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Chapter 1

Normal Breast Tissue or Fibrocystic Change?

The mammary gland, like all glandular organs, consists of parenchyma and stroma. The parenchyma contains ducts (Fig. 1.1) and lobules (Fig. 1.2), which are separated from the stroma by a continuous basement membrane (Fig. 1.3). The entire parenchyma (with the exception of the terminal parts of the lactiferous ducts) consists of a single inner layer of epithelial cells and an outer layer of myoepithelium (Fig. 1.4). Only the epithelial cells contain estrogen and progesterone receptors in their nuclei (Fig. 1.5).

Fig. 1.1

Fig. 1.2

Fig. 1.3

The stroma consists of fibrous tissue and adipose tissue containing lymph vessels, blood vessels, and nerves. More specialized within the lobules and surrounding the ducts, the stroma can be divided into intralobular (mucin-rich, “active”) and interlobular stroma (see Fig. 1.16).

Fig. 1.4

Fig. 1.5

The nipple is the origin of 15 to 25 lactiferous ducts, which branch into segmental, subsegmental, and terminal ducts that with the associated lobules comprise 15 to 25 lobes. The terminal duct and the associated lobule are collectively referred to as the Terminal Ductal-Lobular Unit (TDLU), which is the most important functional unit and the place of origin of most pathologic processes in the breast (Figs. 1.6 and 1.7).

Fig. 1.6

Fig. 1.7

Fig. 1.8

Fig. 1.9

At the beginning of the menstrual cycle, the lobules are relatively small and contain only a minimal amount of secretion, if any, in the lumina of the acini (Figs. 1.8 and 1.11). During the secretory phase of the cycle, the acini produce eosinophilic secretions and the intralobular stroma becomes edematous (Fig. 1.9). Around the time of menstruation, the myoepithelium becomes vacuolated and undergoes apoptosis (Fig. 1.10).

Fig. 1.10

Fig. 1.11

Fig. 1.12

The most obvious changes are seen during the last trimester of pregnancy and during lactation when the TDLUs are enlarged, the number of acini per lobule increases greatly (Fig. 1.12), the cytoplasm in the epithelial cells becomes vacuolated, and rich secretions are produced in large quantities (Fig. 1.13).

Fig. 1.13

Fig. 1.14

Fig. 1.15

Around the time of menopause, but often earlier, involution of the breast tissue occurs.

Involution of the parenchyma results in a diminished number of acini/lobules, lobules, and ducts (compare Fig. 1.14 showing a functioning lobule with Fig. 1.15 showing an involuted lobule, thick-section images).

Figure 1.16 shows a TDLU with normal mucin-rich intralobular stroma. Involution of the intralobular stroma is accompanied either by infiltration of fatty tissue (Fig. 1.17) or by fibrosis (Fig. 1.18). The same is true for the interlobular stroma.

Fig. 1.16

Fig. 1.17

Fig. 1.18

Fig. 1.19

Fig. 1.20

The involution of the parenchyma and the interlobular and intralobular stroma is not necessarily a synchronized process. Functioning lobules can be seen in the presence of interlobular stroma that has undergone fibrous involution (Fig. 1.19) or has been replaced by fat (Fig. 1.20).

The intralobular and the interlobular stroma may undergo either fibrous or fatty involution in varying combinations (Figs. 1.21, 1.22, and 1.23).

Fig. 1.21

Fig. 1.22

Fig. 1.23

The lobules may exhibit a deviated morphology as compared with that described previously. This phenomenon is called Aberration of Normal Development and Involution (ANDI). Some examples of ANDI:

– Apocrine metaplasia (Fig. 1.25) with large cells having granulated eosinophilic cytoplasm (as compared with normal epithelium, Fig. 1.24)

– Clear-cell change (Fig. 1.26)

– Eosinophilic change (Fig. 1.27), appearance of cells with eosinophilic cytoplasm among the cells of the usual type

– Lactational change (Fig. 1.28), milk-producing lobules in the breast of nonpregnant, nonlactating women

– Fibroadenomatoid change (Fig. 1.29) with proliferation of the intralobular stroma and distortion of the acini

– Microcystic involution (Fig. 1.30, galactography image; Fig. 1.31, thick-section image; and Fig. 1.32) if involution of the lobules (diminished number of acini) is associated with dilatation of the acini

A common type of ANDI is adenosis, which is described in detail in Chapter 6.

Fig. 1.24

Fig. 1.25

Fig. 1.26

Fig. 1.27

Fig. 1.28

Fig. 1.29

Fig. 1.30

Fig. 1.31

Fig. 1.32

Some ANDIs represent changes predominantly of the phenotype of the epithelial cells and may lead to accumulation of secretion in the lobule, which in turn may calcify. Other forms of ANDIs represent architectural changes within the lobules, leading to marked enlargement of the TDLUs. The calcifications or the enlarged TDLUs may be mammographically or clinically detected, causing anxiety for the patient and differential diagnostic problems for the radiologist.

Fig. 1.33

Fig. 1.34

The histologically “normal” breast tissue may show numerous aberrations, many of which cannot be detected by clinical or radiologic examination. If these lesions are sufficiently large to be radiologically or clinically detected and, especially when symptomatic, they are more appropriately called “fibrocystic change,” which is still a variation of normal breast morphology.

The difference between ANDIs and fibrocystic change is more quantitative than qualitative. It is impossible to draw a sharp line between microcystic involution and cysts (Figs. 1.33 and 1.34) or between fibroadenomatoid change and fibroadenoma (Figs. 1.35 and 1.36).

Fig. 1.35

Fig. 1.36

The distinction between “normal” or “pathologic” depends on the method of examination. Histology is an extremely sensitive method and may detect many clinically and prognostically unimportant details, which are best characterized as variations and aberrations of the normal breast morphology.

The normal breast tissue contains lobules typical of both the proliferative and secretory and menstrual phases of the menstrual cycle, different combinations of involutional changes, and different ANDIs all at the same time. Consequently, normal breast tissue offers the interested examiner a variable and fascinating picture under the microscope (Figs. 1.37-1.41; Fig. 1.40, thick-section image).

Fig. 1.37

Fig. 1.38

Fig. 1.39

Fig. 1.40

Fig. 1.41

Fig. 1.42

Fig. 1.43

The mammogram represents a black-and-white summation of the morphologic details of the breast. The lobules are visible on a high-quality mammogram as l-to-2-mm nodular densities. Only the silhouettes of the lobules are seen, not the histologic details. A radiologic nodular density may represent a spectrum of histologic changes within the TDLU (Figs. 1.42-1.44). The radiologic linear densities correspond to ducts, fibrous strands, and vessels (Fig. 1.45).

Fig. 1.44

Fig. 1.45

Despite the variability of the histologic picture, the mammographic patterns of the normal breast can be properly classified in only five categories as described by Tabár, Gram and Tot. The basic factor determining the mammographic pattern of the normal breast is the interrelation between the radiopaque fibrous tissue and the radiolucent fatty tissue in the interlobular stroma.

Mammographic pattern I is characterized by Cooper ligaments as well as a harmonic distribution of fatty and fibrous tissue (Figs. 1.46-1.48).

Fig. 1.46

Fig. 1.47

Fig. 1.48

Fig. 1.49

Mammographic pattern II represents breast tissue replaced by fatty tissue with only a few remaining TDLUs (Figs. 1.49 and 1.50).

Fig. 1.50

Pattern I develops over time into pattern II through fatty involution. Hormone replacement therapy may convert pattern II back to pattern I. The mammographic pattern of the normal breast is often characterized as intermediate between patterns I and II or as “involuting pattern I.”

Pattern IN is characterized by a relatively fibrotic area behind the nipple when the remainder of the breast has been replaced by adipose tissue (Fig. 1.51). The same pattern can be produced by advanced ductectasia.

Fig. 1.51

Fig. 1.52

Fig. 1.53

Fig. 1.54

Fig. 1.55

Pattern IV is dominated by somewhat enlarged nodular densities, approximately 3 to 5 mm in size (Figs. 1.52 and 1.53). These densities usually represent different ANDIs, but focal involution of the interlobular stroma with small islands of remaining fibrous tissue may present the same picture (see Fig. 1.43).

Pattern V shows a radiopaque density over the entire gland corresponding to a more collagenous interlobular stroma (Figs. 1.54 and 1.55). Radiologic details (nodular or linear densities) are poorly seen; active and/or atrophic parenchyma may be hidden within this density. Patterns IV and V are stable and do not change during the woman's lifetime.

Conclusions

Comprehensive knowledge of the variations of normal breast morphology enables the pathologist to avoid over-diagnosing normal variations as pathologic processes.

Clinical and radiologic diagnoses assist the pathologist in the delineation of normal tissue from fibrocystic change.

The particular mammographic pattern of breast tissue is an important aid for the pathologist. Detection of pathologic changes in breasts with patterns I, II, and III is relatively easy, but a more detailed histologic analysis of macroscopically and radiologically normal breast tissue is necessary in patients with patterns IV and V.

References

1 Vogel PM, et al. The correlation of histological changes in the human breast with the menstrual cycle. Am J Pathol. 1981;104:23–34.

2 Longacre TA, Bartow SA. A correlative morphologic study of human breast and endometrium in menstrual cycle. Am J Surg Pathol. 1986;10(6):382–393.

3 Hughes LE, et al. Aberrations of normal development and involution (ANDI): a new perspective on pathogenesis and nomenclature of benign breast disorders. Lancet. 1987;2(8571):1316–1319.

4 Gram IT, Funkhouser E, Tabár L. The Tabár classification of mammographic parenchymal patterns. Eur J Radiol. 1997;24:131–136.

5 Tot T, Tabár L, Dean PB. The pressing need for better histologic-mammographic correlation of the many variations in human breast anatomy. Virchows Arch. 2000;437:338–344.

6 Tabár L, Dean PB, Tot T. Teaching atlas of mammography. 3rd ed. Stuttgart, New York: Georg Thieme Verlag; 2001.