Female Reproduction (path) - Breast

Question 0

Risk factors for breast carcinoma

Answer 0

• age, family history
• ethnicity (high rate caucasian but low grade, high mortality in Afr-Am & hispanic)
• hormone exposure (early menarche, duration breast feeding, obesity)
• developed countries

Question 1

Genes associated with breast cancer

Answer 1

BRCA1 - triple neg. breast cancer & ovarian cancer
BRCA2 - high grade ER+ breast cancer
Also: PI3K, p53, PTEN, GATA3

Question 2

4 main genetic subtypes of breast cancer,

determined by PAM50 (molecular test)

Answer 2

• more important in characterizing cancer than grade/TNM
  1. Luminal A - good prog., low recurrence
  2. Luminal B - good prog, high recurrence (high prolif)
  3. HER2 - good response to trastuzamab
  4. Basal-like - poor prognosis

Question 3

types of molecular testing for breast cancer

Answer 3

1. Oncotype

2. PAM50/Prosigna
3. Mammaprint
   * all use fresh frozen plasma

Question 4

Oncotype molec testing

Answer 4

qPCR, used to estimate prognosis for ER+ breast cancer (stage I or II), analyzes 21 genes.
= gold standard for ER+, also works for DCIS

Question 5

Mammaprint molec testing

Answer 5

microarray, analyzes 70 genes to predict prognosis for stage I or II breast cancer.
benefits: binary stratification (no intermediate risk category), splits into 4 molec subtypes, collects LOTS of data

Question 6

Prosigna/PAM50 molec testing

Answer 6

nCounter that analyzes 55 genes, to predict prognosis for breast cancer (for stages I - III);
Benefits: ~accurate ROR (risk of occurence) score, generates intrinsic subtypes

Question 7

indications for breast cancer screening

Answer 7

Low risk:
- age 25-40 = breast exam q1-3 years,
- 40+ = breast exam & mammogram q1-3 yrs
High risk: annual mammogram, breast exam q6 mo…

Question 8

most common causes of mammographic densities

Answer 8

• invasive carcinomas
  
  • higher concern if “spiculated, irregular” mass
• fibroadenomas
• cysts
• • MRI may been good alternative if dense breast tissue**

Question 9

BI-RADs Risk categories for breast cancer

Answer 9

Categories 0-2 = benign, no work-up needed.
Categories 3 = likely benign – follow.
Categories 4-5 = suspicious –> biopsy.
Category 6 = malignant –> need Tx.

Question 10

Reactive/Non-proliferative breast diseases

Answer 10

1. Mastitis (acute or chronic/periductal)
2. Fat Necrosis (from trauma)
3. Galactorrhea

Question 11

Mastitis path

Answer 11

Acute: bacterial (staph aureus), w/ lactation. *should keep breast-feeding!

Chronic: from smoking –> low VitA, w/ nipple retraction.

Question 12

Fat Necrosis of breast (path)

Answer 12

From (slight) trauma or radiation of breast tissue;
Gross: palpable mass, calcified on mammo.
Histo: necrotic fat w/ calcification & giant cells

Question 13

Non-prolif. fibrocystic breast change path

Answer 13

benign, hormone-mediated fibrosis & cyst formation in breast;
* pre-menopause.
Gross: lumpy, @ upper quadrant, w/ “blue-dome” appearance

Question 14

Risks assoc. w/ breast fibrocystic changes

Answer 14

none directly, but depends on type of change:

• apocrine: NO increased risk
• ductal hyperplasia/sclerosing adenosis: risk x2
• atypical hyperplasia: risk x5

Question 15

breast metaplasia (path)

Answer 15

benign, altered appearance/differentiation of epithelium (still mature)
* NO increased risk for carcinoma

Question 16

intraductal papilloma of breast (path)

Answer 16

Benign, fibrovascular projections w/in duct(s).
Sx: bloody nipple discharge (premenopausal)
Histo: w/ both epithelial AND myoepithelial layers. NO atypia.
+/- calcification

Question 17

collagenous spherulosis of breast

Answer 17

distended lobules filled w/ hyaline spheroles.

* often w/ papillomas

Question 18

Sclerosing adenosis of breast (path)

Answer 18

benign, circumscribed proliferation of glandular acini & stromal fibrosis.
w/ radial scar (central nidus).
* calcification common.
** small increased risk bc altered structure**

Question 19

microglandular adenosis of breast (path)

Answer 19

BENIGN, infiltrative non-lobular prolif of small, uniform glands.
*no myoepithelial layer, but NOT cancer!
Very S100 + and ER-
* round edges (NOT angular)

Question 21

Fibroadenoma of breast

Answer 21

most common BENIGN tumor, age <30;
= well-circumscribed stromal & epithelial proliferation.
- pericanalicular: @ duct & gland
- intracanalicular: mostly ductal
- Juvenile: stromal cellularity & epithelial hyperplasia, balanced.

Question 21

3 types of ductal hyperplasia (& assoc. risks)

Answer 21

1. Usual Ductal Hyperplasia: heterogenous, x1.5-2 risk bilateral.
2. Atypical Ductal Hyperplasia: mix of uniform and heterog. cells, x5 risk bilateral.
3. Ductal Carcinoma In Situ: all small, uniform cells. x8-10 risk, ipsilateral. * DCIS = pre-malig!

Question 22

Phyllodes Tumor

Answer 22

breast mass, like fibroadenoma but larger & more cellular stroma;
Histo: “leaf-like” growth pattern, esp. around duct(s).
60% = benign, some w/ mitotic figures.
* malign –> infiltrative edge w/ high cellularity & atypia; mets rare but recurrence common.

Question 24

Ductal Carcinoma In Situ of breast (DCIS)

Answer 24

Pre-malignant proliferation of small, uniform cells.
* does NOT cross BM
Histo: open chromatin, large nuclei, comedo necrosis (inflamm.)
if extends to skin/nipple = Paget’s Disease of breast (ulceration)

Question 25

Invasive Ductal Carcinoma of breast (IDC)

Answer 25

invasive carcinoma from TDLU, = 75% of breast cancer, grades I-III.

• Tubular: well-diff, good prog.
• Mucinous: w/ extracell. mucin, avg age 70yrs.
• Medullary: in sheets, w/ plasma cells & lymphocytes, w/ BRCA1.
• Inflammatory: in dermal lymphatics, no discrete mass, poor prog.

Question 26

Lobular Carcinoma In Situ of breast (LCIS)

Answer 26

malignant proliferation of cells in lobules, does NOT invade BM.
Usually: pre-menopause, multifocal & bilat, incidental finding.
Histo: non-cohesive cells (lack E-cadherin)
Tx: tamoxifen & follow-up.
risk invasion same as DCIS (x8-10)

Question 27

Infiltrative Lobular Carcinoma of breast (ILC)

Answer 27

invasive carcinoma, 10% of breast cancers.
grows in single-file along duct => “signet ring”
* loss of E-cadherin –> multifocal.
Same prognosis as IDC.

Question 27

Mucinous Carcinoma of breast (path)

Answer 27

~rare, special type of invasive ductal carcinoma;
Histo: well-diff. tumor cells “floating in pool of mucin”
*avg. age 70 yrs.
favorable prognosis.

Question 28

Tubular Carcinoma of breast

Answer 28

5% of breast cancers, ER+, low grade;
“special type” of invasive ductal carcinoma.
Histo: well-diff. glands w/ single cell layer (LACKs myoepithelium)
* sharp/angulated edges (vs. round in microglandular adenosis)
good prognosis.

Question 30

Invasive Mucopapillary Carcinoma of breast

Answer 30

uncommon, invasive carcinoma; w/ high rate lymph node mets.
Histo: “inside out” growth pattern
-> brown EMA staining = on OUTside of glands.