Histology - Mammary Gland

Describe the protein component of milk.

Synthesized in the RER, packaged in the Golgi apparatus into MEMBRANE-BOUND SECRETORY GRANULES or VESICLES. Released from the cell by fusion of the granule membrane with the plasma membrane -- MEROCRINE secretory mechanism (EXOCYTOSIS). Lactose also released by exocytosis.

What do you see in an inactive mammary gland?

Ducts with occasional buds of alveoli. Collagenous connective tissue with interspersed fat. Alveoli (terminal ductules) have a CLOSED appearance. Glandular ductal elements (alveoli) are relatively sparse. Most of the lobule seems to be composed of connective tissue. Alveoli are small, scattered, and closed. Adipose tissue is evident in the interlobular regions.

In a histological cross section of the nipple, what should you be able to see?

1. Lactiferous sinus. 2. Sebaceous gland. 3. Epidermis.

What is the difference between male and female breasts?

Differentiation of the mammary glands in embryonic life is similar between the 2 sexes, and in males there is little additional development in postnatal life. So male breast has the same structure as pre-pubertal female breast. In the female, mammary glands undergo extensive structural changes correlated with the functional condition of the reproductive system (e.g. pregnancy, lactation).

What occurs in breast cancer?

The epithelial cells of the mammary ducts and terminal ductules (alveoli) undergo cancerous changes.

What are the two types of carcinomas one can have in the breast? Which is the most common?

1. Lobular carcinomas - Epithelial cancers originating in the terminal ductules of the lobules (from the secretory cells of the alveoli). 2. Ductal carcinomas - Epithelial cancers that arise from the larger ducts of the mammary gland. DUCTAL CARCINOMA is the most frequently occurring type, comprising 50-75% of all breast cancers.

What is a mammary lobule?

ALVEOLI, ALVEOLAR DUCTS, AND THEIR SURROUNDING CONNECTIVE TISSUE TOGETHER COMPRISE A MAMMARY LOBULE.

What are the two forms than breast carcinomas can occur?

1. IN SITU: Confined within the structure of origin. 2. INVASIVE: Penetrating into the surrounding stroma.

How many lobes does each mammary gland contain?

15-25 independent lobes, each with an opening through the nipple.

How many lobes does each breast contain?

15-25 individual mammary gland lobes. These lobes can be subdivided into lobules.

What is the inherited risk of breast cancer?

A small percentage (5-10%) of breast cancers have a clear heritable cause, e.g. mutations in BRCA1 and BRCA2 confer high risk for both breast and ovarian cancers. These carcinoma cells tend not to express estrogen and progesterone receptors, so treatments such as tamoxifen may, in such instances, be ineffective.

Describe the lipid component of milk.

Arises as lipid droplets free in the cytoplasm. LIPID COALESCES TO FORM LARGE DROPLETS, which pass to the apical region of the cell and project into the lumen of the ducts. Droplets are invested with an envelope of plasma membrane and carry some cytoplasm with them as they are released: APOCRINE secretory mechanism. Note: the lipid droplets are invested in plasma membrane from the secretory cells!

Note. Make sure you know the learning objectives.

Basic structure of the mammary gland. Functional subdivisions of the mammary gland and how to recognize these in histological specimens. Cell types of the mammary glands, their functions, and how to recognize them in histological specimens. Basics about how mammary gland structure changes in pregnancy and lactation. How to recognize differences in functional state(s) of the mammary gland in histological specimens. Some basics about breast carcinoma.

Describe what happens to the mammary glands during pregnancy and lactation. Describe this from the histologically perspective.

During PREGNANCY, secretory alveolar cells proliferate extensively in response high levels of estrogen and progesterone. This results in increased branching of ducts and terminal ductules. So LOBULES AND ALVEOLI ARE PROMINENT. During LACTATION, alveoli are fully differentiated. Secretory products of alveolar epithelial cells are abundant. ALVEOLI AND DUCTULES BECOME DISTENDED due to being filled with milk secretions. Once lactation is completed, the gland reverts to the non-pregnant condition.

What is located beneath the areola?

Each duct has a dilated portioned called the lactiferous sinus.

Note.

Each lactiferous duct with its accompanying smaller ducts and alveoli is a gland in itself, and constitutes one of the lobes of the mammary gland. So have mammary epithelial cells even in the duct network. Not just in the alveoli.

What type of glands are the mammary glands?

Each lobe is a compound (which means highly-branched) TUBULOALVEOLAR GLAND. [Yes, this is the same type of gland that is in the prostate]. The secretory units of the glands consists of ducts and alveoli. So just like any other exocrine duct.

What type of epithelium are in the lactiferous sinuses?

Epithelium of the lactiferous sinuses is similar to that of the ducts in the rest of the breast until near the surface: SURFACE EPITHELIUM IS STRATIFIED SQUAMOUS IN TYPE.

What causes female mammary glands to develop during puberty?

Estrogen and progesterone, the female sex hormones.

What do the ducts of the mammary glands go through to reach the nipple?

Go from the alveoli, to the duct, to the lactiferous duct, then to the lactiferous sinus, then exit at the nipple.

What is Paget's disease of the breast?

Individual carcinoma cells can spread from cancerous ductal epithelium through lactiferous sinuses and into surface epidermis, where they form small clusters of neoplastic cells known as Paget's disease of the breast. Presents as "eczema" on the nipple.

What can breast cancer look like on a histological slide?

It can be well-differentiated in that ducts are apparent, but note the absence of any lobular structure. Or it can be NOT well-differentiated. Epithelial cells can be thoroughly mixed with surrounding stromal cells. Or even it can have a "dartboard" appearance aka "Indian filing." These are invasive epithelial cells in single lines/concentric circles in the stroma surrounding ductules. In these three cases they are invasive. In the in situ situation, the distinguishing feature is that the lumena of terminal ductules [alveoli] are obliterated. The terminal ductules are filled with neoplastic epithelial cells.

What are the lobules of the mammary glands lined with?

LOBULES (alveoli and associated ductules) are lined by a continuous layer of MAMMARY EPITHELIAL CELLS. Columnar/cuboidal epithelial cells, specialized for secretion of milk. So lobule comprises the scretory unit of the mammary gland.

What are myoepithelial cells?

MYOEPITHELIAL CELLS lie in a discontinuous layer underneath the secretory epithelial cells. These are the muscle cells around the mammary epithelial cells. Contraction of myoepithelial cells in response to oxytocin = MILK EJECTION REFLEX.

How can breast cancers be responsive to hormones?

Mammary gland epithelial cells are responsive to estrogen and progesterone, so often breast cancers are as well. TAMOXIFEN: therapeutic agent that blocks interaction of estrogen with its nuclear receptors. This can prevent growth of the breast cancer.

What do you see in a proliferating, non-lactating mammary gland?

Numerous alveoli present in each lobule; lobules take on a more glandular appearance. Alveoli are hollow. Ducts appear stalk-like. Dense connective tissue separating lobules is evident; lobular growth compresses connective tissue so that it appears to be reduced in amount.

What is the histological composition of mammary gland epithelial cell?

Polarized structure (typical of an exocrine secretory cell). Abundant RER (mostly basal). Secretory granules or vesicles (filled with dense globular micelles of Golgi-derived membrane plus protein). Lipid droplets (can be throughout the cell or apical).

What is apocrine secretion?

Producing a fluid secretion by pinching off one end of the secreting cells, which then reform and repeat the process.

Describe the branching of the mammary gland.

Recall: Each LOBE is a COMPOUND TUBULOALVEOLAR GLAND. LOBES are further divided into LOBULES: Branching duct system of each lobe ends in several CLUSTERS of blind-ending terminal ductules. These appear as ALVEOLI in histological section. Each CLUSTER, together with its feeding ductule, comprises a mammary LOBULE. LOBULE, aka Terminal Duct Lobular Unit (TDLU), is the functional unit of the mammary gland.

What type of glands are mammary glands?

Specialized accessory glands of the skin, evolved from sweat glands.

What do you see in a lactating mammary gland?

Terminal ductules proliferate, increasing number of alveoli. Interlobular connective tissue reduced to thin sheets/septa. Difficult to identify a lobule. Alveoli are open and filled with secretions. Alveoli very numerous and Alveoli are distended with secretions (resemble colloid-filled follicles of the thyroid gland, except that they are irregular in shape and interconnected). Only a small amount of connective tissue is evident since it is smooshed.

What separates the individual lobes and lobules?

The duct systems of the individual lobes and lobules are separated from one another by a CONNECTIVE TISSUE STROMA containing ADIPOSE CELLS and FIBROCOLLAGENOUS SEPTA. This is just the composition of the breast itself.

What is Casein?

The major protein component of milk. Present as aggregates of a number of different, heavily-phosphorylated protein subunits, which are able to bind high numbers of Ca2+ ions. This keeps calcium from precipitating out in milk.