L33 - PATHOLOGY OF BREAST CANCER

Question 1

List typical clinical presentations of breast cancer? (6)

Answer 1

1) lump or thickening in breast
2) change in size or shape of a breast
3) nipple retraction
4) bloody nipple discharge
5) A rash on a nipple or surrounding area
6) Dimpling of the skin, skin appears inflamed

Question 2

Pathogenesis of Paget’s disease of the breast?

Answer 2

Underlying intraductal or invasive carcinoma

> > Invasion of epidermis by Paget’s cells

> > erosion of the nipple and areola

Question 3

Morphology of Paget’s cells?

Answer 3

large, round to oval, clear cytoplasm (clear halo) and eccentric, hyperchromic nuclei

contain mucin.

Question 4

Clinical presentation of Paget’s disease?

Answer 4

Nipple and areola: red and weeping, occasionally dry, scaly and psoriatic

Question 5

What causes puckering of skin with red, warm, peau d’orange appearance on breasts?

Answer 5

Inflammatory breast cancer

> > blockage of lymph vessels in the skin by cancer cells

Question 6

List 2 non-invasive breast carcinoma

Answer 6

1. Ductal carcinoma-in-situ (DCIS): High grade comedo or Non-comedo Low grade
2. Lobular carcinoma in-situ (LCIS)

Question 7

List Invasive breast carcinoma.

Answer 7

1. Invasive carcinoma of no special type (NST)
2. Special subtypes :
   - Invasive lobular carcinoma
   - Tubular carcinoma
   - Mucinous carcinoma

Question 8

Define the anatomical location of Ductal Carcinoma-in-situ of breasts? Ddx location with LCIS?

Answer 8

confined within the ductal basement membranes

50% are centrally situated, palpable mass

LCIS = Medial + Lateral Upper quadrants

Question 9

Compare the effectiveness of mammography in finding DCIS and LCIS?

Answer 9

DCIS = detectable due to microcalcification and confined involvement

LCIS = easily missed due to no calcification and multicentric involvement

Question 10

Compare the prognosis of high grade and low grade DCIS of breast? How to ddx the two?

Answer 10

High = large pleomorphic cells and central comedo necrosis

High grade = 50% evolve into invasive carcinoma within 5 years

Non-comedo low grade = 30% will develop invasive carcinoma within the next 10-15 years.

Question 11

Describe the extent of involvement of Lobular carcinoma-in-situ?

Answer 11

Multicentric, sometimes bilateral

concentrated within 5 cm of the nipple
@ OUTER + INNER UPPER QUADRANT

Question 12

Prognosis and progression of Lobular carcinoma in situ of the breast?

Answer 12

10 times higher risk of invasive carcinoma: can be ductal or lobular

Question 13

What is the most common type of breast carcinoma?

Answer 13

INVASIVE BREAST CARCINOMA OF NO SPECIAL TYPE (NST):

70% of invasive breast cancers

Question 14

Gross morphology and clinical presentation of Invasive breast carcinoma of no special type (NST)?

Answer 14

FEELS LIKE CRAB!!!!!!!

poorly defined, hard, yellow-grey mass with radiating fibrous trabeculae

Touch = gritty feel and chalky streaks

Question 15

Pathohistology of Invasive lobular carcinoma of breast?

Answer 15

SINGLE CELL INFILTRATION

in single file (INDIAN FILING)

or

arranged as concentric rings around a duct (TARGET-LIKE LESION) of small to medium-sized tumour cells

Question 16

Extent of involvement of Invasive lobular carcinoma of breast?

Answer 16

multifocal and bilateral

poorly circumscribed mass

DCIS = Central 
LCIS = Medial + Upper lateral quadrant

Question 17

Histological feature of Tubular carcinoma of breast? Prognosis?

Answer 17

open tubules lined by single layer of cells

excellent prognosis in the pure form
Distant metatastasis are unlikely

Question 18

Histological feature of Mucinous carcinoma of breast?

Answer 18

islands of tumour cells floating in large lakes of mucin

Question 19

Clinical presentation of mucinous carcinoma of breast? Prognosis?

Answer 19

slow growing** circumscribed mass

bulky, soft**, gelatinous material

excellent prognosis in the pure form

Question 20

2 main modes of breast cancer spread?

Answer 20

Lymphatic and Haematogenous

Question 21

Define the 2 paths of breast cancer spread along lymph nodes.

Answer 21

Lateral tumours&raquo_space; Level I to III Axillary nodes (at outer, upper quadrant)&raquo_space; Supraclavicular LN

Medial and deep carcinoma&raquo_space; Internal mammary chain (medial quadrant)

Question 22

Which organs are most susceptible to breast cancer spread? Triple negative tumours?

Answer 22

Haematogenous spread:

• Bone most common
• Lung
• Liver
• Ovary and adrenals
• Brain

VISCERAL METASTASIS is common for TRIPLE NEGATIVE tumours: negative for estrogen receptors, progesterone receptors, and excess HER2 protein

Question 23

Define Sentinel lymph nodes and it’s clinical implications in breast CA?

Answer 23

first lymph node(s) to which cancer cells are most likely to spread from a primary tumor

Negative finding:

• breast CA not able to spread to nearby LN or organ
• Indication for LN removal as prevention

Question 24

List 7 prognostic factors for breast carcinoma?

Answer 24

• Size
• Histological type and grade
• Presence of DCIS
• Margins of excision
• Lymph node status
• Vascular invasion
• Hormone receptor and HER2 status

Question 25

List types of breast cancer with excellent prognosis?

Answer 25

Mucinous carcinoma | Tubular carcinoma

Question 26

List types of breast cancer with poor prognosis?

Answer 26

Invasive carcinoma of no special type (NST) Pleomorphic invasive lobular carcinoma High grade comedo DCIS LCIS

Question 27

Define the criteria for histological grading of invasive carcinoma?

Answer 27

assessed on – tubule formation – nuclear grade – mitotic rate Grade I > 80% survival in 16 years Grade II < 60% survival in 16 years Grade III < 50% survival in 16 years

Question 28

Classification of DCIS?

Answer 28

Assess: - Margin, size, pathological subtype Classify into Low, intermediate and High nuclear grade DCIS

Question 29

How is prognosis of breast CA linked to lymph nodes?

Answer 29

Prognosis related to the overall number of nodes involved and the level of nodal involvement

Question 30

Which genetic marker indicates use of Herceptin and Doxorubicin-based chemotherapy in breast CA?

Answer 30

HER2 Oncogene expression

Question 31

2 lab dx tests to confirm HER2 status?

Answer 31

Immunohistochemical assay Fluorescent in-situ hybridization (FISH)

Question 32

Define the size of breast cancer for in each TNM stage?

Answer 32

pTis = DCIS (including Paget’s disease) pT1: pT1a < or = 5 mm pT1b 5 - 10 mm pT1c 10 - 20 mm pT2 = tumour 20 - 50 mm pT3 = tumour > 50 mm pT4 = tumour with direct extension to skin or chest wall

Question 33

List different approaches to classify tumours.

Answer 33

- Traditional pathologic prognostic and predictive features - Clinical outcome (prognostic) - Response to therapy (predictive) - Gene expression profiling

Question 34

Define the major breast cancer subtypes based on gene profiling?

Answer 34

Classify by traditional immunomarkers ER, PR and HER2 * Luminal A/B * HER2 * Basal-like

Question 35

Compare the treatment options indicated by Luminal, HER2 and Basal-like breast CA?

Answer 35

Luminal = Endocrine treatment HER 2 = Herceptin, Anthracycline based chemo Basal- like = Platinum, PARP inhibitors

Question 36

Which major breast cancer subtypes based on gene profiling accounts for the most breast cancers?

Answer 36

Luminal = 70% HER2 and Basal-like = 15% each