Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
Breast biopsy specimens come in several sizes. There is the core biopsy, which is a large-bore needle biopsy, and the excisional biopsy, which is like a small lumpectomy . Some institutions perform cytologic studies (fine-needle aspirations), but their usefulness is limited, as many breast diagnoses are more architectural than cytologic. Biopsies are performed, with few exceptions, to rule out malignancy; there are almost no other disease processes that require tissue monitoring. A biopsy specimen with carcinoma or carcinoma in situ will trigger either a lumpectomy, in which a portion of the breast is removed (a partial mastectomy, breast-conserving therapy), or a mastectomy. The mastectomy itself may include sentinel lymph nodes or an entire axillary dissection. Biopsies and most lumpectomy specimens are entirely submitted, and anything that is oriented is inked with four to six colors so we can identify all of the margins later. Mastectomies have only two margins, deep and superficial, and are representatively sampled by quadrant.
The breast is sort of a giant specialized sweat gland , and so it has secretory glands (acini or lobules), arranged like grapes, and ducts, like the grape stems. A single bunch of grapes is a terminal duct lobular unit (TDLU ; Figure 19.1). The ducts from these TDLUs all converge on the nipple, which has multiple large ducts and smooth muscle for ejecting the milk. The breast of a child or male will have ducts but no lobules. During lactation, the lobules fill up with fatty vacuoles of milk, giving them a very characteristic look usually called secretory or lactational change .
Normal breast. (a) The terminal duct lobular unit (TDLU) is arranged like a cluster of grapes, with the duct (arrowhead) as the stem and secretory lobules (arrow) as the grapes. The rounded and circumscribed border of the TDLU is a key feature of noninvasive lesions. (b) The benign breast always has two cell layers, the outer myoepithelial cells (arrow) and the inner epithelial cells (arrowhead). In situ lesions also have two cell layers.
Each lobule and duct is composed of two cell types, the outer myoepithelial layer and the inner epithelial cells (see Figure 19.1). This is an important feature that can separate an in situ lesion (two cell types) from an invasive one (one cell type). The whole structure is bounded by a basement membrane, which is the boundary between in situ and invasive cancers. While there are unusual myoepithelial tumors, in this chapter we will only cover epithelial lesions.
Approach to the Biopsy Specimen
When signing out a core biopsy, there are certain things that should be included in the diagnosis. For malignant lesions, in situ or invasive, it is helpful to give an indication of how differentiated the tumor is, or the grade. Some institutions do not formally grade a core, but you should at least note the nuclear grade (for ductal carcinoma in situ [DCIS] ) or whether it is well/moderate/poorly differentiated (for invasive cancer). These three tiers of differentiation correspond roughly to the three Elston grades .
Second, if microcalcifications were seen on mammography, you must note whether they are present in the specimen and in what context (such as “in association with usual duct hyperplasia”). Failure to find the microcalcifications leads to x-raying the block, calling the radiologist, and cutting deeper levels. Microcalcifications usually are gritty and dark purple, like calcification in other tissues, but occasionally take the sneaky form of calcium oxalate, clear refractile crystals best seen with polarized light (or flipping the condenser down; Figure 19.2).
Calcifications. (a) Microcalcifications in this columnar cell lesion appear as tiny purple rocks (arrow), which may shatter and drag through the tissue, creating telltale scratches in the H&E stain. (b) Calcium oxalate does not pick up hematoxylin and therefore is only visible with a polarizer or when the condenser is flipped down, as in this photograph. The oxalate crystals (arrow) are seen in a duct space, surrounded by foamy macrophages (arrowhead).
Finally, your goal should be to identify the mass or radiographic abnormality the clinicians have detected. If there is no malignancy, you should be looking for some explanation for their findings. Aside from microcalcifications, which do explain a mammographic lesion, you should be looking for anything that could cause a palpable mass, such as fibrosis, cysts or cyst wall, fat necrosis, and benign tumors such as fibroadenomas.
Fibrocystic changes are very common in young women, and many palpable lumps turn out to be nothing more than fibrocystic change. These may be signed out as “Benign breast tissue with fibrocystic changes, including…” and then a list of the features. These features include the following:
Fibrosis : dense pink collagen among the lobules.
Cysts : often visible grossly, thin walled, and full of clear fluid (Figure 19.3).
Fibrocystic disease . In this example, large dilated duct spaces are visible, some with a lining of apocrine metaplasia (arrow). The stroma is dense and fibrotic (pink).
Usual duct hyperplasia : described in detail in a later section.
Adenosis (too many glands or lobules) or sclerosing adenosis : This is a big pitfall because the lobules can look very crowded and worrisome. This is especially true of sclerosing adenosis, in which the proliferative lobules are squeezed together by fibrosis, making them look small and infiltrative (Figure 19.4). The reassuring myoepithelial cell layer can be hard to see. However, sclerosing adenosis should have an overall lobular (circumscribed and rounded) architecture, and myoepithelial cells should be visible in some glands.
Sclerosing adenosis . On high power, this benign lesion looks infiltrative. Tiny tubules are entrapped in a fibrotic stroma, and some tubules are even seen among fat (arrow). Because of the compression, myoepithelial cells are not visible. Clues to the diagnosis include a circumscribed lesion at low power, the lack of desmoplastic reaction, and an intact myoepithelial cell layer seen on immunostains.
Apocrine metaplasia : Breasts are just big sweat glands, remember? Apocrine metaplasia means the epithelial cells lining the ducts look like apocrine glands (Figure 19.5); they acquire a lot of bright pink cytoplasm, can get a hobnail profile protruding into the lumen, and have enlarged nuclei with prominent nucleoli (not unlike Hurthle cell change in the thyroid). It is important to recognize this entity as a metaplastic, not a dysplastic, change.
Apocrine metaplasia in fibrocystic disease. The epithelial cells lining the dilated duct are large and plump, with abundant dark pink cytoplasm, and round nuclei with prominent nucleoli. Secretions (the granular schmutz in the lumen) are common.
Fibroadenomas : A biphasic (two cell types) proliferative lesion. The ducts are proliferating (adenoma), as is the stroma (fibro-). (A similar lesion in the ovary is called an adenofibroma .) This benign tumor has thin, branching ducts set in a sparsely cellular fluffy pink stroma (Figure 19.6). The ducts often have a myxoid pale halo around them, and the proliferative stroma compresses the ducts into slits. Old fibroadenomas may become hyalinized and calcified. Fibroadenomas can occur alone or in association with fibrocystic changes.
Fibroadenoma . At low power, the fibroadenoma is a well-circumscribed nodule (the perimeter is not shown here). Within the lesion, the secretory lobules stand out in slightly edematous (pale) stroma (arrowhead), and the ducts are compressed into slit-like spaces (arrow) by the proliferative stroma.
The phyllodes tumor is another biphasic lesion, which has a similar appearance but a much more cellular stroma than a fibroadenoma. The phyllodes (leaf-like) tumor is graded based on how aggressive the stromal growth pattern is and ranges from benign to malignant. This leaf-like pattern is often indicative of biphasic tumors with a proliferative stroma and is seen in biphasic tumors of other organs.