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1 A 30-year-old woman suffers traumatic injury to her breast
while playing soccer. Physical examination reveals a 3-cm area
of ecchymosis on the left breast. Two weeks later, the patient
palpates a fi rm lump beneath the area where the bruise had
been located. Which of the following is the most likely pathologic
(A) Duct ectasia
(B) Fat necrosis
(C) Fibrocystic change
(D) Granulomatous mastitis
(E) Intraductal papillomatosis


The answer is 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 fi ngers of
fi brous scar tissue that extend into the adjacent breast tissue.
As a result, an irregular, fi xed, hard mass may ensue and
clinically resemble breast cancer. Dystrophic calcifi cation, a
common feature of breast cancer, may also be detected radiographically
in areas of fat necrosis. Thus, the lesions often
require biopsy to establish their benign character. The other
choices are not associated with trauma.
Diagnosis: Fat necrosis of the breast


2. A 50-year-old woman presents with a mass in her left breast
that she fi rst detected 6 months earlier. A fi rm 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


The answer is B: Desmoplasia. Breast cancer is the most
common malignancy of women in the United States, and
the mortality from this disease among women is second only
to that of lung cancer. Invasive, or infi ltrating, ductal car-cinoma is the most common form of breast cancer. In this
cancer stromal invasion by malignant cells usually incites a
pronounced fi broblastic proliferation. This “desmoplasia” creates
a palpable mass, which is the most common initial sign of
ductal carcinoma. Invasive ductal carcinoma usually manifests
as a hard, fi xed mass, which is often referred to as scirrhous
carcinoma. On gross examination, the tumor is typically fi rm
and shows irregular margins. The cut surface is pale gray and
gritty and fl ecked with yellow, chalky streaks. Microscopically,
invasive ductal carcinoma grows as irregular nests and cords
of epithelial cells, usually within a dense fi brous stroma.
Metaplasia (choice E) is the conversion of one differentiated
cell type to another. Lipohyalinosis (choice D) is a particular
form of fi brosis associated with fat deposition. Fibrinolysis
(choice C) is related to clot dissolution.
Diagnosis: Invasive ductal carcinoma of the breast


3 A 54-year-old woman complains of bloody discharge from
her left nipple. Physical examination reveals a 0.5-cm nodule
in the subareolar breast tissue, which is surgically excised.
Histologic examination (shown in the image) reveals cuboidal
and myoepithelial cell–lined vascular connective tissue cores,
which project into the lumen of a major lactiferous duct.
Which of the following is the appropriate diagnosis?

(A) Ductal carcinoma in situ
(B) Intraductal papilloma
(C) Lobular carcinoma in situ
(D) Medullary carcinoma
(E) Paget disease


The answer is B: Intraductal papilloma. Intraductal papilloma
is a benign breast tumor that usually causes nipple discharge
(serous or hemorrhagic) and occurs in the lactiferous
ducts of middle-aged and older women. Because intraductal
papilloma is situated in the large, subareolar ducts, the lesion
may be associated with a serous or bloody nipple discharge.
This lesion must be distinguished from papillomatosis, which
occurs in the peripheral ducts as a component of proliferative
fi brocystic change. Intraductal papillomas are attached to the
wall of the duct by a fi brovascular stalk. The papillomatous
portion consists of a double layer of epithelial cells, an outer
layer of cuboidal or columnar cells, and an inner layer of more
rounded myoepithelial cells. Solitary intraductal papilloma is
not a premalignant lesion or a marker for increased risk of
cancer in the breast. Ductal carcinoma in situ (choice A) and
lobular carcinoma in situ (choice C) feature neoplastic cells
confi ned to ducts and lobules, respectively, and typically lack
myoepithelial cells. Paget disease (choice E) is a form of carcinoma
that involves the epidermis of the nipple and areola.
Diagnosis: Intraductal papilloma


4 A 53-year-old woman discovers a lump in her breast and
physical examination confi rms a mass in the lower, outer
quadrant of the left breast. Mammography demonstrates an
ill-defi ned, stellate density measuring 1 cm. Needle aspiration
reveals malignant ductal epithelial cells. A modifi ed radical
mastectomy is performed. The surgical specimen reveals a
fi rm irregular mass (arrows). Which of the following cellular
markers would be the most useful to evaluate before considering
therapeutic options for this patient?

(A) Collagenase
(B) Estrogen receptors
(C) Galactosyltransferase
(D) Lysosomal acid hydrolases
(E) Myeloperoxidase


The answer is B: Estrogen receptors. Over half of breast
cancers exhibit nuclear estrogen receptor protein. A slightly
smaller proportion also has progesterone receptors. Women
whose cancers possess hormone receptors have a longer
disease-free survival and overall survival than those with earlystage
cancers who are negative for these receptors. The benefi -
cial effects of oophorectomy on survival in patients with breast
cancer led to the use of estrogen antagonists in the treatment
of breast 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 A 35-year-old nulliparous woman complains that her breasts
are swollen and nodular upon palpation. A mammogram
discloses foci of calcifi cation in both breasts. A breast biopsy
reveals cystic duct dilation and ductal epithelial hyperplasia
without atypia (shown in the image). What is the appropriate
(A) Ductal carcinoma in situ
(B) Fibroadenoma
(C) Fibrocystic change
(D) Granulomatous mastitis
(E) Intraductal papilloma


The answer is 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 fi brous stroma, and (3) variable proliferation
of terminal duct epithelial elements. Some of the fl orid
manifestations appear to be indicators for an increased risk for breast cancer. Such lesions are designated proliferative fi brocystic
change. Forms of fi brocystic change that do not carry
an increased risk for the development of cancer, termed nonproliferative
fi brocystic 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 24-year-old woman delivers a 3.5-kg baby and begins
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


The answer is 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 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 fi brosis


The answer is D: Papillomatosis. Proliferative fi brocystic
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 fi brocystic 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 fi brocystic change includes (1) minor degrees
of hyperplasia; (2) fl orid, but cytologically benign hyperplasia;
(3) hyperplasia with cytologic atypia not suffi cient to
warrant a diagnosis of malignancy; and (4) ductal carcinoma
in situ. The other choices do not increase the risk of breast
Diagnosis: Fibrocystic change, proliferative


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


The answer is 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 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
fi rm and nontender. A cytologic smear of the discharge shows
no evidence of acute or chronic infl ammatory cells. Which of
the following is the most likely cause of galactorrhea in this
(A) Adrenal cortical adenoma
(B) Fibroadenoma of the breast
(C) Fibrocystic change of the breast
(D) Pituitary adenoma
(E) Sheehan syndrome


The answer is D: Pituitary adenoma. 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 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 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 fi brous 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) Patients with testicular feminization syndrome
(B) Postmenopausal women
(C) Pubertal girls
(D) Women of reproductive age
(E) Women treated with oral contraceptives


The answer is D: Women of reproductive age. Fibrocystic
change is most often diagnosed in women from their late 20s
to the time of menopause, and some fi brocystic change occurs
in 75% of adult women in the United States. The morphologic
hallmarks of nonproliferative fi brocystic change seen in this
patient are an increase in fi brous stroma and cystic dilation
of the terminal ducts. Fibrocystic change occurs in multiple
areas of both breasts. A dominant cyst or aggregate of fi brous
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 fl uid 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
fi brocystic 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 fi brocystic 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 fi brocystic change.
Diagnosis: Fibrocystic change, nonproliferative


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 fi rm.
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


The answer is C: 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, fi broadenomas are composed
of a mixture of fi brous 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 fi broadenoma
has been removed is doubled. Surgical removal is curative.
Choices A and B are principally associated with BRCA
Diagnosis: Fibroadenoma


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?
(B) C-myc
(C) Estrogen receptor
(D) HER2/neu
(E) Rb-1


The answer is 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/neu
expression (choice D) predict genetic predisposition.
Diagnosis: Breast cancer


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 fi bromyxoid
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
(B) Fibrocystic change with sclerosing adenosis
(C) Formation of intraductal papilloma
(D) Metastasis to regional lymph nodes
(E) Rapid growth

The answer is 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 fi broadenoma has not been established. Development of
invasive ductal carcinoma (choice A) in a fi broadenoma is
Diagnosis: Fibroadenoma


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-defi ned, 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


The answer is 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
identifi ed with a dye or radioactive material. An axillary lymph
node dissection is performed if metastatic tumor is identifi ed
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 signifi cantly 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


A mammogram of a 52-year-old woman demonstrates calcifi -
cations 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%


The answer is 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
classifi ed 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 54-year-old woman presents with a mass in her right breast
that she fi rst palpated 5 days before. A breast biopsy reveals
malignant cells, and a mastectomy is performed. Immunohistochemical
staining is performed for HER2/neu (shown in
the image). Which of the following genetic mechanisms best
accounts for the intensity of staining in this specimen?

(A) Gene amplification
(B) Insertional mutagenesis
(C) Chromosomal nonhomologous crossing over
(D) Polyploidy
(E) Single nucleotide polymorphism

The answer is A: Gene amplifi cation. Overexpression of HER2/
neu is identifi ed in 10% to 35% of primary breast tumors and
is mostly attributable to gene amplifi cation. Amplifi cation 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 the HER2/neu gene
using fl uorescent in situ hybridization. Patients whose tumors
demonstrate HER2 gene amplifi cation benefi t 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. A 45-year-old woman discovers a solitary, freely movable mass
in her right breast on self-examination, which is confi rmed
on physical examination. Mammography demonstrates focal
calcifi cation, with a linear confi guration in the region of the
breast mass. A breast biopsy (shown in the image) reveals
large, pleomorphic epithelial cells confi ned to dilated ducts,
with central zones of necrosis. What is the appropriate pathologic
(A) Colloid carcinoma
(B) Ductal carcinoma in situ, comedocarcinoma type
(C) Medullary carcinoma
(D) Phyllodes tumor
(E) Tubular carcinoma


The answer is 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 calcifi cation. 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 infl ammatory and fi broblastic
response in the surrounding stroma. The cancer may
extend within the duct system beyond the clinically detectable
tumor growth. The consequent diffi culties in obtaining
complete excision of the primary tumor frequently necessitate
mastectomy rather than “lumpectomy.” The chances of
local recurrence as 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
Diagnosis: Comedocarcinoma, ductal carcinoma in situ


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 fi xed to the overlying
skin. A lumpectomy is performed. The surgical specimen
is fi rm, 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
fi broadipose tissue. The tumor histology is shown in the
image. Which of the following risk factors has the strongest
association with this patient’s tumor?

(A) Exposure to carcinogens
(B) Family history
(C) Fibrocystic change
(D) Obesity
(E) Smoking


The answer is B: Family history. The strongest association
with an increased risk for breast cancer is a family history, specifi
cally breast cancer in fi rst-degree relatives (mother, sister,
or daughter). The risk is greater when the relative is affl icted
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 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
(A) Colloid carcinoma
(B) Lobular carcinoma in situ
(C) Malignant phyllodes tumor
(D) Medullary carcinoma
(E) Tubular carcinoma


The answer is 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 fi brosis and chronic
infl ammation 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”
fi nding 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 A 22-year-old woman nursing her newborn develops a tender
erythematous area around the nipple of her left breast. On
physical examination, a purulent exudate is observed to drain
from an open fi ssure. Culture of this exudate will most likely
grow which of the following microorganisms?
(A) Candida albicans
(B) Escherichia coli
(C) Haemophilus infl uenzae
(D) Lactobacillus acidophilus
(E) Staphylococcus aureus


The answer is E: Staphylococcus aureus. This lactating patient
has developed acute mastitis. The most common organisms
isolated are Staphylococcus and Streptococcus. Untreated,
the infection may progress to abscess formation, which is a
complication that necessitates surgical intervention. A fi rm,
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 A 52-year-old woman presents with a 3-month history of a
palpable breast mass. Physical examination confi rms 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 columns,
between strands of connective tissue (shown in the
image). Which of the following is the appropriate diagnosis?
(A) Ductal carcinoma in situ
(B) Invasive ductal carcinoma, tubular type
(C) Invasive lobular carcinoma
(D) Lobular carcinoma in situ
(E) Medullary carcinoma


The answer is C: Invasive lobular carcinoma. Invasive lobular
carcinoma is the second most common form of invasive breast
cancer. Because the amount of fi brosis is variable, the clinical
presentation of invasive lobular carcinoma varies from a
discrete fi rm mass, similar to ductal carcinoma, to a more subtle,
diffuse, indurated area. Microscopically, classic invasive
lobular carcinoma consists of single strands of malignant cells
infi ltrating between stromal fi bers, which is a feature termed
“Indian fi ling” (see photomicrograph). Despite the innocuous
cytologic characteristics of this form of invasive carcinoma,
it is biologically as aggressive as the invasive ductal type.
Twenty-fi ve percent of invasive carcinomas have features of
both ductal and lobular carcinoma. Lobular carcinoma in situ
(choice D) is confi ned 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


22 A 58-year-old woman has a screening mammography and is
found to have a 4-cm circumscribed mass, without calcifi cations,
in her left breast. An excisional biopsy shows solid nests
and sheets of highly pleomorphic cells, with many mitotic fi gures,
surrounded by a dense infi ltrate of lymphocytes. Which
of the following is the most likely diagnosis?
(A) Invasive ductal carcinoma
(B) Invasive lobular carcinoma
(C) Medullary carcinoma
(D) Paget disease
(E) Phyllodes tumor


The answer is C: Medullary carcinoma. Medullary carcinomas
present as fl eshy, bulky tumors measuring 5 to 10 cm in diameter.
They are generally larger at the time they are detected
than infi ltrating ductal carcinomas (average size, 2 to 3 cm).
This invasive tumor presents as a circumscribed mass that
lacks calcifi cations. On gross examination, medullary carcinoma
appears as a well-circumscribed, fl eshy, pale gray mass.
Microscopically, it is composed of sheets of cells that are
highly pleomorphic and have a high mitotic index. The pathologic
defi nition of medullary carcinoma includes a lymphoid
infi ltrate encompassing the periphery of the tumor. Despite
the highly malignant histologic appearance of this neoplasm,
it has a distinctly better prognosis than infi ltrating ductal or
lobular carcinoma. A dense lymphoid infi ltrate is not characteristic
of the other choices.
Diagnosis: Medullary carcinoma of the breast


23 A 45-year-old woman presents with an oozing, reddish patch
on her left nipple (patient shown in the image). The patient
has a history of skin rashes and food allergies and believes
this condition is due to an allergic reaction to her bra. Cytologic
examination of fl uid oozing from the skin lesion reveals
neoplastic cells. Excisional biopsy shows large clear malignant
cells in the epidermis of the areola. Which of the following is
the most likely diagnosis?
(A) Chronic dermatitis
(B) Colloid carcinoma
(C) Intraductal papilloma
(D) Paget disease
(E) Phyllodes tumor


The answer is 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 thenipple 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 A 60-year-old woman presents with a large breast mass that
she fi rst detected 3 months ago. Mammography reveals a wellcircumscribed
mass measuring 8 cm in diameter. A breast
biopsy shows loose fi broconnective tissue with a sarcomatous
stroma, abundant mitoses, and nodules and ridges lined by
cuboidal epithelial cells. Which of the following is the appropriate
(A) Fibroadenoma
(B) Medullary carcinoma
(C) Paget disease
(D) Phyllodes tumor
(E) Tubular carcinoma


The answer is 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 fi broadenomas in their overall architecture
and the presence of glandular and stromal elements. Like
fi broadenoma, benign phyllodes tumor is sharply circumscribed,
and the cut surface is fi rm, glistening, and grayish
white. Microscopically, the stroma of a benign phyllodes
tumor is hypercellular and has mitotic activity. The distinction
from fi broadenoma 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 A 65-year-old woman presents with a palpable breast mass that
she palpated 1 month earlier. Physical examination reveals a
soft, jelly-like tumor measuring 5 cm in diameter. Histologic
examination of a breast biopsy is shown in the image. What is
the appropriate diagnosis?

(A) Colloid carcinoma
(B) Lobular carcinoma
(C) Medullary carcinoma
(D) Paget disease
(E) Phyllodes tumor

The answer is A: Colloid carcinoma. Colloid (mucinous) carcinoma
is an invasive variant that tends to occur in older women.
On cut section colloid carcinoma has a glistening surface and
mucoid consistency. Histologically, it is composed of small
clusters of epithelial cells, occasionally forming glands, fl oating
in pools of extracellular mucin. In its pure form, colloid
carcinoma has a considerably better prognosis than infi ltrating
ductal or lobular carcinoma. However, it is often admixed
with infi ltrating ductal carcinoma, in which circumstance the
prognosis is determined by the ductal component. Abundant
mucin production is not a feature of the other choices.
Diagnosis: Mucinous carcinoma of the breast


26 A 55-year-old man presents with a solitary breast mass and
biopsy reveals malignant cells. Immunohistochemical staining
experiments show that the tumor cells are positive for HER2/
neu and cytokeratins 4 and 11 and negative for estrogen receptors.
What is the most likely diagnosis?
(A) Basal cell carcinoma
(B) Invasive ductal carcinoma
(C) Invasive lobular carcinoma
(D) Medullary carcinoma
(E) Tubular adenoma


The answer is 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 infi ltrating
(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


27 Which of the following is thought to play a role in the development
of cancer in the patient described in Question 26?
(A) BRCA2 mutation
(B) Chronic alcoholism
(C) Gynecomastia
(D) Hyperestrinism
(E) PTEN mutation


The answer is 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