Mills Ch3 Breast

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CHAPTER 3:  Breast

TDLU (14,41). Indeed, the only common lesion thought to arise from large- or medium-sized ducts rather than from the TDLU is solitary intraductal papilloma (Fig. 3.10). The normal lobule consists of a variable number of blind-ending terminal ductules, also called acini, each with its typical double cell layer. The lobular acini are invested by a loose, fibrovascular intralobular stroma with varying numbers of lymphocytes, plasma cells, macrophages, and mast cells. This specialized intralobular stroma is sharply demarcated from the surrounding denser, more highly collagenized, paucicellular interlobular stroma, and stro- mal adipose tissue (Fig. 3.11). One feature of note that is sometimes encountered in the extralobular stroma is the presence of multinucleated giant cells (42). Their signifi- cance is unknown; and, while they may present a disturbing appearance, they should not be mistaken for the malignant cells of an invasive carcinoma (Fig. 3.12). The size of mammary lobules and number of acini per lobule are extremely variable. Russo et al. have described four lobule types (43–45). Type 1 lobules are the most rudi- mentary and are most prevalent in prepubertal and nullipa- rous women, comprising 65% to 80% of the lobules in this group (Fig. 3.2). These lobules are comprised primarily of ducts with sprouting alveolar buds. However in practice, it is not possible to reliably distinguish type 1 lobules (i.e., those that have not fully developed) from those in which the number of acini is reduced due to involution. Type 1 lobules gradually evolve to more mature structures (type 2 and type 3 lobules) through the development of additional alveolar buds. The number of alveolar buds per lobule increases from approximately 11 in type 1 lobules to 47 and 80 in type 2 and 3 lobules, respectively. Recent data suggest that the histologic appearance of normal lobules may influence the risk of subsequent breast cancer. In par- ticular, women whose breast tissue exhibits predominantly type 1 lobules or lobules that have undergone involution have a reduced risk of subsequent breast cancer compared to women with predominantly type 3 lobules or those that have not undergone involution (46–48). While there is

FIGURE 3.9  Immunostain for type IV collagen highlights the basal lamina around the acini of a lobule.

cell layer and serves to demarcate the breast ductal-lobular system from the surrounding stroma (Fig. 3.9). Beyond the basal lamina, the extralobular ducts exhibit a zone of fibro- blasts and capillaries. Elastic tissue is normally present in variable amounts around ducts and is generally more promi- nent in older than in younger women. Elastic fibers are not typically seen around the terminal ducts or lobular acini. The lobule, together with its terminal duct, has been called the TDLU. This represents the structural and functional unit of the breast. During lactation, epithelial cells in both the ter- minal duct and lobule undergo secretory changes. Thus, the terminal ducts are responsible for both secretion and trans- port of the secretions to the extra-lobular portion of the ductal system (15). Subgross anatomic studies have shown that most lesions originally termed “ductal” (e.g., cysts, ductal epithelial hyperplasia, and ductal carcinoma in situ) actually arise from the TDLU, which “unfolds” with coalescence of the acini to produce larger structures resembling ducts. The majority of pathologic changes in the breast, including in situ and inva- sive carcinomas, are generally considered to arise from the

FIGURE 3.10  A schematic representation of the breast, indicating the sites of origin of patho- logic lesions. (Reprinted from Schnitt SJ, Millis RR, Hanby AM, et al. The breast. In: Mills SE, Carter D, Greeson JK, Oberman HA, Reuter VE, Stoler MH, eds. Sternberg’s Diagnostic Surgical Pathology . 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2004:323–398.)