L33- Breast Pathology II Flashcards by Connor Patrick

Breast CA:

(1) age group
(2) cancer type
(sporadic/hereditary)

1- >40y/o, 25% postmenopausal

2- adenocarcinoma

3- both

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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

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list the many risk factors for hereditary breast CA

BRCA1/2

Li Fraumeni syndrome (p53) or variant (CHEK2)

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BRCA1:

(more/less) common than 2
20-40% risk of (2)
chr(3)

1- more

2- ovarian CA, prostatic / pancreatic cancer

3- 17q21

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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

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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

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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%)

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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)

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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

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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

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Comedo DCIS histological appearance

ducts filled with tumor cells

- large central necrosis and calcification (inspissated material- able to be squeezed out like toothpaste)

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non-comedo DCIS = (1)

-(2) histological appearance

1- cribiform DCIS

2- rounded / cookie cutter like spaces

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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

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LCIS histological appearance

lobuar distension
oval, noncohesive cells
no pleomorphism or mitoses

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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

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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

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Paget Disease, breast:

breast CA in (1)% cases
describe carcinoma location: (2) generally via (3) process

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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

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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

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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

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(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

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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

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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

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1- ER+, PR+, HER2/neu+

2- LN metastasis — may respond to chemotherapy

Ductal Carcinoma, NOS, basal like:

(1) genetic associations
(2) aggressiveness

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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

L33- Breast Pathology II Flashcards

(41 cards)