Robbins - Unit 1 - Breast

Question 1

1. A 36-year-old woman has noticed a bloody discharge from the nipple of her right breast for the past 3 days. On physical
   examination, the skin of the breasts appears normal, and no masses are palpable. There is no axillary lymphadenopathy.
   The patient has regular menstrual cycles and is using oral contraceptives. Excisional biopsy is most likely to show which of
   the following lesions in her right breast?

□ (A) Fibroadenoma
□ (B) Phyllodes tumor
□ (C) Acute mastitis
□ (D) Intraductal papilloma
□ (E) Sclerosing adenosis

Answer 1

d) intraductal papilloma

1 (D) Intraductal papillomas are usually solitary and smaller than 1 cm. They are located in large lactiferous sinuses or
ducts, and have a tendency to bleed. Fibroadenomas contain ducts with stroma and are not highly vascular; these lesions
are not located in ducts. Phyllodes tumors also arise from intralobular stroma and can be malignant. They do not invade
ducts to cause bleeding. Abscesses complicating mastitis organize with a fibrous wall. Sclerosing adenosis, a lesion
occurring with fibrocystic changes, has abundant collagen, not vascularity

Question 2

A 28-year-old woman in the third trimester of her third pregnancy discovered a lump in her left breast. The physician
palpated a 2-cm, discrete, freely movable mass beneath the nipple. After the birth of a term infant, the mass appears to
decrease slightly in size. The infant breastfeeds without difficulty. What is the most likely diagnosis?
□ (A) Intraductal papilloma
□ (B) Phyllodes tumor
□ (C) Lobular carcinoma in situ
□ (D) Fibroadenoma
□ (E) Medullary carcinoma

Answer 2

d) fibroadenoma

D) Fibroadenomas are common and may enlarge during pregnancy or late in each menstrual cycle. Most intraductal
papillomas are smaller than 1 cm and are not influenced by hormonal changes. Phyllodes tumors are uncommon and tend
to be larger than 4 cm. Lobular carcinoma in situ is typically an ill-defined lesion without a mass effect. Medullary
carcinomas tend to be large; they account for only about 1% of all breast carcinomas.

Question 3

3 A 30-year-old woman sustained a traumatic blow to her right breast. Initially, there was a 3-cm contusion that resolved
within 3 weeks, but she then felt a firm lump that persisted below the site of the bruise 1 month later. What is the most
likely diagnosis for this lump?
□ (A) Fibroadenoma
□ (B) Sclerosing adenosis
□ (C) Fat necrosis
□ (D) Ductal carcinoma in situ
□ (E) Mammary duct ectasia

Answer 3

c) Fat necrosis

(C) Fat necrosis is typically caused by trauma to the breast. The damaged, necrotic fat is phagocytosed by
macrophages, which become lipid laden. The lesion resolves as a collagenous scar within weeks to months. The firm scar
can mammographically and grossly resemble a carcinoma, however. A fibroadenoma is a neoplasm, and tumors are not
induced by trauma. Sclerosing adenosis is a feature of fibrocystic changes, a common cause of nontraumatic breast
lumps. An intraductal carcinoma may not form a palpable mass lesion. Mammary duct ectasia from inspissated secretions
can induce chronic inflammation and fibrosis, which mimic a carcinoma.

Question 4

4. A 55-year-old man has developed bilateral breast enlargement over the past year. On physical examination, the
   enlargement is symmetric and is not painful to palpation. There are no masses. The patient is not obese and is not taking
   any medications. Which of the following underlying conditions best accounts for these findings?
   □ (A) Micronodular cirrhosis
   □ (B) Chronic glomerulonephritis
   □ (C) Choriocarcinoma of the testis
   □ (D) ACTH-secreting pituitary adenoma
   □ (E) Rheumatoid arthritis

Answer 4

a) micronodular cirrhosis

(A) Micronodular cirrhosis is most often a consequence of chronic alcoholism and impairs hepatic estrogen metabolism,
which can lead to gynecomastia. Chronic renal failure is unlikely to have this consequence. Choriocarcinomas of the testis
produce human chorionic gonadotropin, not estrogens. ACTH-secreting pituitary adenomas cause truncal obesity because
of Cushing syndrome. Rheumatoid nodules can appear in various locations along with rheumatoid arthritis, but they rarely
occur in the breast and are unlikely to be bilateral

Question 5

5. A 44-year-old woman sees her physician because she felt a lump in her left breast 1 week ago. The physician palpates
   a firm, irregular mass in the upper outer quadrant of the left breast. There are no overlying skin lesions. The gross
   appearance of the excisional biopsy specimen is shown in the figure. Which of the following additional findings is most
   likely to be present on physical examination?
   □ (A) Axillary lymphadenopathy
   □ (B) Bloody discharge from the nipple
   □ (C) Painful breast enlargement
   □ (D) Mass in the opposite breast
   □ (E) Cushingoid face

Answer 5

a) Axillary lymphadenopathy

(A) This irregular, infiltrative mass is an infiltrating (invasive) ductal carcinoma, the most common form of breast cancer.
Breast carcinomas are most likely to metastasize to regional lymph nodes. By the time a breast cancer becomes palpable,
lymph node metastases are present in more than 50% of patients. A bloody discharge from the nipple most often results
from an intraductal papilloma. Pain with breast enlargement suggests inflammation. Lobular carcinomas are more often
bilateral, but they are less common than infiltrating ductal carcinomas. Breast cancers are associated in rare cases with
ectopic corticotropin secretion or Cushing syndrome.

Question 6

6 A 25-year-old woman sees her physician because she has noticed a lump in her right breast. The physician palpates a
2-cm, firm, circumscribed mass in the lower outer quadrant. The figure shows the excised mass (A) and the mammogram
(B). What is the most likely diagnosis?
□ (A) Phyllodes tumor
□ (B) Fibrocystic changes
□ (C) Fibroadenoma
□ (D) Fat necrosis
□ (E) Infiltrating ductal carcinoma
□ (F) Mastitis

Answer 6

c) fibroadenoma

(C) Grossly and radiographically, this patient has a discrete mass that in a woman her age is most likely a
fibroadenoma. Phyllodes tumors are typically much larger and are far less common. Fibrocystic changes are generally
irregular lesions, not discrete masses. Fat necrosis and infiltrating cancers are masses with irregular outlines. Mastitis has
a more diffuse involvement, without mass effect

Question 7

7. A 47-year-old woman has noticed a red, scaly area of skin on her left breast that has grown slightly larger over the past
   4 months. On physical examination, there is a 1-cm area of eczematous skin just lateral to the areola. The figure shows
   the microscopic appearance of the skin biopsy specimen. What is the most likely diagnosis?
   □ (A) Apocrine metaplasia
   □ (B) Paget disease of the breast
   □ (C) Inflammatory carcinoma
   □ (D) Lobular carcinoma in situ
   □ (E) Fat necrosis

Answer 7

b) Paget’s dz of the breast

(B) Paget cells are large cells that have clear, mucinous cytoplasm and infiltrate the skin. They are malignant and
extend to the skin from an underlying breast carcinoma. Apocrine metaplasia affects the cells lining the cystically dilated
ducts in fibrocystic change. “Inflammatory carcinoma” does not refer to a specific histologic type of breast cancer; rather, it
describes the involvement of dermal lymphatics by infiltrating carcinoma. In lobular carcinoma in situ, terminal ducts or
acini are filled with neoplastic cells. The overlying skin is unaffected. The macrophages in fat necrosis do not infiltrate the
skin and do not have the atypical nuclei seen in the figure.

Question 8

8 Three weeks after giving birth to a normal term infant, a 24-year-old woman is breastfeeding the infant and notices
fissures in the skin around her left nipple. Over the next 3 days, the region around the nipple becomes erythematous and
tender. Purulent exudate from a small abscess drains through a fissure. Which of the following organisms is most likely to
be cultured from the exudate?
□ (A) Listeria monocytogenes
□ (B) Streptococcus viridans
□ (C) Candida albicans
□ (D) Staphylococcus aureus
□ (E) Lactobacillus acidophilus

Answer 8

d) Staph aureus

(D) Staphylococcal acute mastitis typically produces localized abscesses, whereas streptococcal infections tend to
spread throughout the breast. Listeriosis can be spread by contaminated food, including milk products, not by human milk.
Candida may cause some local skin irritation, but is likely to become invasive only in immunosuppressed patients.
Lactobacillus acidophilus is the organism used to produce fermented nonhuman milk.

Question 9

9 A 27-year-old woman feels a lump in her right breast. She has normal menstrual cycles, she is G3, P3, and her last child
was born 5 years ago. The physician palpates a 2-cm, irregular, firm area beneath the lateral edge of the areola. The
mass is not painful and does not feel firm. There are no lesions of the overlying skin and no axillary lymphadenopathy. A
biopsy specimen shows microscopic evidence of an increased number of ducts, which are compressed because of
proliferation of fibrous connective tissue. Dilated ducts with apocrine metaplasia also are present. What is the most likely
diagnosis?
□ (A) Traumatic fat necrosis
□ (B) Fibrocystic changes
□ (C) Mammary duct ectasia
□ (D) Fibroadenoma
□ (E) Infiltrating ductal carcinoma

Answer 9

b) fibrocystic changes

(B) Fibrocystic changes account for the largest category of breast lumps, statistically about 40% of all breast “lumps.”
These lesions are probably related to cyclic breast changes that occur during the menstrual cycle. In about 30% of cases
of breast lumps, no specific pathologic diagnosis can be made. Fibrocystic changes include ductal proliferation, ductal
dilation (sometimes with apocrine metaplasia), and fibrosis. Fat necrosis may produce a localized, firm lesion that mimics
carcinoma, but histology shows macrophages and neutrophils surrounding necrotic adipocytes, and healing leaves a
Robbins & Cotran Review of Pathology Pg. 482
fibrous scar. Inspissated duct secretions may produce duct ectasia with a surrounding lymphoplasmacytic infiltrate. A
fibroadenoma is a discrete mass formed by a proliferation of fibrous stroma with compressed ductules. Carcinomas have
proliferations of atypical neoplastic cells that fill ducts and can invade stroma.

Question 10

10 A 44-year-old woman noticed a lump in her right breast. On examination, she has an ill-defined, 1-cm mass in the upper
outer quadrant. The mass is cystic on ultrasound. An excision is done, and the mass shows predominantly fibrocystic
changes, but carcinoma also is present. Fine-needle aspirates of both breasts reveal additional foci of similar malignant
cells. Which of the following breast carcinomas is most likely to produce these findings?
□ (A) Ductal carcinoma
□ (B) Lobular carcinoma
□ (C) Malignant phyllodes tumor
□ (D) Medullary carcinoma
□ (E) Mucinous (colloid) carcinoma

Answer 10

b) Lobular carcinoma

(B) Among primary malignancies of the breast, lobular carcinoma in situ (LCIS) is most likely to be bilateral. LCIS may
precede invasive lesions by several years. Lobular carcinoma may be mixed with ductal carcinoma, and it may be difficult
to distinguish them histologically. The other neoplasms listed are less likely to be bilateral and more likely to produce a
mass effect.

Question 11

11 A 56-year-old woman sees her physician for a routine health examination. There are no remarkable findings on
physical examination. A mammogram shows a 0.5-cm irregular area of increased density with scattered microcalcifications
in the upper outer quadrant of the left breast. Excisional biopsy shows atypical lobular hyperplasia. The patient has been
on postmenopausal estrogen-progesterone therapy for the past 10 years. She has smoked 1 pack of cigarettes per day for
the past 35 years. Which of the following conclusions is most pertinent to these findings?
□ (A) She has the BRCA1 gene mutation
□ (B) The postmenopausal estrogen replacement therapy should be stopped
□ (C) Her risk of breast carcinoma is increased
□ (D) She should undergo bilateral simple mastectomies
□ (E) She should stop smoking

Answer 11

c) her risk of breast carcinoma is increased

(C) Atypical lobular hyperplasia and atypical ductal hyperplasia increase the risk of breast cancer fivefold; the risk
affects both breasts and is higher in premenopausal women or women who have a family history of breast cancer. The
BRCA1 mutation accounts for about 10% to 20% of familial breast carcinomas and only a few percent of all breast
cancers. Mastectomies are probably not warranted at this time, but close follow-up is needed. Smoking and exogenous
estrogen therapy are not well-established risk factors for breast cancer

Question 12

12 A 54-year-old woman sees her physician after feeling a lump in her left breast. The physician palpates a firm, irregular
mass in the lower outer quadrant just beneath the lateral margin of the areola. A mammogram shows a 2-cm density with
focal microcalcifications. Excisional biopsy shows intraductal and invasive components of a breast carcinoma.
Immunohistochemical staining shows that the cells are positive for HER2/neu expression, but negative for estrogen
receptor and progesterone receptor expression. Flow cytometry shows a small aneuploid peak and a low S-phase. When
combined with doxorubicin, which of the following drugs is most likely to be useful in treating this patient?
□ (A) Hydroxyurea
□ (B) Celecoxib
□ (C) Raloxifene
□ (D) Tamoxifen
□ (E) Trastuzumab

Answer 12

e) Trastuzamab

(E) The expression of HER2/neu suggests that biotherapy with trastuzumab may have some effectiveness. Drug
names with the suffix -mab are monoclonal antibodies that target a specific biochemical component of cells. This form of
biotherapy is useful because normal breast cells do not have HER2/neu expression. Doxorubicin is a standard
chemotherapeutic agent that is part of various multiagent protocols. Hydroxyurea is a cycle-acting agent that is not useful
in breast cancer. Celecoxib is an inhibitor of cyclooxygenase-2 in the arachidonic acid pathway that forms prostaglandins
as part of an inflammatory reaction. Tamoxifen is an antiestrogenic compound that has effectiveness in the treatment of
breast cancers positive for estrogen receptor.

Question 13

13 A 55-year-old woman has felt a poorly defined lump in her right breast for the past year. On examination, she has a
nontender, firm, 6-cm mass in the upper inner quadrant. There are no lesions of the overlying skin and no axillary
lymphadenopathy. Needle biopsy is done, and microscopic examination of the specimen shows cellular stroma protruding
into spaces lined by a single-layer cuboidal epithelium. The mass is excised with a wide margin, but recurs 1 year later.
After further excision, the lesion does not recur. What is the most likely diagnosis?
□ (A) Fibroadenoma
□ (B) Fibrocystic changes
□ (C) Lobular carcinoma
□ (D) Phyllodes tumor
□ (E) Tubular carcinoma

Answer 13

d) phyllodes tumor

(D) Phyllodes tumors, although grossly and microscopically similar to fibroadenomas, occur at an older age, are larger,
and are more cellular; they can recur locally, but rarely metastasize. Fibrocystic changes can produce a breast lump, but
usually not as large as 6 cm, and without firm areas of cellular stroma. A lobular carcinoma has malignant-appearing
epithelial cells in clusters and rows and may not even produce a mass effect. Tubular carcinomas of the breast are
uncommon, most are less than 1 cm in diameter, and most have small tubular structures in a noncellular stroma.

Question 14

14 A 51-year-old woman has noticed an area of swelling with tenderness in her right breast that has worsened over the
past 2 months. On physical examination, the 7-cm area of erythematous skin is tender and firm. There is swelling of the
right breast, nipple retraction, and right axillary lymphadenopathy. Excisional biopsy is most likely to show which of the
following lesions?
□ (A) Atypical epithelial hyperplasia
□ (B) Phyllodes tumor
□ (C) Fat necrosis
□ (D) Sclerosing adenosis
□ (E) Infiltrating ductal carcinoma

Answer 14

e) Infiltrating ductal carcinoma

(E) The gross appearance of the skin is consistent with invasion of dermal lymphatics by carcinoma—the so-called
inflammatory carcinoma. Nipple retraction and axillary lymphadenopathy also suggest invasive ductal carcinoma. Atypical
ductal hyperplasia may increase the risk of carcinoma, but it does not produce visible surface skin changes. A phyllodes
tumor can be large and sometimes tender, but the overlying skin is typically not affected, and spread to lymph nodes is
uncommon. The feel of fat necrosis on palpation can mimic that of carcinoma, but the skin is not involved. Sclerosing
adenosis is a feature of benign fibrocystic changes and has no skin involvement

Question 15

15 A 39-year-old woman has noticed an enlarging mass in her left breast for the past 2 years. The physician palpates a 4-
cm firm mass. A simple mastectomy is performed with axillary lymph node sampling and plastic reconstruction of the
breast. On gross sectioning, the mass has a soft, tan, fleshy surface. Histologically, the mass is composed of large cells
with vesicular nuclei and prominent nucleoli. There is a marked lymphocytic infiltrate within the tumor, and the tumor has a
discrete, noninfiltrative border. No axillary node metastases are present. The tumor cells are negative for estrogen
receptor and progesterone receptor. What is the most likely diagnosis?
□ (A) Colloid carcinoma
□ (B) Fibroadenoma
□ (C) Infiltrating ductal carcinoma
□ (D) Infiltrating lobular carcinoma
□ (E) Intraductal papilloma
□ (F) Medullary carcinoma
□ (G) Papillary carcinoma
□ (H) Phyllodes tumor

Answer 15

f) medullary carcinoma

(F) Medullary carcinomas account for about 1% to 5% of all breast carcinomas. They tend to occur in women at
younger ages than do most other breast cancers. Despite poor prognostic indicators, such as absence of estrogen
receptors and progesterone receptors (ER-PR), medullary carcinomas have a better prognosis than most other breast
cancers. Perhaps the infiltrating lymphocytes are helpful. Colloid carcinomas occur about as frequently as medullary
carcinomas, but they are often positive for ER-PR, and the prognosis is better than average. Fibroadenomas are small
benign lesions that tend to stop enlarging after menopause, when hormonal stimulation has ceased. Infiltrating ductal and
infiltrating lobular carcinomas tend not to produce large, localized lesions because they are more invasive, and they lack a
distinct lymphoid infiltrate. Intraductal papillomas are unlikely to be larger than 1 cm. True papillary carcinomas are quite
rare, although other types of breast carcinoma may have a papillary component. The phyllodes tumor is typically large, but
it has stromal and glandular components

Question 16

16 A 47-year-old woman has a routine health examination. There are no remarkable findings except for a barely palpable
mass in the right breast. A mammogram shows an irregular, 1.5-cm area of density in the upper outer quadrant. Scattered
microcalcifications are present in the density. A biopsy specimen from this area shows atypical ductal hyperplasia. Which
of the following is the most appropriate advice to give to this patient?
□ (A) There is a risk of cancer in the opposite breast
□ (B) A mastectomy should be performed
□ (C) These changes are related to smoking cigarettes
□ (D) Antibiotic therapy is indicated to treat the lesion
□ (E) The BRCA1 oncogene has been inherited

Answer 16

a) risk of cancer in the opposite breast

(A) Fibrocystic changes without epithelial hyperplasia do not suggest an increased risk of breast cancer. Moderate to
florid hyperplasia increases the risk twofold, and atypical ductal or lobular hyperplasias increase the risk fivefold. The risk
in this patient is not great enough to suggest radical or simple mastectomy at this time. Breast cancers are not associated
with tobacco use. These changes are not the result of infection. The BRCA1 gene accounts for a small percentage of
breast cancers, primarily in families in which cancer onset occurs at a young age.

Question 17

17 A 25-year-old Jewish woman sees her physician after finding a lump in her right breast. On physical examination, a 2-
cm, firm, nonmovable mass is palpated in the upper outer quadrant. No overlying skin lesions and no axillary
lymphadenopathy are present. The figure shows an excisional biopsy specimen. The family history indicates that the
patient’s mother, maternal aunt, and maternal grandmother have had similar lesions. Her 18-year-old sister has asked a
physician to determine whether she is genetically at risk of developing a similar disease. The physician is most likely to
order an analysis of which of the following genes?
□ (A) HER2/neu
□ (B) MYC
□ (C) BRCA1
□ (D) RB
□ (E) Estrogen receptor gene

Answer 17

c) BRCA 1

(C) The biopsy specimen shows an invasive breast cancer. Given the young age of the patient and the strong family
history of breast cancer, it is reasonable to assume that she has inherited an altered gene that predisposes to breast
cancer. There are two known breast cancer susceptibility genes: BRCA1 and BRCA2. Both are cancer suppressor genes.
Specific mutations of BRCA1 are common in some ethnic groups, such as Ashkenazi Jews. HER2/neu is a growth factor
receptor gene that is amplified in certain breast cancers and is a marker of poor prognosis, not susceptibility. Inheritance
o f RB1 mutations predisposes to retinoblastoma and osteosarcomas, not breast carcinomas. Estrogen receptors are
expressed in 50% to 75% of breast cancers. Their presence bodes well for therapy with receptor antagonists. There is no
known relationship between the structure of the estrogen receptor gene and susceptibility to breast cancer.

Question 18

18 A study of women with breast carcinoma is done to determine the presence and amount of estrogen receptor (ER) and
progesterone receptor (PR) in the carcinoma cells. Large amounts of ER and PR are found in the carcinoma cells of some
patients. These receptors are not present in the cells of other patients. The patients with positivity for ER-PR are likely to
exhibit which of the following traits?
□ (A) Higher response to therapy
□ (B) Increased immunogenicity
□ (C) Greater risk of familial breast cancer
□ (D) Higher tumor stage
□ (E) Greater likelihood of metastases
□ (F) Greater aneuploidy with flow cytometry
□ (G) Higher tumor grade

Answer 18

A) Higher response to therapy

(A) The estrogen receptor and progesterone receptor (ER-PR) status helps predict whether chemotherapy with
antiestrogen compounds such as tamoxifen would be effective; however, the correlation is not perfect. The ER and PR do
not affect immunogenicity and are not targets for immunotherapy. In contrast, immunotherapy targeted to the
overexpressed HER2/neu gene is being used. The overall prognosis may be predicted from several factors, including
histologic type, histologic grade, presence of metastases, degree of aneuploidy, and tumor stage. A family history and the
presence of specific mutations such as BRCA1 or BRCA2 correlate with familial risk of breast cancer.

Question 19

19 A 50-year-old woman has a routine health examination. There are no remarkable findings on physical examination, but
a mammogram shows a 1-cm, irregular density in the right breast. A fine-needle aspirate of the lesion contains malignant
cells. The mass is excised, and axillary lymph node sampling is performed. The microscopic features of the neoplasm are
consistent with ductal carcinoma in situ. There are no lymph node metastases. She receives radiation therapy. Which of
the following statements provides the most appropriate advice to the patient?
□ (A) You will probably survive less than 5 years
□ (B) Another cancer is probably present in the opposite breast
□ (C) Distant metastases are unlikely to be found
□ (D) Your family members should be screened for BRCA1 and BRCA2 mutations
□ (E) Flow cytometry can determine whether chemotherapy is warranted

Answer 19

c) distant metasteses are unlikely

(C) At least half of mammographically detected breast cancers are ductal carcinoma in situ (DCIS). This in situ
carcinoma is highly unlikely to metastasize because the cells lack the ability to invade basement membrane. With surgical
excision and radiotherapy, the 5-year survival rate is high, although some tumors may progress to invasive lesions over
time. Lobular carcinomas are most likely to be present in the opposite breast. Patients with BRCA1 or BRCA2 mutations
can have familial breast carcinomas. In these patients, there is usually a strong family history, and the age of onset may be
early. The occurrence of a sporadic breast cancer in a racial group that is not at high risk of familial cancer does not
warrant mutational analysis of BRCA1 and BRCA2. Flow cytometry is useful to suggest prognosis, not treatment

Question 20

20 A 79-year-old, previously healthy woman feels a lump in her right breast. The physician palpates a 2-cm firm mass in
the upper outer quadrant. Nontender right axillary lymphadenopathy is present. A lumpectomy with axillary lymph node
dissection is performed. Microscopic examination shows that the mass is an infiltrating ductal carcinoma. Two of 10 axillary
nodes contain metastases. Flow cytometry on the carcinoma cells shows a small aneuploid peak and high S-phase.
Immunohistochemical tests show that the tumor cells are positive for estrogen receptor, negative for HER2/neu
expression, and positive for cathepsin D expression. What is the most important prognostic factor for this patient?
□ (A) Age
□ (B) Histologic subtype of carcinoma
□ (C) DNA content in the carcinoma
□ (D) Presence of lymph node metastases
□ (E) Expression of stromal proteases in the carcinoma
□ (F) Estrogen receptor positivity
□ (G) Lack of HER2/neu expression in the carcinoma.

Answer 20

d) presence of lymph node metasteses

(D) Many factors affect the course of breast cancer. The involvement of axillary lymph nodes is the most important
prognostic factor. If there is no spread to axillary nodes, the 10-year survival rate is almost 80%. It decreases to 35% to
40% with 1 to 3 positive nodes and to 15% with more than 10 positive nodes. Increasing age is a risk of breast cancer, but
age alone does not indicate a prognosis, and treatment of cancers in the elderly can be successful. Some histologic types
of breast cancer have a better prognosis than others, but staging is a more important factor than histologic type. An
increased DNA content with aneuploidy and a high S-phase suggests a worse prognosis, but staging is still a more
important determinant of prognosis. The expression of stromal proteases, such as cathepsin D, predicts metastases, but in
this case “the horse is out of the barn,” and metastasis has occurred. Estrogen receptor positivity suggests a better
response to hormonal manipulation of the tumor, whereas expression of HER2/neu suggests responsiveness to biotherapy
with the monoclonal antibody trastuzumab.

Question 21

21 A 29-year-old woman and her 32-year-old sister were diagnosed with infiltrating ductal carcinoma of the breast, and
both had bilateral mastectomies. Which of the following risk factors is most significant for this type of cancer?
□ (A) Oral contraceptive use
□ (B) Inheritance of a mutant p53 allele
□ (C) Obesity
□ (D) Multiparity
□ (E) Smoking cigarettes

Answer 21

b) inheritance of a mutant p53 allele

(B) Bilateral breast cancer in very young women in the same family suggests a germline mutation in a tumorsuppressor
gene. The affected genes may be BRCA1, BRCA2, or p53. The BRCA1 and BRCA2 genes account for most
hereditary breast cancers. Establishment of other risk factors is not as secure. Multiparity reduces the risk of breast
cancer.

Question 22

22 A 63-year-old woman feels a small lump in her right breast. The physician palpates a firm area that has a cordlike feel.
No lesions of the overlying skin are present, and there is no axillary lymphadenopathy. A mammogram shows a density
that contains microcalcifications. An excisional biopsy specimen contains soft, white material that is extruded from small
ducts when pressure is applied. Microscopic examination shows ducts that contain large, atypical cells in a cribriform
pattern. What is the most likely diagnosis?
□ (A) Colloid carcinoma
□ (B) Infiltrating ductal carcinoma
□ (C) Infiltrating lobular carcinoma
□ (D) Comedocarcinoma
□ (E) Medullary carcinoma
□ (F) Paget disease of the breast
□ (G) Papillary carcinoma
□ (H) Phyllodes tumor

Answer 22

d) comedocarcinoma

(D) An intraductal carcinoma, or ductal carcinoma in situ (DCIS), may not produce a palpable mass. The necrosis of
the neoplastic cells in the ducts leads to calcification, and the necrotic cells can be extruded from the ducts, giving rise to
the term comedocarcinoma. Such intraductal carcinomas represent about one fourth of all breast cancers. If not excised,
Robbins & Cotran Review of Pathology Pg. 484
the term comedocarcinoma. Such intraductal carcinomas represent about one fourth of all breast cancers. If not excised,
such lesions become invasive. Intraductal carcinoma has several other histologic patterns, including noncomedo DCIS and
Paget disease of the nipple, in which extension of the malignant cells to the skin of the nipple and areola produces the
appearance of a seborrheic dermatitis. Colloid carcinomas occur about as frequently as medullary carcinomas, but they
are often positive for estrogen receptor and progesterone receptor, and the prognosis is better than average. Infiltrating
ductal carcinomas tend to produce irregular, firm, mass lesions because they are more invasive. Infiltrating lobular
carcinomas can have a diffuse pattern without significant mass effect. Medullary carcinomas tend to be large masses;
microscopically, they have nests of large cells with a surrounding lymphoid infiltrate. True papillary carcinomas are rare,
although a papillary component may be present in other types of breast carcinoma. The phyllodes tumor is typically large,
but it has stromal and glandular components

Question 23

23 An epidemiologic study is conducted with male subjects who have been diagnosed with breast carcinoma. Their
demographic data, past medical histories, family histories, and laboratory data are examined to identify factors that
increase the risk of cancer. Which of the following factors is most likely to increase significantly the risk of developing male
breast carcinoma?
□ (A) Gynecomastia
□ (B) Age older than 70 years
□ (C) Asian ancestry
□ (D) Chronic alcoholism
□ (E) BRCA1 gene mutation

Answer 23

b) age older than 70

(B) Male breast cancers are rare, and they occur primarily among the elderly. Additional risk factors include firstdegree
relatives with breast cancer, decreased testicular function, exposure to exogenous estrogens, infertility, obesity,
prior benign breast disease, exposure to ionizing radiation, and residency in Western countries. Gynecomastia does not
seem to be a risk factor. Of cases in men, 4% to 14% are attributed to germline BRCA2 mutations.

Question 24

24 A clinical study is performed on postmenopausal women living in Tampa, Florida, who are between the ages of 45 and
70 years. All have been diagnosed with infiltrating ductal carcinoma positive for estrogen receptor (ER) and progesterone
receptor (PR), which has been confirmed by biopsy and microscopic examination of tissue. None has the BRCA1 or
BRCA2 mutation. Which of the following is most likely to indicate the highest relative risk of developing the carcinomas
seen in this group of women?
□ (A) Age at menarche older than 16 years
□ (B) Age at menopause younger than 45 years
□ (C) First-degree relative with breast cancer
□ (D) Smoking cigarettes (>40 pack-years)

Answer 24

c) first degree relative with breast cancer

(C) The relative risk of breast cancer increases with various factors, but family history is one of the strongest. A history
of bilateral breast disease and earlier age of onset of cancer increase the risk. The earlier age of onset increases the risk
of BRCA1 or BRCA2. A longer reproductive life, with early menarche (<11 years old) and late menopause (>55 years old),
and nulliparity increase the risk of breast cancer, probably because of increased estrogen exposure. “Soft” risk factors
include exogenous estrogens, obesity, and smoking. Mastitis does not affect the risk of breast cancer.

Question 25

25 A 26-year-old woman has felt a breast lump for the past month and is worried because she has a family history of earlyonset
and bilateral breast cancers. On physical examination, there is a firm, 2-cm mass in the upper outer quadrant of her
left breast. A biopsy is done, and the specimen microscopically shows carcinoma. Genetic analysis shows that she is a
carrier of the BRCA1 gene mutation, as are her mother and sister. Which of the following histologic types of breast
carcinoma has the highest incidence in families such as hers?
□ (A) Lobular carcinoma
□ (B) Tubular carcinoma
□ (C) Metaplastic carcinoma
□ (D) Papillary carcinoma
□ (E) Medullary carcinoma

Answer 25

e) Medullary carcinoma

(E) Patients with the BRCA1 gene mutation have a high incidence of medullary carcinomas that are poorly
differentiated, do not express the HER2/neu protein, and are negative for estrogen and progesterone receptors.

Question 26

26 A study of gene expression profiling involving breast biopsies showing invasive carcinoma of no specific type (NST) is
performed. A subset of these cases, comprising about 15% of all cases, has the following characteristics: estrogen
receptor (ER) and progesterone receptor (PR) negative, HER2/neu negative, basal keratin positive, flow cytometry
showing aneuploidy and high proliferation rate, and association with BRCA1 mutations. Which of the following therapies is
most likely to be effective in women with this subset of NST breast cancer?
□ (A) Chemotherapy
□ (B) Radiation
□ (C) Surgery alone
□ (D) Tamoxifen
□ (E) Trastuzumab

Answer 26

a) Chemotherapy

(A) This is the “basal-like” subset of NST breast cancers that is “triple negative” for the usual immunohistochemical
markers. Hence, lack of ER positivity predicts antihormonal therapy with tamoxifen will not be of benefit, and lack of
HER2/neu indicates that trastuzumab will be ineffective. The basal-like cancers are highly aggressive and tend to
metastasize early, so containment with surgery or radiation is unlikely. However, some of them are cured by
chemotherapy. This emphasizes the importance of gene expression profiling, so that treatment is individualized to each
cancer patient for the best chance of success.

Question 27

27. A Tumor Registry tracks patients diagnosed with breast cancer. Statistical analyses are performed regarding survival of
    these patients. Which of the following parameters recorded for these breast cancers is most likely to show the strongest
    correlation with longer patient survival?
    □ (A) Dietary intake
    □ (B) Family history
    □ (C) Gene expression profile
    □ (D) Histologic type
    □ (E) Place of birth
    □ (F) Tumor size

Answer 27

f) Tumor size

(F) The earlier a cancer can be detected, the smaller it is, the less chance it has had to acquire mutations giving it
more aggressive characteristics, and the better the prognosis—simple but profound, and the rationale for cancer
screening. However, broad population screening is difficult to institute in practice. Breast self examination is important, but
too insensitive to detect cancers smaller than 2 cm, so regular mammographic screening is the best tool. Family history
and geography are major influences, and diet a minor influence, on likelihood of developing breast cancer, but don’t
predict prognosis. Once a cancer is diagnosed, the gene expression profile along with histologic type are most important in
determining therapy, but may also help in predicting prognosis. Presence of metastasis is the best (but undesirable)
prognostic factor Finding a breast cancer <1 cm with no metastases predicts a >90% 10-year survival.