Repro-Endo: Breast

Question 1

Responsible for Milk production in the Lobules?

Answer 1

Luminal Cell Layer

Inner cell layer ining the Ducts and Lobules

Question 2

Responsible for Contractile function, propelling the Milk?

Answer 2

Myoepithelial Cell Layer

Outer cell layer lining the Ducts and Lobules

Question 3

Galactorrhea?

Answer 3

Milk production outside of Lactation

Not a symptom of Breast cancer

A/w Nipple stimulation, Prolactinoma, Drugs (Oxytocin, Ptocin)

Question 4

• Erythematous Breast w/ Purulent Nipple discharge
• Pain and Fever
• Abcess or mass may be felt w/in Breast or behind Nipple
• A/w Breast-feeding
• Fissures / Cracks develop in the Nipple
• -> Route of Entry for Microbes
• Bacterial infection of the Breast, Staphylococcus aureus
• Tx: Continued drainage (Breast-feeding) and ABX (Dicloxacillin or Cephalexin) check for Methicillin Resistance

Answer 4

Acute Mastitis

Question 5

• Inflammation of the Subareolar ducts
• Subareolar mass w/ Nipple Retraction
• Relative Vit. A deficiency (Retinoid)
• -> Highly specialized cells require Vit. A (Keratin)
• -> Squamous metaplasia of Lactiferous Ducts
• -> Duct blockage and Inflammation
• A/w Smoking

Answer 5

Periductal Mastitis

Question 6

• Periareolar Mass w/ Green-brown Nipple discharge
  (Inflammatory debris)
• Main ducts fill up w/ Depris
  –> Dilation, Rupture, Inflammation
• May produce Skin and Nipple retraction
• Multiparous Postmenopausal Women
• Chronic Inflammation w/ Plasma cells
• Inflammation w/ Dilation (Ectasia) of Subareolar ducts
• Tx: ABX and Surgery

Answer 6

Mammary Duct Ectasia

Question 7

• Benign, Painless, Breast Mass on physical exam
• Abnormal Calcification on Mammography
  (Saponification)
• Lipid-laden Macrophages w/ Foreign body Giant cells
• Dystrophic Calcification
• Biopsy –> Necrotic fat w/ Calcification of Giant Cells
• Necrosis of Breast fat

Answer 7

Fat Necrosis

Question 8

(3) Benign Breast Tumors

Answer 8

1. Fibroadenoma
2. Intraductal Papilloma
3. Phyllodes Tumor

Question 9

Most common change in Premenopausal Breast?

Answer 9

Fibrocystic change

Question 10

Fibrocystic changes of the Breast?

Answer 10

• “Breast lumps” “Lumpy” vague irregularity of Breast tissue
• 25 - 50 y.o.
• Premenstrual Breast Pain - Bilateral
• Multiple Lesions –> NOT RISK Cancer
• Fibrosis - Hyperplasia of Breast Stroma (5x Risk)
• Cystic - Fluid filled, “Blue-dome appearance” Ductal dilation.
• Sclerosing adenosis - Increased Acini and Intralobular Fibrosis –> Calcification (slight risk cancer 1.5 - 2x)
• Epithelial hyperplasia - Increase Epithelial cell layers in Terminal Duct lobule

Question 11

Intraductal Papilloma

Answer 11

• “Straw colored** and **Bloody” Nipple Discharge
• Premenopausal woman
• Small Tumor, Grows in Lactiferous Ducts** or **Sinuses
  
  • ​Typically beneath Areola
• NO increased risk of Cancer
• Fibrovascular projections lined by Epithelial (Luminal) and Myoepithelial cells (1.5 - 2x risk of Carcinoma)
• Must be distinguished** from **Papillary Carcinoma
• Tx: Surgical excision

Question 12

Papillary Carcinoma?
Distinguished from IntraDuctal Papilloma

Answer 12

• Papillary Carcinoma
  
  • Fibrovascular projections Lined by Epithelial cells WITHOUT Myoepithelial cells
  • Risk of Papilary Carcinoma Increases w/ Age
• -> Postmenopausal women
• Intraductal Papilloma
  
  • ​Fibrovacular projections Lined by Epithelial cells WITH Myoepithelial cells

Question 13

• Small, Well circumscribed “Mobile - Marble like mass”
• Discrete and Movable, Painless / Painful
• Premenopausal, < 25 y.o.
• Sharp Edges
• Estrogen sensitive - Grows during Pregnancy and Painful during Menses, Increases in size w/ Estrogen lvls
• Tumor of Fibrous Tissue and Glands and Stroma
• Benign Tumor, No Risk for Carcinoma
• Most common Benign Neoplasm in

Answer 13

Fibroadenoma

Question 14

• LARGE Bulky mass of Connective tissue Stromal cells
• Fibroadenoma-like Tumor with Overgrowth of the Fibrous component ‘Leaf-like’ projections
• 50 - 60 y.o.
• Post-menopausal women
• Can be Malignant
  
  • Serial mammograms and Biopsy as it grows
  • • Tx: Wide excision

Answer 14

Phyllodes Tumor

Question 15

(9) Risk Factors for Breast Cancer

Answer 15

1. Early Menarch / Late Menopause
2. Nullparity (Fewer Pregnancies, Less Time Breast-feeding)
3. Hormone Replacemnt Therapy (Est. w/out Prog.)
4. Endometrial cancer, Ionizing XRT, Smoking
5. Older age at 1^st Live Birth
6. Obesity (aromatization of androstenedione to Estrone)
7. Family History / Ash. Jew - BRCA mutation, First-degree relative (BRCA 1, BRCA2, p53, RAS, ERBB2, RB1)
8. Atypical Hyperplasia
9. HNPCC - Hereditary Nonpolyposis Colorectal Cancer

Question 16

(3) Overexpression of Receptors in Breast Cancer

Answer 16

1. Estrogen
2. Progesterone
3. HER2/neu (ERBB2 gene)

Question 17

(5) Types of DCIS

Answer 17

1. Comedocarcinoma (necrotic center)
2. Solid
3. Cribiform (sieve-like)
4. Papillary
5. Micropappilary

Question 18

• Cells Fill the Ductal Lumen - Ductal Atypia
• Microcalcifications / Mammographic calcifications
• No Invasion into the Basement membrane
  
  • ​Early Malignancy (1/3) invade
• Malignant proliferation of cells w/in Ducts
• Biopsy of Calcifications –> Benign vs. Malignant
• Hitological subtypes based on Architectures

Answer 18

DCIS (Ductal Carcinoma In Situ)

Question 19

• Histological architecture shows High-grade cells w/ Necrosis and Dystrophic Calcifications w/in the Center of Ducts of Breast
• Ductal
• Caseous Necrosis

Answer 19

Comedocarcinoma of DCIS

Question 20

• Nipple Ulceration (Eczematous) and Erythema
• DCIS that Extends up the Lactiferous Ducts
• Involves the Skin of the Nipple
• Paget cells = Large cells in Epidermis w/ Clear Halo
• A/w underlying DCIS - Carcinoma

Answer 20

Paget Disease of the Breast

Question 21

• Firm, Fibrous, “Rock-hard” mass w/ Sharp margins
• Small, Glandular Duct-like Structures in a Desmoplastic Stroma (70 - 80% of all Breast cancers gray-white tumor
• “Stellate” infiltration - “Star-like” - Fibroplasia
• Mass Detected: Physical exam or Mammography
• A/w Dimpling of Skin or Retraction of Nipple
• (4) Subtypes
  
  • Tubular carcinoma
  • Mucinous carcinoma
  • Medullary carcinoma
  • Inflammatory carcinoma

Answer 21

IDC (Invasive Ductal Carcinoma)

Question 22

Characteristics of Tubular Carcinoma - IDC?

Answer 22

• Well-differentiated Tubules
• Develops in the Terminal ductules
• Lack Myoepithelial cells
• Relatively good prognosis

Question 23

Characteristics of Mucinous Carcinoma - IDC?

Answer 23

• Abundant Extracellular Mucin
• ‘Tumor cells floating in a Mucus pool’
• Older women (avg. age ~ 70 y.o.)
• Relatively Good prognosis

Question 24

Characteristics of Medullary Carcinoma - IDC?

Answer 24

• Large, High-grade cells Growing in Sheets w/ associated Lymphocytes infiltrate and Plasma cells
• Well-circumscribed Mass
• Mimics Fibroadenoma on Mammography
• Increased incidence in BRCA1 carriers
• Relatively good prognosis

Question 25

Characteristics of **Inflammatory Carcinoma** - IDC?

Answer 25

* **_Inflamed_** and **_Swollen_ Breast** * **Peau d'orange** * **No Discrete mass** * **Dimpling of Breast - Nipple retraction** * Often mistaken for Acute Mastitis * Tumor cells _block drainage_ of **Dermal Lymphatics** * Poor prognosis

Question 26

* **"Signet ring cells"** * **ER+ / PR+** * **Dyscohesive Cells Lacking E-cadherin adhesion protein** * **Multifocal** and **Bilateral** * Malignant proliferation of cells in **Lobules w/ no Invasion** **of the Basement membrane** * Does not produce a Mass or Calcifications * Discovered incidently on Biopsy

Answer 26

LCIS (Lobular Carcinoma In Situ)

Question 27

* **Orderly Linear rows of cells - "Indian File"** * or in **Concentric circles** ("Bull's eye") in the **Stroma** Grows in a single-file pattern * **"Signet-ring"** morphology * Inactivation of **E-cadherin** genes **Chromosome 16 --\> No duct formation**

Answer 27

ILC (Invasive Lobular Carcinoma)

Question 28

* Fleshy, Cellular, Lymphocytic Infiltrate * Good Prognosis

Answer 28

Medullary Invasive Carcinoma

Question 29

Risk factors for Gynecomastia?

Answer 29

* **Hyperestrogenism** (Cirrhosis, Testicular tumor, Puberty, Klinefeller Syndrome * **Drugs** **"STACKEDD F's, H's and DD's!"** * Spironolactone (SHBG displacement) * THC - Marijuana * Alcohol * Climetidine * Ketoconazole (SHBG displacement) * Estrogens * Digoxin, DES (activates Estrogen receptors) * Flutamide, Heroin, and Dopamine D₂ antagonists

Question 30

Risk Factors for Breast Cancer in Men?

Answer 30

* _Inactivation of **BRCA2**_ suppressor gene * **_Klinefelter syndrome_** * **Increased Aromatization** of _Androgens to Estrogens_ in **_Leydig cells_** * **Decreased responsiveness** of _Testosterone_ to **_Androgen receptors_**