PATHOLOGY // (CLINPATH) CARDIAC MARKERS

(GENPATH) BREAST REVIEWER

3.01 2.08

Dr. Grig Misiona September 6, 2014

BREAST REVIEWER a. Collagenase
1. A 30-year-old woman suffers traumatic injury to her breast b. Estrogen receptors
while playing soccer. Physical examination reveals a 3-cm c. Galactosyltransferase
area of ecchymosis on the left breast. Two weeks later, the d. Lysosomal acid hydrolases
patient palpates a firm lump beneath the area where the e. Myeloperoxidase
bruise had been located. Which of the following is the most
likely pathologic diagnosis? 5. A 35-year-old nulliparous woman complains that her breasts
a. Duct ectasia are swollen and nodular upon palpation. A mammogram
b. Fat necrosis discloses foci of calcification in both breasts. A breast biopsy
c. Fibrocystic change reveals cystic duct dilation and ductal epithelial hyperplasia
d. Granulomatous mastitis without atypia (shown in the image). What is the appropriate
e. Intraductal papillomatosis diagnosis?

2. A 50-year-old woman presents with a mass in her left breast

that she first detected 6 months earlier. A firm 4-cm mass is
palpated on breast examination. Excisional biopsy reveals
malignant cuboidal cells that form gland-like structures and
solid nests, surrounded by dense collagenous stroma. Which
of the following terms best describes the adaptive response
of this patient’s normal breast tissue to the tumor?
a. Anaplasia
b. Desmoplasia
c. Fibrinolysis
d. Lipohyalinosis
e. Metaplasia

3. A 54-year-old woman complains of bloody discharge from a. Ductal carcinoma in situ

her left nipple. Physical examination reveals a 0.5-cm nodule b. Fibroadenoma
in the subareolar breast tissue, which is surgically excised. c. Fibrocystic change
Histologic examination (shown in the image) reveals d. Granulomatous mastitis
cuboidal and myoepithelial cell:lined vascular connective e. Intraductal papilloma
tissue cores, which project into the lumen of a major
lactiferous duct. Which of the following is the appropriate 6. A 24-year-old woman delivers a 3.5-kg baby and begins
diagnosis? breastfeeding her infant. The patient presents 2 weeks later
with a fever of 38°C (101°F). Physical examination shows no
abnormal vaginal discharge or evidence of pelvic pain but
does reveal redness on the lower side of the left breast. The
patient stops nursing the infant temporarily, but the
symptoms persist, and the entire breast becomes swollen
and painful. What is the most likely diagnosis?
a. Acute mastitis
b. Chronic mastitis
c. Duct ectasia
d. Granulomatous mastitis
e. Lactating adenoma

a. Ductal carcinoma in situ
b. Intraductal papilloma
c. Lobular carcinoma in situ
d. Medullary carcinoma
e. Paget disease
4. A 53-year-old woman discovers a lump in her breast and
physical examination confirms a mass in the lower, outer
quadrant of the left breast. Mammography demonstrates an
ill-defined, stellate density measuring 1 cm. Needle
aspiration reveals malignant ductal epithelial cells. A
modified radical mastectomy is performed. The surgical
specimen reveals a firm irregular mass (arrows). Which of
the following cellular markers would be the most useful to
evaluate before considering therapeutic options for this
patient?
7. A 35-year-old woman consults her family physician because
of painful swelling of her breasts, particularly as she
approaches the end of her menstrual cycle. On self-
examination she recently felt a tender nodule in the right
breast. Physical examination reveals an irregular nodularity
of both breasts with diffuse tenderness. Examination of the
axilla is negative. A mammogram demonstrates irregular
areas of density in the lower, outer quadrants of both
breasts. Which of the following histopathologic features is
considered to be a risk factor for the development of
carcinoma in this patient?
a. Apocrine metaplasia
b. Cystic change
c. Duct ectasia
d. Papillomatosis
e. Stromal fibrosis

8. A 60-year-old man presents with painless, bilateral

enlargement of both breasts. The patient has a history of
nodular prostatic hyperplasia and is taking medication for
hypercholesterolemia. Physical examination reveals no
discrete breast masses or axillary lymph node enlargement.
Which of the following is the most likely underlying cause of
breast enlargement in this patient?
a. Chronic glomerulonephritis
b. Cirrhosis
c. Nonseminomatous germ cell neoplasm
d. Parathyroid adenoma
e. Progressive systemic sclerosis

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PATHOLOGY // (CLINPATH) CARDIAC MARKERS
9. A 30-year-old woman presents with nipple discharge of 3
weeks in duration. Physical examination reveals a white
discharge from both nipples. The patient has not
menstruated for the past 4 months, and she is not pregnant.
The breasts are firm and nontender. A cytologic smear of the
discharge shows no evidence of acute or chronic
inflammatory cells. Which of the following is the most likely
cause of galactorrhea in this patient?
a. Adrenal cortical adenoma
b. Fibroadenoma of the breast
c. Fibrocystic change of the breast
d. Pituitary adenoma
e. Sheehan syndrome
10. A woman consults her physician because of painful
swelling of her breasts. Physical examination reveals
nodularity of both breasts. Mammography shows irregular
areas of increased density in the lower, outer quadrants of
both breasts. A breast biopsy reveals increased fibrous
stoma, cystic dilation of the terminal ducts, and varying
degrees of apocrine metaplasia. This patient’s condition is
most commonly seen in which of the following groups?
a. with testicular feminization syndrome
b. Postmenopausal women
c. Pubertal girls
d. Women of reproductive age
e. Women treated with oral contraceptives
11. A 22-year-old woman presents with a painless nodule in
the lower outer aspect of her right breast that she has had
for 2 months. The nodule appears to be freely movable,
sharply demarcated from the surrounding parenchyma,
and firm. A mammogram demonstrates a circumscribed,
homogeneous density. A biopsy of the breast mass is
shown in the image. Which of the following best estimates
the risk of subsequent invasive breast cancer developing
in this patient?
a. Greater than 90% lifetime risk
b. Greater than 50% lifetime risk
c. Risk is doubled
d. Risk is halved
e. No risk at all
12. A 20-year-old woman asks for your advice regarding her
risk of developing breast cancer. Her mother, maternal
aunt, and maternal grandmother all developed breast
cancer. She would like to know if she has a genetic
predisposition. Laboratory tests for mutations in which of
the following genes would be most likely to answer your
patient’s question?
a. BRCA1
b. C-myc
c. Estrogen receptor
d. HER2/neu
e. Rb-1
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13. A 26-year-old woman presents with a breast mass that
was detected on self-examination 1 week earlier.
Mammography reveals a round, sharply demarcated 1-cm
nodule in the right breast (shown in the image). Biopsy of
the breast mass shows neoplastic epithelial ductal
structures situated within a fibromyxoid stroma. The
patient refuses further treatment and informs you that she
wishes to become pregnant. Which of the following is the
most likely effect of pregnancy on this breast lesion?
a. Development of invasive ductal carcinoma within the
lesion
b. Fibrocystic change with sclerosing adenosis
c. Formation of intraductal papilloma
d. Metastasis to regional lymph nodes
e. Rapid growth
14. Upon self-examination, a 53-year-old woman discovers a
lump in her left breast. Physical examination reveals a
palpable lump about 1 cm in diameter in the outer
quadrant of the left breast. No palpable lymph nodes are
found in the axilla. Mammography reveals an ill-defined,
stellate density measuring 1 cm in the left breast. Fine-
needle aspiration of the mass discloses malignant
epithelial cells. A partial mastectomy is performed and
shows invasive ductal adenocarcinoma. Which of the
following is the most important prognostic factor for this
patient?
a. Estrogen receptor status of the tumor tissue
b. Histologic grade of the tumor
c. Inherited BRCA1 gene mutation
d. Somatic mutation of the p53 tumor suppressor
gene
e. Status of the axillary lymph nodes
15. A mammogram of a 52-year-old woman demonstrates
calcifications in her left breast. No axillary lymph node
enlargement is detected on physical examination. An
excisional biopsy is shown in the image. If this patient
foregoes further treatment, which of the following best
estimates her risk of developing invasive carcinoma in this
breast over the next 20 years?
a. 1%
b. 5%
c. 30%
d. 90%
e. 100%
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16. A 54-year-old woman presents with a mass in her right a. Exposure to carcinogens
breast that she first palpated 5 days before. A breast b. Family history
biopsy reveals malignant cells, and a mastectomy is c. Fibrocystic change
performed. Immunohistochemical staining is performed for d. Obesity
HER2/neu (shown in the image). Which of the following e. Smoking
genetic mechanisms best accounts for the intensity of
staining in this specimen? 19. A 58-year-old woman presents with an irregular nodularity
that has developed in her right breast over the past 3
months. Mammography demonstrates irregular densities
in both breasts. A needle biopsy of one breast lesion is
shown. An excisional biopsy of the contralateral breast
shows similar histology. Which of the following is the most
likely pathologic diagnosis?

a. Gene amplification
b. Insertional mutagenesis
c. Chromosomal nonhomologous crossing over
d. Polyploidy
e. Single nucleotide polymorphism
a. Colloid carcinoma
17. A 45-year-old woman discovers a solitary, freely movable b. Lobular carcinoma in situ
mass in her right breast on self-examination, which is c. Malignant phyllodes tumor
confirmed on physical examination. Mammography d. Medullary carcinoma
demonstrates focal calcification, with a linear configuration e. Tubular carcinoma
in the region of the breast mass. A breast biopsy (shown
in the image) reveals large, pleomorphic epithelial cells 20. A 22-year-old woman nursing her newborn develops
confined to dilated ducts, with central zones of necrosis. a tender erythematous area around the nipple of her left
What is the appropriate pathologic diagnosis? breast. On physical examination, a purulent exudate is
observed to drain from an open fissure. Culture of this
exudate will most likely grow which of the following
microorganisms?
a. Candida albicans
b. Escherichia coli
c. Haemophilus influenza
d. Lactobacillus acidophilus
e. Staphylococcus aureus

21. A 52-year-old woman presents with a 3-month history

of a palpable breast mass. Physical examination confirms a
1-cm nodule in the upper outer quadrant of the right breast.
A biopsy reveals small cuboidal cells, with round nuclei and
prominent nucleoli. The cells are arranged in single cell
a. Colloid carcinoma columns, between strands of connective tissue (shown in the
b. Ductal carcinoma in situ, comedocarcinoma type image). Which of the following is the appropriate diagnosis?
c. Medullary carcinoma
d. Phyllodes tumor
e. Tubular carcinoma

18. A 50-year-old woman has been aware of a mass in her

left breast for the past 6 months. A 4-cm mass is palpated
on examination. The mass is hard, tender, and fixed to the
overlying skin. A lumpectomy is performed. The surgical
specimen is firm, has poorly defined margins, and cuts
with a gritty sensation. The cut surface is gray, opaque,
and slightly depressed. Streaks of gray connective tissue
extend into the surrounding fibroadipose tissue. The tumor
histology is shown in the image. Which of the following risk
factors has the strongest association with this patient’s a. Ductal carcinoma in situ
tumor? b. Invasive ductal carcinoma, tubular type
c. Invasive lobular carcinoma
d. Lobular carcinoma in situ
e. Medullary carcinoma

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PATHOLOGY // (CLINPATH) CARDIAC MARKERS 2.08
22. A 58-year-old woman has a screening mammography 26. Which of the following is thought to play a role in the
and is found to have a 4-cm circumscribed mass, without development of cancer in the patient described in
calcifications, in her left breast. An excisional biopsy Question 26?
shows solid nests and sheets of highly pleomorphic cells, a. BRCA2 mutation
with many mitotic figures, surrounded by a dense infiltrate b. Chronic alcoholism
of lymphocytes. Which of the following is the most likely c. Gynecomastia
diagnosis? d. Hyperestrinism
e. PTEN mutation

ANSWERS
1. B. Fat necrosis
A history of trauma can usually be elicited in cases of fat
necrosis occurring in the breast. Initially, the lesion consists
of necrosis of adipocytes and hemorrhage, after which
phagocytic cells remove the lipid debris. Fibroblastic
proliferation during healing leads to fingers of fibrous scar
tissue that extend into the adjacent breast tissue. As a result,
an irregular, fixed, hard mass may ensue and clinically
resemble breast cancer. Dystrophic calcification, a common
feature of breast cancer, may also be detected
a. Invasive ductal carcinoma
radiographically in areas of fat necrosis. Thus, the lesions
b. Invasive lobular carcinoma
often require biopsy to establish their benign character. The
c. Medullary carcinoma
other choices are not associated with trauma.
d. Paget disease
Diagnosis: Fat necrosis of the breast
e. Phyllodes tumor
2. B. Desmoplasia
23. A 45-year-old woman presents with an oozing, reddish
Breast cancer is the most common malignancy of women in
patch on her left nipple (patient shown in the image). The
the United States, and the mortality from this disease among
patient has a history of skin rashes and food allergies and
women is second only to that of lung cancer. Invasive, or
believes this condition is due to an allergic reaction to her
infiltrating, ductal carcinoma is the most common form of
bra. Cytologic examination of fluid oozing from the skin
breast cancer. In this cancer stromal invasion by malignant
lesion reveals neoplastic cells. Excisional biopsy shows
cells usually incites a pronounced fibroblastic proliferation.
large clear malignant cells in the epidermis of the areola.
This “desmoplasia” creates a palpable mass, which is the
Which of the following is the most likely diagnosis?
most common initial sign of ductal carcinoma. Invasive
ductal carcinoma usually manifests as a hard, fixed mass,
which is often referred to as scirrhous carcinoma. On gross
examination, the tumor is typically firm and shows irregular
margins. The cut surface is pale gray and gritty and flecked
with yellow, chalky streaks. Microscopically, invasive ductal
carcinoma grows as irregular nests and cords of epithelial
cells, usually within a dense fibrous stroma. Metaplasia
(choice E) is the conversion of one differentiated cell type to
another. Lipohyalinosis (choice D) is a particular form of
fibrosis associated with fat deposition. Fibrinolysis (choice C)
is related to clot dissolution.
Diagnosis: Invasive ductal carcinoma of the breast

3. B. Intraductal papilloma
a. Chronic dermatitis Intraductal papilloma is a benign breast tumor that usually
b. Colloid carcinoma causes nipple discharge (serous or hemorrhagic) and occurs
c. Intraductal papilloma in the lactiferous ducts of middle-aged and older women.
d. Paget disease Because intraductal papilloma is situated in the large,
e. Phyllodes tumor subareolar ducts, the lesion may be associated with a
serous or bloody nipple discharge. This lesion must be
24. A 60-year-old woman presents with a large breast mass distinguished from papillomatosis, which occurs in the
that she first detected 3 months ago. Mammography peripheral ducts as a component of proliferative fibrocystic
reveals a well-circumscribed mass measuring 8 cm in change. Intraductal papillomas are attached to the wall of the
diameter. A breast biopsy shows loose fibroconnective duct by a fibrovascular stalk. The papillomatous portion
tissue with a sarcomatous stroma, abundant mitoses, and consists of a double layer of epithelial cells, an outer layer of
nodules and ridges lined by cuboidal epithelial cells. cuboidal or columnar cells, and an inner layer of more
Which of the following is the appropriate diagnosis? rounded myoepithelial cells. Solitary intraductal papilloma is
a. Fibroadenoma not a premalignant lesion or a marker for increased risk of
b. Medullary carcinoma cancer in the breast. Ductal carcinoma in situ (choice A) and
c. Paget disease lobular carcinoma in situ (choice C) feature neoplastic cells
d. Phyllodes tumor confined to ducts and lobules, respectively, and typically lack
e. Tubular carcinoma myoepithelial cells. Paget disease (choice E) is a form of
carcinoma that involves the epidermis of the nipple and
25. A 55-year-old man presents with a solitary breast mass areola.
and biopsy reveals malignant cells. Immunohistochemical Diagnosis: Intraductal papilloma
staining experiments show that the tumor cells are positive
for HER2/neu and cytokeratins 4 and 11 and negative for 4. B. Estrogen receptors
estrogen receptors. What is the most likely diagnosis? Over half of breast cancers exhibit nuclear estrogen receptor
a. Basal cell carcinoma protein. A slightly smaller proportion also has progesterone
b. Invasive ductal carcinoma receptors. Women whose cancers possess hormone
c. Invasive lobular carcinoma receptors have a longer disease-free survival and overall
d. Medullary carcinoma survival than those with early-stage cancers who are
e. Tubular adenoma negative for these receptors. The beneficial effects of
oophorectomy on survival in patients with breast cancer led
to the use of estrogen antagonists in the treatment of breast

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PATHOLOGY // (CLINPATH) CARDIAC MARKERS
cancer. In general, antiestrogen therapy seems to prolong
disease-free survival, particularly in postmenopausal and
node-positive women. It also lowers the risk of cancer in the
contralateral breast. The latter discovery has led to the use
of antiestrogens as chemoprevention in women at high risk
for developing breast cancer. None of the other choices are
related prognostically to breast carcinoma.
Diagnosis: Invasive ductal carcinoma of the breast
5. C. Fibrocystic change
Fibrocystic change of the breast refers to a constellation of
morphologic features characterized by (1) cystic dilation of
terminal ducts, (2) relative increase in fibrous stroma, and (3)
variable proliferation of terminal duct epithelial elements.
Some of the florid manifestations appear to be indicators for
an increased risk for breast cancer. Such lesions are
designated proliferative fibrocystic change. Forms of
fibrocystic change that do not carry an increased risk for the
development of cancer, termed nonproliferative fibrocystic
change, are far more prevalent. Ductal carcinoma in situ
(choice A) features apparently malignant epithelial cells that
have not penetrated the basement membrane. Intraductal
papilloma (choice E) occurs in the subareolar lactiferous
ducts. None of the remaining incorrect choices feature cystic
duct dilation.
Diagnosis: Fibrocystic change, proliferative
6. A. Acute mastitis
Acute mastitis is a bacterial infection of the breast. It may be
seen at any age, but by far the most frequent setting is in the
postpartum lactating or involuting breast. This disorder is
usually secondary to obstruction of the duct system by
inspissated secretions. The other choices are not typically
associated with fever.
Diagnosis: Acute mastitis
7. D. Papillomatosis
Proliferative fibrocystic change increases the risk of cancer.
The most common proliferative change is an increase in the
number of cells lining the dilated terminal ducts, described
as ductal epithelial hyperplasia. Proliferative fibrocystic
change can, at times, become exuberant and form papillary
structures within the lumen of the distended ductule
(papillomatosis). The morphologic spectrum of ductal
hyperplasia in patients with proliferative fibrocystic change
includes (1) minor degrees of hyperplasia; (2) florid, but
cytologically benign hyperplasia; (3) hyperplasia with
cytologic atypia not sufficient to warrant a diagnosis of
malignancy; and (4) ductal carcinoma in situ. The other
choices do not increase the risk of breast cancer.
Diagnosis: Fibrocystic change, proliferative
8. B. Cirrhosis
Gynecomastia refers to an enlargement of the adult male
breast and is morphologically similar to juvenile hypertrophy
of the female breast. In the adult man, gynecomastia is
caused by an absolute increase in circulating estrogens or
by a relative increase in the estrogen/androgen ratio.
Gynecomastia associated with excess estrogens occurs with
(1) the intake of exogenous estrogens, (2) the presence of
hormone-secreting adrenal or testicular tumors, (3) the
paraneoplastic production of gonadotropins by cancers, and
(4) metabolic disorders, such as liver disease and
hyperthyroidism, which are characterized by increased
conversion of androstenedione into estrogens.
Gynecomastia is often idiopathic, in which case it is
commonly unilateral. The other choices are not associated
with gynecomastia.
Diagnosis: Gynecomastia
9. D. Pituitary adenomas
Pituitary adenomas are benign neoplasms of the anterior
lobe of the pituitary, which are often associated with excess
secretion of pituitary hormones and evidence of
corresponding endocrine hyperfunction. They occur in both
sexes at almost any age but are more common in men
between the ages of 20 to 50 years. Small, nonfunctioning
pituitary adenomas are found incidentally in as many as 25%
of adult autopsies. Hyperprolactinemia is the most common
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endocrinopathy associated with pituitary adenomas.
Prolactin secreted by pituitary lactotrophic adenomas may
cause galactorrhea, most often in young women.
Galactorrhea is not associated with the other choices.
Diagnosis: Prolactinoma
10. D. Women of reproductive age
Fibrocystic change is most often diagnosed in women from
their late 20s to the time of menopause, and some fibrocystic
change occurs in 75% of adult women in the United States.
The morphologic hallmarks of nonproliferative fibrocystic
change seen in this patient are an increase in fibrous stroma
and cystic dilation of the terminal ducts. Fibrocystic change
occurs in multiple areas of both breasts. A dominant cyst or
aggregate of fibrous connective tissue containing smaller
cysts may manifest as a discrete mass, prompting biopsy to
exclude the possibility of cancer. The large cysts often
contain dark fluid that imparts a blue color-the so-called
“blue-domed cysts of Bloodgood.” Aspiration of a large cyst
will usually cause it to collapse and the mass to disappear. A
frequent concomitant of nonproliferative fibrocystic change is
an alteration of the epithelial lining, termed apocrine
metaplasia. The metaplastic cells are larger and more
eosinophilic than the cells that usually line the ducts and
resemble apocrine sweat gland epithelium. The frequency of
fibrocystic change decreases progressively after menopause
(choice B). Fibrocystic change is not encountered during
puberty (choice C). Oral contraceptives (choice E) do not
increase the frequency of fibrocystic change.
Diagnosis: Fibrocystic change, nonproliferative
11. B. Risk is doubled
Fibroadenoma is the most common benign neoplasm of the
breast and is composed of epithelial and stromal elements
that originate from the terminal duct lobular unit.
Fibroadenomas are usually found in women between the
ages of 20 and 35, although they may occur in adolescent
girls. The tumor is round and rubbery, is sharply demarcated
from the surrounding breast, and thus, is freely movable.
The cut surface appears glistening gray-white. On
microscopic examination, fibroadenomas are composed of a
mixture of fibrous connective tissue and elongated epithelial
ducts (see photomicrograph). This connective tissue, which
forms most of the tumor, often compresses the proliferated
ducts, reducing them to curvilinear slits. The risk of
subsequent invasive cancer in a breast from which a
fibroadenoma has been removed is doubled. Surgical
removal is curative. Choices A and B are principally
associated with BRCA mutations.
Diagnosis: Fibroadenoma
12. A. BRCA1
BRCA1 is a tumor suppressor gene that has been
implicated in the pathogenesis of hereditary breast and
ovarian cancers. Mutations in this tumor suppressor gene
are thought carried by 1 in 200 to 400 people in the United
States. Germline point mutations and deletions
in BRCA1 place a woman at a remarkable 60% to 85%
lifetime risk for breast cancer. Moreover, breast cancer
develops in more than half of these women before the age
of 50 years. It is currently suspected that mutated BRCA1 is
responsible for 20% of all cases of inherited breast cancer
(about 3% of all breast cancers). Somatic mutations
in BRCA1 are uncommon in sporadic (nonfamilial) breast
cancers. Women with BRCA1 mutations are also at greater
lifetime risk of ovarian cancer. Estrogen receptor
expression (choice C) is often increased in breast cancer
cells, but the gene for the estrogen receptor is not mutated.
Neither estrogen receptor status nor HER2/neuexpression
(choice D) predict genetic predisposition.
Diagnosis: Breast cancer
13. E. Rapid Growth
Fibroadenomas commonly enlarge more rapidly during
pregnancy and cease to grow after the menopause.
Although they are hormonally responsive, a causal
relationship between hormones and the pathogenesis of
fibroadenoma has not been established. Development of
invasive ductal carcinoma (choice A) in a fibroadenoma is
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rare.
Diagnosis: Fibroadenoma
14. E. Status of the axillary lymph nodes
Although all of the choices are prognostic indicators for
breast cancer, the most important prognostic factor at the
time of diagnosis is stage. A sentinel node assessment
often is performed intraoperatively to assess the status of
the ipsilateral lymph nodes. The sentinel lymph node is the
most proximate lymph node and is assumed to be the initial
site of nodal metastasis. It is identified with a dye or
radioactive material. An axillary lymph node dissection is
performed if metastatic tumor is identified in the sentinel
lymph node. The presence of invasion indicates that tumor
cells have access to lymphatic and blood vascular channels
in the stroma, increasing the possibility of metastases to
regional lymph nodes and distant sites. The prognosis for
women with distant metastases (stage IV) is poor in terms
of survival, but palliative treatment may significantly prolong
life. With the expanding use of screening mammography,
more than half of the breast cancers currently diagnosed in
the United States manifest as stage I disease, and almost
all of these women will be cured by surgery.
Diagnosis: Invasive ductal carcinoma of the breast
15. C. 30%
The biopsy reveals intraductal carcinoma in situ, which
arises in the terminal duct lobular unit, greatly distorting the
ducts by its growth. Intraductal carcinoma in situ has two
main histologic types, namely comedocarcinoma and
noncomedocarcinoma. Noncomedocarcinomas exhibit a
spectrum of cytologic atypia. The patterns are classified as
micropapillary, cribriform (shown in the image), and solid.
The tumor cells and nuclei are smaller and more regular
than those of the comedo type. Noncomedo intraductal
carcinoma in situ is less likely than the comedo type to
incite a desmoplastic response in the surrounding tissue.
Ductal carcinoma in situ, treated only by biopsy, carries a
20% to 30% risk of developing invasive carcinoma in the
same breast over the ensuing 20 years. The risk of cancer
in the contralateral breast is also increased. Choices A and
B are incorrect because they suggest that the risk of
invasive carcinoma is very small, whereas choices D and E
are far too great.
Diagnosis: Ductal carcinoma in situ
16. A. Gene Amplification
Overexpression of HER2/neu is identified in 10% to 35% of
primary breast tumors and is mostly attributable to gene
amplification. Amplification or overexpression
of HER2/neu has also been described in cancers of the lung,
ovary, and stomach. Overexpression can be determined by
immunohistologic detection of the c-erbB2 protein on the cell
membrane or by analysis of theHER2/neu gene using
fluorescent in situ hybridization. Patients whose tumors
demonstrateHER2 gene amplification benefit from therapy
with a monoclonal antibody (Herceptin) that selectively binds
to the extracellular domain of the protein. Although the other
genetic processes occur in some cancers, they are unrelated
to HER2/neu expression.
Diagnosis: Breast cancer
17. B. Ductal carcinoma in situ, comedocarcinoma type
Intraductal carcinoma in situ of the comedo type is
composed of very large, pleomorphic cells that have
abundant eosinophilic cytoplasm and irregular nuclei,
commonly with prominent nucleoli, and typically grows in a
solid pattern. Central necrosis is a prominent factor. The
necrotic debris may undergo dystrophic calcification. On
gross examination, the cut surface shows distended ducts
containing pasty necrotic debris resembling comedos,
hence the term comedocarcinoma. Although the malignant
cells do not invade through the basement membrane of the
ducts, this form of carcinoma in situ commonly incites a
chronic inflammatory and fibroblastic response in the
surrounding stroma. The cancer may extend within the duct
system beyond the clinically detectable tumor growth. The
consequent difficulties in obtaining complete excision of the
primary tumor frequently necessitate mastectomy rather
than “lumpectomy.” The chances of local recurrence as
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either in situ or invasive cancer are substantially greater in
the case of the comedo subtype than the noncomedo
subtype. Colloid carcinoma (choice A) features abundant
mucin production. Medullary carcinoma (choice C) is
composed of sheets of invasive and pleomorphic cells.
Phyllodes tumor (choice D) demonstrates proliferation of
spindly stromal cells. Tubular carcinoma (choice E) is an
invasive well-differentiated carcinoma with well-formed
small duct structures.
Diagnosis: Comedocarcinoma, ductal carcinoma in situ
18. B. Family History
The strongest association with an increased risk for breast
cancer is a family history, specifically breast cancer in first-
degree relatives (mother, sister, or daughter). The risk is
greater when the relative is afflicted at a young age or with
bilateral breast cancer. A woman who has two sisters with
breast cancer, one of whom had bilateral tumors, or a
mother and sister who show the same pattern has a greater
than 25% chance of developing breast cancer by age 70
years. Fibrocystic change (choice C) also has an increased
risk of breast cancer (proliferative lesions), but the relative
risk does not approach that of family history.
Diagnosis: Invasive ductal carcinoma of the breast
19. B. Lobular carcinoma in situ
Lobular carcinoma in situ arises in the terminal duct lobular
unit. Malignant cells appear as solid clusters that pack and
distend the terminal ducts but not to the extent of ductal
carcinoma in situ. The lesion does not usually incite the
dense fibrosis and chronic inflammation so characteristic of
intraductal carcinoma in situ and is, therefore, less likely to
cause a detectable mass. It is not uncommon for lobular
carcinoma in situ to be an “incidental” finding in a biopsy
that was prompted by benign changes. As with intraductal
carcinoma in situ, 20% to 30% of women with lobular
carcinoma in situ receiving no further treatment after biopsy
will develop invasive cancer within 20 years of diagnosis.
However, about half of these invasive cancers will arise in
the contralateral breast and may be either lobular or ductal
cancers. Thus, lobular carcinoma in situ, more than ductal
carcinoma in situ, serves as a marker for an enhanced risk
of subsequent invasive cancer in both breasts. The
histologic appearance is not consistent with any of the other
choices.
Diagnosis: Lobular carcinoma in situ
20. E. Staphylococcus aureus
This lactating patient has developed acute mastitis. The
most common organisms isolated
areStaphylococcus and Streptococcus. Untreated, the
infection may progress to abscess formation, which is a
complication that necessitates surgical intervention. A firm,
walled-off, nontender abscess may be mistaken for cancer.
Acute bacterial mastitis may be treated successfully by
aggressive mechanical suction, with frequent emptying of
the breasts, and by the administration of antibiotics. None
of the other pathogens are ordinarily seen in acute mastitis.
Diagnosis: Acute mastitis
21. C. Invasive lobular carcinoma
Invasive lobular carcinoma is the second most common
form of invasive breast cancer. Because the amount of
fibrosis is variable, the clinical presentation of invasive
lobular carcinoma varies from a discrete firm mass, similar
to ductal carcinoma, to a more subtle, diffuse, indurated
area. Microscopically, classic invasive lobular carcinoma
consists of single strands of malignant cells infiltrating
between stromal fibers, which is a feature termed “Indian
filing” (see photomicrograph). Despite the innocuous
cytologic characteristics of this form of invasive carcinoma,
it is biologically as aggressive as the invasive ductal type.
Twenty-five percent of invasive carcinomas have features
of both ductal and lobular carcinoma. Lobular carcinoma in
situ (choice D) is confined to the lobule. Invasive ductal
carcinoma may share features of invasive lobular
carcinoma, but it usually forms glands, particularly the
tubular type (choice B).
Diagnosis: Invasive lobular carcinoma
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PATHOLOGY // (CLINPATH) CARDIAC MARKERS 2.08
22. C. Medullary carcinoma
Medullary carcinomas present as fleshy, bulky tumors
measuring 5 to 10 cm in diameter. They are generally
larger at the time they are detected than infiltrating ductal
carcinomas (average size, 2 to 3 cm). This invasive tumor
presents as a circumscribed mass that lacks calcifications.
On gross examination, medullary carcinoma appears as a
well-circumscribed, fleshy, pale gray mass. Microscopically,
it is composed of sheets of cells that are highly pleomorphic
and have a high mitotic index. The pathologic definition of
medullary carcinoma includes a lymphoid infiltrate
encompassing the periphery of the tumor. Despite the
highly malignant histologic appearance of this neoplasm, it
has a distinctly better prognosis than infiltrating ductal or
lobular carcinoma. A dense lymphoid infiltrate is not
characteristic of the other choices.
Diagnosis: Medullary carcinoma of the breast

23. D. Paget disease

Paget disease of the nipple refers to an uncommon variant
of ductal carcinoma, either in situ or invasive, that extends
to involve the epidermis of the nipple and areola. This
condition usually comes to medical attention because of an
eczematous change in the skin of the nipple and areola.
Microscopically, large cells with clear cytoplasm (Paget
cells) are found singly or in groups within the epidermis.
The prognosis of Paget disease is related to that of the
underlying ductal cancer. Eczematous change in the skin of
the nipple and areola are not features of the other choices.
Diagnosis: Paget disease of the breast

24. D. Phyllodes tumor

Phyllodes tumor of the breast is a proliferation of stromal
elements accompanied by a benign growth of ductal
structures. These tumors usually occur in women between
30 and 70 years of age. Phyllodes tumors resemble
fibroadenomas in their overall architecture and the
presence of glandular and stromal elements. Like
fibroadenoma, benign phyllodes tumor is sharply
circumscribed, and the cut surface is firm, glistening, and
grayish white. Microscopically, the stroma of a benign
phyllodes tumor is hypercellular and has mitotic activity.
The distinction from fibroadenoma is made not on the size,
but on the histologic and cytologic characteristics of the
stromal component. Malignant phyllodes tumors have an
obviously sarcomatous stroma with abundant mitotic
activity, and the stromal component is increased out of
proportion to the benign duct elements. They are usually
poorly circumscribed, with invasion into the surrounding
breast tissue. Sarcomatous elements are not features of
the other choices.
Diagnosis: Phyllodes tumor of the breast

25. B. Invasive ductal carcinoma

Cancer in the male breast is uncommon and accounts for
less than 1% of all cases of breast cancer. The most
common subtype is infiltrating (invasive) ductal carcinoma.
Because there is less fat in the male breast, invasion of
chest wall muscles is more frequent at the time of
diagnosis. For tumors of the same stage, however, the
prognosis for male breast cancer is similar to that of female
breast cancer. Choice A is a skin tumor and the other
choices (C, D, and E) are rare in the male breast.
Diagnosis: Male breast cancer, invasive ductal carcinoma
of the breast

26. A. BRCA2 mutation

Predisposing factors for the development of breast cancer in
men are largely unknown, although mutations in
the BRCA2 gene increase the risk of this tumor. Choices B, C,
and D are not risk factors for breast cancer in
men. PTEN mutations (choice E) are associated with
endometrial intraepithelial neoplasia and endometrial
adenocarcinoma.
Diagnosis: Male breast cancer

Transcribers: theCUTEST :P Page 7 of 7