Breast Pathology II

Question 1

What are some miscellaneous malignant tumours?

Answer 1

Malignant Phyllodes tumour (sarcomatous stromal component), angiosarcoma, lymphoma, metastatic tumours

Question 2

What are some examples of metastatic tumours?

Answer 2

Carcinoma = bronchial, ovarian serous carcinoma, clear cell carcinoma of kidney
Malignant melanoma, soft tissue tumours

Question 3

What are some ductal precursor lesions?

Answer 3

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

Question 4

What are some lobular precursor lesions?

Answer 4

Atypical lobular hyperplasia, lobular carcinoma in-situ

Question 5

What is a breast carcinoma?

Answer 5

A malignant tumour of breast epithelial cells = technically an adenocarcinoma but just called a carcinoma

Question 6

Where do breast carcinomas arise?

Answer 6

Glandular epithelium of the terminal duct lobular unit

Question 7

What is an in-situ breast carcinoma?

Answer 7

Carcinoma confined within basement membrane of acini and ducts = cytologically malignant but non-invasive

Question 8

How are in-situ breast carcinomas classed?

Answer 8

Lobular or ductal = non-obligate precursors of invasive carcinoma

Question 9

What are the two types of lobular in-situ carcinoma?

Answer 9

Atypical lobular hyperplasia = <50% lobule involved

Lobular carcinoma in-situ = >50% lobule involved

Question 10

What occurs in lobular in-situ carcinoma?

Answer 10

Intra-lobular proliferation of characteristic cells = solid proliferation

Question 11

What are some features of lobular in-situ carcinomas?

Answer 11

Small intermediate-sized nuclei
ER positive
Intracytoplasmic lumens/vesicles
Frequently multifocal and bilateral

Question 12

What gene mutation is associated with lobular in-situ carcinomas?

Answer 12

Deletion and mutation of CDH1 gene = E-cadherin negative

Question 13

How are lobular in-situ carcinomas usually detected?

Answer 13

Usually incidental finding = calcification on mammogram

Question 14

Can you detect lobular in-situ carcinomas grossly?

Answer 14

No = not palpable or visible grossly

Question 15

What happens to the incidence of lobular in-situ carcinomas after menopause?

Answer 15

It decreases

Question 16

What is the risk of progression of lobular in-situ carcinomas?

Answer 16

Atypical lobular hyperplasia = 10% risk

Lobular carcinoma in-situ = 20%

Question 17

What is the management of lobular in-situ carcinoma?

Answer 17

If found on core biopsy = excision or vacuum biopsy

If found on vacuum/excision biopsy = follow up

Question 18

What are the different types of intraductal proliferation?

Answer 18

Epithelial hyperplasia of usual type, columnar cell change, columnar cell change with atypia, atypical ductal hyperplasia, ductal carcinoma in-situ

Question 19

What is the risk of progression to invasive carcinomas associated with intraductal proliferation?

Answer 19

Epithelial hyperplasia = 2x risk
Atypical ductal hyperplasia = 4x risk
Low grade ductal carcinoma in-situ = 10x risk

Question 20

How common is ductal carcinoma in-situ?

Answer 20

Accounts for 15-20% of breast malignancies

Question 21

Where do ductal carcinomas in-situ occur?

Answer 21

Terminal duct lobular unit = characteristically unicentric

Question 22

What is the cytological appearance of ductal carcinoma in-situ?

Answer 22

Malignant epithelial cells = confined within basement membrane of duct, may involve lobules

Question 23

What is it called when ductal carcinoma in-situ involves the nipple skin?

Answer 23

Paget’s disease of nipple = high grade ductal carcinoma in-situ extending along ducts to reach epidermis of nipple

Question 24

How common is progression of ductal carcinoma in-situ?

Answer 24

75% progress to invasion following incisional biopsy

Question 25

What is the management of ductal carcinoma in-situ?

Answer 25

Surgery, adjuvant radiotherapy, chemotherapy

Question 26

What is a microinvasive carcinoma?

Answer 26

Rare = high grade ductal carcinoma in-situ with invasion <1mm, treat as high grade ductal carcinoma in-situ

Question 27

What is an invasive breast carcinoma?

Answer 27

Malignant epithelial cells which have breeched the basement membrane = infiltration of normal tissues with risk of metastasis and death

Question 28

What are the risk factors for developing invasive breast carcinoma?

Answer 28

Age, previous breast disease, Western European, obesity and low levels of physical exercise, alcohol, high fat intake, smoking, hormones (HRT, OCP, endogenous)

Question 29

What features of the reproductive history are risk factors for developing invasive breast carcinoma?

Answer 29

Age at menarche, age at first birth, parity, breastfeeding, age at menopause

Question 30

What are some genetic influences for developing invasive breast carcinoma?

Answer 30

BRAC1/2 = 2% of all breast cancers, 45-65% risk TP53 mutation = early onset, Li Fraumeni syndrome PTEN mutation = Peutz-Jeghers syndrome

Question 31

What is the 5 year survival rate of invasive breast carcinoma?

Answer 31

87%

Question 32

How common is invasive breast carcinoma?

Answer 32

Commonest female cancer and 2nd commonest cause of cancer death in women

Question 33

What are the stages of invasive breast carcinoma?

Answer 33

Local invasion = stroma of breast, skin, muscles of chest Lymphatics = regional draining lymph nodes Blood-borne metastases = bone, liver, lungs, abdominal viscera, brain, female genital tract

Question 34

What is the classification of invasive breast carcinoma?

Answer 34

Ductal (70%), lobular (10%), mixed (10%), mucinous, medullary, tubular, cribriform, papillary

Question 35

How are invasive breast carcinomas graded?

Answer 35

3 categories each given a score of 1-3 = tubular differentiation, nuclear pleomorphism, mitotic activity

Question 36

What is the grading of invasive breast carcinomas?

Answer 36

Grade 1 = score of 3-5 Grade 2 = score of 6 or 7 Grade 3 = score of 8 or 9

Question 37

What are the intrinsic breast cancer subtypes?

Answer 37

``` Basal-like = ER-, HER2-, basal CK+ Normal breast-like = ER-, non-epithelial Luminal A = ER+, low proliferation Luminal B = ER+, high proliferation Luminal C = ER+, high proliferation HER2 = ER-, HER2+ ```

Question 38

How common is hormone receptor involvement in invasive breast carcinomas?

Answer 38

80% are ER positive, 67% are PgR positive, 14% are HER2 positive

Question 39

What does oestrogen receptor (ER) expression predict?

Answer 39

Response of invasive breast carcinoma to anti-oestrogen therapy

Question 40

How common is HER2 involvement in invasive breast carcinoma?

Answer 40

Overexpression and amplification seen in 15% and predicts response to trastuzamab

Question 41

What are the predictive factors of invasive breast carcinomas?

Answer 41

ER and HER2 involvement

Question 42

How are invasive breast carcinomas staged?

Answer 42

Direct invasion of adjacent tissues = T0-4 Lymphatic spread = N0-3 Blood-borne spread = M0-1

Question 43

What prognostic indices can be used for invasive breast carcinomas?

Answer 43

Nottingham prognostic index, Adjuvant!Online, NHS predict

Question 44

What does the Nottingham prognostic index consist of?

Answer 44

Histopathology only = grade and stage | 0.2 x tumour diameter (cm), tumour grade (1-3), lymph node status (1-3)

Question 45

What does the Adjuvant!Online prognostic index consist of?

Answer 45

Histopathology + ER + clinical factors

Question 46

What does the NHS predict prognostic index consist of?

Answer 46

Histopathology + ER + HER2 + clinical factors + mode of detection