Breast Pathology

Question 1

Breast Development

Answer 1

• Mammary ridges along body at 15 wks gestation then involute everywhere but typical breast area
• At term, 15-25 mammary ducts and sebaceous glands that come together near epidermis
• Glands cont to grow in proportion to body growth in both
  genders
• Right b/f puberty, duct system grows more rapidly in girls in response to estrogen
• During puberty, extensive growth, branching, canalization of lobular-alveolar units at tips of branches (cont thru pubertal development)

Question 2

Basic Breast Histology / Anatomy

Answer 2

• 8-10 large ducts starting at nipple –> terminal ducts w/ lobules
• Intralobular stroma - loose stroma immediately around lobules
• Interlobular stroma - fat-predominant outside ductal system
• Ea gland surrounded by 2 cell layers - basal cell layer (spindle, myoepithelial for contraction) and luminal cell layer (cuboidal, plump) w/ loose stroma b/n individual glands

Question 3

How does breast tissue look during pregnancy?

Answer 3

Adenosis (inc glands) and foamy secretions

Question 4

Traumatic Fat Necrosis

Answer 4

• Mimics carcinoma clinically - local swelling +/- bruising
• Usually follows trauma (seatbelt in car accident)
• Resolves spontaneously
• Chronic inflammatory cells and macrophages +/- multi-nucleated giant cells

Question 5

Fibrocystic Change

Answer 5

• COMMON (50% women)
• Sex steroid hormone responsive
• Proliferative (>2 cell layers) v non-proliferative (no inc risk)
• Grossly - cysts surrounded by white/tan fibrotic area
• Histo - swollen/dilated cysts, adenosis (inc glands), PINK fibrosis, apocrine change in cells lining glands (metaplasia)
• Apocrine metaplasia = still have single basal layer but luminal layer has extensions of cytoplasm (“cytoplasm snouts”)

Question 6

Fibroadenoma

Answer 6

• COMMON (in young women)
• Inc in loose intralobular stroma that then compresses lobule epithelium
• Grossly - very well demarcated
• Histo - uniform stroma proliferation around glands

BENIGN; NO INC RISK CANCER

Question 7

Gynecomastia

Answer 7

• Small, sub-areolar swelling (usually bilateral)
• Causes -
  
  • Drugs - estrogem , digitialis, spironolactone
  • Cirrhosis, malnutrition
  • Estrogen secreting tumor or Leydig cell tumor
  • Klinefelter’s
• No clear assn w/ breast cancer
• Histo - epithelial hyperplasia (> 2 cell layers) w/ halo around ducts from periductal edema

Question 8

Intraductal Papilloma

Answer 8

• Fibrovascular core - see pink fibers and vessels w/in duct lumen
• Can cause bloody nipple d/c

Question 9

Sclerosing Adenosis

Answer 9

• inc # glands but contained w/in same lobule shape / pattern
• Only inc risk cancer if proliferative (proliferative if > 2 cell layers)

Question 10

Ductal Hyperplasia

Answer 10

• Can be mild (no inc risk), moderate (1.5 - 2X inc risk) or atypical (4-5X inc risk)
• Atypia = more blue (nuclei) and bridging b/n adjacent cells

Question 11

LCIS

Answer 11

(general bilateral risk –> ductal carcinoma)

• Preserved myoepithelial cell layer; still has BM; confined to ducts
• More often multifocal and bilateral
• Usually not associated w/ micro-calcifications on Xray but found incidentally
• Histo - fills duct so do not even see lumens, no room for central comedonecrosis
• E-cadherin -

Question 12

DCIS

Answer 12

(ipsilateral risk)

• Preserved myoepithelial cell layer; still has BM; confined to ducts
• Most commonly associated w/ micro- calcifications on XRay
• Histo - cookie-cutter punches out areas; comedonecrosis (pink material w/o nuclei in lumen) and calcifications

Question 13

Invasive Ductal Carcinoma

Answer 13

• No myoepithelial cell layer (lose p63 stain marker); haphazard invasion into surrounding stroma
• Histo - areas of necrosis, atypia (nucleoli, mitoses, pleomorphism); nests of cells (not straight lines)
• E-cadherin + (maintain tight junctions)

Question 14

Invasive Lobular Carcinoma

Answer 14

• Less common than ductal
• Histo - targetoid / linear appearance (“indian file”); not as haphazard; tumor cells in straight lines; cells have more abundant cytoplasm and nuclei pushed to side; bland cells
• E-cadherin -

Question 15

3 Ductal Carcinoma Variants

Answer 15

ALL HAVE GOOD PROGNOSIS

1 - Mucinous - see tumor cells floating in mucin

2 - Tubular - low-grade atypia (look normal) but lose basal cell layer so only 1 cell layer (p63-); angulated glands

3 - Medullary - sheets of tumor cells

Question 16

Phyllodes Tumor

Answer 16

• Borderline or malignant variety of fibroadenoma (INTRALOBULAR STROMA AFFECTED)
• More blue stroma and atypia

Question 17

Angiosarcoma

Answer 17

• Mesenchymal tumor primarily in young pts

- Stewart-Treves Syndrome - angiosarcoma in skin of pt w/ lymphedema after mastectomy (5-10 yrs after tx)

Question 18

What types of lymphomas are associated w/ breast?

Answer 18

• Primary (NHL, MALT, Burkitt); all B cells
• Secondary
• Anaplastic large cell lymphomas associated w/ breast implants; chronic inflammatory reaction w/ abnormal T cells
  
  • Serous fluid (present w/ swelling) - when drain notice it is lymphoma

Question 19

Paget’s Disease of Breast

Answer 19

• In situ carcinoma of lactiferous ducts w/ extension into epidermis
• Eczema-like rash (excoriations), d/c, crusting
• 95% associated w/ underlying ductal type carcinoma
• Histo - large cells w/ abundant cytoplasm
• R/o melanoma

Question 20

General Risk Stratification

Answer 20

Non-proliferative Lesions = no inc risk invasive carcinoma

• Cysts
• Papillary apocrine change
• Mild hyperplasia

Proliferative W/o Atypia = 1.5 to 2X higher risk

• Moderate (florid) Ductal Hyperplasia
• Intraductal Papilloma
• Proliferative Sclerosing Adenosis
• Complex Sclerosing Lesions
• Complex Fibroadenomas

Atypical Hyperplasia or Proliferative w/ Atypia = 4-5X higher risk

• Atypical Ductal Hyperplasia
• Atypical Lobular Hyperplasia

Carcinoma In Situ = 8-10X higher risk