Breast Pathology 2

Question 1

4 non-carcinomatous breast cancers?

Answer 1

malignant phyllodes tumour (sarcomatous stromal component)
angiosarcoma
lymphoma
metastatic

Question 2

which cancers often metastasise to the breast?

Answer 2

carcinoma of bronchus, ovary and kidney
malignant melanoma
soft tissue tumours (leiomyosarcoma)

Question 3

definition of carcinoma?

Answer 3

malignant tumour of epithelial cells

Question 4

where does breast carcinoma arise?

Answer 4

glandular epithelium of the terminal duct lobular unit (TDLU)

Question 5

breast carcinomas are actually what type?

Answer 5

adenocarcinoma

- but just called breast carcinoma

Question 6

ductal precursor lesions?

Answer 6

epithelial hyperplasia of usual type
columnar cell change (+/- atypia)
atypical ductal hyperplasia
ductal carcinoma in situ

Question 7

lobular precursor lesions?

Answer 7

lobular in situ neoplasia

• atypical lobular hyperplasia
• lobular carcinoma in situ

Question 8

what is an in situ carcinoma?

Answer 8

confined within basement membrane of acini and ducts
cytologically malignant but non-invasive
non-obligate precursor of invasive carcinoma

Question 9

classification of breast carcinoma in situ?

Answer 9

lobular

ductal

Question 10

2 historic entities of lobular in situ carcinoma?

Answer 10

atypical lobular hyperplasia (ALH)
- <50% of lobule involved
lobular carcinoma in situ (LCIS)
- >50% of lobule involved

Question 11

histology of lobular in situ neoplasia?

Answer 11

intra-lobular proliferation of characteristic cells

• small nuclei
• solid proliferation
• intra cytoplasmic lumens/vacuoles
• ER positive
• E cadherin negative

Question 12

features of lobular in situ neoplasia?

Answer 12

often multifocal and bilateral
less common after the menopause
not palpable, not visible grossly
may calcify (mammography)
usually an incidental finding

Question 13

significance of lobular in situ neoplasia?

Answer 13

gives 8X higher risk of invasive carcinoma

LCIS = highest risk

Question 14

how is lobular in situ neoplasia managed?

Answer 14

if found on core biopsy = excision or vacuum biopsy to exclude higher grade lesion
if found on vacuum or excision biopsy = follow up and clinical trials

Question 15

types of intraductal proliferation?

Answer 15

epithelial hyperplasia of usual type
columnar cell change (lesion)
columnar cell change with atypia
atypical ductal hyperplasia
ductal carcinoma in situ

Question 16

how does intraductal proliferation affect risk of progression to invasive carcinoma?

Answer 16

epithelial hyperplasia of usual type = 2X risk
atypical ductal hyperplasia = 4X risk
DCIS = 10X risk

Question 17

features of ductal carcinoma in situ?

Answer 17

arises in TDLU
characteristically unicentric (single duct system)
may involve lobules (cancerisation)
may involve nipple skin (pagets)
cytologically malignant epithelial cells confined to basement membrane

Question 18

what is pagets disease of the nipple?

Answer 18

high grade DCIS extending along ducts to reach the epidermis of the nipple
still in situ carcinoma (non-invasive)
causes indendation etc of skin around nipple

Question 19

classification of DCIS?

which is most significant in terms of progression to invasive carcinoma?

Answer 19

cytological grade (most significant)
histological type
presence of necrosis (comedo)

Question 20

significance of DCIS in terms of progression?

Answer 20

risk factor for development of invasive carcinoma

true precursor for invasive carcinoma

Question 21

how is DCIS managed?

Answer 21

diagnosis
surgery
adjuvant radiotherapy
chemoprevention (endocrine therapy)

Question 22

what is a microinvasive carcinoma?

Answer 22

DCIS which has invaded the basement membrane but <1mm
rare
treated as high grade DCIS

Question 23

what is invasive breast carcinoma?

Answer 23

malignant epithelial cells have breaches the basement membrane
infiltration of normal tissues

Question 24

peak incidence for breast cancer?

Answer 24

50-70 (when breast screening is offered)

Question 25

risk factors for breast carcinoma?

Answer 25

age
reproductive history (more oestrogen stimulation over life = higher risk - i.e early menarche and late menopause, not breastfeeding etc)
hormones (endogenous and exogenous - OCP, HRT etc)
previous breast disease
geography’ (western europe)
lifestyle
genetics

Question 26

genetics in breast cancer?

Answer 26

1st degree relative affected = double risk

BRCA 1 and BRCA2 (causes 45-64% lifestyle risk)

Question 27

survival rates in breast cancer?

Answer 27

96% at 1 year
87% at 5 years
78% at 10 years

Question 28

how common is breast cancer?

Answer 28

most common female cancer
2nd commonest cause of cancer death
1 in 8 will get it
increasing evidence

Question 29

natural history of breast carcinoma?

Answer 29

local invasion (stroma of breast, skin, chest wall muscles)
lymphatics (regional draining lymph nodes)
blood-bourne (bone, liver, brain, lungs, abdominal viscera, female genital tract)

Question 30

how is breast cancer classified?

Answer 30

morphology (type, grade)
gene profile (intrinsic sub-type)
hormone receptor expression (oestrogen receptor, progesterone receptor, HER2)

Question 31

most common breast carcinomas?

Answer 31

ductal
lobular
mixed
medullary

Question 32

how is breast cancer graded?

Answer 32

measure of tumour differentiation (how similar it is to parent tissue)
assessment of tubular differentiation (1-3)
nuclear pleomorphism (1-3) and mitotic activity (1-3)
- score 3-5 = grade 1
- score 6-7 = grade 2
- score 8-9 = grade 3

Question 33

intrinsic breast cancer sub-types?

Answer 33

basal like
HER2
normal breast like
luminal A/B/C

Question 34

most common hormone receptor classifications?

Answer 34

80% are ER positive (oestrogen receptor)
67% are PgR positive
14% are HER2 positive

Question 35

significance of oestrogen receptor (ER)?

Answer 35

expression of ER predicts response to oestrogen therapy such as

• oophrectomy
• tamoxifen
• aromatase inhibitors (letrozole)
• GnRH antagonists (goserilin [zoladex])

Question 36

what is HER2?

Answer 36

human epidermal growth factor receptor 2

overexpression or amplification predicts response to trastuzumab (herceptin)

Question 37

trastuzumab?

Answer 37

AKA herceptin

- modified mouse monoclonal antibody???

Question 38

how is breast carcinoma staged?

Answer 38

TNM
T0-4
N0-3
M0-1

Question 39

predictive and prognostic factors in invasive carcinoma?

Answer 39

ER (PgR)

HER2

Question 40

prognostic indices used for breast carcinoma?

Answer 40

nottingham prognostic index
adjuvant online
NHS PREDICT