Pathology

IV. Nonneoplastic Conditions

Objectives:

After completing this section you will be able to:

• list the common nonneoplastic lesions of the breast
• describe clinical features
• describe histologic features and identify the lesions
• indicate the risk for subsequent breast cancer associated with each lesion

1. Galactocele

   A galactocele is a cystic dilatation of a breast duct as a result of obstruction by inspissated secretions. The cyst contains fluid resembling milk or inspissated secretion. The lesion is uncommon and usually occurs during lactation.

   Microscopically, the cysts are lined by cuboidal or flat epithelium with cytoplasmic vacuolization due to lipid accumulation. Cyst wall, when present, is fibrous. There is little or no inflammation but rupture incites an inflammatory response in the surrounding tissue.

2. Fibrocystic change

Fibrocystic change encompasses a group of morphologic changes that often produce palpable lumps and which are characterized by various combinations of cysts, fibrous overgrowth, and epithelial proliferation. Some of these changes are entirely innocuous while others are associated with increased risk of subsequent carcinoma. A diagnosis of fibrocystic change should therefore specify the components of the morphologic changes present. The changes involve the terminal duct lobular unit are common microscopic findings in otherwise normal breasts.

The cause of fibrocystic change is not known. It is the single most common disorder of the breast. The condition is diagnosed frequently between the ages of 20 and 55 and decreases progressively after the menopause. Fibrocystic change presents with asymptomatic masses in the breast, which are discovered by palpation. The masses vary from diffuse small irregularities (lumpy bumpy breast) to a discrete mass or masses. It may also present with pain, which may be cyclical with midcycle or premenstrual discomfort. Pain may be focal or diffuse and may or may not be associated with the lumps.

Fibrocystic change. Low power view showing multiple cysts and foci of epithelial hyperplasia.

 

Cysts

The cysts, which arise in the TDLU, usually unilocular. Smaller cysts are not discernable on gross examination but clusters of small cysts may be palpable. Large cysts often contain brown fluid, which gives a blue color to the intact cyst, the blue-domed cyst of Bloodgood.

Histologically, cysts may be lined by flattened epithelium, columnar epithelium with features of apocrine cells or may completely lack an epithelial lining.

Single cyst without epithelial lining.

Multiple cysts some lined by metaplastic apocrine cells (lower left).

Apocrine metaplasia

This refers to a histologic alteration of the epithelium of TDLUs in which the cells resemble apocrine sweat gland epithelium. Embryologically, the breasts arise from the same anlage that produces apocrine glands. However, apocrine glands are not part of the normal histologic components of the breast, nevertheless any benign proliferative lesion may contain cells with the cytologic features of apocrine cells.

There are no specific gross features associated with apocrine metaplasia. The condition is seen most frequently in the epithelial lining of cysts. It consists of cuboidal to tall columnar cells with fine granular, eosinophilic cytoplasm, and round, uniform, basally placed nuclei with single central, small nucleoli. ‘Snouts’ or ‘blebs’ protrude from the apical surface into the glandular lumen. Cells lining cysts may be flattened or may form florid papillary proliferations, which may show bridging. Mitoses are almost never seen in ordinary apocrine metaplasia.

Apocrine metaplasia.

Sclerosing adenosis

This condition most often occurs as an incidental microscopic finding but may manifest as a palpable mass that may be mistaken clinically for cancer. It is almost always associated with other forms of fibrocystic change. Diffuse microcalcifications are commonly seen in the lesion, which may mimic carcinoma on mammography.

Microscopically, sclerosing adenosis consists of proliferation of ductular structures and stroma with distortion of the TDLU. Multiple altered lobules may be seen. The proliferated ductules may be compressed and deformed producing whorls and cords that may mimic infiltrating carcinoma, particularly in the center of the lesion.

Epithelial hyperplasia

Epithelial or ductal hyperplasia describes a proliferative condition that is manifested histologically as an increase in the cellularity of the epithelium of the TDLU. It is a microscopic finding, which cannot be predicted clinically or by mammographic examination. The lesion may coexist with other features of fibrocystic change, but in some cases may form the predominant pattern.

Epithelial hyperplasia ranges from mild through florid but typical (i.e. without atypia) to cytologic atypia short of malignancy. There is increase in epithelial layer lining, which distends the terminal ducts and ductules. The epithelial proliferation may either form papillary tufts projecting into the lumen with a tendency to bridge and create arcades or form solid masses which fill the lumen and may have irregular fenestrations. Individual cell borders are inconspicuous so that the cell mass has a syncytial appearance. Nuclear spacing is uneven leading to overcrowding and nuclear overlap in areas and nucleoli are inconspicuous or absent. Often two distinct cell populations, epithelial and myoepithelial cells, may be discerned.

Atypical hyperplasia has some of the architectural and cytologic features of carcinoma in situ but lack the complete criteria for that diagnosis and is categorized as ductal or lobular in type.

Clinical Significance

Page and Dupont have studied the relationship between fibrocystic change and the relative risk of developing subsequent invasive carcinoma (NEJM 312:146-151, 1985). The study has formed the basis of a consensus statement adopted by the College of American Pathologists and the American Cancer Society (Arch Pathol 110:171, 1986). The statement is summarized below:

No increased risk

Cyst, apocrine metaplasia, sclerosing adenosis, fibrosis and mild hyperplasia (more than 2 but less than 4 cells thick)

Slightly increased risk (1.5 to 2X)

Hyperplasia- moderate or florid, solid or papillary (refers to extensive degrees of epithelial proliferation)

Papilloma with fibrovascular core (peripheral papilloma)

Moderately increased risk (5X)

Atypical hyperplasia (AH) — ductal or lobular

Note: Central intraduct papilloma is not included in the consensus statement because there were not enough cases for analysis.

The risk of cancer subsequent to unilateral biopsy-proven proliferative changes affects both breasts.

Relative risk is modified by other factors. In the Page and Dupont study:

1. The additional presence of calcification increased the relative risk of AH from 4.0 to 6.5.
2. AH with a family history has 8.4 times the risk of nonproliferative change with a family history and 11 times the risk of nonproliferative without a family history.

It must be noted that although frequency of breast cancer in previously biopsied women with proliferative changes exceeds that of unbiopsied normal controls, only a small proportion of patients with proliferative lesions (rarely exceeds 10%) develop cancer. This is because the relative risks obtained in the Page and Dupont studies are based on the assumption that relative risk remains constant over time. If it is assumed that relative risk varies with time (as it ought to), then the relative risk of a woman with AH who remains free of breast cancer for 10 years after the diagnosis is halved (Dupont and Page Human Pathology 20:723-725, 1989). AHs are therefore not obligate precursor lesions for breast cancer, but they can progress to cancer, remain unchanged or possibly regress over time.