breast pathology 1
DESCRIPTION
iNTENDED FOR PATHOLOGY UG AND PG STUDENTS.TRANSCRIPT
Breast pathology - 1
Dr.CSBR.Prasad, M.D.
Cases
Cases
Cases
Cases
Left image – affected breast Right image – Normal breast
Cases
60yo male
Cases
Cases
1 2
Cases
Cases
Cases
Cases
Cases
Breast pathology
Mammary gland – Normal features
1. Covered by skin & subcutaneous tissue
2. Rests on pectoralis muscle
3. Pectoral fascia separates it from the pectoral muscles
Breast – Normal features
• Modified skin appendage.
• Composed of specialized epithelium and stroma that gives rise to both benign and malignant lesions.
• 6-10 major ductal system originate at the nipple.
• Keratinizing sq.epithelium of overlying skin continues into the ducts and then abruptly changes to a double layered cuboidal epithelium.
• Surrounding areolar skin is pigmented & supported by smooth muscle.
• Normal duct system micro Source: Ackerman’s Surgical Pathology 9th Ed, 1765p
• Morphofunctional unit of the organ is SINGLE
GLAND composed of 2major parts:
1-TDLU (secretory unit of the gland)
a-lobule
b-terminal ductule
2-Large duct system
Breast – Normal features
• Importance of division of mammary gland
unit into 2 major portions resides in its
relation to disease of this organs.
• TDLU (FCD, Ductal hyperplasia,
Carcinoma)
• Large duct system (Solitary papilloma,
ductectasia, rare ductal carcinomas)
Breast – Normal features
Normal anatomy and possible
pathological lesions
3910 Source: Ackerman’s Surgical Pathology 9th Ed, 1765p
Histology
Histology
Epithelium & Stroma:
• Ducts and lobules are lined by 2 cell types
1-Myoepithelial cell lying on the BM.
2-Epithelial cells lines the lumen.
• Stroma
1-Interlobular stroma
2-Intralobular stroma (hormonally responsive)
The normal microscopic appearance of female breast tissue is shown here. There is a larger duct to the right and lobules to the left. A collagenous stroma extends between the structures (Interlobular – Red stars). Intralobular stroma is hormonally responsive (Blue Stars). A variable amount of adipose tissue can be admixed with these elements.
Normal histology
Source: webpath
Normal histology
At high magnification, the appearance of a normal breast acinus is shown here. Note the epithelial cells lining the lumen demonstrate apocrine secretion with snouting, or cytoplasmic extrusions, into the lumen. A layer of myoepithelial cells, some of which are slightly vacuolated, is seen just around the outside of the acinus.
Source: webpath
Epithelial markers
• EMA
• Milk Fat Globule Membrane antigen
• alfa-Lactalbumin
Source: Ackerman’s Surgical Pathology 9th Ed, 1765p
Normal histology
An immunoperoxidase stain with antibody to actin demonstrates the myoepithelial cell layer around the breast acinus. The myoepithelial cells are contractile and are very sensitive to oxytocin.
Source: webpath
Markers for Myoepithelium
• S-100 protein
• P-Cadherin
• SMA
• Calponin
• Smooth muscle myosin-heavy chain
• Maspin
• Caldesmon
• p63
Source: Ackerman’s Surgical Pathology 9th Ed, 1765p
Disorders of development
1. Milk line remnants.
2. Accessory axillary breast tissue.
3. Congenital nipple inversion.
Milk line remnants
“POLYTHELIA”
Epidermal thickening along the milk line
extending from axilla to perineum.
The classification established by Kajava in 1915 is still valid: (De Cholnoky,
1939)
1. Complete SN: Nipple + areola + glandular breast tissue
2. SN: Nipple + glandular tissue (no areola)
3. SN: Areola + glandular tissue (no nipple)
4. Aberrant glandular tissue only
5. SN: Nipple + areola + pseudomamma (fat tissue that replaces the
glandular tissue)
6. SN: Nipple only (the most common SN)
7. SN: Areola only (polythelia areolaris)
8. Patch of hair only (polythelia pilosa)
Milk line remnants
Disorders of development
Milk line remnants
In some persons normal ductal system extends into subcutaneous tissue of the chest wall and into the axillay fossa.
Importance: Therapeutic mastectomy might remove the entire breast but not remove all breast epithelium.
Hence cannot compeltely eliminate the risk of developing breast cancer.
Disorders of development
Accessory axillary breast tissue
Disorders of development
Accessory axillary breast tissue
It may be bilateral or unilateral.
Importance: may be mistaken for carcinoma
or inflammation.
Disorders of development
Congenital nipple inversion
Disorders of development
Congenital nipple inversion
Clinical presentations
• Symptomatic:
1. Pain
2. Palpable mass
3. Nipple discharge
• Asymptomatic (mammography screening)
1. Densities
2. Calcifications
Clincal presentations
PAIN
• Mastalgia / mastodynia
• Cyclical / non-cyclical
1. Ruptured cyst
2. Injury
3. Infection
4. Some times without any specific lesion
Note: only about 10% of breast carcinoma patients present
with pain.
• Notable points:
1. Masses must be distingusihed from the normal nodularity of the breast.
2. Breast masses usually does not become palpable until it’s about 2cms in diameter.
3. Likelyhood of malignancy in a papable mass increses with age
---- <40yrs (only 10% of masses are malignant)
---- >50yrs (about 60% of the masses are malignant)
Clincal presentations
PALPABLE MASSES
• Gains importance only if it’s
1. Spontaneous &
2. Unilateral
Clincal presentations
Nipple discharge
• Types of discharges:
1. Milky (>prolactin, hypothyroidism, anovulatory
cycle, OCs, M-Dopa, phenothiazines) (Not
associated with malignancy)
2. Serosanguinous (most commonly associated
with benign lesion)
3. Bloody (most commonly associated with benign
lesion – duct papillomas)
Clincal presentations
Nipple discharge
Acute mastitis
• Pyogenic infections
• Occurs during first few weeks of lactation
• Pathogens:
1. Staphylococcus
2. Streptococcus
1. Breast mass
2. Fever
3. Erythematous painful breasts
4. If not Tx it may spread to entire breast
Complictions:
---fibrous scarring
---may be mistaken for carcinoma
Acute mastitis
Acute mastitis
During lactation, or at other times with dermatologic conditions that allow cracks and fissures to form in the skin of the nipple, infectious organisms can invade into breast and result in acute inflammation, and this may progress to breast abscess formation (Circle). The most common organism is Staphylococcus aureus. Organization with fibrous scar formation around the abscess can mimic a carcinoma on physical examination, by mammography, and grossly.
Acute mastitis
While breast-feeding the baby, the skin of the breast may become irritated and inflamed. The skin may fissure, predisposing to infection. Acute mastitis typically involves just one breast and is most often caused by Staphylococcus aureus, though other bacterial organisms such as streptococci can produce this condition, with neutrophilic infiltrates microscopically. If untreated by antibiotic therapy, spread of infection and abscess formation can occur.
Granulomatous mastitis
• Chronic non-specific mastitis
Etiology:
1. Systemic granulomatous disease (Sarcoidosis, Wegener’s)
2. Inections (TB, Fungal)
3. Silicone breast implants
4. Idiopathic (hypersensitivity to luminal secretions)
Periductal mastitis
Recurrent sub areolar abscesses
“ZUSKA disease”
• Painful erythematous subareolar masses
• >90% are smokers (vit-A deficiency)
• Seen both in males and females
• Not associated with lactation
Subareolar abscess with fistulous opening at the edge of areola
Periductal mastitis
Recurrent sub areolar abscesses
“ZUSKA disease”
Pathlogy:
1. Keratinization of epithelium extending to an abnormal depth into the orifices of the nipple ducts.
2. Keratin plugs block the ductal system and causes dilatation & eventual rupture of the ducts.
3. Intense chronic granulomatous inflammatory response develops to ketain spilled into periductal tissue.
Periductal mastitis
Recurrent sub areolar abscesses
“ZUSKA disease”
• 3945
Periductal mastitis
Recurrent sub areolar abscesses
“ZUSKA disease”
Source: Robbins Pathologic basis of disease, 8th ed. 1125p
Mammary ductectasia
• 4th to 7th decade of life.
• Usually seen in multiparous women.
• NOT assocated with cigarette smoking.
Clinically:
• Nipple discharge.
• Retraction of nipple.
• Palpable dilated ducts in the subareolar area.
• Gross:
1-Poorly defined indurated area.
2-Ropyness of the surface.
3-c/s shows dilation of one or more large
ducts containing cheesy inspissated
secretions.
Mammary ductectasia
• Microscopically:
1-Dilated ducts with necrotic & atrophic epithelium
2-Lumen filled with powdery debri and foam cells
3-Periductal & insterstitial chronic inflammaotry cell infiltration (Ly, Plas, Histio, Giant cells)
Note: Plasma cell mastitis (when numerous plasma cells are seen)
Obliteration mastitis (when inflammatory scarring obliterates the lumen of the ducts)
Mammary ductectasia
• 3955
Mammary ductectasia
Source: Ackerman’s Surgical Pathology 9th Ed.
FAT NECROSIS
• Usually seen in obese & pendulous breasts
• Generally iniciated by trauma or prior
surgery
• It presents as painless palpable mass
• 3914
FAT NECROSIS
Gross:
1. Central pale cystic area of necrosis
2. Chalky white areas
FAT NECROSIS
FAT NECROSIS
• Lipid filled spaces surrounded by neutrophils, lymphocytes,
plasma cells and histiocytes having foamy cytoplasm
• FB type giant cell reaction
• Fibrosis & calcifiction
FAT NECROSIS
• Lipid filled spaces surrounded by neutrophils, lymphocytes,
plasma cells and histiocytes having foamy cytoplasm
• FB type giant cell reaction
• Fibrosis & calcifiction
Non-proliferative breast changes – FCD
Non-proliferative breast changes – FCD
• Form palpable masses
• Calcifications
• Spontaneous unilateral nipple discharge
• They mey disappear after FNAC
There are 3 principle patterns of morphologic
changes
1. Cyst formation with apocrine metaplasia
2. Fibrosis
3. Adenosis
Non-proliferative breast changes – FCD
CYSTS:
• Cysts form by dilation and unfolding of lobule.
• Cystic lobules coalesce to form larger cysts.
• Cysts lined by flattened atrophic or apocrine epithelium
• Papillary projections
• Calcification is common (‘Milk of calcium’)
Non-proliferative breast changes – FCD
Fibrocystic Change (FCC)
This is the gross appearance of fibrocystic changes in the breast. A 1.5 cm cyst is
noted here. This can lead to palpation of an ill-defined "lump" in the breast.
Sometimes, fibrocystic changes produce a more diffusely lumpy breast.
Source: webpath
This is the histologic appearance of fibrocystic changes in breast. There are cystically dilated ducts, areas of lobules that are laced with abundant fibrous connective tissue (sclerosing adenosis), and stromal fibrosis. There is even a small area of microcalcification seen just to the upper right of center. No atypical changes are seen here.
Fibrocystic Change (FCC)
Source: webpath
Another example of microscopic fibrocystic changes of the breast are shown here.
Fibrocystic changes account for the majority of "breast lumps" that are found in
women of reproductive years, particularly between age 30 and menopause.
Fibrocystic Change (FCC)
Source: webpath
There is prominent apocrine change of the cells lining the cysts in this example of
fibrocystic changes of breast. Note the tall, pink, columnar nature of the
epithelial cells. This appearance is benign.
Fibrocystic Change (FCC)
Source: webpath
FIBROSIS:
Rupture & release of secretory material into
the adjacent stroma elicit inflammation and
fibrosis.
ADENOSIS:
Increase in number of acini per lobule
‘Blunt duct adenosis’
Non-proliferative breast changes – FCD
Prominent sclerosing adenosis, one of the features of fibrocystic changes, is demonstrated
by the appearance of a proliferation of small ducts in a fibrous stroma. Although it is
benign, the gross and mammographic appearance may mimic carcinoma, and it can be
difficult to distinguish from carcinoma on frozen section.
Fibrocystic Change (FCC)
Source: webpath
FCC
This mammogram demonstrates a
suspicious lesion that could be a
carcinoma or just an area of
pronounced sclerosis with
fibrocystic changes. On biopsy, this
was benign.
Source: webpath
PROLIFERATIVE LESIONS
1-without atypia
2-with atypia
PROLIFERATIVE LESIONS
Proliferative breast disease
without atypia
• Rarely form palpable masses
• They are often detected
---radiographically (densities, calcifications)
---in biopsies
• Proliferation of ductal epithelium & or stroma
without cellular abnormalities suggestive of
malignancy
Entities include:
1. Florid epithelial hyperplasia
2. Sclerosing adenosis
3. Complex sclerosing lesion
4. Papillomas
5. Fibroadenomas with complex features
Proliferative breast disease
without atypia
EPITHELIAL HYPERPLASIA:
• Def: presence of >2 cell layers of epithelium
• >4 cell layers designates it as moderate to florid
hyperplasia
• When they fill the lumen it can be differentiated
from CIS by finding fenestrations are the
periphery of the cellular masses.
Proliferative breast disease
without atypia
SCLEROSING ADENOSIS:
• Increase in # of acini per terminal duct at least twice the normal.
• Normal lobular arrangement is maintained.
• Acini are characteristically dilated at the periphery.
• Myoepithelial cells are usually prominent.
• Sclerosis
• Calcifications are frequently present with in the lumen of acini.
Proliferative breast disease
without atypia
COMPLEX SCLEROSING LESION:
• Stellate scar
• Centrally entrapped glands in hyalinized stroma
Complex sclerosing lesion include:
1. Radial scar
2. Radial scar related lesion with sclerosing
adenosis, papilloma formation
3. Epithelial hyperplasia
Proliferative breast disease
without atypia
PAPILLOMAS:
• Multiple branching fibrovascular cores
• Lined by luminal & myoepithelial cells
• Growth occurs within a dilated duct
• Epithelial hyperplasia and apocrine metaplasia are frequently seen
• Large duct papillomas are single and situated nearer to the nipple
• Small duct papillomas are multiple and located deeper within ductal system (more prone for Ca.)
Proliferative breast disease
without atypia
These breast ducts demonstrate epithelial hyperplasia. The epithelial cells are multilayered. There is no atypia. Thus, just as with fibrocystic changes such as fibrosis, cysts, and sclerosing adenosis, there is no increased risk for carcinoma. Source: webpath
More florid ductal epithelial hyperplasia of the breast is shown here. There is a slightly increased risk (1.5 to 2 times normal) for breast carcinoma when such changes are present. Source: webpath
• This includes:
1-ADH
2-ALH
Proliferative breast disease
with atypia
Proliferative breast disease
with atypia - ADH
This is atypical ductal epithelial hyperplasia of the breast. A significantly
increased risk (5 times normal) for breast carcinoma occurs with
cytologically atypical epithelial hyperplasia.
Proliferative breast disease
with atypia - ALH
END
Contact:
Dr.CSBR.Prasad, M.d.,
Associate Professor of Pathology,
Sri Devaraj Urs Medical College,
Kolar-563101,
Karnataka,
INDIA.