Babylon University
Colleague of Medicine
Dr.Ahmed Raji
Fourth Stage
Lecture 2
Breast Pathology
Benign Epithelial Lesions
The benign epithelial lesions of the breast have been divided into three groups,
according to the risk of developing breast cancer:
(1) Nonproliferative breast changes.
(2) Proliferative breast disease.
(3) Atypical hyperplasia.
Nonproliferative Breast Changes (Fibrocystic Changes)
This group includes a number of morphologic changes which includes: cystic changes,
fibrosis, adenosis, which are often grouped under the term fibrocystic changes.
These lesions are termed nonproliferative to distinguish them from “proliferative”
changes, which are associated with a more increased risk of breast cancer.
These changes usually present as ill-defined mass.
Morphology.
(1) Cystic change:
Small cysts form by the dilation of lobules, and it may coalesce to form larger cysts.
Cysts are lined either by a flattened atrophic epithelium or by metaplastic apocrine cells,
and contain turbid, semi-translucent fluid, the diagnosis is confirmed by the
disappearance of the cyst after fine-needle aspiration of its contents.
(2) Fibrosis:
Cysts frequently rupture, releasing secretory material into the adjacent stroma. The
resulting chronic inflammation and fibrosis contribute to the palpable firmness of the
breast.
(3) Adenosis (blunt duct adenosis):
Adenosis is defined as an increase in the number of acini per lobule. A normal
physiologic adenosis occurs during pregnancy, the acini are often enlarged but are not
distorted.
Proliferative Breast Disease without Atypia
These are group of changes that are commonly detected as
1 - Mammographic densities
2 - Mammographic calcifications
3 - Incidental findings in specimens from biopsies performed for other reasons.
4 - As nipple discharge: more than 80% of large duct papillomas produce a nipple
discharge
5 - As small palpable masses.
Although each lesion can be found in isolation, typically more than one lesion is present
together.
These lesions are characterized by proliferation of ductal epithelium and/or stroma
without cytologic or architectural features suggestive of carcinoma.
These changes includes: moderate or florid epithelial hyperplasia, sclerosing adenosis,
papilloma, complex sclerosing lesion (radial scar) and fibroadenoma.
Epithelial Hyperplasia: Normal breast ducts and lobules are lined by a double layer
of myoepithelial cells and luminal cells, epithelial hyperplasia is defined by the
presence of more than two cell layers.
Papillomas: Papillomas are composed of multiple branching fibrovascular cores, each
having a connective tissue axis lined by luminal and myoepithelial cells, growth
occurs within a dilated duct.
Fibroadenoma: This is the most common benign tumor of the female breast, most
occur in women in their 20s and 30s, and they are frequently multiple and bilateral.
The epithelium of the fibroadenoma is hormonally responsive, and an increase in size
due to lactational changes during pregnancy, which may be complicated by infarction
and inflammation, can mimic carcinoma. The stroma often becomes densely hyalinized
after menopause and may calcify.
Fibroadenomas were originally grouped with other “proliferative changes without
atypia” in conferring a mild increase in the risk of subsequent cancer. However, in one
study the increased risk was limited to fibroadenomas associated with cysts larger than
0.3 cm, sclerosing adenosis, epithelial calcifications, or papillary apocrine change
(“complex fibroadenomas”)
Morphology of fibroadenoma:
Grossly
freely movable, well-circumscribed, rubbery, grayish white nodules that vary in size
from less than 1 cm to large tumors that can replace most of the breast and often
contain slitlike spaces.
Microscopically
Delicate, cellular, and often myxoid stroma resembles normal intralobular stroma. The
epithelium may be surrounded by stroma or compressed and distorted by it, in older
women, the stroma typically becomes densely hyalinized and the epithelium atrophic.
Proliferative Breast Disease with Atypia
Proliferative disease with atypia includes
1 - Atypical ductal hyperplasia and
2 - Atypical lobular hyperplasia.
Atypical ductal hyperplasia is present in 5% to 17% of specimens from biopsies
performed for calcifications and is found less frequently in specimens from biopsies for
mammographic densities or palpable masses.
Atypical lobular hyperplasia is an incidental finding and is found in fewer than 5% of
specimens from biopsies performed for any reason.
Morphology.
Atypical ductal hyperplasia consists of a relatively monomorphic proliferation of
regularly spaced cells, sometimes with cribriform spaces. It is distinguished from
DCIS by being limited in extent and only partially filling ducts.
Atypical lobular hyperplasia consist of a proliferation of cells identical to those of
lobular carcinoma in situ, but the cells do not fill or distend more than 50% of the
acini within a lobule.
Clinical Significance of Benign Epithelial Changes
Multiple epidemiologic studies have classified the benign changes in the breast and
determined their association with the later development of invasive cancer.
Nonproliferative changes do not increase the risk of cancer.
Proliferative disease is associated with a mild increase in risk.
Proliferative disease with atypia confers a moderate increase in risk.
Both breasts are at increased risk.
Risk reduction can be achieved by bilateral prophylactic mastectomy or treatment with
estrogen antagonists, such as tamoxifen.
However, more than 80% of women with atypical hyperplasia will not develop breast
cancer, and many choose careful clinical and radiologic surveillance over intervention.
TABLE -Epithelial Breast Lesions and the Risk of Developing Invasive
Carcinoma.
Pathologic Lesion
NONPROLIFERATIVE
changes)
Relative Risk
BREAST
CHANGES
(Fibrocystic
1.0
Duct ectasia
Cysts
Apocrine change
Mild hyperplasia
Adenosis
PROLIFERATIVE DISEASE WITHOUT ATYPIA
1.5 to 2.0
Moderate or florid hyperplasia
Sclerosing adenosis
Papilloma
Complex sclerosing lesion (radial scar)
Fibroadenoma with complex features
PROLIFERATIVE DISEASE WITH ATYPIA
4.0 to 5.0
Atypical ductal hyperplasia (ADH)
Atypical lobular hyperplasia (ALH)
CARCINOMA IN SITU
Lobular carcinoma in situ (LCIS)
Ductal carcinoma in situ (DCIS)
8.0 to 10.0
Carcinoma of the Breast
Carcinoma of the breast is the most common malignancy in women.
A woman who lives to age 90 has a one in eight chance of developing breast cancer. In
2007 an estimated 178,480 women were diagnosed with invasive breast cancer, 62,030
with carcinoma in situ, and over 40,000 women died of the disease.
Only lung cancer causes more cancer deaths in women living in the United States.
Risk factors
Age
The incidence rises throughout a woman's lifetime, peaking at the age of 75–80 years
and then declining slightly thereafter.
Age at Menarche
Women who reach menarche when younger than 11 years of age have a 20% increased
risk compared with women who are more than 14 years of age at menarche. Late
menopause also increases risk.
Age at First Live Birth
Women who experience a first full-term pregnancy at ages younger than 20 years have
half the risk of nulliparous women or women over the age of 35 at their first birth.
First-Degree Relatives with Breast Cancer
The risk of breast cancer increases with the number of affected first-degree relatives
(mother, sister, or daughter), especially if the cancer occurred at a young age.
Atypical Hyperplasia
A history of prior breast biopsies, especially if revealing atypical hyperplasia, increases
the risk of invasive carcinoma. There is a smaller increase in risk associated with
proliferative breast changes without atypia.
Race/Ethnicity
Non-Hispanic white women have the highest rates of breast cancer. The risk of
developing an invasive carcinoma within the next 20 years at age 50 is 1 in 15 for this
group, 1 in 20 for African Americans, 1 in 26 for Asian/Pacific Islanders, and 1 in 27
for Hispanics, social factors such as decreased access to health care and lower use of
mammography may well contribute to these disparities, but biologic differences also
play an important role.
Estrogen Exposure
Postmenopausal hormone replacement therapy increases the risk of breast cancer 1.2to 1.7-fold, and adding progesterone increases the risk further.
Oral contraceptives have not been shown convincingly to affect breast cancer risk but
do decrease the risk of endometrial and ovarian carcinomas. Reducing endogenous
estrogens by oophorectomy decreases the risk of developing breast cancer by up to
75%. Drugs that block estrogenic effects (e.g., tamoxifen) or block the formation of
estrogen (e.g., aromatase inhibitors) also decrease the risk of breast cancer.
Breast Density
High breast radiodensity is a strong risk factor for developing cancer. High density is
correlated with young age and hormone exposure, and clusters in families. High breast
density may be related to less complete involution of lobules at the end of each
menstrual cycle, which in turn may increase the number of cells that are potentially
susceptible to neoplastic transformation.
Radiation Exposure
Radiation to the chest, whether due to cancer therapy, atomic bomb exposure, or nuclear
accidents, results in a higher rate of breast cancer. The risk is greatest with exposure at
young ages and with high radiation doses.
Carcinoma of the Contralateral Breast or Endometrium
Approximately 1% of women with breast cancer develop a second contralateral breast
carcinoma per year.
Geographic Influence
Breast cancer incidence rates in the United States and Europe are four to seven times
higher than those in other countries. The risk of breast cancer increases in immigrants
to the United States with each generation. The factors responsible for this increase are
of considerable interest because they are likely to include modifiable risk factors.
Reproductive history (number and timing of pregnancies), breastfeeding, diet, obesity,
physical activity, and environmental factors all probably play a role.
Diet
Large studies have failed to find strong correlations between breast cancer risk and
dietary intake of any specific type of food. Coffee addicts will be pleased to know that
caffeine consumption may decrease the risk of breast cancer. On the other hand,
moderate or heavy alcohol consumption increases risk.
Obesity
There is decreased risk in obese women younger than 40 years as a result of the
association with anovulatory cycles and lower progesterone levels late in the cycle. In
contrast, the risk is increased for postmenopausal obese women, which is attributed to
the synthesis of estrogens in fat depots.
Exercise
There is a probable small protective effect for women who are physically active. The
decrease in risk is greatest for premenopausal women, women who are not obese, and
women who have had full-term pregnancies.
Breastfeeding
The longer women breastfeed, the greater the reduction in risk, lactation suppresses
ovulation and may trigger terminal differentiation of luminal cells, the lower incidence
of breast cancer in developing countries largely can be explained by the more frequent
and longer nursing of infants.
Environmental Toxins
There is concern that environmental contaminants, such as pesticides, have estrogenic
effects on humans. Possible links to breast cancer risk are being investigated
intensively, but definitive associations have yet to be made.
Tobacco
Cigarette smoking has not been clearly associated with breast cancer but is associated
with the development of periductal mastitis.