Pathology of Breast Cancer Flashcards
What is the most common carcinoma in women (excluding skin cancer)?
- Breast cancer
What are the 6 risk factors related to breast carcinoma?
- mostly related to estrogen exposure:
1. female
2. age (post menopausal)
3. early menarche/late menopause
4. obesity (adipose can convert androgens to estrone).
5. atypical hyperplasia
6. first-degree relative (sister, mother, or daughter)
** What is DUCTAL CARCINOMA IN SITU (DCIS)?
- MALIGNANT proliferation of cells with NO INVASION of the basement membrane.
- detected as CALCIFICATION on mammography.
- usually multifocal
Remember, what 2 other benign issues can cause calcifications in the breast
- fat necrosis
- sclerosing adenosis
*** What type of necrosis is most common in DCIS?
- COMEDO type= high grade cells with NECROSIS and DYSTROPHIC CALCIFICATION in CENTER of ducts.
** What is DCIS that extends up the ducts to the skin of the nipple?
- PAGET’S DISEASE of the nipple.
- presents as nipple ulceration and erythema.
** With what is PAGET’S DISEASE of the nipple almost always associated?
- an underlying carcinoma
*** What is INVASIVE DUCTAL carcinoma (IDC)?
- most common type of invasive carcinoma of the breast, accounting for more than 80% of cases.
- forms DUCT-LIKE structures and presents as MASS (clinically detected= 2 cm or mammography detected= 1 cm) and often STELLATE.
What can advanced tumors of IDC cause?
- DIMPLING of the skin or RETRACTION of the nipple.
What will a biopsy of IDC show?
- DUCT-LIKE structures in a desmoplastic stroma (connective tissue growing with tumor for support).
- loss of myoepithelial layer
*** What are the 4 special subtypes of IDC?
- TUBULAR carcinoma
- MUCINOUS carcinoma
- MEDULLARY carcinoma
- INFLAMMATORY carcinoma
*** What will you see on histology with TUBULAR IDC?
- well-differentiated tubules that LACK myoepithelial cells.
* GOOD PROGNOSIS
*** What will you see on histology with MUCINOUS IDC?
- abundant extracellular MUCIN (tumor cells floating in a mucus pool) seen in ELDERLY women.
- crepitant to palpation
- GOOD PROGNOSIS
*** What will you see on histology with MEDULLARY IDC?
- large, high-grade cells growing in sheets with associated lymphocytes and plasma cells.
- presents with well-circumscribed mass
- BRCA1 carriers.
- more common in JAPANESE.
- GOOD PROGNOSIS
*** What will you see with INFLAMMATORY IDC?
- carcinoma of dermal LYMPHATICS.
- presents as inflamed, swollen breast (tumor cells block drainage of lymphatics) with no discrete mass.
- POOR PROGNOSIS
With what can INFLAMMATORY IDC sometimes be mistaken?
- acute mastitis
With what can medullary IDC mimic?
- fibroadenOMA due to presentation of well-circumscribed mass.
** What is LOBULAR CARCINOMA IN SITU (LCIS)?
- MALIGNANT proliferation of cells in lobules with NO invasion of the basement membrane.
- DYSCOHESIVE cells LACKING E-CADHERIN adhesion protein (like the glue that allows these cells to stick to one another), making it more likely to metastasize.
How is LCIS found?
- incidentally bc it does not produce a mass or calcifications.
Is LCIS often multifocal and bilateral (both breasts)?
YES
How do you treat LCIS?
- TAMOXIFEN and close follow up
*** What is INVASIVE LOBULAR CARCINOMA?
- grows in SINGLE-FILE pattern (bc remember they lack E-cadherin)
- cells may exhibit SIGNET-RING morphology (like diffuse gastric carcinoma).
How do we stage breast cancer?
TNM staging:
- Tumor
- lymph Nodes
- distant Metastasis
** What is the most IMPORTANT prognostic factor?
- METASTASIS
* However, the most USEFUL is spread to AXILLARY LYMPH noes, bc most patients don’t present with metastasis.
How do we determine spread to axillary lymph nodes?
- SENTINEL NODE BIOPSY (allows us to take the minimum amount of lymph nodes so we don’t unnecessarily take out all the lymph nodes leading to arm swelling, while still accurately diagnosing the metastasis).
What predictive factors?
- predict the response to treatment
*** What are the 3 key predictive factors of breast cancer? (aka factors that will predict our pt’s response to treatment)
- estrogen receptor (ER)= OLDER women.
- progesterone receptor (PR)
- HER2/neu gene amplification (overexpression)= growth factor receptor (protoncogene that when amplified becomes an oncogene). Usually YOUNGER white women.
What tumors will be responsive to antiestrogenic agents like tamoxifen?
- ER and PR associated tumors
* both receptors are located in the NUCLEUS
What medication do we use to treat HER2 receptor positive tumors?
- TRASTUZUMAB (Herceptin)= antibody against HER2 receptor
What are TRIPLE-NEGATIVE tumors?
- negative for ER, PR, and HER2= POOR PROGNOSIS
- AFRICAN AMERICAN women are most common.
- most BRCA1
What percent of breast cancer cases are due to HEREDITARY breast cancer?
- 10%
What features suggest hereditary breast cancer?
- multiple first-degree relatives with breast cancer.
- tumor at PREmenopausal age.
- multiple tumors
** What are the most important single gene mutations for HEREDITARY breast cancer?
- BRCA1= breast (remember MEDULLARY IDC association) and ovarian carcinoma (most often SEROUS) or can arise in FALLOPIAN tube as well.
- BRCA2= breast carcinoma in MALES.
If a woman chooses to undergo a prophylactic mastectomy due to genetic propensity (BRCA1 or 2), does she still need to be watched carefully?
YES bc some breast tissue may still remain.
How does male breast cancer present? (RARE, 1% of all breast cancers)
- subareolar mass (usually IDC bc men don’t develop many lobules; mostly ducts) under nipple in older males.
- may produce nipple discharge
With what is male breast cancer associated?
- BRCA2
- Klinefelter syndrome
Are BRCA1 and 2 carriers more common in Ashkenazi Jews?
YES
What is secretory carcinoma?
- rare, primarily in CHILDREN.
- “PUSHING MARGINS”
What is metaplastic carcinoma?
- ductal carcinoma with sarcoma-like stroma and may have cartilagenous and/or osseous areas.
*** When can angiosarcoma occur from breast cancer?
- 5-10 years POST-RADIATION THERAPY for breast carcinoma
What is Stewart-Treves syndrome?
- lymphedema of arm occurring due to removal of axillary lymph nodes.
What are the stages for breast cancer?
- stage 1= invasive carcinoma less than 2 cm.
- stage 2= invasive carcinoma greater than 2 cm with lymph node involvement.
- stage 3= invasive carcinoma greater than 3 cm with more than 4 lymph nodes involved.
- stage 4= distant metastasis.
What happens with sentinel node excision?
- often sent for FROZEN section diagnosis.
- pathologist makes slides out of frozen tissue and reads them immediately.
- stain with CYTOKERATIN, looking for malignant epithelial cells.
Does breast cancer tend to spread to lung and bone?
YES because it often spreads by hematogenous means.
Do poorly differentiated tumors tend to do better with chemo?
YES bc they are dividing more rapidly, which is the target of chemo.
Does increased or decreased proliferative capacity of tumors tend to have a poorer prognosis?
- increased proliferative capacity, bc you are going through more cell cycles.
What stain do we use for nuclear proteins expressed in actively proliferating cells?
- Ki67
What type of breast cancer is most common?
Luminal A= estrogen receptor +
What are the 3 unfavorable types of breast cancer?
- Signet ring
- Basal-like
- Inflammatory
* the rest have a good prognosis.
What things can present as a lump/mimic breast cancer?
- fibroadenoma
- intraductal papilloma (may have bloody discharge)
- lactating adenoma
- sclerosing adenosis
- radial scar
- fat necrosis
What are some tricky tumors that look alike on histology?
- fibroadenoma vs. malignant phyllodes tumor
- papilloma vs papillary carcinoma
- lactating adenoma vs. ductal carcinoma in situ
- fat necrosis vs. invasive ductal carcinoma
- radial scar vs. tubular carcinoma
- atypical duct hyperplasia vs. ductal carcinoma in situ
*** What are the take home points of this lecture?
- carcinoma in situ does not break through the basement membrane.
- the most common invasive breast cancer is ductal carcinoma, followed by lobular carcinoma.
- ER, PR, and HER2 are important for prognosis and treatment.
