Flashcards in Module 3: Breast: Cancer Deck (42):
Now moving onto breast cancer. What are the pre-disposing factors?
BRCA 1 and 2
Obesity (due to increased estrogen)
Granulosa Theca ovarian tumor (due to increased estrogen)
What is the most important pre-disposing factor in elderly women?
What is the most important pre-disposing factor in middle aged women?
Family history and then nulluparity
Why are breast carcinoma lumps hard and fixed?
Fixed to underlying skin and pectoralis major
--extremely desmoplastic (fibrotic)
What is the most common location for breast carcinoma?
Upper outer quadrant
What is the origin of all types of breast cancer?
Terminal Duct Lobular Unit (TDLU)
Breast carcinoma is spread through lymphatics, what is the order?
Axillary , Supraclavicular and Internal Mammary (thoracic)
Once breast carcinoma has infiltrated the lymphatics, what is a key symptom? what are other symptoms?
Peau d'orange: due to lymph edema or lymph obstruction
nipple retraction (Ductal carcinoma -- desmoplasia -- fibrosis of cooper's ligaments)
Bloody nipple discharge
What is the most accurate test for all breast cancers?
Eventually from the lymphatics there will be metastasis from to the blood, then where?
--most common cancer in lung
In regards to prognosis what are indicators of a poor prognosis?
1. Greater than 2cm bad prognosis
2. Lymph node spread and Peau d orange
4. Her2New (EGFR) positive bad = extremely aggressive and herceptin is used to treat but does not cross blood brain barrier
5. Cathepsin D: (enzyme destroys basement membrane) is bad because allows invasion and metastasis
6. Aneuploidy is always bad
In regards to good prognosis what are indicators of a good prognosis?
1. ER/PR positive: can treat with tamoxifen
--tamoxifen increases chances of endometrial carcinoma
Now moving onto the types of breast cancer. There are two types Ductal and Lobular. Give some general features
Non-Infiltrating (Carcinoma in Situ)
--Ductal Carcioma in Situ (DCIS)
***comedo (high grade)
** Non-comedo (Solid, cribiform, papillary, micropapillary)
--Lobular Carcinoma In Situ (LCIS)
-Ductal (no special type): 80%
--Mucinous, medullary, papillary, metaplastic: 4-5%
First discussion will be on Lobular Carcinoma in Situ, which again is a non-infiltrating carcinoma. What is the origin and general features?
Origin: Terminal Duct Lobular Unit
Predisposing factors are the same for breast cancer
Asymptomatic most commonly: incidental finding without a mass
Usually unilateral but can be bilateral
Dyscohesive lacking E-cadherin
What is the histology for lobular carcinoma in Situ (slide 6 to the left)?
Atypical terminal duct lobular unit in an entire lobule
***atypical proliferation of inner cuboidal epithelial cells (response to estrogen)
Overall architecture of lobule is preserved
Ducts all still have single layer of outer myoepithelial cells (hence why its In-situ)
Now moving onto invasive lobular carcinoma, what are the general histological features?
--No intact lobule architecture
***due to loss of outer myoepithelial cells
***therefore invasion into the stroma
--invades interlobular first
What is the presentation for a patient with invasive lobular carcinoma?
No distinct mass
Usually unilateral and can be bilateral
--poorly outlined and indurated
TDLU origin with E-cadherin mutation
There are three types of invasive lobular carcinoma seen on biopsy, each card will go through one.
1. Indian File Cells: intralobular invaded first then interlobular -- malignant cells in the stroma
---single file of tumor cells, round and uniform (Seen in slide 6)
What is the second type of invasive lobular carcinoma?
2. Bull's Eye Pattern: tumor cells around normal acini and ducts
What is the third type of invasive lobular carcinoma?
3. Signet Ring Histology
--Mucin within cytoplasm
--PAS positive with metastasis to ovaries (Krukenberg)
Moving onto Ductal Carcinoma first we will discuss ductal carcinoma in situ (which again in non infiltrating). What are some features?
Slide 6b (right):
Obstruction of lactiferous duct: with intact single outer myoepithelial layer
**Origin: terminal duct lobular unit (TDLU)
More common calcification and no mass not yet cancer
Proliferation of Inner cuboidal epithelial cells
What is seen on mammogram in a patient with ductal carcinoma in situ?
Large amounts of calcification and necrosis
--asymptomatic found on mammogram; no mass
There are two types of ductal carcinoma in-situ. The first is Comedo, what are some features?
Comedo (intraduct tumor):
--high grade cells with necrotic center and dystrophic calcification
**less often ER,PR positive, Her2Neu positive
**Necrotic Center= cells inspissated materials (toothpaste secretions from the nipple)
--no mass because not yet invasive
The second type of ductal carcinoma in situ is Paget's Diease. What are some features?
Type of DCIS almost always associated with underlying intraductal carcinoma
What kind of cells are seen in Paget's Disease?
Paget Cells/Toker Cells
--hyperchromatic nucleus, perinuclear halo and mucin filled cytoplasm) migrate retrograde to the nipple
-use PAS stain
--turn into Toker cells once cells get outside the nipple
How do patients with Paget's Disease DCIS, present?
Nasty nipple changes: crusting, fissures, hyperemia, oozing and bloody nipple discharge (patients can get breast infections)
--pruritic erythematous eruption may be mistaken for eczema.
8a: the erythema and ulceration on the nipple due to migration of the cells from ductal carcinoma in situ
8b: migration of the malignant cells (PAS+) towards the epidermis of areola/nipple. Malignant cells have a pale cytoplasm and stand out among compared to the squamous cells in the epidermis (hyperchromatic nucleus with halo)
Paget cells in epidermis =?
Paget cells in DERMIS =?
--invasive ductal cancer (this is a complication)
The last topic to cover is invasive ductal carcinoma. What are some features?
Origin: Terminal Duct Lobular Unit
From either DCIS or de novo
Scirrhous (Dense demoplasia: thats why stroma looks pink): pictured in lab slide 7b.
Cords/nests of cells
There are several different types of Invasive Ductal Carcinoma, each card will go through one.
1. Luminal A (40-55%)
--ER +, PR +, Her2/Neu negative
--Postmenopausal, slow growing, well to moderate differentiation, responds well to hormonal treatment, decreased response to standard chemotherapy
--very low grade so KI67 negative
--Tx with tomoxifin
--best prognosis of all the invasive ductal carcinomas
What is the second type of invasive ductal carcinoma?
2. Luminal B: (15-20%)
--ER +,PR+, express Her2New +/-
--more likely to have LN mets, may respond to chemo
--very high grade so KI67+
--Tx: with tomoxifin b/c ER+
What is the third type of invasive ductal carcinoma?
3. Normal Breast like (6-10%)
--ER +, Her2/New negative
--Usually well differentiated
--less than 2cm usually
--best prognosis because of size
What is the fourth type of invasive ductal carcinoma?
4. Basal Like (13-25%)
--Triple negative (ER-/PR-/HER2/Neu-)
--BRCA 1+, younger females, medullary/metaplastic/cancer with fibrotic core
--High grade, aggressive, mets to brain, 15-20% complete response to chemo, cure possible in chemo responsive group
--more common in African Americans
--lots of p53 mutations
--tx with anything
What is the fifth type of invasive ductal carcinoma?
5. Her2 Positive (7-12%)
---ER negative; Her2 +; PR-
---Poorly differentiated and high frequency of brain mets, which makes herceptin use hard
--lots of p53 mutations and very aggressive
Mucinous (Colloid) Carcinoma is another carcinoma of the breast. What are some features?
--rare, well differentiated tumor in older women
--associated with solid/noninvasive papillary CA
Medullary Carcinoma of the Breast is another carcinoma. What is the appearance on histology?
Fried Egg Appearance
--sheet of monomorphic cells with prominent nucleus, nucleolus, cytoplasm contains glycogen
--fried egg cells are the neoplastic cells
Scanty fibrous stroma containing reactive lymph nodes
--tumor cells attracting lymphocytes
Outer myoepithelial lost
All fried egg cells are radiosensitive. what are the tumors?
Who do you see Medullary carcinoma in?
Young patients with BRCA mutations
Finally what are some features of Inflammatory cirrhosis?
Young Black Women
---swollen, erythematous breast due to dermal lymphatics obstruction by tumor
---underlying carcinoma diffusely infiltrative ---poor prognosis
--clinically mimics an abscess
What are some features of male breast cancer?
Gynecomastia = male analog of FCC
--relative or absolute increase in estrogen, reduced androgens/testicular androgen loss
---cirrhosis, Klinefelter syndrome, estrogen therapy, drugs, alcohol, marijuana, heroin, retroviral and anabolic steroids
Button Like Nodule Beneath Areola
The mammography (BIRAD) score stratifies patients into risk groups. it assesses what?