Flashcards in Module 3: Breast: Normal, Inflammations, FCC, fibroadenoma, Phylloides, Intraductal pap Deck (41):
Lets begin with the basic histology of the breast. What are the three basic structures seen?
1. Fat Cells
3. Terminal Duct Lobular Unit (TDLU)
--this is the functional unit of the breast lined by double layer of cells: outer myoepithelial cells (closer to the intralobular stoma) and inner cuboidal epithelial cells (facing the lumen)
What are the two types of stroma?
Intralobular: between ducts but within lobule
Interlobular stroma: between the lobules
What is the pathway that breast milk travels?
Terminal Duct Lobular Unit ---- lactiferous Duct --- Lactiferous Sinus --- Nipple
Describe the histology slides seen in younger vs older females?
Younger: many TDLU make up a lobule
Older females: more fat cells than stroma and hence why breasts get saggy with age
Clinically explain cancer and mammograms
Fat (radiolucent) is black and stroma (radiopaque) is white on a mammogram
--and cancer is white due to dystrophic calcification
--therefore in an older person easy to see cancer since in older persons the breast is mostly fat (black)
--In a younger person breast cancer is hard to see because most of the breast is stroma (White)
Describe the histology seen in the breast of a pregnant women.
Proliferation/hyperplasia of lobules under the influence of estrogen in pregnancy
--physiological adenosis of the acini (functional unit)
Which cells make milk and which ones squeeze the milk out?
Inner cuboidal epithelial cells make milk
Outer myoepithelial cells contract to squeeze milk from lumen --- lactiferous duct --- lactiferous sinus -- nipple
Which epithelial cells are considered the gatekeepers of the stroma?
Outer myoepithelial cells -- lost in carcinoma
Moving onto the next change in the breast tissue is Fibrocystic change. What is the origin, etiology and pathogenesis for this change?
Etiology: Unopposed estrogen
---women of reproductive age
Pathogenesis: exaggerated response of BOTH breasts to estrogen
What is the presentation for Fibrocystic changes to the breast?
Women of reproductive age present with bilateral cyclical mastalgia (pain during the menstrual cycle -- which points to the estrogen pathogenesis)
What does a physician place in their report if they feel fibrocystic change?
Lumpy Bumpy Breast
--breast is also tender
What are two types of Fibrocystic change?
First lets start with the Simple/Non-proliferative FCC. What are some features seen on histology?
--Abnormally distended or dilated ducts
*each of these ducts maintains a double layer of cells (inner cuboidal and outer myoepithelial)
--Apocrine metaplasia (seen in proliferative as well) (start to look like sweat glands)
*very eosinophilic cytoplasm and benign finding
NO MALIGNANT POTENTIAL
Now for proliferative, what are some features?
--Epithelial hyperplasia leads to increased malignant potential
-Inner cuboidal cells (respond to estrogen) --- multilayering
What are the three types of Proliferative FCC?
Ductal Proliferative FCC
Sclerosing Adenosis (hyperplasia of glands) Fibrosis (desmoplasia): w.o atypica
Lobular Proliferative FCC
First lets start with sclerosing adenosis fibrosis, what are some features?
1. Mimics breast cancer the most (Clinically and histologically)
2. Many terminal duct lobular units
3. Very eosinophilic cytoplasm
4. Low chance of malignant transformation because ducts are still lined by normal epithelium.
--single layer of inner cuboidal and outer myoepithelial
5. Fibrosis of intralobular stroma
Next lets move on to ductal proliferation, what are some features?
1. Proliferation of inner cuboidal layers
--multiple layers of inner cuboidal
--still single layer of myoepithelial
2. Undergoes atypia
** becomes atypical ductal proliferative FCC also called Ductal Carcinoma in Situ that has a high chance of malignant transformation: undergoes dysplasia
3. Can becomes invasive ductal adenocarcinoma
--destruction of outer myoepithelial layer
and therefore allows invasion
Finally the last type of fibrocystic change is Lobular Proliferative FCC. What are some features?
1. All ducts in a lobule are proliferative (entire lobule affected)
2. Undergoes atypica
--highest chance of malignant transformation, called LCIS: lobular carcinoma in situ
3. Finally can become invasive carcinoma
--loss of outer myoepithelium
List in order the greatest to the least chance of FCC becoming malignant
Atypical Lobular --- Atypical Ductal ---- Lobular --Ductal ---- Sclerosing Adenosis
On trans-illumination of a patient with FCC, what do you see?
Patients with FCC can get what in the uterus?
Endometrial hyperplasia and this can lead to endometrial carcinoma
Also polycystic ovarian syndrome/ovarian tumor
--possible source of elevated estrogen
Now moving on to the various inflammations that can occur in breast pathology. What is acute mastitis?
Usually when breast feeding -- cracks + bacterial infection --- red/painful breast + fever
--Staph: small, localized under nipple (may leave residual indurated scar)
--Strep: whole breast, marked swelling tenderness (heals w/o scar)
What is seen on histology of a patient with Acute Mastitis?
Histology: Necrotic cell debris with neutrophil rich infiltrates
What is mammary duct ectasia?
Plasma Cell Mastitis also called Granulomatous Mastitis
--dilated duct ruptures and releases plasma cells and inflammatory cells
*Periareolar mass with thick white nipple secretions
*May lead to nipple retraction and induration which mimics carcinoma
What is traumatic fat necrosis?
History of trauma or breast surgery
Large, pendulous breasts
Mimics carcinoma clinically
Fat necrosis, cholesterol clefts, neutrophils, lipid laden macrophages
Later: lymphocytes, fibrosis, cysts +/- calcification
Finally what is the bodies reaction to breast implants?
Cosmetic: paraffin or silicone
---Histology: epitheloid cells, foreign body giant cells and macrophages
Next topic is fibroadenoma of the breast tissue. What is the etiology ?
Most common benign breast tumor (single, discrete encapsulated nodule 1-10cm)
Women of reproductive age
--estrogen does not cause: only makes bigger
--grow bigger in pregnancy, granuloa theca tumor and polycystic ovarian disease and regress at menopause
--Behaves similar to a leiomyoma
**uterine fibroids not cause by estrogen, but do grow with it .
What is the origin and presentation for a patient with a fibroadenoma?
Origin: intralobular stroma
Presentation: found by women on self examination
**Breast mass: mobile, non tender and hard to grasp (defined and well circumscribed)
What does the mammogram show for patients with fibroadenoma?
Excisional Biopsy is the best test for fibroadenoma, what are the two classifications?
1. Ducts that look like slits: intracanalicular (left)
2. Ducts that look circular or ovoid: pericanalicular (right image)
--both types of benign (No clinical relevance of naming)
--no chance of malignant transformation
Moving on to the next mass in the breast tissue is a Phylloides Tumor (Cystosarcoma phylloides). What is the etiology and origin?
Unilateral in post menopausal women (60-70s)(Note age is a big difference form fibroadenoma)
--origin: intralobular stroma
--etiology: unknown (for sure not estrogen)
Can be benign or malignant
called cystosarcoma phylloides because the origin is stroma of the connective tissue
What is the presentation for a patient with Phylloides Tumor?
Post-Menopausal women with unilateral pendulous breast (aka big swinging breast)
What is seen on biopsy in patients with phylloides tumor?
Biopsy is the best test:
Phylloides tumor (Cystosacroma Phylloides) can be either benign, borderline or malignant. What are the defining features of each?
Benign: Zonal hypercellularity, mold atypia stromal cells, no stromal overgrowth and mitosis less than 5/HPF
Borderline: Zonal hypercellularity, moderate atypical stromal cells, no stromal overgrowth and mitosis 5-10/HPF
Malignant: More mitosis and hypercellularity of the interlobular stroma (Invasion has now occurred)
What are complications of Phylloides Tumor (Cystosarcoma)?
Small chance of benign to malignant
--most malignant are de novo
--does not spread through lymph nodes (only breast cancer that does not spread through lymph nodes)
--Hematogenous spread: liver, lung, brain, bone, kidney
Finally the last topic for this card set is Intraductal Papilloma. What is the morphology seen on slide 5?
Lumen contains papilloma
Papilloma lined by inner cuboidal and outer myoepithelial cells
--arrowheads: inner cuboidal facing lumen
--arrows: outer myoepithelial facing the core Core Composed:
CT, Fibroblasts and Blood Vessels
What is the etiology and origin of intraductal papilloma?
Origin: small duct: TDLU
Large duct: lactiferous ducts
What are the sites for large duct and small duct papillomas?
Large Duct: solitary situated in lactiferous sinuses of nipple
Small Duct: multiple and located deeper in the ductal system
What are the signs and symptoms associated with intraductal papilloma
Seen in Pre-Menopausal Women (35-55)
---most common cause of blood nipple discharge in women of reproductive age
---small subareolar tumor a few millimeters in diameter
--nipple retraction is rare
What is the best investigation for a patient with intraductal papilloma?
---papilloma into the lumen of the lactiferous ducts if benign layers are normal