Now, let's get a closer look.

The mammary glands of each breast consist of about 15 to 25 sections called lobes with each
lobe containing many smaller structures called lobules.
Each lobule consists of a large number of alveolar glands, which are the small sac-like structures that produce milk.
The milk produced by the alveolar glands drain into the terminal ducts that join together to form the intralobular ducts.
These ducts converge further and form the lactiferous ducts, which drain the lobes and eventually lead to the nipple.
All of the lobules and ducts are also surrounded by fibro-fatty tissue that provide a supportive and protective function.
Before pregnancy, the mammary glands are considered to be in an inactive state, and they’re structurally different
from mammary glands that are in the active state.
The active state occurs during pregnancy and during lactation after childbirth.
During pregnancy, the alveolar glands and the duct system will grow in preparation to produce milk for a newborn baby.
This low power image is an example of lactating mammary glands in the active state.
A portion of a lobe can be seen surrounded by a thick layer of connective tissue that contains a small number of fat
cells or adipocytes within the connective tissue as well.
Within the lobe, thinner layers of connective tissue separate the lobe into lobules.
In a neighboring lobe, we can also see a couple of large lactiferous ducts.
These ducts are lined with a double layer of columnar or cuboidal cells with a surrounding layer of connective tissue.
If we take a closer look at one of the lobules, we can see some of the smaller intralobular ducts that are typically lined
with 1 to 2 layers of cuboidal cells that also have a thin layer of connective tissue that surround the ducts. In this image
of a different lobule, we can see a good example of a few alveoli and a longitudinal cross-section of the terminal duct
that’s responsible for draining the milk produced by these alveoli.
Both the terminal ducts as well as the alveoli are lined with either cuboidal or columnar secretory cells.
The supportive tissue between the ducts and alveoli is called the intralobular stroma.
It consists mostly of loose connective tissue, but it also contains small blood vessels, fibroblasts, plasma cells, a few
adipocytes, and myoepithelial cells.
Although the wavy connective tissue can be easily seen in this image, some of the other structures can’t be identified as
easily since the intralobular stroma is typically very thin and sparse in mammary glands that are in the active state.
Now, if we compare mammary glands in the active state to an image of an inactive or resting mammary gland, the most
significant difference seen histologically is the nearly complete absence of the milk producing alveoli, which we can see
even in these lower power images.
As a result, the majority of the resting mammary glands consist of connective tissue and adipose tissue.
The lactiferous ducts will still be present, but they’ll typically be smaller and will often appear flattened or collapsed.
But the lining of these ducts are still the same, with a double layer of columnar or cuboidal cells.
The general structure of the terminal ductules are also still the same in resting mammary glands, with a simple cuboidal
epithelium and a surrounding intralobular space that consists of connective tissue, fibroblasts, myoepithelial cells, and in
this image we can also see a small blood vessel present in the upper right.
Myoepithelial cells surround the terminal ducts, but they also surround the lactiferous ducts and alveoli.
During breast-feeding, increased oxytocin will stimulate these smooth muscles to contract and lead to milk ejection from
the nipple.
The myoepithelial cells are typically located between the secretory cells and the basement membrane, so they are also
an important histological marker for the presence and progression of primary breast carcinomas.
As a breast tumor progresses, the reduction or disappearance of myoepithelial cells may suggest a transition to an
infiltrating or invasive status.
Alright, as a quick recap… The mammary glands consist of alveolar glands that are organized into lobules along with the
terminal and intralobular ducts that drain the alveoli.
The active state starts during pregnancy, when the lobules increase in both size and total number, and
the alveolar glands become the most prominent structures in the breast.
The inactive or resting state is when an adult female is not pregnant or breast-feeding. In this state, the ducts are smaller
and the secretory alveoli are undeveloped.
In both states, the alveoli and terminal ducts are lined with cuboidal or columnar secretory cells, the intralobular ducts
will have 1 to 2 layers of cuboidal cells, and the lactiferous ducts will have 2 layers of columnar or cuboidal cells.
Summary
Mammary glands are organs that produce milk for nursing infants. The mammary gland is composed of lobules, which
are clusters of cells that produce milk, and ducts, which are the channels that transport the milk to the nipples. The
lobules and ducts are surrounded by a layer of adipose tissue, which provides insulation and helps protect the
delicate mammary gland tissue.
The mammary gland is supplied with blood vessels and lymphatic vessels, which provide nutrients and remove waste
products from the gland. The nipple is supplied with nerves that provide sensation and facilitate nursing.

Definition / general
Mammary glands located on the upper anterior thorax that produce and secrete milk in females
Essential features
Adult female breast consists of branching ducts and acini; the acini group together to form lobules
Ductal - lobular system: composed of ducts and acini lined by a dual inner (luminal) epithelial cell layer and outer (basal)
myoepithelial cell layer, resting on a basement membrane, enveloped by stroma
Exhibits physiologic histomorphologic changes during menstrual cycle, pregnancy / lactation, menopause, exogenous
hormone therapy

Histology
Ductal - lobular system:
Consists of large lactiferous ducts that open to the surface of the nipple via lactiferous sinuses, which branch into ducts
and terminal ductules which terminate in acini
Acini are grouped together in clusters to form lobules (terminal duct lobular unit)
Ductal - lobular system is arranged in series of segments (5 - 10)
Cellular lining of the ductal - lobular system is bilayered and consists of:
Inner (luminal) epithelial cells: cuboidal to columnar epithelium with pale eosinophilic cytoplasm
Outer (basal) myoepithelium: variably distinctive, varies in appearance from flattened cells with compressed nuclei to
prominent epithelioid cells with abundant clear cytoplasm, can sometimes have myoid appearance
Both epithelial and myoepithelial cells thought to arise from a bipotent progenitor cell (Oncotarget 2017;8:10675)
Basement membrane surrounds mammary ducts, ductules and acini (Virchows Arch A Pathol Anat Histopathol
1992;421:323)
Basement membrane contains type IV collagen and laminin, demarcates ductal - lobular system from the surrounding
stroma
Transgression of the myoepithelial layer and basement membrane by tumor cells defines invasion
Stroma:
Consists of varying amounts of fibrous tissue and adipose tissue and can be divided into:
Interlobular stroma:
Surrounds large ducts and terminal duct lobular units (TDLUs), denser, more collagenous than intralobular connective
tissue
Multinucleated giant cells of unknown significance are sometimes present (Virchows Arch 2001;439:768)
Intralobular stroma: surrounds acini within TDLUs, loose, contains fibroblasts, scattered inflammatory cells and
histiocytes
Nipple - areolar complex: skin variably pigmented, contains numerous sebaceous glands
Independent of hair follicles, except at periphery of areola; contains dense fibrous stroma with bundles of smooth
muscle
Montgomery tubercles: sebaceous glands sharing ostium with a lactiferous duct, more prominent during pregnancy and
lactation
Epidermis may contain occasional clear cells, either clear keratinocytes or Toker cells (epidermally located mammary
duct epithelium)
Toker cells found in 10% of normal nipple (Histol Histopathol 2009;24:367)
Stratified squamous epithelium extends into duct lumens for 1 - 2 mm (Clin Radiol 2012;67:e42)

Pregnancy / lactation
Dramatic increase in the number of lobules, as well as acinar units
Increased epithelial cell proliferation and lobuloalveolar differentiation
Decrease in intralobular and interlobular stroma
Second and third trimester:
Increase in size of epithelial cells and cytoplasmic vacuolization, myoepithelial cells difficult to discern
Lactation:
Abundant secretory material and prominent cytoplasmic vacuoles, epithelial cells may have bulbous or hobnail
appearance
Myoepithelial cells remain inconspicuous
Rarely areas of infarction (Exp Ther Med 2015;10:1888)