DISCUSSION: Nipple discharge is surgically significant when it is grossly bloody and when it

appears at a single duct orifice on one nipple. Bloody discharge is usually due to a benign
intraductal papilloma; however, intraductal carcinoma in the large ducts under the nipple can be
the cause of bloody discharge, and pathologically the lesion is frequently a large papillary tumor
that has become malignant. Paget's disease of the nipple is also due to intraductal carcinoma
arising in subareolar ducts, but it rarely is associated with nipple discharge. Subareolar mastitis
may produce nipple discharge, but it is purulent and not bloody. Inflammatory carcinoma is not
associated with nipple discharge.

2. Which of the following conditions is associated with increased risk of breast cancer?
A. Fibrocystic mastopathy.
B. Severe hyperplasia.
C. Atypical hyperplasia.
D. Papillomatosis.
Answer: C

DISCUSSION: Fibrocystic mastopathy, or fibrocystic disease, was once thought to increase the
risk of breast cancer; however, later studies of the pathologic findings in fibrocystic complex
found an increased cancer risk only for patients whose biopsies showed atypical hyperplasia.
Severe hyperplasia is a pathologic term that refers to the amount of hyperplasia and is
frequently seen in the biopsy specimens of young women; it is a misleading term and is not
associated with a disease risk. Papillomatosis is also part of the fibrocystic complex and is a
frequent finding in benign breast biopsies; it does not confer an increased risk of cancer.

3. Which of the following breast lesions are noninvasive malignancies?

A. Intraductal carcinoma of the comedo type.
B. Tubular carcinoma and mucinous carcinoma.
C. Infiltrating ductal carcinoma and lobular carcinoma.
D. Medullary carcinoma, including atypical medullary lesions.
Answer: A

DISCUSSION: Tubular, mucinous, and medullary carcinomas are histologic variants of

infiltrating ductal cancer and are all invasive malignancies. Infiltrating lobular cancer is a
particular histologic variant of invasive breast cancer characterized by permeation of the stroma
with small cells that resemble those found in the breast lobule or acinus. Intraductal carcinoma
refers to a malignancy of ductal origin that remains enclosed within duct structures. This
noninvasive proliferation can undergo central necrosis, which frequently calcifies to form the
microcalcifications seen on mammography. The central necrosis within enlarged and back-to-
back ductal structures resembles comedoes and gives rise to the term comedocarcinoma, now
reserved for this histologic variety of intraductal carcinoma.

4. Which of the following are the most important and clinically useful risk factors for breast
cancer?
A. Fibrocystic disease, age, and gender.
B. Cysts, family history in immediate relatives, and gender.
C. Age, gender, and family history in immediate relatives.
D. Obesity, nulliparity, and alcohol use.
Answer: C

DISCUSSION: The most important risk factors for breast cancer are the patient's age, gender,
and a family history of breast cancer in immediate relatives (sisters, mother, daughter). The age-
adjusted incidence of breast cancer increases with age. Breast cancer does occur in males, but the
disease is far more common in women. Family history is important when breast cancer occurs
within the immediate family; history of breast cancer in more distant relatives (grandmothers,
cousins, aunts) is less important. In addition, age factors into the risk associated with family
history. An affected young primary relative is far more significant as a risk factor than an older
relative with breast cancer. The other important risk factor not listed here is a history of breast
cancer, either within the conserved ipsilateral breast or in the contralateral breast. Again, age
plays an important modifying role; as the age at which breast cancer was first diagnosed
increases, the risk of a subsequent second cancer decreases. Although patients with fibrocystic
disease are at increased risk for breast cancer, risk concentrates in those patients with fibrocystic
disease who show atypical epithelial hyperplasia within breast ducts. Obesity, nulliparity, and
alcohol all appear to increase risk slightly and are important to the epidemiologic study of breast
cancer; however, the effect of these factors is not sufficient to warrant their use in common
clinical practice.