Benign Epithelial Lesions 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)

These lesions might come to clinical attention when they mimic carcinoma by producing palpable lumps, mammographic densities or calcifications, or nipple discharge. The involved areas, by palpation, may have an ill-defined diffuse increase in consistency as well as discrete nodularities. Cysts are the most common cause of a palpable mass and are alarming when they are solitary, firm.

Fibrocystic disease is most frequently seen, between the ages of 25 and 45 years. the exact pathogenesis remains unknown ,and its primarily affects the TDLU.
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.



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 (cells have an abundant granular, eosinophilic cytoplasm, with round nuclei) This is a very common change. There is no evidence that patients with atypical apocrine metaplasia are at an increased risk for the development of carcinoma.
The cysts either contain turbid or semi-translucent fluid, some of these cysts have a bluish cast when seen from the outside (‘blue dome cysts’).

(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 :
Adenosis is defined as an increase in the number of acini per lobule. A normal physiologic adenosis occurs during pregnancy.In nonpregnant women, adenosis can occur as a focal change. The acini are often enlarged but are not distorted as seen in sclerosing adenosis . Calcifications are occasionally present within lumens .

Proliferative Breast Disease without Atypia
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.
These changes rarely form palpable masses. More commonly, they are detected as mammographic densities (e.g., complex sclerosing lesions or sclerosing adenosis), as calcifications (e.g., sclerosing adenosis), or as incidental findings in biopsies performed for other reasons (e.g., hyperplasia), as nipple discharge ( more than 80% of large duct papillomas produce a nipple discharge).
Although each lesion can be found in isolation, typically more than one lesion is present together.
1-Epithelial Hyperplasia: Normal breast ducts and lobules are lined by a double layer of basally located myoepithelial cell layer (cells with dark, compact nuclei and scant cytoplasm) and luminal cell layer (cells with larger oval nuclei, and more abundant cytoplasm), epithelial hyperplasia is defined by the presence of more than two cell layers.Hyperplasia is moderate to florid when there are more than four cell layers.
The features that we have found most helpful in the identification of the benign nature of the proliferation are the following:
Nuclei that are oval ,normochromatic (rather than hyperchromatic), small, single, indistinct nucleoli; scanty or no mitotic activity, cytoplasm that is acidophilic and finely granular rather than pale and homogeneous.Presence of myoepithelial cells,presence of foamy macrophages and absence of necrosis.
2-Sclerosing Adenosis: The number of acini per terminal duct is increased to at least double the number found in uninvolved lobules. The average age of the patient is about 30 years.
The normal lobular arrangement is maintained. The acini are compressed and distorted by dense stroma in the central portions of the lesion but characteristically dilated at the periphery. The elongated and compressed proliferating tubules are lined by two cell types that are themselves elongated along the tubular axisie i.e myoepithelial cells are usually prominent. Calcifications are frequently present within the lumens of the acini and necrosis are absent.
3-Complex Sclerosing Lesion (Radial Scar)
The components of this lesion are sclerosing adenosis, papilloma formation, and epithelial hyperplasia. Radial scars are stellate lesions characterized by a central nidus of entrapped glands in a densely fibrotic stroma surrounded by radiating arms of epithelium with varying degrees of cyst formation and hyperplasia. These lesions can resemble irregular invasive carcinomas mammographically or on gross examination.

4-Papillomas
Its neoplastic papillary growth within a duct. Intraductal papilloma of the breast occurs at an average age of 48 years. It can arise in large or small ducts; clinically it can give rise to bloody nipple discharge and may be palpable in a subareolar location.
Gross features: the lesion is usually solitary (approximately 90% of cases are solitary), soft and fragile,but its diameter rarely exceeds 3 cm, a point of importance in the differential diagnosis with papillary carcinoma ,.
Microscopical features:: 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.
5-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 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:
Gross features:
The tumor is freely movable, spherical, well-circumscribed, rubbery, grayish white nodules that vary in size from less than 1 cm to large tumors may reach up to 10 cm in diameter. large tumors are referred to as giant fibroadenoma and often contain slitlike spaces.
Microscopical features
There is a loose fibroblastic stroma containing epithelium– lined duct- like spaces of various forms and sizes,with presence of fibrous capsule .
There are intracanalicular when the connective tissue invaginates into the glandular spaces so that it appears to be within them, and pericanalicular when the regular round or oval glandular configuration of the glands is maintained. Often, both types of growth are seen in the same lesion. The tubules are composed of cuboidal or low columnar cells with round uniform nuclei resting on a myoepithelial cell layer. 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
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
It 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
It consists 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.