Breast carcinoma. Etiology, pathogenesis, clinic-morphological types and histological variants
1 in 8 women will get breast cancer, there are three etiological areas:
- 1. Genetic changes
- a. Overexpression of HER2/NEU
- b. Amplification of RAS and MYC
- c. BRCA1 and BRCA2 mutations, which cause about ⅓ of familial breast cancers
- 2. Hormonal influences
- a. Endogenous estrogen hormone imbalance post menopause is a a major RF
- 3. Environmental variables
Classifications
- Noninvasive
- Ductal carcinoma in situ (DCIS)
- Lobular carcinoma in situ (LCIS)
- Invasive (infiltrative)
- Invasive ductal carcinoma (most common type)
- Invasive lobular carcinoma
- Medullary carcinoma
- Colloid carcinoma
- Tubular carcinoma
- Others
Non Invasive carcinomas
- Both DCIS and LCIS arise from terminal duct lobular unit, DCIS fills and distorts ducts, LCIS expands but does not alter acini of lobules, both are confined by basement membrane and don’t invade
- DCIS has solid, comedo, cribriform, papillary and micropapillary types. Necrosis can also occur. Calcifications are frequently seen also, excellent prognosis.
- Paget disease of nipple is caused by extension of DCIS up lactiferous ducts and into the contiguous skin of the nipple, producing crusting exudate
- LCIS has uniform appearance, monomorphic cells with round nuclei in cohesive clusters. Rarely calcify and unlikely to be detected, LCIS can be a precursor to more dangerous other cancers.
Remember: Paget disease of the nipple looks like eczema: a red, crusted, weeping nipple on one side. Under the microscope, large pale Paget cells sit inside the nipple epidermis, and an underlying carcinoma (DCIS or invasive) is almost always present. A one-sided nipple 'eczema' that does not heal must be biopsied.
Invasive carcinoma
- Invasive ductal carcinoma
- Majority of cancers, usually associated with DCIS (LCIS less commonly)
- Causes desmoplastic response causing breast fat to become fibrotic and hard
- Microscopic appearance is heterogenous, invasion of lymphovascular spaces can be seen, ⅔ express estrogen or progesterone receptors
- Invasive lobular carcinoma
- Consists of identical cell morphology to LCIS, ⅔ associated with LCIS
- Cells invade single file into stroma, correlates with mutation of E-cadherin protein
- May be diffusely invasive or single mass
- Frequently metastasis to CSF, serosal surfaces, GI tract, ovaries and bone
- Inflammatory carcinoma
- Defined by clinical presentation of swollen, red breast, without palpable mass
- Low survival rate
H&E, invasive ductal carcinoma: nests and cords of tumour cells infiltrating desmoplastic stroma and fat (left); enlarged pleomorphic nuclei at high power (right).