Breast Disease Flashcards
ANATOMY AND HISTOLOGY of breast
- “modified sweat gland”
- 15-20 lobes, each acting as an independent glandular unit with a lactiferous duct opening to the nipple
o Functional unit is the “Terminal Duct Lobular Unit” (TDLU)
o TDLU→intralobular ducts →interlobular ducts→lactiferous duct
o Interlobular stroma is present between lobes & divides each lobe into numerous lobules
o Intralobular stroma surrounds each TDLU
Many TDLU in close proximity to each other will empty into a lactiferous duct
- lactiferous duct will travel to nipple. Right before they reach the nipple, the lactiferous duct transforms into lactiferous sinuses
- lining of major ducts ranges from double-layered cuboidal epithelium in the smaller ducts (those closest to TDLU)→to pseudostratified columnar→to stratified squamous epithelium in largest ducts (those nearest the nipple)
- luminal (lining epithelium) with surrounding myoepithelial layer and basement membrane
- TDLU has central lumen, which is surrounded by an inner layer of ep cells. The ep cells are the functional cells of the breast and secrete milk. The inner ep cells are surrounded by myoepithelial cells, which is surrounded by basement membrane
- in cancer, the inner layer of ep cells undergo cancerous change
- the cancer is in situ if the ep cells are surrounded by the myoepithelial cell and basement layer still. And invasive if not surrounded
Terminal ductal-lobular unit
Composed of lobule and terminal duct
- non-proliferative (fibrocystic) changes
- proliferative changes without atypia
- proliferative changes with atypia (atypical hyperplasia)
- in situ carcinoma
- invasive carcinoma
Large lactiferous ducts & sinuses & nipple
- intraductal papillary lesions
- duct ectasia
- squamous metaplasia of lactiferous ducts
- subareolar abscess
- mastitis
- nipple adenoma
- paget’s disease of the nipple
Intralobular stroma
- fibroadenoma
- phyllodes tumour
- PASH (in notes)
Interlobular stroma
- fat necrosis
- benign mesenchymal tumours
- malignant mesenchymal tumours/SARCOMAS
- PASH (in lecture)
List of BENIGN BREAST lesions/DISORDERS
Mastitis
Fibroadenoma
Non-proliferative lesions/Fibrocystic Change
Proliferative lesions without Atypia
Proliferative lesions with Atypia aka atypical hyperplasia
Mastitis
Most cases occur during lactation/breastfeeding/chestfeeding
Predisposing factors: cutaneous fissures in nipples & breast engorgement
Etiologic agents: Staphylococci & Steptococci
Signs & Symptoms: breast is tense, hot, red, painful; axillary lymphadenopathy; general signs
and symptoms of acute infection, tender axillary lymph nodes
Differential diagnosis: inflammatory carcinoma
Complications: abscess formation requiring surgical drainage; healing of area by fibrosis may
result in fixation of overlying skin mimicking carcinoma
Fibroadenoma
Most common cause of a benign breast mass
May occur at any age, but most common in female patients between ages of 20 and 35 years
Features:
o Discrete, mobile, usually non-tender breast mass
o Rounded/lobulated contours
o Firm to rubbery texture
o No dimpling/retraction of overlying skin
o Composed of both stromal and epithelial elements
o No atypia, rare stromal mitoses
Can be excised
More aggressive counterpart of a fibroadenoma: phyllodes tumour
Non-proliferative/Fibrocystic Change, Proliferative Change without Atypia, Proliferative Change with Atypia
Although the term “fibrocystic disease” is frequently used by both clinicians and pathologists, this does not represent a distinct entity, either clinically or pathologically.
- Clinically, this term has been applied to a condition in which there are palpable breast masses that fluctuate with the menstrual cycle and may be associated with pain and tenderness.
However, at least 50% of female patients have palpably irregular breasts and, in many patients, these palpable lumps represent physiologic changes rather than a pathologic process.
- Thus, the term “fibrocystic change” is a more appropriate term to use.
The removal of the word disease also removes the implication that all of the changes encompassed by this term are associated with an increased risk of carcinoma development.
- Indeed, the vast majority of patients designated as having fibrocystic change are not at any increased risk for developing breast cancer.
Several studies have shown that by separating the various histologic components of fibrocystic change, subgroups of patients with different risks for breast carcinoma development may be identified.
Non-proliferative lesions
aka Fibrocystic change
- no increased risk for subsequent breast
cancer
o cysts
o apocrine change
o duct ectasia
o fibrosis
o mild hyperplasia
Proliferative lesions without atypia
mildly increased risk for subsequent breast cancer: RR X 1.5-2
o florid/moderate epithelial hyperplasia
o intraductal papillomas
o sclerosing adenosis
o complex sclerosing lesion/radial scar
o complex fibroadenoma
Proliferative lesions with atypia
aka atypical hyperplasias
- moderately increased risk for subsequent breast cancer: RR X 4-5
o atypical ductal hyperplasia
o atypical lobular hyperplasia
BREAST CANCER EPIDEMIOLOGY AND RISK FACTORS
Lifetime risk of breast cancer is approximately 1 in 8 for females living in North America
Important epidemiologic considerations and risk factors include:
o Age & sex
- F > M
- 75% occur in the 50+ age group
o Family history
- 80% sporadic, 20% family history
o Geographic factors
- Americas/Europe > Asia/Africa
o Race/ethnicity
- Genetic, social determinants of health
- white women have most breast cancer
- black women has less breast cancer than white women, have tend to have it at younger ages and have more aggressive versions
o Reproductive history
- early menarche
- nulliparity (never been pregnant)
- no Breast feeding
- older age at first pregnancy
o Ionizing radiation
- especially if exposure occurs while breast is still developing
o Others: obesity, hormone replacement, mammographic density, EtOH
FAMILIAL BREAST CANCER
Approximately 20% of cases of breast cancer are associated with a penetrant dominant genetic predisposition.
- Clinical suspicion is warranted if:
o there are 3 or more affected members in a family
o breast cancer occurs in a patient <35 years of age
o patient has bilateral breast cancer
o family has members with breast and ovarian cancers as well as endometrial and colon cancers or sarcomas in both females and males
Penetrance: the proportion of individuals carrying a particular variation of a gene that also express an associated phenotype
High penetrance mutations (5-7%)
- familial breast and ovarian cancer (BRCA1/2)
- Li-fraumeni (p53)
- cowden syndrome (PTEN)
- Peutz-Jeghers (STK11)
Moderate penetrance mutations (< 3%)
- Li-fraumeni variant (CHEK2)
- Ataxia Telangiectasia (ATM)
Low penetrance mutations (>10%)
- much of the genetic component of breast cancer risk remains uncharacterized and probably arises from combinations of flow-penetrance variants that, individually, might be quite common in the population
Of all families with a strong family history, about 40-45% will have an abnormality in the BRCA1
gene (chromosome 17) and about 30-40% will have an abnormality in the BRCA2 gene
(chromosome 13)
Other mutated genes associated with familial breast cancer include TP53 (Li-Fraumeni
Syndrome) and PTEN (Cowden Syndrome)
Using molecular genetic techniques, it is possible to identify individuals who have these
abnormal genes, and who are therefore at high risk of developing breast cancer. The best way to manage such patients clinically is, however, still uncertain.
CLASSIFICATION OF BREAST CANCER
Non-invasive (in situ) carcinoma (i.e. carcinoma confined to ducts or lobules by an intact myoepithelial cell layer)
* ductal carcinoma in situ (DCIS)
* lobular carcinoma in situ (LCIS)
Invasive
* ductal carcinoma aka no special type
* special type:
o lobular carcinoma
o tubular carcinoma
o mucinous carcinoma
o cribriform carcinoma
o medullary carcinoma
o metaplastic carcinoma
o combined
Paget’s disease of the Nipple:
- Special clinical and histological manifestation of either DCIS or invasive carcinoma.
Inflammatory Carcinoma:
- Special clinical manifestation of invasive carcinoma, often with characteristic accompanying histological features.
