Pathology/ Histology Flashcards

Question 1

Q

In cerebral amyloid angiopathy, what typically
occurs with respect to the basal membrane and
the internal elastic lamina of the affected vessels?
A. The basal membrane thins, and the internal
elastic lamina thickens.
B. The basal membrane thickens, and the internal elastic lamina fragments.
C. The basal membrane fragments, and the
internal elastic lamina thickens.
D. The basal membrane is unaffected, and the
internal elastic lamina fragments.
E. The basal membrane thickens, and the internal elastic lamina is unaffected

Answer

A

B. The basal membrane thickens, and the internal elastic lamina fragments.

In cerebral amyloid angiopathy, amyloid deposits
form in the walls of vessels, making them friable
and prone to hemorrhage. Congo red staining
reveals the amyloid deposits.

Question 2

Q

This image shows a specimen from cerebral white
matter. What is the underlying pathology?
A. Creutzfeldt-Jakob disease
B. Multiple sclerosis
C. Subacute infarction
D. Sarcoidosis

Answer

A

B. Multiple sclerosis

Multiple sclerosis is a demyelinating disease
(thus causing white matter pathology). Histologically, demyelination is seen along with a paucity
of oligodendrocytes. Newly demyelinated axons are
irregularly dilated and nonuniform. There is an
infiltration of lymphocytes in active lesions. (A) In
Creutzfeldt-Jakob disease, there are spongiform
changes of the gray matter, with a loss of neurons
and gliosis. Amyloid-like plaques also can be seen.
(C) In subacute cerebral infarctions, macrophages
predominate (after the neutrophils of acute infarctions), and neural cytoplasm is eosinophilic with
pyknotic nuclei. Numerous reactive astrocytes are
seen around zones of rarefaction (reduced cellular
density). (D) In neurosarcoidosis, there are noncaseating granulomas with numerous surrounding
lymphocytes. The absence of granulomas in this
specimen argues against sarcoidosis.

Question 3

Q

Malignant peripheral nerve sheath tumors commonly have what set of immunohistochemical
features?
A. Alterations in chromosome 17, S-100, and
nestin
B. Alteration in chromosome 22, GFAP, and CD10
C. Alterations in chromosome 6, vimentin, MIB-1
D. Alterations in chromosome 4, AFP, and CD20
E. Alterations in chromosome 18, HCG, and
desmin

Answer

A

A. Alterations in chromosome 17, S-100, and
nestin

S-100 is a sensitive marker for malignant
peripheral nerve sheath tumors (MPNSTs), but it
is not seen in all cases, as it is positive in only 50
to 90% of MPNSTs. Higher grade tumors tend to
have an even lower incidence of S-100 positivity.
CD56 also is sensitive but not specific for MPNSTs.
Recent studies highlight that nestin expression is
one of the most sensitive and specific markers for
these tumors. The tumors also are associated with
chromosome 17 mutations, as about 50% of them
occur in individuals with neurofibromatosis type 1.
(B) Chromosome 22 abnormalities are seen in neurofibromatosis type 2. GFAP (glial fibrillary acidic
protein) is a marker found in the intermediate filaments of some glial cells (primarily astrocytes).
CD10 often is used as a marker for various types of
lymphomas. (C) Chromosome 6 abnormalities can
be associated with Parkinson disease or Dandy-Walker malformation. Vimentin is a marker for
sarcoma. MIB-1 is a proliferation marker. (D) Chromosome 4 abnormalities are associated with
Huntington and Parkinson disease among other
condition. AFP (α-fetoprotein) can be a useful
marker for diagnosing germ cell tumors, especially
yolk sac tumors. CD20 is a B-cell marker. (E) Trisomy of chromosome 18 results in Edwards syndrome. HCG is a marker for choriocarcinomas and
germ cell tumors. Desmin is a marker for muscle
intermediate filaments.

Question 4

Q

A pathologist reports that a resected mass displays
basophilic psammoma bodies with mesenchymal
and epithelial cells that stain for vimentin and
epithelial membrane antigen. Dural feeders in a
sunburst pattern were noted in the lesion on preoperative angiogram. What is the likely pathology?
A. Dural arteriovenous fistula
B. Arteriovenous malformation
C. Meningioma
D. High-grade glioma
E. Hemangioblastoma

Answer

A

C. Meningioma

Meningiomas are marked by vimentin, epithelial
membrane antigen (EMA), and sometimes progesterone receptor immunoreactivity. They typically
are dural based and may contain psammoma bodies. (A) Dural arteriovenous fistulas (dural arteriovenous malformations) are as described below for
answer B, except that they have dural vessels as the
feeding and draining vessels. They have no distinct
nidus. (B) Arteriovenous malformations appear
histologically as vascular channels of various wall
thicknesses, in which arteries connect to veins
without an intermediate capillary. Early draining
veins are demonstrated on angiograms. There is a
gross nidus on imaging. (D) Like all glial tumors,
high-grade gliomas stain for glial fibrillary acidic
protein. High-grade gliomas also can display gross
elements of cysts, degeneration, mitotic figures,
and necrosis. (E) Hemangioblastomas stain richly
for reticulin, are positive for vimentin, and negative
for EMA. They do not have calcifications, mitotic
figures, or necrosis. Microscopically, they are seen
as capillaries with hyperplastic endothelial elements with stromal cells and vacuoles. They do not
stain with EMA.

Question 5

Q

What type of craniopharyngioma occurs in children, and with what type of keratin is it typically
associated?
A. Adamantinomatous; dry
B. Adamantinomatous; wet
C. Papillary; dry
D. Papillary; wet
E. Both adamantinomatous and papillary; dry

Answer

A

B. Adamantinomatous; wet

Adamantinomatous craniopharyngiomas typically occur in children, in contrast to papillary
craniopharyngiomas, which occur more frequently
in adults. The former contains “wet” keratin (keratinocytes in a loose stellate reticular zone), whereas
the latter contains “dry” keratin. Both cause surrounding gliosis and have Rosenthal fibers present.

Question 6

Q

The most common neurologic manifestation of HIV
infestation is:
A. Toxoplasmosis
B. Primary central nervous system lymphoma
C. AIDS dementia complex
D. Encephalitis
E. Vacuolar myelopathy

Answer

A

C. AIDS dementia complex

AIDS dementia complex is seen in 50% of AIDS
patients and is characterized by the triad of cognitive dysfunction, behavioral changes, and motor
deficits. (A) Toxoplasmosis is seen in 10% of AIDS
cases at autopsy and is the most common cause of
focal neurologic symptoms in AIDS patients. Treatment is with pyrimethamine and sulfadiazine.
(B) Primary central nervous system lymphoma
(B-cell origin) is seen in 5% of AIDS cases at autopsy.
The Epstein-Barr virus frequently is detected in
the affected cells. (D) Encephalitis is characterized
by microglial nodules in white matter and subcortical gray matter, with focal demyelination and
neuronal loss. Multinucleated giant cells may be
seen and are unique to HIV infection. (E) Vacuolar
myelopathy (diagnosed during pathological tissue
examination) may be symptomatic or asymptomatic, and is detected in 50% of AIDS cases at autopsy.
Myelopathy may involve the posterior and lateral
columns of the lower thoracic cord and is detected
clinically in less than 50% of AIDS patients.

Question 7

Q

What neurotoxic agent is responsible for causing
primarily a myelinopathy?
A. Amiodarone
B. Bismuth
C. Lead
D. Mercury
E. Methanol

Answer

A

A. Amiodarone

Amiodarone is associated with myelinopathy,
which also may be seen with other agents such
as hexachlorophene, perhexiline, and toluene. The
other agents listed as options more typically cause
a neuropathy.

Question 8

Q

What type of hematoma occurs in the loose connective tissues of the scalp that may cross sutures, may
require blood transfusions, and does not calcify?
A. Subgaleal hematoma
B. Subperiosteal hematoma
C. Subdural hematoma
D. Temporalis contusion

Answer

A

A. Subgaleal hematoma

Subgaleal hematomas are associated with linear, nondisplaced skull fractures in children. They
can cross sutures as they separate the galea from
the periosteum. They may present as fluctuant
masses. (B) Subperiosteal hematomas (also known
as cephalohematomas) are seen in newborns and
are associated with parturition. Bleeding elevates
the periosteum, but the extent is limited by the
sutures. Subperiosteal hematomas usually are firm
and can calcify. (C) Subdural hematomas are not in
the scalp. (D) Temporalis contusions are intramuscular and are not in the loose connective tissue of
the scalp.

Question 9

Q

A 43-year-old patient presents with a large,
enhancing mass with a necrotic center with mass
effect and significant vasogenic edema. Following
resection, histology demonstrated neovascularization with endothelial proliferation and pseudopalisading around areas of necrosis. Histopathology
was significant for a TP53 mutation. What is the
most likely diagnosis?
A. Primary glioblastoma
B. Secondary glioblastoma
C. Rhabdoid meningioma
D. Medulloblastoma
E. Chordoma

Answer

A

B. Secondary glioblastoma

A high-grade glial neoplasm with neovascularization and necrosis is diagnostic for glioblastoma.
The younger age of this patient and the presence
of a TP53 mutation argue for a secondary glioblastoma through malignant degeneration. In contrast, primary glioblastomas are associated with
EGFR amplification in older patients. (C) Rhabdoid meningiomas are grade III meningiomas that
often behave aggressively and are not glial tumors.
(D) Medulloblastomas have small, densely packed,
undifferentiated cells and often are referred to as
blue cell tumors given their hypercellularity and
scant cytoplasm. They are WHO grade IV tumors.
(E) Chordomas are low-grade tumors distinguished
by the pathological finding of physaliphorous cells.

Question 10

Q

What syndrome is associated with tumors in the
optic/visual pathways with histology demonstrating Rosenthal fibers?
A. Von Hippel–Lindau
B. Neurofibromatosis type 1
C. Neurofibromatosis type 2
D. Tuberous sclerosis
E. Sturge-Weber

Answer

A

B. Neurofibromatosis type 1

Neurofibromatosis type 1 is associated with
optic gliomas (usually pilocytic in nature) in which
histology can demonstrate Rosenthal fibers. These
fibers also are seen in Alexander disease and in
areas of gliosis. (A) Von Hippel–Lindau disease is
associated with hemangioblastomas, which are
the most common primary tumors of the posterior
fossa. Hemangioblastomas do occur in the retinae. (C) Neurofibromatosis type 2 is associated
with bilateral vestibular schwannomas and the
MISME syndrome (multiple inherited schwannomas, meningiomas, and ependymomas). Patients
can have retinal hamartomas. (D) Tuberous sclerosis is associated with subependymal giant cell
astrocytomas and cortical tubers. Retinal tumors
(hamartomas) can occur. (E) Sturge-Weber syndrome is associated with cortical atrophy and calcifications, an ipsilateral port-wine facial nevus,
meningeal venous proliferation, and contralateral
seizures. Patients can have retinal angiomas.

Question 11

Q

The sellar mass shown in this image, if hormonally
active, most likely secretes:
A. Adrenocorticotrophic hormone
B. Follicle-stimulating hormone
C. Growth hormone
D. Prolactin
E. Vasopressin

Answer

A

D. Prolactin

The pituitary adenoma is characterized by a
monomorphic proliferation of cells. The most common secreting adenoma is prolactinoma, followed
by growth hormone adenoma.

Question 12

Q

The eosinophilic cytoplasmic inclusion shown in
this image of a patient with Alzheimer disease represents what histological entity?
A. Amyloid body
B. Granulovacuolar degeneration
C. Hirano body
D. Lewy body
E. Neurofibrillary tangle

Answer

A

C. Hirano body

Hirano bodies are eosinophilic cytoplasmic
inclusions within neurons. They are composed of
actin, and have a paracrystalline appearance with
electron microscopy. (A) Amyloid usually does not
accumulate in the cytoplasm of neurons. (B) Evidence of granulovacuolar degeneration (small dark
dots inside a vacuole in the cytoplasm of neurons)
also is seen in this field. (D) Lewy bodies typically
are seen in Parkinson disease. (E) Neurofibrillary
tangles are elongated, filamentous, cytoplasmic
inclusions in neurons in Alzheimer disease.

Question 13

Q

A 65-year-old man has diffuse muscle wasting with
spasticity, slowed movements, and muscle cramping. The section shown in this image was taken
from the anterior horn cell region of the lumbar
spinal cord. The most likely diagnosis is:
A. Amyotrophic lateral sclerosis
B. Multiple system atrophy
C. Spinal muscular atrophy type 1
D. Spinal muscular atrophy type 2
E. Syphilis

Answer

A

A. Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is marked by a loss
of neurons in the anterior horn cell region as seen
in the image accompanying the question. Patients
often have symptoms of both upper and lower
motor neuron disease. (C, D) The spinal muscular
atrophies (types I and 2) may show a pathology
similar to that of amyotrophic lateral sclerosis
but present earlier in life (childhood or infancy).
(E) Degeneration of the posterior columns is the
hallmark of tabes dorsalis associated with syphilis.

Question 14

Q

A germinal matrix hemorrhage with intraventricular hemorrhage and ventricular enlargement represents what grade of lesion?
A. Grade 1
B. Grade 2
C. Grade 3
D. Grade 4
E. Grade 5

Answer

A

C. Grade 3

Germinal matrix hemorrhages are a complication of prematurity. Grade 3 germinal matrix
hemorrhages show rupture of the blood from the
germinal matrix into the ventricles with ventricular expansion. (A) Grade 1 germinal matrix hemorrhages are limited to the germinal matrix. (B) Grade
2 germinal matrix hemorrhages show rupture of
the blood from the germinal matrix into the ventricles without ventricular expansion. (D) Grade 4
germinal matrix hemorrhages show intraventricular hemorrhage and hemorrhage into hemispheric
parenchyma (periventricular venous infarct). Parenchymal involvement is worse than ventricular
involvement because the latter can be treated with
cerebrospinal fluid diversion. (E) Grade 5 germinal
matrix hemorrhages do not exist in this schema.

Question 15

Q

Small, round, eosinophilic neuronal cell inclusions
known as Bunina bodies are associated with what
disease?
A. Alzheimer disease
B. Amyotrophic lateral sclerosis
C. Huntington chorea
D. Machado-Joseph disease
E. Olivopontocerebellar atrophy of Menzel

Answer

A

B. Amyotrophic lateral sclerosis

Bunina bodies are a feature of amyotrophic lateral sclerosis and are seen in areas of neuronal loss
in the anterior horn cell region of the spinal cord.
(A) Hirano bodies are eosinophilic cytoplasmic
inclusions within neurons seen in patients with
Alzheimer disease. (C–E) Prominent neuronal
inclusions typically are not seen in Huntington
chorea, Machado-Joseph disease, or olivopontocerebellar atrophy of Menzel.

Question 16

Q

A bruise of the skin and underlying tissue on the
scalp with hemorrhage defines a(n)
A. Abrasion
B. Avulsion
C. Contusion
D. Laceration
E. Scrape

Answer

A

C. Contusion

A contusion is defined as a bruise when referring to skin and soft issue. In the brain, a contusion
translates into an infarct secondary to trauma.
(A) An abrasion represents a scrape of the skin (i.e.,
a surface injury). (B) An avulsion is a large tear of
the tissue creating a tissue flap. (D) A laceration is
the result of blunt force injury causing a tear in the
skin and underlying soft tissues.

Question 17

Q

What immunohistochemical profile is most consistent with metastatic melanoma, shown in this
image?
A. Epithelial membrane antigen and cytokeratin
AE1/3 positivity
B. Glial fibrillary acidic protein and S-100 protein
positivity
C. Melan-A and HMB-45 positivity
D. S-100 protein and progesterone receptor
positivity
E. TTF-1 and synaptophysin positivity

Answer

A

C. Melan-A and HMB-45 positivity

Melanomas stain with antibodies to S-100 protein, melan-A (MART 1), and HMB-45 and do not
stain with the other antibodies listed as options.

Question 18

Q

The neoplasm shown in this image arises from what
cellular origin?
A. Chondrocytes
B. Ependymal cells
C. Epithelial cells
D. Nevoid cells
E. Notochord remnants

Answer

A

E. Notochord remnants

The tumor shown in the image accompanying
the question represents a chordoma. It contains
epithelioid cells with a vacuolated cytoplasm arranged against a chondromyxoid-like stroma. These
tumors arise from notochordal remnants, especially
in the clival or the sacrococcygeal regions.

Question 19

Q

A biopsy is taken targeting a midline mass. The
frozen section appearance of the biopsy is shown
in this image. The best diagnosis for the frozen section is:
A. Normal hypothalamus
B. Normal neurohypophysis
C. Normal pineal gland
D. Optic chiasm
E. Pilocytic astrocytoma

Answer

A

C. Normal pineal gland

The tissue sample shown in the image accompanying the question demonstrates a vaguely lobular
arrangement of cells against a fibrillary-type background, consistent with normal pineal gland tissue.
Calcifications commonly are seen in the gland.
Occasionally, gliotic cysts, sometimes with Rosenthal fibers, also are present.

Question 20

Q

This fontal convexity mass shown in this image is
thought to represent an eosinophilic granuloma.
The best stain to prove that the macrophage cells
are Langerhans histiocytes is one staining:
A. CD1a
B. CD15
C. CD45RB
D. CD68
E. HAM56

Answer

A

A. CD1a

CD1a is the best and most specific stain to highlight Langerhans histiocytes. By electron microscopy, these cells contain Birbeck granules (likened
to tennis rackets). (D, E) CD68 and HAM56 are
macrophage markers that are not specific for
Langerhans cells.

Question 21

Q

The paraspinal soft tissue mass shown in this image
was diagnosed as a granular cell tumor. The granular quality of the cytoplasm is due to an increased
number or amount of:
A. Endoplasmic reticulum
B. Lysosomes
C. Mitochondria
D. Neurofilaments
E. Ribosome

Answer

A

B. Lysosomes

The cytoplasmic granularity of the tumor shown
in the image accompanying the question is due to
an increased number of large lysosomes.

Question 22

Q

The cerebellopontine angle mass shown in this
image is associated with alterations in what gene?
A. NF2
B. TP53
C. PTEN
D. SOD1
E. TSC2

Answer

A

A. NF2

The tumor shown in the image accompanying
the question represents a schwannoma. Tumor cells
typically are elongated with pointed nuclear ends.
The pleomorphism displayed represents what is
sometimes referred to as “ancient change,” which
does not impact prognosis. Schwannomas are
associated with neurofibromatosis type 2 and may
show alterations in the NF2 gene. (B) TP53 gene
mutations are seen in Li-Fraumeni syndrome.
(C) PTEN gene mutations are observed in a variety
of cancers including secondary glioblastomas.
(D) SOD1 gene mutations occur in apoptosis and amyotrophic lateral sclerosis. (E) TSC2 gene mutations are seen in tuberous sclerosis.

Question 23

Q

What type of metastatic brain tumor generally is
considered radiosensitive to whole brain radiation
therapy?
A. Thyroid
B. Renal
C. Melanoma
D. Breast
E. Sarcoma

Answer

A

D. Breast

(A–E) Each of these tumors generally is described
as being highly resistant to radiation therapy, with
the exception of breast cancer, which is moderately
sensitive. Highly sensitive tumors include small
and germ cell tumors, lymphoma, leukemia, and
multiple myeloma.

Question 24

Q

A 32-year-old man with mental retardation and a
history of seizures presents for resection of a tumor
associated with hydrocephalus. Histology shows
fibrillary areas alternating with large cells containing generous amounts of eosinophilic cytoplasm.
On what chromosome(s) can abnormalities associated with this disease be found?
A. Chromosome 17p
B. Chromosomes 9q and 16p
C. Chromosomes 1p and 19q
D. Chromosomes 3q, 7q, and 7p
E. Chromosome 15

Answer

A

B. Chromosomes 9q and 16p

Tuberous sclerosis is an autosomal dominant disease characterized by seizures, mental retardation,
and sebaceous adenomas; 10 to 15% of patients
present with subependymal giant cell astrocytomas, which occur at the foramen of Monro and can
cause hydrocephalus. Pathology of the subependymal giant cell astrocytomas shows large cells with
abundant cytoplasm and prominent nucleoli. Vascular proliferation and necrosis can be seen without being suggestive of a more malignant tumor.
(A) Chromosome 17p is associated with TP53 gene
mutations. Li-Fraumeni syndrome is characterized by TP53 mutations and is associated with a
25 times increased risk for developing malignant
tumors by age 50. (C) Chromosome 1p and 19q
deletions can be seen in oligodendrogliomas, and
these mutations often predict a better response to
chemotherapy with a longer tumor-free survival.
(D) Chromosomes 3 and 7 are associated with the
development of cavernomas. (E) Chromosome 15
is associated with Angelman and Prader-Willi
syndromes, characterized by seizures and mental
retardation but not tumors.

Question 25

Q

The lesion shown in this image is best classified
as a(n):
A. Craniopharyngioma
B. Colloid cyst
C. Dermoid cyst
D. Endodermal cyst
E. Epidermoid cyst

Answer

A

C. Dermoid cyst

The cyst lining is characterized by squamous
epithelium and shows evidence of skin adnexal
structures in the cyst wall that may include structures such as sebaceous glands, apocrine glands,
hair, or eccrine glands. These findings are consistent with a dermoid cyst.

Question 26

Q

The tumor shown in this image represents what
pathology?
A. Chondroma
B. Chondrosarcoma
C. Chordoid meningioma
D. Chordoma
E. Teratoma

Answer

A

B. Chondrosarcoma

The tumor shown in the image accompanying
the question is marked by a malignant spindled
cell component next to an atypical cartilaginous
component, consistent with a chondrosarcoma.

Question 27

Q

A 7-year-old previously healthy girl presented with
progressive ataxia and palsy of cranial nerves VI
and VII. Representative scans from an MRI study
are shown in these images. What is a characteristic
of this entity?
A. There is a high incidence of distal metastases.
B. Hydrocephalus is an early complication.
C. Most pontine tumors have high-grade histology.
D. Calcifications frequently are identified

Answer

A

C. Most pontine tumors have high-grade histology.

The axial T2 and contrast-enhanced T1-weighted
images demonstrate a nonenhancing, infiltrative,
expansile lesion involving the pons, most compatible with a diffuse infiltrative pontine glioma. These
lesions are more common in children than in
adults. Histologically, they may originate from astrocytes, oligodendrocytes, or ependymal cells, but
the great majority (95%) are astrocytic. Most brainstem gliomas arise in the pons, and most pontine
tumors have a high-grade histology, being either
anaplastic astrocytomas or glioblastomas. In contrast, tumors arising in the tectum and cervicomedullary junction as well as those that are cystic
or exophytic usually are low grade. Enhancement
is variable. Prognosis usually is poor, even for presumed low-grade histologies. (A) Diffuse intrinsic
pontine gliomas are aggressive lesions, but they
rarely metastasize to distant sites. Instead, they
tend to infiltrate along anatomic fiber tracts and
can extend cranially to involve the midbrain and
thalami. (B) Hydrocephalus is a late complication
of diffuse intrinsic pontine gliomas, and is more
commonly seen in tectal lesions. (D) Calcifications
are unusual in diffuse intrinsic pontine gliomas.

Question 28

Q

The dural-based, glial fibrillary acidic protein (GFAP)
negative mass shown in this image represents a(n):
A. Chondrosarcoma
B. Gliosarcoma
C. Hemangiopericytoma
D. Metaplastic meningioma
E. Osteosarcoma

Answer

A

E. Osteosarcoma

The malignant tumor shown in the image accompanying the question is marked by bone formation
(the dark purple material). Osteosarcoma is the
best diagnosis for this tumor. These lesions rarely
may represent a primary tumor arising in the
meninges or skull or distant metastatic disease.
(A) Chondrosarcomas contain atypical cartilage
within the tumor. (B) Glial fibrillary acidic protein
(GFAP) negativity rules out a gliosarcoma. (C) Hemangiopericytomas often are malignant meningeal
tumors that lack bone formation. (D) Metaplastic
meningiomas are benign tumors marked by meningothelial cells intermixed with benign mesenchymal tissue such as bone or cartilage.

Question 29

Q

On the histological level, the morphological changes
of hypoxic ischemia typically are first observed how
soon after the precipitating event?
A. 3 hours
B. 6 hours
C. 12 hours
D. 36 hours
E. 48 hours

Answer

A

C. 12 hours

The earliest changes indicating ischemic damage
are apparent in neuronal cells at 12 to 24 hours
after the precipitating event. The cells shrink in
size, acquire cytoplasmic hypereosinophilia, and
show nuclei shrinkage (the “red and dead” look).

Question 30

Q

The chromogranin positive staining mass shown in
this image is most likely to arise in what location?
A. Cerebellum
B. Filum terminale
C. Frontal lobe
D. Lateral ventricle
E. Pons

Answer

A

B. Filum terminale

The tumor shown in the image accompanying
the question represents a paraganglioma, which
generally is marked by cells arranged in loose
nests (zellballen). The nests of cells are delimited
by spindled, S-100–positive staining sustentacular
cells. The tumor cells in the nests stain with neural markers such as chromogranin and neuronspecific enolase. In the central nervous system,
paragangliomas most commonly arise in the spinal
cord region.

Question 31

Q

The lytic skull lesion shown in this image was
biopsied in a 72-year-old man who also has a history of recently developing renal failure. The lesion
most likely will stain with what antibody?
A. CD3
B. CD5
C. CD45
D. CD79
E. CD138

Answer

A

E. CD138

The lesion shown in the image accompanying the
question is composed of plasma cells and represents a plasma cell dyscrasia. CD138 is an antibody
that targets plasma cells. These lesions typically
demonstrate evidence of monoclonality with either
kappa or lambda immunostaining.

Question 32

Q

What is the most common site of origin of the cystic mass shown in this image?
A. Cerebellopontine angle
B. Foramen of Monro
C. Lumbar cord
D. Temporal lobe
E. Sella

Answer

A

A. Cerebellopontine angle

This simple squamous epithelial-lined cyst represents an epidermoid cyst. It lacks the adnexal
structures that mark a dermoid cyst. Epidermoid
cysts most commonly arise in the cerebellopontine
angle region.

Question 33

Q

A tear in the middle meningeal artery is most likely
responsible for a hemorrhage in what space or
location?
A. Epidural space
B. Intraventricular space
C. Subarachnoid space
D. Subdural space
E. Thalamus

Answer

A

A. Epidural space

Over 90% of epidural hemorrhages are associated with a skull fracture and are associated with
a torn middle meningeal artery. Less commonly,
epidural hemorrhages result from a dural sinus
tear or a tear in the middle meningeal vein.

Question 34

Q

How long after a diffuse axonal injury can dystrophic axons be visualized with β-amyloid precursor
protein staining?
A. 2 hours
B. 4 hours
C. 8 hours
D. 12 hours
E. 24 hours

Answer

A

A. 2 hours

Usually within 2 hours of diffuse axonal injury,
axonal swelling can be visualized with β-amyloid
precursor protein immunostaining.

Question 35

Q

The pathological findings seen in the vastus lateralis muscle shown in this image from a 32-year-old
woman are consistent with what pathology?
A. Dermatomyositis
B. Inclusion body myositis
C. Polyarteritis nodosum
D. Polymyositis
E. Sarcoidosis

Answer

A

A. Dermatomyositis

The biopsy shown in the image accompanying
the question demonstrates predominantly perivascular-based chronic inflammation and atrophy
around the perimeter of the muscle fascicles (perifascicular atrophy). Perifascicular atrophy in the
setting of an inflammatory myopathy is highly
suggestive of dermatomyositis.

Question 36

Q

The muscle shown in this image is from a 4-year-old
boy who has proximal muscle weakness, a positive
Gower sign, and calf muscle hypertrophy. Abnormal staining with what antibody is anticipated?
A. Dysferlin
B. Dystrophin
C. Merosin
D. Sarcoglycan alpha
E. Spectrin

Answer

A

B. Dystrophin

The clinical history is suggestive of Duchenne
muscular dystrophy. The biopsy is marked by a
prominent variation in muscle fiber size with
increased endomysial fibrosis. One would anticipate an absence of membrane staining with dystrophin antibody in this case.

Question 37

Q

This right temporal lobe cyst shown in this image
is classified best as a(n):
A. Arachnoid cyst
B. Choroid plexus cyst
C. Cystic meningioma
D. Ependymal cyst
E. Epidermoid cyst

Answer

A

A. Arachnoid cyst

The cyst shown is lined by a thin layer of meningothelial cells or arachnoid cap cells, consistent
with an arachnoid cyst.

Question 38

Q

A 72-year-old man presents with muscle weakness,
atrophy, and a biopsy shown in this image. The
pathological process is likely to respond to what
therapy?
A. Statins
B. Intravenous IgG
C. Methotrexate
D. Steroids
E. No available therapies

Answer

A

E. No available therapies

The pathological findings shown in the image
accompanying the question are consistent with inclusion body myositis. The biopsy shows inflammation, a variation in muscle fiber size, and rimmed
vacuoles (vacuoles with basophilic granularity).
Currently, there is no known effective treatment
for inclusion body myositis.

Question 39

Q

The findings in the NADH-stained section of skeletal muscle shown in this image are associated with
what underlying pathological process?
A. CCTG repeats
B. Loss of myosin filaments
C. Mitochondrial myopathy
D. Nemaline rod myopathy
E. Ryanodine receptor gene mutation

Answer

A

E. Ryanodine receptor gene mutation

The findings in the biopsy illustrate a core myopathy, one of the congenital myopathies marked by
a focal decrease in oxidative activity as manifested
by the staining pattern. The condition generally is
inherited as an autosomal dominant condition and
is associated with mutations in the ryanodine receptor gene. There is an association of this condition with malignant hyperthermia.

Question 40

Q

A 2-year-old boy presents with vacuolar changes
on muscle biopsy. The vacuoles are filled with glycogen and stain with acid phosphatase, as shown
in this image. The patient’s most likely diagnosis is:
A. Acid maltase deficiency
B. Debrancher enzyme deficiency
C. Hypokalemic periodic paralysis
D. Myophosphorylase deficiency
E. Phosphofructokinase deficiency

Answer

A

A. Acid maltase deficiency

Glycogen-filled vacuoles suggest a glycogen storage disease. Acid maltase deficiency is the only one
of the glycogenoses that is lysosomal associated
and stains with acid phosphatase (a lysosomal associated enzyme).

Question 41

Q

What protein is unlikely to form cerebral amyloid?
A. Cystatin C
B. Gelsolin
C. Kappa light chain protein
D. Prion protein

Answer

A

C. Kappa light chain protein

Most of the amyloid encountered in the brain
is β-amyloid. Less commonly, other proteins may
arrange themselves in a β-pleated sheet configuration to form amyloid. Kappa light chain protein is
unlikely to deposit in the brain. (A) Cystatin C is a
serum indicator of kidney function and may be involved in Alzheimer amyloid. (B) Gelsolin is a regulator of actin filament assembly/disassembly and
is associated with β-amyloid formation in the brain.
(D) Prion protein causes spongiform encephalopathy

Question 42

Q

A CAG trinucleotide repeat in what gene is associated with Huntington disease?
A. Ataxin-2 gene
B. CACNAIA gene
C. Chorein gene
D. HTT gene
E. Myotonin gene

Answer

A

D. HTT gene

The trinucleotide repeat in the HTT gene that
encodes the huntingtin protein is associated with
Huntington disease. The normal CAG repeat length
is up to 35 repeats, whereas in Huntington disease,
there are 36 or more repeats. (A, B) Ataxin-2 and
CACNA1A gene repeats are associated with forms
of hereditary spinocerebellar ataxia. (C) Chorein
gene alterations are associated with a rare condition known as neuroacanthocytosis. (E) The myotonin gene is implicated in myotonic dystrophy.

Question 43

Q

The pathology illustrated with the Bielschowsky
stain shown in this image is encountered most
commonly in what disease process?
A. Alzheimer disease
B. Diffuse Lewy body disease
C. Ganglioglioma
D. Mitochondrial encephalopathy
E. Pick disease

Answer

A

A. Alzheimer disease

The globular, extracellular structures highlighted
with the silver stain represent senile plaques and
are associated most classically with Alzheimer disease. Current pathological diagnostic criteria rely
on plaque and neurofibrillary tangle counts as well
as an assessment of the distribution of amyloid
deposition. Plaques are composed variably of neuritic processes (highlighted with the silver stain),
amyloid, and associated microglial cells.

Question 44

Q

An antibody for what protein best highlights the
structures shown in this Bielschowsky stain image?
A. α-synuclein
B. Congo red
C. Glial fibrillary acidic protein
D. Tau
E. Thioflavin S

Answer

A

D. Tau

The dark-staining, elongated structures located
within the cytoplasm of neurons represent neurofibrillary tangles. They can be highlighted with tau
immunostaining. (A) α-synuclein is a good stain to
highlight Lewy bodies. (B, E) Congo red and thioflavin S stains highlight amyloid.

Question 45

Q

What tumor pathology consists of tumor cells
forming cuffs around blood vessels?
A. Germinoma
B. Ependymoma
C. Chordoma
D. Lymphoma
E. Hemangioblastoma

Answer

A

D. Lymphoma

Lymphomas often are B cell in origin and are
identified by white blood cells with angiocentric
growth patterns forming perivascular cuffs by
tumor cells. (A) Germinomas show large, epithelioid cells with abundant PAS-positive cytoplasm.
The cells have irregular nuclei that may have
prominent nests of lymphocytes with occasional
granulomatous inflammation. (B) Ependymomas
classically have dark, small nuclei with perivascular
and true rosettes. (C) Chordomas characteristically are described by physaliphorous cells and represent
a remnant of the nucleus pulposus. (E) Hemangioblastomas have numerous capillary channels lined
by a single layer of endothelium surrounded by
reticulin.

Question 46

Q

The presence of xanthochromia, high protein, and
clotting of the cerebrospinal fluid is referred to as:
A. Queckenstedt syndrome
B. Coup de poignard of Michon
C. Froment sign
D. Froin syndrome
E. Foix-Alajouanine

Answer

A

D. Froin syndrome

Froin syndrome is stagnation of the cerebrospinal fluid (CSF) from an inflammatory or neoplastic lesion, causing increased exudation from the
tumor itself and activation of coagulation factors.
(A) A positive Queckenstedt test is a failure of jugular vein compression to increase CSF pressure,
which it will normally do in the absence of a block
of the venous outflow. (B) Coup de poignard of Michon is sudden excruciating back pain with subarachnoid hemorrhage in patients with a spinal
vascular malformation. (C) A positive Froment sign
(during an evaluation of the ulnar nerve) occurs
when a patient is unable to grasp a sheet of paper
between his thumb and extended index finger and
will instead pinch the paper, as the action of the
weak adductor pollicis (ulnar innervated) is substituted for the action of the strong flexor pollicis
longus (anterior interosseous innervated). (E) FoixAlajouanine is an acute/subacute neurologic deterioration without hemorrhage in patients with a
spinal vascular malformation.

Question 47

Q

The cyst shown in this image is situated near the
foramen of Monro. What is an unlikely presenting
symptom for the most likely lesion?
A. Headache
B. Incontinence
C. Personality change
D. Seizure
E. Sudden death

Answer

A

D. Seizure

The epithelial-lined cyst shown in the image accompanying the question represents a colloid cyst.
Seizures are not an expected presenting symptom.
(A, B, E) Headaches, incontinence, and even sudden
death can occur with the development of hydrocephalus secondary to colloid cysts, especially if a
“ball-valving” phenomenon occurs.

Question 48

Q

The eosinophilic deposits shown in this image
represent amyloid accumulation in a patient with
suspected Alzheimer disease. What is the single
best stain to prove the diagnosis?
A. β-amyloid
B. Luxol fast blue
C. Mucicarmine
D. Prussian blue
E. Trichrome

Answer

A

A. β-amyloid

β-amyloid is the best and most specific stain for
the type of amyloid that accumulates in patients
with Alzheimer disease. (B) Luxol fast blue is a
myelin stain. (C) Mucicarmine stains mucin such
as in an adenocarcinoma. (D) Prussian blue is an
iron stain. (E) Trichrome highlights connective tissue and collagen.

Question 49

Q

A lesion with a vascular nature is resected, and the
pathology lab reports that the lesion is consistent
with a vascular hamartoma with irregular thickand thin-walled sinusoidal vascular channels without intervening brain tissue. What is the diagnosis
for this lesion?
A. Capillary telangiectasia
B. Cavernous malformation
C. Venous angioma
D. Arteriovenous malformation
E. Dural arteriovenous fistula

Answer

A

B. Cavernous malformation

Cavernous malformations appear on MRI with
hemosiderin and a “popcorn-like” appearance,
with irregular thick- and thin-walled sinusoidal vascular channels without intervening neural parenchyma, large feeding arteries, or draining veins.
(A) Microscopically, capillary telangiectasias have
slightly enlarged capillaries with low flow and intervening neural tissue. (C) Venous malformations
(venous angiomas, also known as developmental
venous anomalies) are abnormal veins draining
normal brain. They often present as a starburst
pattern (caput medusa on angiogram) and are
associated with cavernomas. (D) Arteriovenous malformations appear as tangles of abnormal vessels
of various diameters separated by gliotic tissue
without an intervening capillary bed. There may
be evidence of prior hemorrhage. (E) Dural arteriovenous fistulas are true arteriovenous shunts
within the leaflets of the dura matter and usually
are found adjacent to dural sinuses.

Question 50

Q

Sturge-Weber disease is inherited in what fashion?
A. Autosomal dominantly
B. Autosomal recessively
C. X-linked recessively
D. Sporadically with no obvious genetic
transmission

Answer

A

D. Sporadically with no obvious genetic

Sturge-Weber disease has no known genetic
transmission and is characterized by a facial nevus
in the ophthalmic division of the trigeminal nerve,
along with leptomeningeal venous angiomas and
intracortical tram-track calcifications.

Question 51

Q

The cytoplasmic inclusion shown in this image is
most likely associated with a mutation in what gene?
A. SNCA
B. PARK1
C. PARK2
D. PARK5
E. PARK8

Answer

A

A. SNCA

The neuron displayed with the eosinophilic cytoplasmic inclusion also has brown melanin pigment
in its cytoplasm, with these components representing a Lewy body. α-synuclein (encoded by the
SCNA gene) is the best stain for highlighting Lewy
bodies. The most common gene to be affected in
familial cases of Parkinson disease is the SCNA
gene. Less commonly, alterations in the various
PARK genes have been described in the disease.

Question 52

Q

A man presents for genetic counseling with deafness, skeletal abnormalities, mental retardation,
and coarse facial features. He is found to have an
autosomal recessive mucopolysaccharidosis. What
is the patient’s enzyme deficiency?
A. L-iduronidase
B. Iduronate sulfatase
C. Galactose 6-sulfatase and β-galactosidase
D. Sulfatase B
E. β-glucuronidase

Answer

A

A. L-iduronidase

The described patient has Hurler syndrome.
(B) Iduronate sulfatase deficiency (Hunter syndrome) causes symptoms similar to those seen in
Hurler syndrome, except that Hunter syndrome is
milder, without mental retardation, with minimal
corneal involvement, slower progressing, and with
a life span into adulthood. (C) Galactose 6-sulfatase
and β-galactosidase deficiencies (Morquio syndrome) are inherited in an autosomal recessive
manner and are characterized by severe skeletal
abnormalities, ligamentous laxity, dwarfism, myelopathy, and a lack of mental retardation. (D) Sulfatase B deficiency (Maroteaux-Lamy) presents with
carpal tunnel syndrome, valvular heart disease, and
without mental retardation. (E) β-glucuronidase
deficiency is inherited in an autosomal recessive
manner and is characterized by moderate mental
retardation, corneal clouding, hydrocephalus, hepatosplenomegaly, and various bony changes.

Question 53

Q

Klippel-Feil syndrome is associated with what common findings?
A. Low posterior hairline, brevicollis, and
decreased neck motion
B. Sebaceous adenomas, mental retardation, and
seizures
C. Anorectal malformation, anterior sacral
defects, and presacral masses
D. Dementia, urinary incontinence, and gait
instability

Answer

A

A. Low posterior hairline, brevicollis, and
decreased neck motion

Klippel-Feil syndrome is a congenital fusion of
two or more cervical vertebrae due to the failure
of normal segmentation of cervical somites that
is characterized by a low posterior hairline, shortened neck, and limitations in neck motion. The
condition also can be associated with scoliosis,
torticollis, pterygium colli (neck webbing), and
Sprengel deformity (inability to raise the scapula).
(B) Sebaceous adenomas, mental retardation, and
seizures represent a triad associated with tuberous sclerosis. (C) Anorectal malformation, anterior
sacral defects, and presacral masses are seen in the
Currarino triad, which typically presents with constipation secondary to the anorectal malformation. (D) Dementia, urinary incontinence, and gait
instability are seen in conjunction with normal
pressure hydrocephalus.

Question 54

Q

Axonal spheroids are seen with what neurologic
pathology?
A. Friedreich ataxia
B. Huntington disease
C. Cerebral infarction
D. Amyotrophic lateral sclerosis

Answer

A

D. Amyotrophic lateral sclerosis

Axonal spheroids are seen in amyotrophic lateral
sclerosis, diffuse axonal injury, and HallervordenSpatz disease.

Question 55

Q

The best diagnosis for the mucin and glial fibrillary
acidic protein (GFAP)-positive spinal cord mass
shown in this image, presenting in a 33-year-old
man with a 4-year history of lower back pain, is:
A. Meningioma
B. Metastatic adenocarcinoma
C. Myxopapillary ependymoma
D. Paraganglioma
E. Schwannoma

Answer

A

C. Myxopapillary ependymoma

The findings are most consistent with a myxopapillary ependymoma (WHO grade I). (A, D, E)
These tumor types often are in the differential diagnosis due to location rather than histomorphology. (B) Metastatic adenocarcinomas also can be
mucin positive but would be unusual in such a
young patient and are generally glial fibrillary acidic
protein negative.

Question 56

Q

The Prussian blue stain shown in this image highlights increased iron accumulation in a patient with
a PANK2 gene mutation. The iron accumulation
most commonly is seen in what location in the
central nervous system?
A. Basal ganglia
B. Cerebellum
C. Cervical and lumbar spinal cord
D. Hippocampus
E. Pons

Answer

A

A. Basal ganglia

PANK2 gene mutations are associated with neuronal degeneration with brain iron accumulation (formerly known as Hallervorden-Spatz disease).
The increased iron accumulation preferentially
deposits in the basal ganglia region and is accompanied by neuronal loss and gliosis.

Question 57

Q

A 22-year-old woman with seizures for 12 years
has hippocampal sclerosis pathology, as shown in
this image. What two regions of the hippocampus
usually are affected most severely?
A. CA1 and CA2
B. CA1 and CA3
C. CA1 and CA4
D. CA2 and CA4
E. CA3 and CA4

Answer

A

C. CA1 and CA4

In hippocampal sclerosis, the most severely involved areas are the CA1 and CA4 regions; however, neuronal loss may be present in any of the
hippocampal regions.

Question 58

Q

Multisystem atrophy (cerebellar predominant type)
is characterized by what pathological or clinical
finding?
A. Atrophy of the putamen
B. Dysautonomia
C. Neuronal loss in the striatonigral system
D. Rigidity and dystonia
E. Ubiquitin positive tangles

Answer

A

B. Dysautonomia

Dysautonomia is a feature present in multisystem atrophy in both the parkinsonian and cerebellar predominant types. The cerebellar type usually
presents with gait and limb ataxia, dysarthria, and
oculomotor disturbances. It is marked by atrophy
of and loss of neurons in the cerebellum, middle
cerebellar peduncles, and pons. Ubiquitin and tau
immunoreactive glial cytoplasmic inclusions may
be seen.

Question 59

Q

A mutation in what gene is associated with 20% of
familial cases of amyotrophic lateral sclerosis?
A. PTEN
B. SMN1
C. SMN2
D. SOD1
E. TARDBP

Answer

A

D. SOD1

Ten percent of patients with amyotrophic lateral
sclerosis have an autosomal dominant pattern of
familial disease. Twenty percent of familial cases
are due to a mutation in the gene encoding the
Cu/Zn superoxide dismutase 1 protein on chromosome 21. Less commonly, familial cases have been
associated with mutations in the TARDBP gene on
chromosome 1.

Question 60

Q

The optic nerve shown in this image was sampled
at autopsy. The most likely pathology observed is:
A. Cytomegalovirus infection
B. Diffuse astrocytoma
C. Fungal infection
D. Pilocytic astrocytoma
E. Sarcoidosis

Answer

A

A. Cytomegalovirus infection

The occasional large cells marked by prominent
intranuclear inclusions are suggestive of a viral
infection (e.g., cytomegalovirus). A few of the large
cells also have small, brightly eosinophilic cytoplasmic inclusions as well, which sometimes can
be encountered with cytomegalovirus infection.

Question 61

Q

The vascular changes seen in the recurrent glioblastoma shown in this image are most likely due
to what process?
A. Amyloid accumulation
B. Chemotherapy effects
C. Radiation effects
D. Tumor involution
E. Tumor progression

Answer

A

C. Radiation effects

The thickened or sclerosed appearance of the
blood vessels in this case is typical of the vascular
changes observed following radiation therapy. Sometimes these changes are accompanied by chronic
inflammatory cells and necrosis of the adjacent tissue with infiltration by macrophages.

Question 62

Q

This lesion shown in this image most commonly
arises in what central nervous system location?
A. Cervical spinal cord
B. Fourth ventricle
C. Frontal lobe
D. Lumbosacral spinal cord
E. Temporal lobe

Answer

A

B. Fourth ventricle

The low-grade tumor shown in the image accompanying the question is marked by loose aggregates
of tumor cell nuclei with intervening hypocellular
zones. Microcysts frequently are present in this
tumor. These pathological findings are consistent
with a subependymoma (WHO grade I). Although
they can arise in the spinal cord, the fourth ventricle is a more common site.

Question 63

Q

The lateral ventricular mass shown in this image,
presenting in a 26-year-old woman, is associated
with what mutation or disease?
A. Notch3 mutation
B. PTEN mutation
C. Tuberous sclerosis
D. Turcot syndrome
E. Von Hippel–Lindau disease

Answer

A

C. Tuberous sclerosis

As its name suggests, large astrocytic cells compose this intraventricular subependymal giant cell
astrocytoma. This tumor sometimes is associated
with tuberous sclerosis along with subependymal
hamartomas and cortical tubers.

Question 64

Q

The IDH-1–positive staining tumor shown in this
image also is likely to show what characteristic?
A. ATRX protein staining
B. Chromosome 10p deletion
C. EGFR protein staining
D. P53 protein staining
E. PTEN protein mutation

Answer

A

A. ATRX protein staining

Oligodendrogliomas generally show retention of
ATRX protein staining (in contrast to a subset of
diffuse astrocytomas).

Answer 65

A

D. Deletion on chromosome 1p

Prognosis for anaplastic oligodendrogliomas is
best predicted by looking for large deletions on chromosomes 1p and 19q. The deletions are thought by
many to be part of the definition of these tumors.
Although high mitotic count and cell proliferation
indices and necrosis are associated with higher
grade oligodendrogliomas, the chromosome deletions are more predictive of chemoresponsiveness
and outcome.

Answer 66

A

B. IDH-1

IDH-1 antibody does not stain reactive or inflammatory lesions including gliosis. A subset of diffuse
or fibrillary astrocytomas and most oligodendrogliomas stain with IDH-1 antibody. (A, E) GFAP and
S-100 antibodies stain astrocytes in both processes.
(C) More cells stain with Ki-67, a cell proliferation
marker in astrocytomas versus gliosis; however,
there is significant overlap in the ranges of observed labeling indices with Ki-67 in both processes,
so it has little value unless the labeling index is
moderately high. (D) Only widespread positivity
with p53 antibody would be useful in indicating
a tumor, as low levels of staining may be seen in
both processes and is nonspecific.

Answer 67

A

D. B12

A deficiency in vitamin B12 (cobalamin) can
result in degeneration of the posterior columns of
the spinal cord, referred to as subacute combined
degeneration. The lateral columns of the upper
thoracic and lower cervical spinal cord also may
be involved. (A) Vitamin B1 (thiamine) deficiency
can lead to Wernicke encephalopathy, Korsakoff
psychosis, or Beriberi. (B) Vitamin B2 (riboflavin)
deficiency can cause stomatitis and a red, scaly
rash. (C) Vitamin B6 (pyridoxine) deficiency is
associated with isoniazid and hydralazine use, and
causes lower limb paresthesias, pain, and weakness. (E) Vitamin C deficiency results in scurvy,
with early symptoms of malaise, lethargy, and
painful gums.

Answer 68

A

A. BRAF

This astrocytic tumor is marked by the presence
of clustered eosinophilic material known as eosinophilic granular bodies. This finding is suggestive
of a pilocytic astrocytoma, which sometimes is associated with BRAF gene alterations. (B–D) Alterations in these genes generally are not encountered
in pilocytic astrocytomas and are more common in
diffuse or fibrillary astrocytomas.

Answer 69

A

A. Associated with focal cortical dysplasia

The image accompanying the question presents
a WHO grade I dysembryoplastic neuroepithelial
tumor. These tumors are associated with chronic
epilepsy and most frequently arise in the temporal
lobe. Ki-67 indices are typically low, often less than
5%. The tumor has a blistered appearance grossly.
It often is associated with adjacent cortical architectural disorganization (focal cortical dysplasia).

Answer 70

A

A. Ependymoma

True rosettes (tumor cells arranged around a central lumen) are characteristic of an ependymoma.
(C, E) Rosettes and perivascular pseudorosettes are
not typical features of myxopapillary ependymomas and subependymomas. (D) Retinoblastomas
of the eye contain similar true rosettes (FlexnerWintersteiner rosettes).

Answer 71

A

A. Streptococcus species

Streptococcus species are the most common
pathogens found in brain abscesses across all ages and typically stem from adjacent sinus or ear
infections. (B, E) Staphylococcus species and enteric
bacilli are common pathogens in brain abscesses
due to trauma. (C, D) Bacteroides and Proteus species are common pathogens in brain abscesses in
neonates, along with Citrobacter species and gramnegative bacilli.

Answer 72

A

D. Adjacent sinus or ear infections

Adjacent sinus or ear infections account for about
40% of brain abscesses due to the ability of pathogens to spread along valveless venous channels that
are the cranial sinuses. (E) Hematogenous spread
from distant infections accounts for about 30% of
brain abscesses. Hematogenous spread of pathogens tends to produce abscesses in the middle
cerebral artery territory and often causes multiple
abscesses.

Answer 73

A

C. Grade III

An astrocytoma with necrosis, vascular proliferation, and moderate pleomorphism is WHO grade IV.

Answer 74

A

D. P53 protein mutation

The p53 tumor suppressor protein is encoded by
the TP53 gene on chromosome 17, and mutations
result in Li-Fraumeni syndrome. Individuals with
Li-Fraumeni syndrome are at risk for developing a
variety of tumors throughout their bodies, including primitive neuroectodermal tumors and astrocytomas in the brain, breast cancer, and soft tissue
and bone sarcomas. (A) Turcot syndrome has been
linked to gene mutations in the MLH1, MSH2, MSH6,
and PMS2 genes and predisposes individuals to
medulloblastomas and glioblastomas. (B) Merlin
protein is a tumor suppressor protein encoded by
the neurofibromin 2 gene on chromosome 22.
Mutations in merlin are seen in individuals with
neurofibromatosis type 2, which is associated with
bilateral acoustic neuromas, meningiomas, astrocytomas, and ependymomas. (C) The neurofibromin
1 protein is mutated in individuals with neurofibromatosis type 1. This chromosome 17 abnormality
predisposes possessors to optic gliomas, astrocytomas, and neurofibromas. (E) The von Hippel–Lindau
tumor suppressor gene mutation (chromosome 3)
is seen in von Hippel–Lindau disease and results in
an increased risk for developing hemangioblastomas and endolymphatic sac tumors.

Answer 75

A

E. Synaptophysin

Central neurocytomas most commonly arise in
the lateral ventricles and demonstrate diffuse,
strong immunoreactivity with synaptophysin
antibodies, consistent with their neural lineage.
(A) CD34 is a vascular marker. (B) Epithelial membrane antigen stains carcinomas and meningiomas. (C, D) Glial fibrillary acidic protein and S-100
protein stain astrocytic tumors, among others.

Answer 76

A

E. WHO grade III anaplastic astrocytoma

Ki-67 is a cell proliferation marker that stains a
nuclear protein that is produced during the proliferative phases of the cell cycle. Staining results
typically are reported as a percentage of positive
staining tumor cells in the area of the tumor with
the most staining (labeling index). The rate of cell
proliferation is more than what would be expected
in a WHO grade I or II neoplasm and is most consistent with a higher grade neoplasm.

Answer 77

A

B. WHO grade II

This tumor represents a pleomorphic xanthoastrocytoma. It is one of the few astrocytic tumors
that has a rich connective tissue matrix that can be
highlighted with a reticulin stain. Despite the cellularity and marked atypia of the tumor cells in
this neoplasm, the majority of these tumors are
considered to be WHO grade II neoplasms. Rare
WHO grade III pleomorphic xanthoastrocytomas
are marked by increased mitotic activity or necrosis.

Answer 78

A

E. Sturge-Weber syndrome

The photomicrograph shown in the image
accompanying the question demonstrates some
surface cortex on the right and a proliferation of
blood vessels in the meninges (angiomatosis). The
history and pathological image are suggestive of
Sturge-Weber syndrome. (A) There are no tumor
cells between the blood vessels, as one would
encounter in an angiomatous meningioma.

Answer 79

A

D. Nasal glioma

The presence of ectopic neural/brain tissue in
the nasal area is referred to as a nasal glioma, even
though it is not really a glioma in the traditional
sense. The usual differential diagnosis with the
described lesion is encephalocele if the lesion
is connected to the brain itself. Angiofibromas meningiomas, and pituitary adenomas occasionally can arise as masses in the nasal cavity but
look very different histologically

Answer 80

A

D. Atypical teratoid/rhabdoid tumor

Atypical teratoid/rhabdoid tumors are associated
with INI1 and chromosome 22 abnormalities and
stain positively for vimentin, epithelial membrane
antigen, and glial fibrillary acidic protein, among
others. (A) Chromosomal deletions in chromosome 17p and not 22 are seen with medulloblastomas and other primitive neuroectodermal tumors.
(B) The most common chromosomal changes in
ependymomas are amplification of chromosome
1q and loss of chromosomes 6q, 17p, and 22q, with
chromosome 1q amplification being most likely to
lead to intracranial tumor recurrence. (C) Astrocytomas can be associated with a variety of syndromes and their associated chromosomal changes,
including neurofibromatosis types 1 and 2, tuberous sclerosis, retinoblastoma, Li-Fraumeni, and
Turcot syndromes. (E) Chromosome 22 abnormalities can be seen with schwannomas, but INI1
mutations are not seen.

Answer 81

A

E. Thiamine deficiency

The changes described are associated with thiamine deficiency and Wernicke-Korsakoff syndrome.
The brownish discoloration of the mammillary
bodies is due to small hemorrhages.

Answer 82

A

D. Syringobulbia

A glial-lined cavitation in the brainstem area is
referred to as syringobulbia. In the spinal cord, a
comparable lesion is called syringomyelia. (A) Diplomyelia refers to duplication of spinal cord segments. (B) Hydromyelia is a dilation of the central
spinal canal. (C) Iniencephaly refers to failure of
closure of the posterior vertebral arches of the rostral cervical vertebrae and usually is associated
with abnormalities of the brainstem.

Answer 83

A

B. Hemorrhagic infarct

The acute angle branching hyphae shown in the
image accompanying the question are consistent
with Aspergillus. Aspergillus tends to be angioinvasive, and consequently presents most commonly with hemorrhagic infarcts. Less commonly,
one can encounter an abscess or meningitis with
Aspergillus.

Answer 84

A

D. Open neural tube defect

Elevated amniotic fluid levels of α-fetoprotein
and acetylcholinesterase are associated with open
neural tube defects (i.e., defects in which there is a
lack of skin covering exposed meninges or central
neuroglial tissue). The risk of such defects can be
reduced with adequate maternal folate consumption.

Answer 85

A

C. Germinoma

The pineal region is a common location for
germinomas. In addition to Parinaud (dorsal midbrain) syndrome, precocious puberty and other
endocrine manifestations commonly are associated with this malignant neoplasm. Histologically,
the classic findings with germinomas are aggregates of nonneoplastic lymphocytes (small dark
blue cells) and large tumor cells with abundant
cytoplasm, large nuclei, and prominent nucleoli.

Answer 86

A

B. Hemangioblastoma

A WHO grade I tumor, hemangioblastoma is
commonly seen in the cerebellum as a brightly
enhancing mass associated with a cystic component. Histologically, these tumors are rich in capillaries (hence their name despite their histogenesis
remaining unknown), with intervening large “epithelioid” cells with foamy cytoplasm and hyperchromatic nuclei called stromal cells.

Answer 87

A

C. Prematurity

Germinal matrix hemorrhage is associated
strongly with prematurity and results from the
increased susceptibility of these patients to hypoxia/
ischemia. Germinal matrix hemorrhage can extend
into the ventricles, leading to intraventricular hemorrhage, which is associated with serious sequelae.

Answer 88

A

D. Glioblastoma, WHO grade IV

The microphotograph accompanying the question shows a hypercellular neoplasm with characteristic pale areas of necrosis surrounded by viable
tumor cells. This type of necrosis is called pseudopalisading necrosis and is characteristic of glioblastomas (WHO grade IV) and other high-grade
lesions.

Answer 89

A

B. Schwannoma

Antoni A (compact spindled areas) and Antoni B
(loosely organized and less cellular areas of mucinous stroma and fibrillary collagen) areas are
typical of schwannomas. (A) Neurofibromas often
stain with neurofilament and have axons coursing through them. (C) Malignant peripheral nerve
sheath tumors often involve multiple fascicles and
are characterized by uniform spindle cells with
hyperchromatic nuclei arranged in fascicles. Necrosis and a high mitotic index are seen.

Answer 90

A

A. Alzheimer disease

Pathological findings in Alzheimer disease include deposition of extracellular β-amyloid in
neuritic plaques and intracellular neurofibrillary
tangles composed of hyperphosphorylated tau
and ubiquitin proteins. (B) Pick disease (frontotemporal dementia) is characterized by tauopathy
(a neuronal/glial inclusion of tau). (C) CreutzfeldtJakob disease is associated with abnormal prion
PrPSc, and has the classic findings of 14-3-3 protein
in the cerebrospinal fluid and periodic sharp waves
and spikes on electroencephalography. (D) Dementia with Lewy bodies has eosinophilic intracytoplasmic neuronal inclusions (Lewy bodies) that
contain α-synuclein and tau proteins. (E) Huntington disease is due to a CAG trinucleotide repeat on
chromosome 4 and is not associated with intra- or
extracellular inclusion bodies.

Answer 91

A

A. Putamen

The basal ganglia are the most common site of
hypertensive hemorrhage. Of the basal ganglia,
the putamen is the most common location for
hypertension-related hemorrhage. This is followed
by the thalamus, the pons, and the dentate nuclei
of the cerebellum. Lobar hemorrhages can occur
with hypertension in the subcortical white matter,
but they more often are associated with amyloidosis in the elderly.

Answer 92

A

B. Chromosomes 1p and 19q co-deletion

The histopathological features in this case are of
an oligodendroglioma. Tumor cells have round, uniform nuclei with an artifactual perinuclear halo.
Branching, delicate blood vessels are present within
the tumor. Most oligodendrogliomas show a codeletion of the short arm of chromosome 1 (1p)
and long arm of chromosome 19 (19q). The presence of this co-deletion is associated with a better
response to chemotherapy and longer survival.

Answer 93

A

B. Angiocentric glioma

Angiocentric gliomas are rare, low-grade lesions
most commonly seen in the temporal lobe in young
patients with chronic epilepsy. The tumor, as
shown in the image accompanying the question, is
marked by perivascular pseudorosette-like structures. Ependymomas also may have similar rosette
structures but are predominantly intraventricular
in location.

Answer 94

A

D. Neuroblastoma

Homer-Wright rosettes lack a central canal or
capillary and are seen classically in neuroblastomas, medulloblastomas, primitive neuroectodermal
tumors (PNETs), and retinoblastomas. Their lumens
contain dense neuropil. Flexner-Wintersteiner
rosettes are seen classically in retinoblastomas but
also occur in pineoblastomas. They have no fiberrich neuropil in their centers and resemble photoreceptor rods/cones ultrastructurally. (A) Ependymal
rosettes form central lumens, whereas pseudorosettes form zones of fibrillary processes around
blood vessels. Pseudorosettes are seen much more
commonly in ependymomas and are more sensitive for a diagnosis of ependymoma than true
rosettes. (C) Pineocytomatous/neurocytic rosettes
are seen in pineocytomas/central neurocytomas
and are similar to Homer-Wright rosettes but are
larger and more regular

Answer 95

A

E. Papillary and rhabdoid

Meningothelial, transitional, and fibrous are
the most common meningioma subtypes. Clear
cell, chordoid, and atypical meningiomas are WHO
grade II. Atypical meningiomas are characterized
by increased mitotic activity (four or more mitotic
figures per high power microscopic field), brain
invasion, or a tumor with three or more other
worrisome features (e.g., patternless/sheet-like
growth patterns, hypercellularity, small cell change,
necrosis, and prominent nucleation). Anaplastic
meningiomas are grade III, characterized by obvious malignant features resembling carcinoma/
melanoma or high-grade sarcoma or mitotic activity in excess of 19 mitotic figures per 10 high power
fields. Papillary and rhabdoid tumors also are considered WHO grade III.

Answer 96

A

C. Pilocytic astrocytoma

The most common histological type of optic
pathway/hypothalamic glioma in the pediatric population is pilocytic astrocytoma, which comprises
the majority of prechiasmatic tumors. Other common tumor types are low-grade fibrillary astrocytoma, ganglioglioma, and, rarely, malignant glioma.

Answer 97

A

C. Cytomegalovirus infection

Neurons infected by cytomegalovirus show large
intranuclear eosinophilic inclusions known as Cowdry A (or just Cowdry) bodies. Smaller cytoplasmic
inclusions also can be present in infected cells.

Answer 98

A

E. Oligodendroglioma

Oligodendrogliomas have a “chicken wire” vasculature with a delicate network of branching capillaries, whereas the “fried egg” appearance is an artifactual perinuclear clear space following delayed
formalin fixation (thus not seen in frozen sections). (A) Germinomas have sheets of large cells with round nuclei, distinct cell borders, and often are infiltrated with lymphocytes. (B) Ependymomas often show rosettes or perivascular pseudorosettes. (C) Pleomorphic xanthoastrocytomas are described by their large cells with abundant intracytoplasmic vacuoles due to lipid accumulation.

Answer 99

A

A. Streptococcus species

Sixty percent of cerebral abscesses are polymicrobial. Streptococcus species are the most frequent
organisms found, with 33 to 50% of abscesses being
anaerobic or microaerophilic. Streptococcus milleri
can be seen in frontoethmoidal sinusitis. (B) Escherichia coli abscesses are seen in neonates and
following brain surgery. (C) Bacteroides is a common abscess former from otitis media/mastoiditis.
(D) Actinomyces abscesses can be seen with odontogenic sources. (E) Staphylococcus epidermidis
abscesses can be seen after neurosurgical procedures

Answer 100

A

E. Pilocytic astrocytoma

The microphotograph shows the classic “biphasic” pattern of a pilocytic astrocytoma. Compacted
eosinophilic areas (center) contrast with loose,
microcystic zones (sides). Rosenthal fibers (not
shown) also are frequently seen.