Introduction

Remarkable advances in breast imaging over the past decade have provided a variety of noninvasive means to assist in the evaluation of patients with breast disorders. Nevertheless, at the present time, histologic examination of tissue specimens remains the cornerstone for the diagnosis of breast diseases, and an understanding of normal breast histology is essential for accurate evaluation of such specimens. It should be noted, however, that what constitutes normal histology in the breast varies according to gender, age, menopausal status, phase of the menstrual cycle, pregnancy, and lactation, among other factors. Therefore, determination of whether a given breast specimen is normal or shows pathologic alterations must take these variables into consideration.

Embryology

Development of the human mammary gland begins during the fifth week of gestation, at which time thickenings of the ectoderm appear on the ventral surface of the fetus. These mammary ridges, also known as milk lines, extend from the axilla to the groin. Except for a small area in the pectoral region, the bulk of these ridges normally regress as the fetus continues to develop. Failure of regression of other portions of the milk lines can result in the appearance in postnatal life of ectopic mammary tissue or accessory nipples anywhere along the milk lines; this phenomenon is most commonly encountered in the axilla, inframammary fold, and vulva.

The earliest stages of breast development are largely independent of sex steroid hormones. After the fifteenth week of gestation, the developing breast exhibits transient sensitivity to testosterone, which acts primarily on the mesenchyme. Under the influence of testosterone, the mesenchyme condenses around an epithelial stalk on the chest wall to form the breast bud, the site of mammary gland development. Solid epithelial columns then develop within the mesenchyme, and these ultimately give rise to the lobes or segments of the mammary gland. Portions of the fetal papillary dermis encase the developing epithelial cords and eventually give rise to the vascularized fibrous connective tissue that surrounds and invests the mammary ducts and lobules. The more collagen-rich reticular dermis extends into the breast to form the suspensory ligaments of Cooper, which attach the breast parenchyma to the skin. Portions of the mesenchyme differentiate into fat within the collagenous stroma between the twentieth and thirty-second weeks of gestation. During the last eight weeks of gestation, the epithelial cords canalize and branch, forming lobuloalveolar structures as a result of mesenchymal paracrine effects. A depression in the epidermis, the mammary pit, forms at the convergence of the lactiferous ducts. The nipple forms by evagination of the mammary pit near the time of birth.

During the last few weeks of gestation the fetal mammary gland is responsive to maternal and placental steroid hormones, and, as a result, the epithelial cells in the acinar units exhibit secretory activity. At the time of birth, withdrawal of the maternal and placental sex steroids stimulates prolactin secretion, which in turn stimulates colostrom secretion. At this time, both male and female neonates exhibit palpable enlargement of the breast bud. As the serum levels of maternal and placental sex steroid hormones and prolactin decline during the first month of life, secretory activity ends, and the gland regresses and becomes inactive. At this stage, and until puberty, the breast consists primarily of lactiferous ducts that exhibit some branching without evidence of progressive alveolar differentiation, although some rudimentary lobular structures may persist.

Another feature that may be seen in the fetal breast is extramedullary hematopoiesis, and this may persist in the periductal stroma until 4 months of age.

Adolescence

Adolescent breast development in the female begins with the onset of puberty and the cyclic secretion of estrogen and progesterone. However, a variety of other steroid and peptide hormones are also required for proper mammary gland development. The ducts elongate, branch, and develop a thickened epithelium due primarily to the influence of estrogen . The process of ductal growth and branching is largely independent of progesterone. There is an increase in the density of periductal connective tissue, also as a result of relative estrogen dominance. Deposition of stromal adipose tissue occurs, and it is this adipose tissue that is largely responsible for the enlargement and protrusion of the breast disk at this time. Cyclical exposure to progesterone following exposure to estrogen during ovulatory cycles promotes lobuloacinar growth, as well as connective tissue growth. Although the majority of breast development occurs during puberty, this process continues into the third decade, and terminal differentiation of the breast is only induced by pregnancy.

The adolescent male breast is composed of fibroadipose tissue and ducts lined by low cuboidal cells.