.C
D.D
E.E
F.F
A
B
C
D
E
F
Lewy bodies (E),
the hallmark of Parkinson’s disease, are intracellular
cytoplasmic inclusions containing an eosinophilic core
surrounded by a pale halo. They are predominantly found in
the substantia nigra and consist of ubiquitin, neurofilaments,
CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small
eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains;
however, they are best identified with ubiquitin staining
techniques. Hirano bodies (A) are eosinophilic cytoplasmic
inclusions composed of actin and actin-associated proteins;
they are particularly prominent in the CAl sector of the
hippocampus in patients with Alzheimer’s disease (AD) and
Pick’s disease. Neurofibrillary tangles (D) are intraneuronal
inclusions composed of phosphorylated tau, which is a
rnicrotubule-associated cytoskeletal protein. Phosphorylated
tau forms helical filaments, which can be found within the
neocortex and pyramidal cells of the hippocampus in
patients with AD. The microscopic hallmark of Pick’s disease is the Pick body (B), which is a spherical cytoplasmic
inclusion (composed of phosphorylated tau) that is mildly
basophilic and contains a well-demarcated margin. Negri
bodies (C) are oval or round cytoplasmic inclusions that can
be found throughout the CNS but are most prominent in
Purkinje cells. The appearance of Negri bodies is similar to
that of red blood cells (Ellison, pp. 288-289, 504, 513- 514,
552,556-559,570- 572).
Match the inclusion body with the associated
photomicrograph using each answer once: Hirano body
A.A
B.B
C.C
D.D
E.E
F.F
A
B
C
D
E
F
Lewy bodies (E),
the hallmark of Parkinson’s disease, are intracellular
cytoplasmic inclusions containing an eosinophilic core
surrounded by a pale halo. They are predominantly found in
the substantia nigra and consist of ubiquitin, neurofilaments,
CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small
eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains;
however, they are best identified with ubiquitin staining
techniques. Hirano bodies (A) are eosinophilic cytoplasmic
inclusions composed of actin and actin-associated proteins;
they are particularly prominent in the CAl sector of the
hippocampus in patients with Alzheimer’s disease (AD) and
Pick’s disease. Neurofibrillary tangles (D) are intraneuronal
inclusions composed of phosphorylated tau, which is a
rnicrotubule-associated cytoskeletal protein. Phosphorylated
tau forms helical filaments, which can be found within the
neocortex and pyramidal cells of the hippocampus in
patients with AD. The microscopic hallmark of Pick’s disease is the Pick body (B), which is a spherical cytoplasmic
inclusion (composed of phosphorylated tau) that is mildly
basophilic and contains a well-demarcated margin. Negri
bodies (C) are oval or round cytoplasmic inclusions that can
be found throughout the CNS but are most prominent in
Purkinje cells. The appearance of Negri bodies is similar to
that of red blood cells (Ellison, pp. 288-289, 504, 513- 514,
552,556-559,570- 572).
Match the inclusion body with the associated
photomicrograph using each answer once: Lewy body
A.A
B.B
C.C
D.D
E.E
F.F
A
B
C
D
E
F
Lewy bodies (E),
the hallmark of Parkinson’s disease, are intracellular
cytoplasmic inclusions containing an eosinophilic core
surrounded by a pale halo. They are predominantly found in
the substantia nigra and consist of ubiquitin, neurofilaments,
CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small
eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains;
however, they are best identified with ubiquitin staining
techniques. Hirano bodies (A) are eosinophilic cytoplasmic
inclusions composed of actin and actin-associated proteins;
they are particularly prominent in the CAl sector of the
hippocampus in patients with Alzheimer’s disease (AD) and
Pick’s disease. Neurofibrillary tangles (D) are intraneuronal
inclusions composed of phosphorylated tau, which is a
rnicrotubule-associated cytoskeletal protein. Phosphorylated
tau forms helical filaments, which can be found within the
neocortex and pyramidal cells of the hippocampus in
patients with AD. The microscopic hallmark of Pick’s disease is the Pick body (B), which is a spherical cytoplasmic
inclusion (composed of phosphorylated tau) that is mildly
basophilic and contains a well-demarcated margin. Negri
bodies (C) are oval or round cytoplasmic inclusions that can
be found throughout the CNS but are most prominent in
Purkinje cells. The appearance of Negri bodies is similar to
that of red blood cells (Ellison, pp. 288-289, 504, 513- 514,
552,556-559,570- 572).
Match the inclusion body with the associated
photomicrograph using each answer once: Pick body
A.A
B.B
C.C
D.D
E.E
F.F
A
B
C
D
E
F
Lewy bodies (E),
the hallmark of Parkinson’s disease, are intracellular
cytoplasmic inclusions containing an eosinophilic core
surrounded by a pale halo. They are predominantly found in
the substantia nigra and consist of ubiquitin, neurofilaments,
CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small
eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains;
however, they are best identified with ubiquitin staining
techniques. Hirano bodies (A) are eosinophilic cytoplasmic
inclusions composed of actin and actin-associated proteins;
they are particularly prominent in the CAl sector of the
hippocampus in patients with Alzheimer’s disease (AD) and
Pick’s disease. Neurofibrillary tangles (D) are intraneuronal
inclusions composed of phosphorylated tau, which is a
rnicrotubule-associated cytoskeletal protein. Phosphorylated
tau forms helical filaments, which can be found within the
neocortex and pyramidal cells of the hippocampus in
patients with AD. The microscopic hallmark of Pick’s disease is the Pick body (B), which is a spherical cytoplasmic
inclusion (composed of phosphorylated tau) that is mildly
basophilic and contains a well-demarcated margin. Negri
bodies (C) are oval or round cytoplasmic inclusions that can
be found throughout the CNS but are most prominent in
Purkinje cells. The appearance of Negri bodies is similar to
that of red blood cells (Ellison, pp. 288-289, 504, 513- 514,
552,556-559,570- 572).
Match the inclusion body with the associated
photomicrograph using each answer once: Neurofibrillary body
A.A
B.B
C.C
D.D
E.E
F.F
A
B
C
D
E
F
Lewy bodies (E),
the hallmark of Parkinson’s disease, are intracellular
cytoplasmic inclusions containing an eosinophilic core
surrounded by a pale halo. They are predominantly found in
the substantia nigra and consist of ubiquitin, neurofilaments,
CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small
eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains;
however, they are best identified with ubiquitin staining
techniques. Hirano bodies (A) are eosinophilic cytoplasmic
inclusions composed of actin and actin-associated proteins;
they are particularly prominent in the CAl sector of the
hippocampus in patients with Alzheimer’s disease (AD) and
Pick’s disease. Neurofibrillary tangles (D) are intraneuronal
inclusions composed of phosphorylated tau, which is a
rnicrotubule-associated cytoskeletal protein. Phosphorylated
tau forms helical filaments, which can be found within the
neocortex and pyramidal cells of the hippocampus in
patients with AD. The microscopic hallmark of Pick’s disease is the Pick body (B), which is a spherical cytoplasmic
inclusion (composed of phosphorylated tau) that is mildly
basophilic and contains a well-demarcated margin. Negri
bodies (C) are oval or round cytoplasmic inclusions that can
be found throughout the CNS but are most prominent in
Purkinje cells. The appearance of Negri bodies is similar to
that of red blood cells (Ellison, pp. 288-289, 504, 513- 514,
552,556-559,570- 572).
Match the inclusion body with the associated
photomicrograph using each answer once: Bunina body
A.A
B.B
C.C
D.D
E.E
F.F
A
B
C
D
E
F
Lewy bodies (E),
the hallmark of Parkinson’s disease, are intracellular
cytoplasmic inclusions containing an eosinophilic core
surrounded by a pale halo. They are predominantly found in
the substantia nigra and consist of ubiquitin, neurofilaments,
CY.- synuclein, and CY.~ crystallin. Bunina bodies (F) are small
eosinophilic cytoplasmic inclusions that are observed in patients with ALS. They can be demonstrated with H&E stains;
however, they are best identified with ubiquitin staining
techniques. Hirano bodies (A) are eosinophilic cytoplasmic
inclusions composed of actin and actin-associated proteins;
they are particularly prominent in the CAl sector of the
hippocampus in patients with Alzheimer’s disease (AD) and
Pick’s disease. Neurofibrillary tangles (D) are intraneuronal
inclusions composed of phosphorylated tau, which is a
rnicrotubule-associated cytoskeletal protein. Phosphorylated
tau forms helical filaments, which can be found within the
neocortex and pyramidal cells of the hippocampus in
patients with AD. The microscopic hallmark of Pick’s disease is the Pick body (B), which is a spherical cytoplasmic
inclusion (composed of phosphorylated tau) that is mildly
basophilic and contains a well-demarcated margin. Negri
bodies (C) are oval or round cytoplasmic inclusions that can
be found throughout the CNS but are most prominent in
Purkinje cells. The appearance of Negri bodies is similar to
that of red blood cells (Ellison, pp. 288-289, 504, 513- 514,
552,556-559,570- 572).
Match the medication with the associated complication, using each answer once, more than once, or not at all: Muscle pain
A. Isotretinoin
B. Tamoxifen
C. Interleukin-2
D. Cyclosporine
E. Al1ti-CD3
F. Vinblastine
G. Vincristine
H. Carboplatin
I. None of the above
A
B
C
D
E
F
G
H
I
Match the medication with the associated complication, using each answer once, more than once, or not at all: Pseudo tumor cerebri
A. Isotretinoin
B. Tamoxifen
C. Interleukin-2
D. Cyclosporine
E. Al1ti-CD3
F. Vinblastine
G. Vincristine
H. Carboplatin
I. None of the above
A
B
C
D
E
F
G
H
I
Match the medication with the associated complication, using each answer once, more than once, or not at all: Decreased visual acuity
A. Isotretinoin
B. Tamoxifen
C. Interleukin-2
D. Cyclosporine
E. Al1ti-CD3
F. Vinblastine
G. Vincristine
H. Carboplatin
I. None of the above
A
B
C
D
E
F
G
H
I
Match the medication with the associated complication, using each answer once, more than once, or not at all: Peripheral neuropathy, hearing loss, cortical blindness
A. Isotretinoin
B. Tamoxifen
C. Interleukin-2
D. Cyclosporine
E. Al1ti-CD3
F. Vinblastine
G. Vincristine
H. Carboplatin
I. None of the above
A
B
C
D
E
F
G
H
I
Match the medication with the associated complication, using each answer once, more than once, or not at all: Hypertrichosis
A. Isotretinoin
B. Tamoxifen
C. Interleukin-2
D. Cyclosporine
E. Al1ti-CD3
F. Vinblastine
G. Vincristine
H. Carboplatin
I. None of the above
A
B
C
D
E
F
G
H
I
Match the medication with the associated complication, using each answer once, more than once, or not at all: Tremor
A. Isotretinoin
B. Tamoxifen
C. Interleukin-2
D. Cyclosporine
E. Al1ti-CD3
F. Vinblastine
G. Vincristine
H. Carboplatin
I. None of the above
A
B
C
D
E
F
G
H
I
Match the medication with the associated complication, using each answer once, more than once, or not at all: Parkinsonism
A. Isotretinoin
B. Tamoxifen
C. Interleukin-2
D. Cyclosporine
E. Al1ti-CD3
F. Vinblastine
G. Vincristine
H. Carboplatin
I. None of the above
A
B
C
D
E
F
G
H
I
Match the medication with the associated complication, using each answer once, more than once, or not at all: Decreased ADH secretion
A. Isotretinoin
B. Tamoxifen
C. Interleukin-2
D. Cyclosporine
E. Al1ti-CD3
F. Vinblastine
G. Vincristine
H. Carboplatin
I. None of the above
A
B
C
D
E
F
G
H
I
Match the medication with the associated complication, using each answer once, more than once, or not at all: Primary CNS lymphoma
A. Isotretinoin
B. Tamoxifen
C. Interleukin-2
D. Cyclosporine
E. Al1ti-CD3
F. Vinblastine
G. Vincristine
H. Carboplatin
I. None of the above
A
B
C
D
E
F
G
H
I
What is depicted in this gross specimen?
A. Alcoholic cerebellar degeneration
B. Metastatic tumor
C. Multiple sclerosis
D. Chiari malformation
E. Aqueductal stenosis
A
B
C
D
E
Note the prominent atrophy of the cerebellar vermis
in this gross specimen depicting alcoholic cerebellar degeneration (Ellison, pp. 488- 489).
What is depicted in this gross specimen?
A. Acoustic neuroma
B. Tuberculosis
C. Epidermoid tumor
D. Basilar apex aneurysm
E. Optic nerve glioma
A
B
C
D
E
Note the prominent epidermoid within the right
cerebellopontine angle cistern in this gross specimen
(Ellison, pp. 737- 739).
What is depicted in the photomicrograph below?
A. Coccidioidomycosis
B. Histoplasmosis
C. Toxoplasmosis
D. Cryptococcalmeningitis
E. Mucormycosis
A
B
C
D
E
Note the prominent spherules containing endospores in this photomicrograph depicting coccidioidomycosis. The spherules and enclosed endospores usually appear
basophilic when stained with H&E but are better demonstrated by methenamine silver impregnation. Pulmonary
infection can occur in the absence of underlying disease and is generally self-limiting, although there may be residual
fibrosis and calcification. Coccidioidomycosis is most often
associated with occupations involving exposures to large
amounts of dust. Hematogenous spread is rare and is most
often seen in patients with diabetes, immunosuppression, or
pregnancy. CNS involvement is usually a late, terminal event
(Ellison, pp. 362 363) .
What is depicted in this gross specimen?
A. Purulent meningitis
B. Traumatic brain injury
C. Embolic stroke
D. Watershed infarct
E. None of the above
A
B
C
D
E
This gross section depicts prominent exudates along
the cerebral convexities as well as focal areas of hemorrhage
and thrombosed veins; these are characteristic of purulent
meningitis (Ellison, pp. 328 330).
What is depicted in the photomicrograph below?
A. Glomeruloid vascular proliferation of a glioblastoma
B. Homer-Wright rosette of a pinealcytoma
C. Microglial nodule
D. Angiomatous meningioma
E. Neuronophagia
A
B
C
D
E
Note the glomeruloid vascular proliferation in this
photomicrograph depicting a glioblastoma (Ellison, p. 631)
