11/19- Breast Pathology Flashcards
What are the functions of the normal mammary gland?
- Newborn survival
- Nursing- transfer immunity, maternal bonding, post-partum uterine involution
- Sexual organ- implications for cancer treatment
Describe breast anatomy
- 6-10 major segmental duct systems that emerge at nipple.
- Successive duct branching into small terminal duct lobular units (TDLU), where most cancers originate.
- Supporting stroma: fat, connective tissue and blood vessels.
What is seen here?
Breast histology
- Close up TDLU
Ducts and lobules are formed of what cell types? Function?
- Myoepithelial cells: contractile, milk ejection
- Epithelial cells: milk production
Describe the makeup of the stroma
- Dense fibroconnective tissue
- Adipose tissue
- Blood vessels
Key fact: genes important in controlling development may be those contributing to cancer when altered
:(
What is seen here?
Atrophy
What is seen here?
Lactational changes
What is seen here?
TLDU
What are nonproliferative changes in benign breast disease?
Inflammatory condition:
- Acute mastitis
(- Duct ectasia)
- Granulomatous mastitis
Fibrocystic changes
What are proliferative changes in benign breast disease?
- May mimic cancer clinically and histologically
- Increased risk of breast cancer
Case 1)
- 32 yo patient with breast mass
- Last delivery 1 yr ago
- Exam: warm breast with ulceration
- Imaging: breast mass highly suspicious
- BIRADS 4C What do you expect on biopsy?
Granulomatous mastitis
What is seen here?
Granulomatous mastitis
What is seen here?
Granulomatous mastitis
What causes acute mastitis?
Usually during lactation
- Bacterial infection
- Erythema and swelling can mimic inflammatory breast cancer
What is seen in duct ectasia?
- Dilation of ducts
- Inspissated secretions
- Inflammation of nlobules
What is seen in granulomatous mastitis (process)? What causes it?
- Unknown etiology
- Immune reaction to antigens during lactation
What are fibrocystic changes?
- What % of women
- Composition
- Consequences
- Lumpy, sometimes tender breasts
- Very common: 60% of women, usually premenopausal
- Composed of cysts (fluid filled sacs, tender), fibrosis, adenosis
- Mass effect, tiny microcalcifications on mammogram, need biopsy to distinguish from cancer
What is seen here?
Fibrocystic changes
How can you divide proliferative breast lesions?
- Without atypical cellular changes
- With atypia
What are some conditions that are proliferative without atypia?
- Usual ductal hyperplasia: several cell layers with mixed cell population, ER+
- Sclerosing adenosis: proliferation of glands within a fibrotic stroma, microcalcifications
- Intraductal papilloma: growth inside duct, can cause nipple discharge
- Fibroadenoma: most common benign growth, not precancerous
Case 2)
- 45 yo woman with bloody nipple discharge
- Clinical: No pain
- Imaging: Dilated duct with solid intraluminal growth BIRADS 4A
What do you expect from pathology?
Intraductal papilloma
What is seen here?
Intraductal papilloma
Case 3)
- 28 yo female with palpable mass, 2 cm
- Clinical: circumscribed, not fixed
- Imaging: Round, well circumscribed
What do you expect from pathology?
Fibroadenoma
- If you see someone in 20s with breast mass, THINK FIBROADENOMA
What is seen here?
Fibroadenoma
What is seen here?
Fibroadenoma
What is seen here?
Fibroadenoma
What are some different types/categories of hyperplasias?
- Usual type ductal hyperplasia
- Columnar cell lesions
- Apocrine hyperplasia and apocrine adenosis
Describe usual type ductal hyperplasia
- Risk
- Cells
- Genetics
- Not a precursor
- Mixed cell population
- No or rare random genetic alteration
Describe columnar cell lesions
- Risk
- Genetics
- Loss of 16q ~ FEA, ADH
- Low grade DCIS, ALH and LCIS
Describe apocrine hyperplasia and apocrine adenosis
- Risk
- Genetics
- Precursor to high grade arm
- Multiple genomic alterations
What is seen here?
UDH: usual type ductal hyperplasia
Describe proliferative lesions with atypia (premalignant lesions).
Types? Cell populations?
- Miniature version of carcinoma in situ
- Having some but not all the features of in situ
- Homogeneous cell population (clonal)
- Cytologic atypia
Types:
- Atypical ductal hyperplasia: ADH
- Atypical lobular hyperplasia: ALH
- Flat epithelial atypia: FEA
What is seen here? Genetics?
Premalignant (16q-)
Case 4)
- 43 yo woman first mammogram
- Clinical: No symptoms
- Imaging: Microcalcifications 4B
- Stereotactic core biopsy with clip placement
What is expected on pathology? Next procedure?
Atypical ductal hyperplasia
- Next: needle guided excision
- This diagnosis requires surgical excision
What is seen here?
Atypical Ductal Hyperplasia
- Nice, round lumens
- Can see calcifications
- This will not require radiotherapy
Breast cancer is the #__ cancer in women
Breast cancer is the #1 cancer in women
(2. lung/bronchus, 3. colon/rectal)
Breast cancer is the #__ cause of cancer deaths in women
(__% of cancer deaths)
Breast cancer is the #2 cause of cancer deaths in women
(15% of cancer deaths)
How has incidence of breast cancer changed in recent years?
… dunno, but stopping so much hormone replacement therapy has helped
Look at this helpful picture for breast cancer development
Describe the distribution of histologic types of breast cancer
- In situ
- Invasive
- In situ: 15-30%
- Invasive: 70-85%
What are the different types of infiltrating carcinomas?
- Infiltrating “ductal” carcinoma, no special type
- Infiltrating carcinoma, special type
- Tubular
- Mucinous
- Medullary
- Lobular classic
Describe genetic changes/risk factors for breast cancer pathogenesis
- Certain growth factors
- Hormonal changes
Process:
- Genetic changes accumulate in ductal/lobular cells
- E and P act as promoters
What are the two basic types of breast cancer (in terms of inheritance)?
- Hereditary: 5-10% of all cases
- Sporadic: 90-95% of cases
What are risk factors for breast cancer?
- Age (young menarche, older first live birth)
- First degree relatives
- Breast biopsies
- Race (worse tumors in Af Am)
- HRT
- Diet/obesity/exercise (high levels of testosterone; transform into estrogen in women)
- Breast feeding
Sporadic breast cancer is due to what?
- Age of onset
- Due to accumulation of mutations that are not inherited
- No or less profound family history
- Older onset (66% occur in patients older than 50 years)
Describe hereditary breast cancer
- What % of breast cancer cases
- Genetics?
- Age of onset
- Breast cancer ~ inheritance 5-10%
- Early onset breast cancer (25-50 years)
- Mutant gene defective in DNA repair
- BRAC-1 and BRAC-2 account for half
- Hereditary breast cancer syndromes
What cancers do BRCA1 and 2 involve?
BRCA1:
- Breast
- Fallopian tube
- Ovary
BRCA2:
- Breast
- Ovary
- Pancreas
- Prostate
What cancers are associated with TP53 gene (Li Fraumeni syndrome)?
- Breast
- Brain
- Sarcoma
- Leukemia
What syndrome does the PTEN gene cause? Associated cancers?
Cowden’s syndrome
- Breast
- Ovary
- Thyroid
- Colon
Describe the histology of BRCA1 associated tumors
- IDC 3/3
- Medullary like
- Basal
- Triple negative in majority
- Tumor necrosis
- Lymphoplasmacytic infiltrate
- DCIS and LCIS are seen less frequently
What is seen here?
BRCA1 histology
Describe the histology of BRCA2 associated tumors
- IDC/pILC
- Grade 2-3/3
- DCIS and LCIS seen = as non-carriers
- Luminal
- ER+ PR+
- Rare HER 2+
What is seen here?
BRCA2 histology
Describe the histology for the genes:
- CDH1
- CHEK2
- PALB2
CDH1
- Invasive lobular carcinoma CHEK2
- Invasive lobular carcinoma PALB2
- ER, PR, HER2: all negative
- BASAL CK negative
- KI67 high
What are the two major pathways in the molecular evolution of breast cancer?
Low grade arm
- ER/PR+ HER2 –
- Basal markers negative
- Low genetic instability
- 16q loss
High grade arm
- ER/PR –
- HER2 or basal markers positive
- Genetically advanced lesions
- Loss: 8p 11q 13q 14q
- Gains: 1q 5p 8q 17q
- Amplifications: 6q22, 8q22, 11q13, 17q12, 17q22-24
Describe the molecular taxonomy of breast cancer
High throughput, microarray-based gene expression methods; to determine the molecular features of breast cancer for:
- Histological grade
- Metastatic propensity
- Response to therapy
Describe the molecular classification of breast cancer via gene profiling
- Luminal A
- Luminal B
- HER2
- Basal
- Luminal A: ER+PR+, HER2-, low KI67
- Luminal B: ER+PR+/-, HER2+/-, high KI67
- HER2: HER2+
- Basal: triple negative
Case 5)
- 50 yo female
- Mammogram 2 years ago: Normal
- Mammogram now: New calcifications, pleomorphic, branching, linear, segmental, BIRADS 5
- Stereotactic core biopsy with clip placement
Describe pathology (?)
Pathology:
- Ductal carcinoma in situ
- Nuclear grade 3/3 by SBR criteria
- Central comedo necrosis with calcifications
What is seen here?
Continuum of DCIS with ER positivity/negativity
Case 6)
- 61 yo female
- Yearly mammograms: Starting at 50 yo
- 2013 mammogram: spiculated mass 1.2 cm, BIRADS 5
- Ultrasound guided core biopsy:
- Infiltrating ductal carcinoma, no special type
- Histological grade: 2/3 by ESBR criteria
- ER+, PR+, HER2 -, KI67 22%
What should be done?
Surgery: Segmental mastectomy + SLN
What is seen here?
Infiltrating “Ductal” Carcinoma of No Special Type
What is the paradigm for targeted therapy?
- ER+: Tamoxifen, other endocrine therapies
- HER2+: Trastuzumab
What are prognostic markers (major and minor)?
Major:
- In Situ, invasive
- Metastases
- Lymph node mets
- Locally advanced
- Inflammatory Ca
Minor:
- Histological types
- Tumor grade
- Receptors
- LVI
- Proliferative rate
What are predictive markers?
- Estrogen receptor
- Progesterone receptor
- HER2
What is seen here?
Predictive markers: ER/PR positive
What is seen here?
Predictive markers: HER2 negative
What is seen here?
Predictive markers: HER2 positive
What are multi-gene tests done in evaluating breast cancer/risk?
- Oncotype Dx by Genomic Health (21 gene signature).
- Prosigna ROR by NanoString (50 gene signature).
- IHC4 (ER, PR, HER2, and Ki67).
- EndoPredict or Epclin by Sividon, (12 gene signature plus clinical).
- MammaPrint by Agendia (70 gene signature).
- Genomic Grade Index (Qiagen Marseille, 97 gene signature).
- Breast Cancer Index (HoxB13/IL17 ratio + Molecular Grade Index, bio Theranostics).
Describe Oncotype Dx RS (recurrence score)
- Developed in patients treated with tamoxifen.
- Most used test in the US.
- Classifies patients into low, intermediate or high risk at 10 yrs.
- Validated in multiple data sets and predicts recurrence in first 5 yrs.
- Low and ?intermediate risk do not benefit from chemo even if they have 1-3 nodes positive.
- Not as good a predictor of late recurrence as ROR or IHC4. Prelim data suggests it predicts late recurrence in patients with high tumor ER expression.
The 21-gene recurrence score (RS) assay predicts what?
Distant Relapse at 10 Years if 5 Years Tamoxifen
What is seen here? Stage?
Breast cancers, stage I
What is seen here? Stage?
Breast cancer, stage IV
How to improve breast cancer mortality?
- Understand genetics, biology, structure of the normal breast.
- Differentiate benign conditions from cancer.
- Recognize premalignant conditions for prevention.
- Identify contributory gene alterations to predict cancer development and identify new treatment targets.
