breat cancer

Question 1

where do breast cancers arise

Answer 1

they arise in the ducts (terminal duct lobular unit)

Question 2

ER (+)

Answer 2

HER (-) is seen in 50%-65%

Question 3

HER2 (+) and ER(+/-)

Answer 3

seen in 10% - 20% cases

Question 4

triple (-) ER,PR and HER2

Answer 4

seen in 10% - 20% cases

Question 5

hereditary breast cancer genes

Answer 5

they are they BRCA-1 and BRCA-2 genes
- 1st degree relatives effected!

Question 6

BRCA 1

Answer 6

breast + ovary; pancreas
- usually triple (-) ER, PR, HER2/NEU

Question 7

BRCA 2

Answer 7

more in males breast and prostate

Question 8

Li-Fraumeni syndrome gene

Answer 8

P53

Question 9

cowen syndrome gene

Answer 9

PTEN

Question 10

peutz-JEghers syndrome gene

Answer 10

LKB1/STK11

Question 11

ataxia telengiectasia

Answer 11

AKM

Question 12

what is the major risk factor to sporatic breast cancer

Answer 12

expososure to hormones

Question 13

why does too much estrogen cause increase chance to cancer

Answer 13

estrogen stimulates TGFa and PDGF and fibroblast growth factor which will promote tumor development through paracrine and autocrine mechanisms

Question 14

CF of ductal carcinoma in situ

Answer 14

• no mass produced
• CALCIFICATION seen
  *recall that calcifation is also seen in hte fibrocystic disease, sclerosing adenosis and fat necrosis. hence need to confrim via biopsy

tx: anti-estrogen ex- tamaxifen

Question 15

morephology of ductal carcinoma in situ

Answer 15

5 patterns:
1. comendo carcinoma- centrally placed necrotic debris surronded by pleomorhphic cells in the duct. tooth paste like necrotic tissue extruded from transected ducts

2. solid- filling and plugging of ductal lumina with tumor cells
3. cribiform- neat punched out fenestrarions in the intraductal tumour
4. papillary- intraductal papillary projections of tumour cells which lack a fibrovascular stalk
5. micropapillary- papillae often have club shaped cells comprasing the micropapillae

Question 16

path of lobular carcionoma in-situ

Answer 16

loss of E-cadherin

Question 17

CF of lobular carcinoma in-situ

Answer 17

bilateral
in younger women
no masses
no calcifaction

Question 18

lobular carcionoma in-situ morpholgy

Answer 18

• uniform dyscohesive cells with round nuclei
  -tumor cells fill and distend the acini
  -lobular pattern is present
  -ER and PR +

tx- tamoxifen

Question 19

invasive infiltrating carcinoma
CF

Answer 19

palpable mass

dimpling of skin

retraction of nipple (desmoplasia)

lymphatic involvement- peau-d-orange

Question 20

invasive ductal carcinoma morphology

Answer 20

gross- firm to hard, gritty on cutting due to elastotic stroma and foci of calcifacation

micro- tumor comprises of malignant cells in cords, nests , tubules, anastomosing masses and mixtures of all these invading into the stroma

• desmoplasis/retraction of the nipple is seen

Question 21

invasive lobular carcinoma CF

Answer 21

bilateral and multicentric within the same breast

no desmplasia

metasizes to peritoneum, retroperitoneum, leptomeninges, GIT and ovaries

Question 22

invasice lobular carcinoma path

Answer 22

biallelic loss of CDH1-E cadherin

Question 23

histology of invasive lobular carcinoma

Answer 23

dyscohesive tumor cells infiltrating the stroma in rows and cords of single cells

SIGNET RING CELLS

Question 24

medullary carcioma of breast morpholgy

Answer 24

gross- soft and fleshy well circumscribed

micro- syncitium like sheets of large cells with pleomorphic nuclei, pushing tumor border, mitosis ++

dense lymphocytic infiltration around tumor margins

triple (-)

Question 25

colloid/mucinous CA cf

Answer 25

slow rate of growth soft or rubbery gelatinous small islets of tumor cells floating in lakes of mucin

Question 26

inflammatory carcinoma path

Answer 26

- extensive invasion and obstruction of dermal lymphatics

Question 27

inflammatory carcinoma CF

Answer 27

- swollen, erythematous breast with pain and peau d' orange skin - underlying cancer is diffusely infiltrative -does not form a palpable mass -poor prognosis- always widely metastatic

Question 28

pagets disease morphology

Answer 28

- tumor cells are large and vacuolated cells with high N:C ratio and PAS (+)

Question 29

pagets diease path

Answer 29

it is a extension of the DCIS within the ductal system into the nipple skin without breaching the basement membrane - it basically a rare manifestation of underlying invasive breast cancer

Question 30

pagets diease CF

Answer 30

erythematous lesion, frequently fissures, ulcerated, crusted and oozing *Pruritic- mistaken for eczema

Question 31

expressions of pagents disease

Answer 31

- epithelial membrane antigen (EMA) and low molecular weight cytokeratins CK7 CK20 -overexpress HER2 and ER and PR

Question 32

what are the prognositc factors of cancer of breast

Answer 32

1. distant side metastasis 2. lymph node spread is the 2nd most imporant 3. tumor size 4. ER/PR and CA- responds to hormonal manupulation 5. HER2 expression has poor survival

Question 33

triple negative conditons

Answer 33

seen in medullary ca and many ca with BRCA1 mutation have high proliferation rate and worse prognosis

Question 34

HER2 (+)

Answer 34

can be treated with Trastuzumab which is a monoclonal Ab specific to HER2

Question 35

phyllodes tumor morpholgy

Answer 35

gross- grey-white cystic cavaties micro- bulbous nodules of proliferating stroma covered by epithelum - cystic spaces contain LEAF LIKE extensions -stroma is more celluar; increase in mitosis - pleomorphism with atypia of stromal elements

Question 36

phyllodes tumor

Answer 36

arise from inta-lobular stroma benign- mutation in MED12 malignant- mutation in TERT- encodes telomerase presents at 60-70s low grade- recur locally but rarely metastasize high grade- behave aggressive and spread by stromal component regardless of grade lymh node spread is rare . local recurrences common

Question 37

Fibroadenoma

Answer 37

new growth composed of both epithelial and stromal intralobular components most common benign tumor of the female breast - palpable mass- freely movable from surrounding breast - it increases in size and tenderness in pregency and regresses after menopause

Question 38

fibroadenoma path

Answer 38

1. specialized intralobular stroma elaborates GF- acts on the epithelium- causes proliferation: clonal cytogenetic aberrations confined to the stroma 2. women receiveing cyclosporin after a renal transplant 3. MED12 mutation 2/3rd- also in uterine leiomyoma and phyllodes **lesions of the interlobular stroma include benign soft tissue found elsewhere in the body, such as hemangiomas, lipomas. the only maligancy of note is angisarcoma-- occurs after local radiotherapy

Question 39

micro of fibroadenoma

Answer 39

biphasic- both components benign proliferation of intra-loublar stroma surrounding and often pushing and distorting the associated epithelium, which forms slit like spaces or glands FNAC (+)