Chapter 4: Pathology of Breast Disorders
Functional unit of the breast is the terminal ductal lobular unit.
The entire lobular and ductal structure of the breast is lined by two layers of cells:the inner epithelial layer and the outer myopepithelial layer.
“Breast cancer” typically refers to breast carcinoma that arises by preferential growth of the inner epithelial layer.
Benign Disorders:
Fibrocystic change-pathologic condition that correlates with ‘lumpy’ breasts.
This term is applied to a plethora of benign changes in the breast, which are best categorized based on the subsequent risk of development of breast carcinoma.
Three categories:
Non-proliferative lesions:
Proliferative lesions without atypia
Atypical hyperplasia
Nonproliferative Lesions
This is the most common category of breast disorders and includes cysts, papillary apocrine change, mild hyperplasia of the usual type, and epithelial-related calcifications.
Women with these lesions do not incur a higher risk of development of breast carcinoma than that of women who had no breast biopsy (relative risk, 0.89)
Proliferative Lesions without Atypia
Women with these lesions have a slight risk of developing breast carcinoma, 1.5 to 2 times greater than the general population. This category includes moderate or florid hyperplasia of the usual type, sclerosing adenosis, small duct papillomas, and fibroadenomas.
Sclerosis adenosis is the most common lesion and refers to expanded lobular units with a proliferation of both acini and intervening stroma. Microcalcifications are frequently seen and correspond to “benign calcifications” seen on mammography.
Functional unit of the breast is the terminal ductal lobular unit.
The entire lobular and ductal structure of the breast is lined by two layers of cells:the inner epithelial layer and the outer myopepithelial layer.
“Breast cancer” typically refers to breast carcinoma that arises by preferential growth of the inner epithelial layer.
Benign Disorders:
Fibrocystic change-pathologic condition that correlates with ‘lumpy’ breasts.
This term is applied to a plethora of benign changes in the breast, which are best categorized based on the subsequent risk of development of breast carcinoma.
Three categories:
Non-proliferative lesions:
Proliferative lesions without atypia
Atypical hyperplasia
Nonproliferative Lesions
This is the most common category of breast disorders and includes cysts, papillary apocrine change, mild hyperplasia of the usual type, and epithelial-related calcifications.
Women with these lesions do not incur a higher risk of development of breast carcinoma than that of women who had no breast biopsy (relative risk, 0.89)
Proliferative Lesions without Atypia
Women with these lesions have a slight risk of developing breast carcinoma, 1.5 to 2 times greater than the general population. This category includes moderate or florid hyperplasia of the usual type, sclerosing adenosis, small duct papillomas, and fibroadenomas.
Sclerosis adenosis is the most common lesion and refers to expanded lobular units with a proliferation of both acini and intervening stroma. Microcalcifications are frequently seen and correspond to “benign calcifications” seen on mammography.
Atpical Hyperplasia
Atypical hyperplasia confers a risk of development of breast cancer that is 3.5-5 times that of the reference population. This category includes both atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH).
Radial Scars and Complex Sclerosing Lesions
Radial scars are typically small areas of scarring (less than 1 cm) surrounded by glandular elements.
Benign Neoplasms
Fibroadenoma
Fibroadenomas typically present as painless, mobile, rubbery masses. They are usually solitary but occasionally multiple. Most often present in the upper-outer quadrant and slightly more common in the left breast.
Solitary (Large Duct) Intraductal Papilloma
These tumors typically arise in a large duct in the subareolar region and present with unilateral hemorrhagic discharge.
Phyllodes Tumor
Character may be benign to malignant. Phyllodes tumors tend to have local recurrences and should be widely excised.
Lobular Carcinoma in Situ (LCIS)
LCIS is a rare multicentric entity that can not be identified clinically or on gross examination.
The invasive carcinoma that may develop may be either ductal or lobular.
LCIS is more common in younger, premenopausal women, and the mean age of diagnosis is 44 to 46 years.
LCIS is commonly bilateral and multicentric (present in more than one quadrant).
LCIS is typically an incidental finding in a breast biopsy done for a mammographically detectable lesion, which may be calcifications in adjacent sclerosing adenosis or other proliferative lesions.
Estrogen receptor (ER) is typically over expressed in cells of LCIS, whereas Her-2/neu is not. E-cadherin is a useful marker to distinguish lobular and ductal proliferations because it is preferentially expressed in ductal proliferations.
Most women with LCIS do not develop invasive carcinoma on follow-up, but it does confer a relative risk from 6.9 to 12. The carcinomas that develop are mostly invasive ductal carcinoma.
LCIS is best considered to be a risk factor rather than a precursor of invasive carcinoma. Thus, the surgical management of LCIS does not aim for negative margins, and radiation therapy has no role in management of LCIS.
Ductal Carcinoma in Situ
Ductal carcinoma in situ (DCIS) comprises lesions in which the neoplastic growth of ductal cells is restricted within the ductal system.
DCIS is considered to be a direct precursor of invasive carcinoma.
The incidence of carcinoma in patients with DCIS varies from 11% to 53% and occurs in the ipsilateral breast.
Mammographic abnormalities, which commonly show microcalcifications, are the most common presentation of DCIS.
Comedo DCIS refers to central necrosis in the ducts that are lined by poorly differentiated cells. Comedo DCIS is invariably associated with calcifications.
Comedo necrosis was the only factor found to correlate with ipsilateral recurrence in a multivariate analysis of nine histologic features of DCIS.
The distinction between LCIS and DCIS can usually be made with E-cadherin staining. E-cadherin shows no staining in lobular proliferations.
Low Grade DCIS tends to be ER and PR positive and Her2/neu negative.
High Grade DCIS tends to be ER/PR positive and Her2/neu positive.
Tamoxifen decreases recurrence rates in patients with DCIS.
DCIS specimens should be inked for margins. In NSABPB-17, only the presence of a tumor-filled duct in contact with the inked margin was categorized as a positive margin.
Silverstein et al. showed that quantification of the distance of DCIS from the margin is useful, and greater than 1 cm is deemed to be a negative margin.
Paget’s Disease of the Nipple
Association of eczematous changes in the nipple with underlying mammary carcinoma. Paget’s disease of the nipple refers to the extension of underlying breast cancer to the skin of the nipple.
Paget’s disease presents as scaling and erythema of the nipple-areola complex.
95% of cases of Paget’s have underlying carcinoma, invariably ductal, and often associated with comedo-type DCIS.
Immunohistochemical stains are useful to distinguish Paget’s from melanoma and clear cells of the epidermis.
Her2/neu, epithelial membrane antigen, and polyclonal CEA are expressed in Paget’s CK 7 is positive in both Toker cells and Paget’s disease.
Atypical hyperplasia confers a risk of development of breast cancer that is 3.5-5 times that of the reference population. This category includes both atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH).
Radial Scars and Complex Sclerosing Lesions
Radial scars are typically small areas of scarring (less than 1 cm) surrounded by glandular elements.
Benign Neoplasms
Fibroadenoma
Fibroadenomas typically present as painless, mobile, rubbery masses. They are usually solitary but occasionally multiple. Most often present in the upper-outer quadrant and slightly more common in the left breast.
Solitary (Large Duct) Intraductal Papilloma
These tumors typically arise in a large duct in the subareolar region and present with unilateral hemorrhagic discharge.
Phyllodes Tumor
Character may be benign to malignant. Phyllodes tumors tend to have local recurrences and should be widely excised.
Lobular Carcinoma in Situ (LCIS)
LCIS is a rare multicentric entity that can not be identified clinically or on gross examination.
The invasive carcinoma that may develop may be either ductal or lobular.
LCIS is more common in younger, premenopausal women, and the mean age of diagnosis is 44 to 46 years.
LCIS is commonly bilateral and multicentric (present in more than one quadrant).
LCIS is typically an incidental finding in a breast biopsy done for a mammographically detectable lesion, which may be calcifications in adjacent sclerosing adenosis or other proliferative lesions.
Estrogen receptor (ER) is typically over expressed in cells of LCIS, whereas Her-2/neu is not. E-cadherin is a useful marker to distinguish lobular and ductal proliferations because it is preferentially expressed in ductal proliferations.
Most women with LCIS do not develop invasive carcinoma on follow-up, but it does confer a relative risk from 6.9 to 12. The carcinomas that develop are mostly invasive ductal carcinoma.
LCIS is best considered to be a risk factor rather than a precursor of invasive carcinoma. Thus, the surgical management of LCIS does not aim for negative margins, and radiation therapy has no role in management of LCIS.
Ductal Carcinoma in Situ
Ductal carcinoma in situ (DCIS) comprises lesions in which the neoplastic growth of ductal cells is restricted within the ductal system.
DCIS is considered to be a direct precursor of invasive carcinoma.
The incidence of carcinoma in patients with DCIS varies from 11% to 53% and occurs in the ipsilateral breast.
Mammographic abnormalities, which commonly show microcalcifications, are the most common presentation of DCIS.
Comedo DCIS refers to central necrosis in the ducts that are lined by poorly differentiated cells. Comedo DCIS is invariably associated with calcifications.
Comedo necrosis was the only factor found to correlate with ipsilateral recurrence in a multivariate analysis of nine histologic features of DCIS.
The distinction between LCIS and DCIS can usually be made with E-cadherin staining. E-cadherin shows no staining in lobular proliferations.
Low Grade DCIS tends to be ER and PR positive and Her2/neu negative.
High Grade DCIS tends to be ER/PR positive and Her2/neu positive.
Tamoxifen decreases recurrence rates in patients with DCIS.
DCIS specimens should be inked for margins. In NSABPB-17, only the presence of a tumor-filled duct in contact with the inked margin was categorized as a positive margin.
Silverstein et al. showed that quantification of the distance of DCIS from the margin is useful, and greater than 1 cm is deemed to be a negative margin.
Paget’s Disease of the Nipple
Association of eczematous changes in the nipple with underlying mammary carcinoma. Paget’s disease of the nipple refers to the extension of underlying breast cancer to the skin of the nipple.
Paget’s disease presents as scaling and erythema of the nipple-areola complex.
95% of cases of Paget’s have underlying carcinoma, invariably ductal, and often associated with comedo-type DCIS.
Immunohistochemical stains are useful to distinguish Paget’s from melanoma and clear cells of the epidermis.
Her2/neu, epithelial membrane antigen, and polyclonal CEA are expressed in Paget’s CK 7 is positive in both Toker cells and Paget’s disease.
