Pathology Of The Breast Flashcards
Anatomy and Histology
6-10 ductal systems originate at the nipple
Keratinizing squamous epithelium overlying the skin continues into the ducts and then abruptly changes into a double layer cuboidal epithelium
Successful branching of large ducts eventually leads to terminal duct lobular unit, in an adult woman the terminal duct branches into a grapelike cluster of small acini to form a lobule
Each ductal system occupies a quarter of the breast
In normal breasts Ducts and Lobules are lined by 2 cell types
A low flattened discontinuous layer of contractile cells containing myofilaments lies on the basement membrane (assist in milk ejection and maintaining the normal structure and function of the lobule and basement membrane)
A second layer of epithelial cells lines the lumens (luminar cells of terminal duct and lobule produces milk but those lining the large duct system do not)
Majority of breast stroma contains dense fibrous connective tissue admixed with adipose tissue (interlobular stroma)
Life cycle changes
Prepubertal, follicular phase, menstrual phase, pregnancy changes, lactation changes and involution.
(Prepubertal breast)
Prepubertal breast in both males and females consist of the large duct system ending in terminal ducts with minimal lobule formation. At menarche terminal ducts give rise to lobules and interlobular stroma increases in volume. There is paucity of adipose tissue hence breast appears radio dense
(Follicular phase of menstrual cycle)
The combined stimulatory effect of estrogen and progesterone on the breast during the premenstrual phase of the cycle accounts for the sense of fullness commonly experienced by women
(Menstrual Phase)
When menstruation occurs the fall in estrogen and progesterone levels is followed by epithelial cells apoptosis and disappearance of stroma edema thus regression of the size of the lobules
(Pregnancy Changes)
It is only with the onset of pregnancy that the breast assumes its complete morphological maturation and functional activity
A. Lobules increase in number and size and thus loses the stroma epithelial relationship so that by the end of pregnancy the breast is composed entirely of lobules separated by scanty amount of stroma
B. Montgomery tubercles( numerous dermal cells in the areaola become more prominent and function in nipple lubrication)
C. By third trimester secretory vacuoles of lipid material are found within the epithelial cells of TDLU but mill production is inhibited by high level of progesterone
(Lactation changes)
-breast produces colostrum (rich in protein) which changes to milk (fat and calories) within first 10 days as progesterone level drops
- breast milk nourishes the baby as well as provide protection against infections and allergies
- maternal antibodies augment infants own developing defences (IgA, neutrophils, lymphocytes, macrophages, cytokines, lysozyme)
- Drugs, Radioactive compounds and viruses can also pass through thus post partum health of mother influences the child
(Involution)
After 3rd decade, long before menopause lobules and specialized stroma starts to involute
In some lobules almost totally disappear leaving only ducts creating morphologic pattern resembling male breast but in most there’s sufficient estrogen secretion from adrenal glands or stores of body fat to maintain vestigial remnants of lobules
Radio dense fibrous interlobular stroma of the young female breast is replaced by radiolucent adipose tissue
Disorders of the breast
Disorders of development
Inflammatory disorders
Neoplastic disorders (benign and malignant) & for benign ( proliferative and non proliferative)
Disorders of Development
A. Milk line Remnants— supernumerary nipples or breasts along the milk line which extends from the axilla to the perineum, as a result of persistence of epidermal thickenings along the milk line
B. Accessory Axillary Breast Tissue— (Tail of spence) in some women the normal ductal system extends into subcutaneous tissue of the chest wall and into the axillary fossa
C. Congenital Nipple Inversion
D. Macromastia — causing physiological discomfort and pain
Inflammations
(Acute Mastitis)
Occurs early during lactation when the breast is vulnerable to staph aureus and less commonly streptococci infections
Staph infections produce localized area of acute inflammation progressing to formation of single or multiple abscesses
Strep infections produce a diffuse spreading infection that eventually involves entire breast
Treated with antibiotics and rarely surgical drainage
(Peri ductal mastitis)—seen in smokers
A.K.A Zuska Disease, Squamous metaplasia of lactiferous ducts, recurrent subareolar abscess
Affects both gender, painful erythematous subareolar mass.
Women present with fibrosis, scarring causing inverted nipple but in most the inverted nipple is due to the inflammatory response
(Fat Necrosis)
Painless palpable mass, Skin thickening or retraction, mammographic density or calcifications
Majority of women give history of trauma or prior surgery
(Lymphocytic Mastopathy)— autoimmune disease of breast
Single or multiple palpable hard masses, in some cases bilateral or detected as mammographic densities. Too hard to obtain needle biopsy
Common in women with type 1 DM or autoimmune thyroid disease
(Granulomatous mastitis)
Very rare
Only parous women are affected
Hypothesized that its a hypersensitivity reaction
Mondor’s disease
Rare benign disease of the breast
Thrombophlebitis of superficial veins of chest wall
Cord like induration of breast
Resolves spontaneously
Benign (Non proliferative breast change)
Fibrocystic change
Macroscopic and microscopic changes that occur due to the exaggerated and uncoordinated response of the ducts and stroma to the cyclic hormonal stimulation during the menstrual cycl
3 main histological changes Fibrosis Cystic dilation of the ducts Adenosis Apocrine metaplasia
What happens in Fibrosis, cystic dilatation of the ducts, adenosis and apocrine metaplasia
(Fibrosis)
The dense interlobular fibrous tissue expands into the lobules replacing the loose interlobular connective tissue
(CDOD)
Strands of fibrous tissue constricts the ducts segmentally preventing the secretions from coming out thus leading to the distal dilatation of the terminal ducts
(Adenosis)
This term denotes changes that occur from the proliferation of terminal duct cells which are grouped around the centrally dilated ducts
(Apocrine metaplasia)
Duct cells are lined by cells with granular eosinophilic cytoplasms and small nuclei
Presence signifies benign lesion
Proliferative breast changes without Atypia
Disorders characterized by proliferation of ductal or stroma epithelium without cellular abnormalities suggestive of malignancy
- Moderate or florid epithelial hyperplasia
- Sclerosing adenosis
- Complex sclerosing lesions
- Papillomas
- Fibroadenomas with complex features
Epithelial Hyperplasia and Papillomas
In normal breast only Myoepithelial cells and a single layer of Luminal cells are present above the basement membrane
Epithelial hyperplasia is the presence of more than 2 cell layers
Hyperplasia is moderate to florid when they’re more than 4 cell layers. The proliferating epithelium often including both luminal and myoepithelial cells fills and distends the ducts and lobules
Pappilomas
Pappilomas are composed of multiple branching fibrovascular cores, each having a connective tissue axis lined by luminal and myoepithelial cells
Proliferative disease with atypia (abnormalities)
ADH and ALH (Atypical Ductal Hyperplasia and Atypical Lobular Hyperplasia)
Cellular proliferations resembling Ductal carcinoma in situ(DCIS) and Lobular carcinoma in situ(LCIS) but lack quantitative and qualitative features for a diagnosis or carcinoma in situ
CLINICAL SIGNIFICANCE OF ADH AND ALH
Non proliferative changes don’t increase risk of cancer
Proliferative changes is associated with mild increase risk of cancer
Proliferative diseases with atypia confers moderate increase in risk for cancer
Commonest breast lesion and commonest breast tumor
The former is Fribrocystic changes of breast and the latter is fibroadenoma( a benign breast tumor)
Benign tumors commoner in 20-35 years and malignant in much older
Phyllodes tumor can be benign, borderline and malignant
Intraductal carcinoma, a benign tumor that leads to bleeding from the nipple
15 Risk factors for breast cancer
Aging Family history Menstrual history( early menarche and late menopause) Nulliparity Proliferative breast disease and hyperplasia Atypical hyperplasia Carcinoma in situ Race Estrogen exposure Radiation exposure Diet Geographic influence Obesity Exercise Breast feeding Environmental toxins Tobacco
Carcinomas
Divided into Non invasive and Invasive
DCIS( intraductal carcinoma)
—pre invasive form of breast carcinoma
LCIS Pre invasive form of lobular carcinoma Less common than DCIS 30% will progress into invasive carcinoma Lesions are bilateral
STAGING
Stage 0-IV
0— DCIS or LCIS (5 year survival rate 92%)
1— invasive carcinoma 2cm or less in diameter without nodal involvement (5 year survival rate 87%)
2— invasive carcinoma 5cm or less with up to 3 involved axillary nodes or greater than 5cm without nodal involvement (5 year survival rate 75%)
3— invasive carcinoma 5cm or-less with 4 or more involved axillary nodes or greater than 5cm with nodal involvement (5 year survival rate 46%)
4— any breast cancer with distant metastases (5 year survival rate 13%)
