Breast PATH

Question 1

Most common non-skin malignancy in the world ?

Answer 1

BREAST CANCER*
By age 90, one in eight women will get breast cancer.

Question 2

Breast cancer RFs

Answer 2

• Age: Increasing age.
• Family: 1st degree relatives with breast cancer, and their age at diagnosis. BRCA or other familial
  syndromes.
• Lifestyle: Higher socioeconomic status, obesity, lack of exercise.
• Oestrogen exposure: Early menarche, late menopause, high age at first live birth or nulliparity,
  exogenous oestrogen exposure.
• Breast Factors: Dense breasts, never breastfed, previous breast cancer or atypia, previous irradiation.
• (Note: no clear link with smoking)**

Question 3

Breast cancer associatitions

Answer 3

• BRCA1 and 2.
• Hamartoma syndromes: Cowden and Peutz-Jegher
• High risk germline mutations: Li-Fraumeni (p53) Ataxia Telangiectasia (ATM gene)

Question 4

Breast cancer can arise without a pre-cursor, T or F ?

Answer 4

T
- Known precursor lesion is DCIS with a 1% per year conversion to IDC. Carcinoma may also arise on its own.

Question 5

DCIS morphology..any invasion?

Answer 5

Tumour cells limited to ducts and lobules by the basement membrane.

Microinvasion <1 mm is allowed.

Question 6

DCIS 2 types

Answer 6

Comedo
- central necrosis
- calcifications in ducts

Non-comedo
- Solid
- Cribiform
- Micropapillary
- Papillary

Question 7

Define paget’s disease

Answer 7

DCIS
- If they go out the ducts to the skin but still don’t breach the basement membrane it is called Paget disease of the nipple.
- Pagets often signals underlying invasive carcinoma.

Question 8

DCIS cancer progression risk, and how many bilateral ?

Answer 8

• Progress to cancer at 1% per year.
• Bilateral in 10-20% of cases

Question 9

Define LCIS (Lobular Carcinoma in Situ)

Answer 9

Dyscohesive malignant cells with loss of E-cadherin adhesion protein (same for ALH, LCIS, ILC).

Question 10

LCIS cancer risk increase % ?

Answer 10

May or may not be a precursor lesion (Robbins 8th edition says 1% per year progress to cancer too). But
increases risk of cancer in both breasts 8 – 12 times. Bilateral in 20-40%.

The invasive cancer may be lobular or ductal (mostly IDC)*

Question 11

LCIS mammogram ?

Answer 11

• Incidentally discovered as they are invisible on mammography.

Question 12

ILC (invasive lobular carcinoma) morphology ?

Answer 12

• may be diffusely infiltrating with no mass, only palpable firmness, or a mass lesion with poorly defined margins
• dyscohesive, single filed (indian file)
• Signet ring mucin cells common*
• Luminal A*
• Rate of bilaterality is controversial. Traditionally thought to be increased. Now thought similar to normal IDC at 5-10% (Robbins).

Question 13

Which type of Inavsive ductal carcinoma has the worst prognosis ?

Answer 13

• NOS (Luminal A, same as ILC)

Question 14

Which subtype of invasive ductal carcinoma has the best prognosis ?

Answer 14

• Tubular
• Malignant cells arranged in well formed tubules lacking the myoepithelial layer (ie just epithelial cells
  then basement membrane).

Question 15

Tubular carcinoma association ?

Answer 15

• Often associated low grade DCIS, and associated with radial scars

Question 16

Medullary Carcinoma epi?

Answer 16

• Younger people with BRCA1

Question 17

Medullary Carcinoma micro ?

Answer 17

o Solid syncytial growth pattern (cells connected to each other) with a lymphocytic infiltrate.

o Over-expression of E-cadherin explains why the cells are all stuck together and this limits spread somewhat so it has a slightly better prognosis than IDC NST.

Question 18

Mucinous (Colloid) Carcinoma epi ?

Answer 18

• Older women in 70s
• Good prognosis
• Clustered of floating mucin

Question 19

Luminal A features

Answer 19

Luminal A
- ER, PR positive
- HER2 negative
- Most common type
- Low grade, best prognosis
- Most likely to have bone mets
- use Tamoxifen which blocks oestrogen
- use Letrozole blocks conversion into oestrogen

Question 20

Luminal B features

Answer 20

Luminal B
- ER, PR positive
- HER2 variable
- mets to bone too
- worse prognosis than A

Question 21

Basal-like features

Answer 21

• Triple negative
• High grade tumour with worst prognosis
• Most associated with BRCA mutations
• Mets to lungs, brain, etc

Question 22

HER-2 enriched features

Answer 22

• ER, PR negative
• HER2 positive
• mid to high grade tumors
• Treated with Herceptin

Question 23

Fibroadenoma RFs ?

Answer 23

• Cyclosporin* (renal transplant commonly)
• HRT
• Fibrocystic change
• Increase in size with Lactation, Pregnancy, Infarction

Question 24

Composition of Fibroadenoma

Answer 24

• Biphasic tumour with stromal and epithelial elements
• Arise from loose intralobular septa
• Stromal elements: monoclonal (neoplastic)
• Glandular elements: Polyclonal
• Epithelial component: Hormone sensitive

Question 25

Fibroadenoma macro appearance ?

Answer 25

- Greyish looking cut surface with slit like spaces. - Expanded stroma, similar to intralobular stroma, Growth pattern may be intracanalicular (stroma invaginates into the ducts) or pericanalicular where the stroma surrounded the ducts. - No mitoses

Question 26

Prognosis / Complication of Fibroadenoma

Answer 26

Even after biopsy proven, should follow up for 6-12 months to ensure no rapid growth. If this is seen, the lesion may actually be a Phyllodes tumour (StatDx). Accurate differentiation between the two based on a needle biopsy is 85-95%. Rarely foci of cancer can develop within a fibroadenoma. Slightly increased risk of carcinoma, esp if complex features. Phyllodes may also develop from FA sometimes.

Question 27

Phyllodes benign or malignant

Answer 27

They exist on a spectrum – the majority are benign (>75%), but can be borderline or malignant. High grade tumours resemble malignant sarcomas. Leaf like growths

Question 28

Epi of Phyllodes vs Fibro

Answer 28

Fibroadenoma - 20-30 Phyllodes - 45-50, asian

Question 29

Phyllodes microscopy

Answer 29

The 2 key features of PT are: - Stromal hypercellularity - Presence of benign glandular elements. It is the amount and cellularity of the stromal component that determines whether the neoplasm is called a fibroadenoma or a phyllodes tumour.

Question 30

Treatment of Phyllodes

Answer 30

Treated with wide local excision. Main risk is local recurrence. No need for nodal dissection. Radiation reduces risk of recurrence. No role for chemotherapy.

Question 31

What are Prolfierative lesions with increased relative risk of cancer

Answer 31

WITHOUT atypia = 1.5 – 2 x increased risk  Usual ductal hyperplasia  Sclerosing adenosis  Complex sclerosing lesion / radial scar  Papilloma WITH atypia > 4 x incresed risk  ADH  ALH  Classic LCIS

Question 32

Sclerosing adenosis can mimic what histologically ?

Answer 32

mimic invasive cancer histologically

Question 33

Radial scar associated with trauma ?

Answer 33

Not associated with trauma or surgery.

Question 34

Precursor lesions: These are non-obligate precursors and most will not become cancer left untreated

Answer 34

1. Atypical ductal hyperplasia : - Resembles DCIS but only partly fills ducts and measures <2mm - Presents as calcification on mammo - Requires excision biopsy to confirm the true extent (if >2mm it is DCIS) 2. Atypical lobular hyperplasia : - Cells identical to LCIS but do not fill or distend more than 50% of acini in a lobule - Cells show loss of e-cadherin

Question 35

Lymphocytic Mastopathy (Sclerosing Lymphocytic Lobulitis) - mammo features - associated with?

Answer 35

- single or multiple hard palpable masses or mammographic densities. - areas of densely collagenized stroma, a feature that may make it difficult to obtain lesional tissue by needle biopsy. Assoc: - T1DM - Autoimmune thyroid disease

Question 36

Which breast cancer is HER2 negative ?

Answer 36

Micropapillary / Papillary

Question 37

Which luminal type most associated with BRCA1 mutation ?

Answer 37

Basal-type (triple negative) - Medullary breat cancer - Majority BRCA1 are triple negative**