L33- Breast Pathology II Flashcards
Breast CA:
- (1) age group
- (2) cancer type
- (sporadic/hereditary)
1- >40y/o, 25% postmenopausal
2- adenocarcinoma
3- both
list the many risk factors for sporadic breast CA
- peaks 75-80 y/o
- early menarche, late menopause, later age at first live birth
- FHx, race/ethnicity, US > Japan, Taiwan
- atypical hyperplasia
- high estrogen (replacement therapy or obesity / high fat diet)
-radiation exposure
list the many risk factors for hereditary breast CA
BRCA1/2
Li Fraumeni syndrome (p53) or variant (CHEK2)
BRCA1:
- (more/less) common than 2
- 20-40% risk of (2)
- chr(3)
1- more
2- ovarian CA, prostatic / pancreatic cancer
3- 17q21
BRCA2:
- (more/less) common than 1
- 10-20% risk of (2)
- chr(3)
1- less
2- ovarian CA, (inc risk male breast CA), prostatic / pancreatic CA
3- 13q12
Li Fraumeni:
-syndrome = (1) mutation and (2) cancers
-variant = (3) mutation and (4) cancers
1- p53
2- breast, sarcoma, leukemia, brain tumor, adrenal cortex
3- CHEK2
4- prostate, thyroid, kidney, colon
list the types of Breast carcinomas
Non-infiltrating = Carcinoma in situ:
- DCIS (ductal carcinoma in situ): comedo/high grade, non-comedo, Paget’s disease
- LCIS (lobular carcinoma in situ)
Infiltrating carcinoma:
- ductal, 80%
- lobular, 10%
- tubular / cribiform, 6%
- mucinous, medullary, papillary, metaplastic (4-5%)
All brease CAs arise from (1) cells.
DCIS / LCIS classification is based on (2)
1- cells in the terminal duct lobular unit
2- resemblance to normal involved spaces (ductal or lobular)
DCIS:
- usually (uni-/bi-lateral)
- (2)% chance of malignancy, (3)% chance of death
- (4) Tx
1- unilateral, 80-90%
2- untreated low-grade DCIS chance of malignancy is 1% per year
3- 2%
4- mastectomy (95% curative), breast conservation surgery
Comedo DCIS = (1):
- (2)% chance of invasion with (high/low) recurrence rate
- (3) are related genes
1- high grade DCIS, intraductal tumor
2- 60%
3- high
4- ER, PR, HER2Neu positive
Comedo DCIS histological appearance
- ducts filled with tumor cells
- large central necrosis and calcification (inspissated material- able to be squeezed out like toothpaste)
non-comedo DCIS = (1)
-(2) histological appearance
1- cribiform DCIS
2- rounded / cookie cutter like spaces
LCIS:
- (older/younger) women mostly
- usually (uni-/bi-lateral)
- (3)% chance of malignancy
- (4) genetic association
1- younger (incidental finding usually)
2- unilateral, 60-80%
3- untreated low-grade LCIS chance of malignancy is 1% per year
4- loss of E-cadherin
LCIS histological appearance
- lobuar distension
- oval, noncohesive cells
- no pleomorphism or mitoses
LCIS:
- (1) clinical appearance
- (2) Tx
-incidental biopsy finding, no calcifications or densities on mammography
Tx- close f/u and mammographic screening OR bilateral prophylactic mastectomy
LCIS:
- (1) clinical appearance
- (2) Tx
-incidental biopsy finding, no calcifications or densities on mammography
Tx- close f/u and mammographic screening OR bilateral prophylactic mastectomy
Paget Disease, breast:
- breast CA in (1)% cases
- describe carcinoma location: (2) generally via (3) process
1- 1-4%
2- intraductal carcinoma in large duct –> spread to skin, areola, nipple
3- extend from a DCIS via ductal system via latiferous sinuses into nipple skin
Paget disease, breast:
- (1) clinical presentation
- (2) examination notes
1- unilateral pruritic erythematous eruption with a scale crust — may be mistaken for eczema
2- palpable mass may not be present — may have underlying DCIS in same breast
Paget disease, breast:
- (1) biopsy results
- related to (2) expression
- (3) is present in 99.99% of cases
1- large hyperchromatic nucleus with halo
2- (poorly differentiated cells via) HER2/neu overexpression — ER negative
3- underlying intraductal or invasive carcinoma
Infiltrating ductal carcinoma, NST
-size and description
(no special type)
- Scirrhous- hard, dense desmoplasia
- 3-4 cm, infiltrative edge
- cords / nests of cells depend on level of differentiation
- necrosis, calcification
-molecular classification correlated to prognosis / response to therapy
Ductal carcinoma, NOS molecular classifications distribution
Luminal A, 40-55%
Luminal B, 15-20%
Basal like, 13-25%
HER2 positive, 7-12%
Ductal Carcinoma, NOS, luminal A:
- (1) genetic associations
- (2) onset / growth pattern
- (3) aggressiveness
1- ER+, HER2/neu-
2- postmenpausal, slow growing
3- well or moderate differentiation –> responds well to hormonal Tx and small number to chemotherapy
Ductal Carcinoma, NOS, luminal B:
- (1) genetic associations
- (2) aggressiveness
1- ER+, PR+, HER2/neu+
2- LN metastasis — may respond to chemotherapy
Ductal Carcinoma, NOS, basal like:
- (1) genetic associations
- (2) aggressiveness
1- ER-, PR-, HER2/neu-, BRCA1+, younger females
2- high grade, metastasis to brain, few complete chemotherapy
Ductal Carcinoma, NOS, HER2+:
- (1) genetic associations
- (2) aggressiveness
1- ER+, HER2+
2- poorly differentiated — high frequency brain metastasis
Medullary Carcinoma:
- (1) physical exam appearance
- (2) histological appearance
- (3) prognosis
1- fleshy, soft, well-circumscribed (can be confused with benign lesion)
2- large syncytial sheets of large oval cells, little stroma, lymphoplasmacytic immune response, well circumscribed
3- good
Lobular carcinoma:
- (1) genetic association
- (2) are an added difficulty to Dx
- (3) frequent metastatic sites
- (4) general apperance
1- loss of E-cadherin
2- 25% cases have subtle mammographic / palpable abnormalities
3- leptomeninges, GIT, ovaries, uterus, peritoneum
4- poorly outline, indurated, non-distinct mass + minimal dysplasia
Lobular carcinoma histological appearance
-discohesive infiltrating tumor cells: signet ring cells
Single file: (foot-prints of Indians on the sand in linear fashion) - single file tumor cells, round and uniform
Bull’s eye pattern: tumor cells around normal acini / ducts +/- ductal carcinoma (= mixed pattern)
Inflammatory breast carcinoma:
- (1) age and race affected most
- (2) clinical appearance
- (3) aggressiveness
1- young black women
2- swollen erythematous breast via dermal lymphatic obstruction by tumor (mimics non-neoplastic inflammatory lesions)
3- underlying carcinoma is diffusely invasive — poor prognosis
Pair the breast tumors with the following:
- non-metastasizing
- uncommonly metastasizing
- metastasizing
NON: DCIS, LCIS
UNcommon: colloid, medullary, papillary
Metastasizing: all others
list parameters evaluated from resection specimen
- size, type, grade, distance to margin
- lymphatic space invasion
- LN status if pos.: <0.2mm, 0.2-2mm, >2mm
- hormonal receptor status: ER, PR (estrogen, progesterone)
what is the purpose and subsequent actions of ER/PR testing
-estrogen or progesterone receptor positive tumor –> predicts likelihood of benefit of endocrine Tx
Positive: >1% tumor in sample is positive => endocrine Tx
Negative: <1% tumor in sample is positive — Oncologist decision for endocrine therapy
describe ER/PR status and endocrine therapy response rate
(estrogen/ER- 60% of cancers, progesterone/PR // Tx w/ Tamoxifen)
-ER+/PR+ –> 60-70% response rate, less chemo
-ER-/PR+ –> 50%
-ER+/PR- –> 40%
ER-/PR- –> <10%
HER2 = (1- include family)
- chr(2)
- (3) function
- (4) purpose in testing
1- human epidermal GFR2, EGF familt
2- chr17q21
3- regulates cell proliferation, survival, motility, invasion
4- prognostic / predictive marker —– 25% have overexpression –> worse prognosis (brain metastasis)
describe role of HER2 status in Tx
-lack of response to chemotherapy and hormonal therapy
Tx: Herceptin / Trastuzumab therapy
- humanized monoclonal Ig against HER2
- can’t cross BBB, not for metastatic disease
- ~20% Her2+ Pts respond
Major prognostic factors for breast CA
- distant metastasis
- absence of distant metastasis: axillary LN status, then size
Others: invasive v In situ, locall advanced CA, inflammatory CA
Minor prognostic factors for breast CA
Histological: subtype, grade,
- ER/PR receptors, HER2, lymphovascular invasion
- proliferative rate, DNA content, gene expression profiling
-response to neoadjuvant Tx
Mammography:
- can catch up (1)% of cancers
- mainly (2) cancers
1- 60-80%
2- Intraductal carcinoma; FCC- proliferative, sclerosin adenosis, radial scar
Breast CA Tx
- lumpectomy
- simple mastectomy +/- LN
- postoperative irradiation
- chemotherapy
- immunotherapy (herceptin)
- hormone therapy (tamoxifen)
Gynecomastia = (1) analog in men:
- (2) risk factors
- (3) microscopic changes
1- FCC analog
2- inc estrogens (endo-/exo-genous), reduced androgens + cirrhosis, Klinefelter’s (XXY), alcohol / marijuana / heroin, antiretroviral therapy, anabolic steroids, testicular neoplasms
3- intraductal hyperplasia with dense collagenous CT
Male breast carcinoma:
- (1) risk factors
- (2) character / aggressiveness
- (3) IHC results usually
1- reduced testicular function, XXY, FHx, exogenous ER, age, infertility, obesity, breast disease hx, ionizing radiation
2- rapid infiltration (less breast substance) — similar staging / Tx as females
3- ER+ tumors
