Breast Pathology Flashcards
Lesions of large ducts (4)
Duct ectasia
Squamous metaplasia of lactiferous ducts
Large duct papilloma
Paget disease
Lesions of intralobular stroma (2)
Fibroadenoma
Phyllodes tumor
Lesions of interlobular stroma (4)
Fat necrosis
Lipoma
Fibromatosis
Sarcoma
What gross and microscopic changes occur in the breast in younger women vs. older women?
Younger womens’ breasts are generally more fibrous which makes detecting abnormalities more difficult.
Older womens’ breast have more fat tissue and are easier to evaluate on mammography.
What is the presentation of milk line remnants?
They present as painful pre-menstrual enlargements. They are hormonally sensitive and can be found anywhere along the milk line (axilla to perineum).
What is the significance of accessory breast tissue?
Some women have extensions of the normal ductal system into the subcutaneous tissue of the chest wall or axilla.
They confer a greater risk for malignancy and can be removed via mastectomy. This does not eliminate the risk for malignancy, however.
What is the significance of congenital nipple inversion?
Not impressive. Acquired nipple inversion is much more concerning (cancer or inflammatory disease of the breast).
What are the 4 most common symptoms of breast disease?
Pain
Palpable mass
“Lumpiness” without palpable mass
Nipple discharge
What are the 3 most common palpable lesions of the breast?
Cysts, fibroadenomas and invasive carcinomas
What is acute mastitis? What may happen grossly to the breast?
What organism is most commonly implicated?
What should be done/recommended to the patient?
Inflammation of the breast within the first month of breastfeeding most often from infection. The nipple may crack or fissure.
Staph aureus
Antibiotics are given and patients are advised to continue breastfeeding.
What is the presentation of squamous metaplasia of lactiferous ducts?
What are 2 risk factors?
What is the classic morphological finding?
Painful, erythematous, subareolar mass
Inverted nipple
Smoking and vitamin A deficiency
Keratinizing squamous metaplasia of the nipple ducts
What is the presentation of duct ectasia?
What age does it occur?
What is tricky about it?
What cells are found on histology?
A palpable periareolar mass that is often accompanied by thick, white nipple secretions and occasionally skin retraction.
40-50 y/o
The irregularity of the mass mimics invasive carcinoma
Lipid-laden macrophages
What is the presentation of fat necrosis?
What is a common history?
A painless mass, skin thickening or retraction, or mammographic densities or calcifications.
Trauma or prior surgery.
What is the presentation of lymphocytic mastopathy?
It is most common in women with which 2 underlying conditions?
Single or multiple palpable masses or radiographic densities.
T1DM and autoimmune thyroid disease.
What are the 2 mechanisms that granulomatous inflammation can manifest in the breast?
Either from systemic granulomatous diseases (granulomatosis with polyangiitis, sarcoidosis, Tb, etc.) or disorders localized to the breast.
What are the 3 principal morphologic changes found in non-proliferative breast changes (fibrocystic changes)?
Cystic change, often with apocrine metaplasia
Fibrosis (when cysts rupture, fibrosis may ensue)
Adenosis (increase in acini per lobule - normal in pregnancy)
What is a lactational adenoma?
A palpable mass found in pregnant or lactating women. They are non-neoplastic and occur due to exaggerated local response to hormones.
What are the 4 proliferative breast lesions without atypia?
Epithelial hyperplasia - often incidental
Sclerosing adenosis - compressed and distorted acini which may present as a mass, density or calcificatin
Complex sclerosing lesions (radial scar) - irregular shape and can mimic breast carcinoma grossly and histologically
Papillomas - they grow in a dilated nipple duct and often produce a bloody nipple discharge
What is the microscopic appearance of gynecomastia? (2)
What are 2 associated risk factors?
Increased dense collangenous CT
Epithelial hyperplasia of the duct lining with tapering micropapillae
Liver disease
Drugs/alcohol
How is DCIS vs. LCIS detected?
DCIS - mammography most often (calcification or mass)
LCIS - incidental
What defines the morphological appearance of comedo DCIS? (2)
What is the appearance on mammography?
Tumor cells with pleomorphic, high-grade nuclei
Areas of central necrosis
Clustered or linear and branching areas of calcification
What are the 2 variants of non-comedo DCIS?
Cribiform DCIS - rounded (cookie-cutter) spaces within the ducts or a solid DCIS pattern
Micropapillary DCIS - bulbous protrusions without a fibrovascular core
What loss of function mutation is found in LCIS?
E-cadherin (CDH1 gene) - leads to discohesion of cells
Which CIS is more commonly bilateral?
LCIS (20-40% are BL)
What are the 3 risk factors for progression of DCIS?
Nuclear grade and necrosis
Extent of disease
Positive surgical margins
LCIS is a risk factor for…
Invasive lobular carcinoma or either breast
What receptors are expressed in LCIS?
ER+ and PR+
*no over-expression of HER2
What is the presentation of Paget disease of the nipple?
What is the significance?
What are the genetics?
Unilateral erythematous eruption with a scaly crust. Pruritis is common and can be mistaken for eczema.
A palpable mass is found on 50-60% of patients and almost all of them have underlying invasive carcinoma.
ER- HER2+
What is the most common genetic profile found in breast cancer? Second most common? Least common?
Most common: ER+ HER2-
Second most: HER2+
Least common: ER- HER2-
What 2 genes are associated with 80-90% of “single gene” familial breast cancers and 3% of all breast cancers?
BRCA1 and BRCA2
What are the 4 major risk factors for sporadic breast cancer?
Age at menarche and menopause
Reproductive history
Breastfeeding
Exogenous estrogen exposure
BRCA1
% of single gene hereditary breast cancers
Other cancer associations
What is the differentiation?
Other mutations?
52% (2% of all breast cancers)
Ovarian, pancreas, fallopian tube
Poorly differentiated and triple negative (“basal-like”)
TP53 mutations
BRCA2
% of single gene hereditary breast cancers
Other cancer associations
What is a unique association?
32% (1% of all breast cancers)
Ovarian, male breast cancer, pancreas, stomach, melanoma, Gb, bile duct, pharynx
May cause a rare form of Fanconi anemia
TP53 (Li-Fraumeni)
% of single gene hereditary breast cancers
Other cancer associations
What other genetic changes are common?
3% (<1% of all breast cancers)
Sarcoma, leukemia, brain tumors, adrenal tumors
ER-, HER2-
What is the pathway of development of breast cancer with a germline BRCA2 mutation?
- BRCA2 mutation
- Flat epithelial atypia
- PIK3CA mutation
- Atypical ductal hyperplasia
- DCIS
- ER+, HER2- “luminal” cancer
What is the pathway of development of breast cancer with a germline BRCA1 mutation?
- BRCA1 mutation
- TP53 mutation
- DCIS
- ER-, HER2- “basal-like” cancer
What is the pathway of development of breast cancer with a germline TP53 mutation?
- TP53 mutation
- HER2 amplification
- Atypical apocrine adenosis
- DCIS
- HER2+ “HER2 enriched”
Low proliferation: ER+, HER2- (40-55%)
Level of differentiation
Typical patient groups (2)
Metastatic pattern
Relapse pattern
Complete response to chemo?
Level of differentiation: well or moderately differentiation
Typical patient groups: older women, men (cancers detected by mammography)
Metastatic pattern: bone, viscera and brain
Relapse pattern: late, >10 years, long-term survival
possible with metastases
Complete response to chemo? <10% (poor)
High proliferation: ER+, HER2- (10%)
Level of differentiation
Typical patient groups
Metastatic pattern
Relapse pattern
Complete response to chemo?
Level of differentiation: poorly differentiated
Typical patient groups: BRCA2 carriers
Metastatic pattern: bone, viscera and brain
Relapse pattern: intermediate
Complete response to chemo? 10% (poor)
HER2+ (20%)
Histological cell type
Typical patient groups (3)
Metastatic pattern
Relapse pattern
Histological cell type: apocrine
Typical patient groups: young women, non-white women, TP53 carriers
Metastatic pattern: bone, viscera and brain
Relapse pattern: short, survival with metastases is rare
ER-, HER- (15%)
Typical patient groups (4)
Metastatic pattern
Relapse pattern
Complete response to chemo?
Typical patient groups: young women, BRCA1 carriers, AA and Hispanics
Metastatic pattern: bone, viscera and brain
Relapse pattern: short, survival with metastases is rare
Complete response to chemo? 30%
Ki67+ on protein stain
High proliferative ER+ HER2-
ER+ on protein stain
Low proliferation ER+ HER2-
The outcome for women with breast cancer depends on… (2)
Biologic features of the carcinoma (molecular or histologic type)
Extent of spread at the time of diagnosis (stage)
In the absence of distance metastases, what is the most important prognostic factor of breast cancer?
Axillary LN involvement
Therapy for HER2+ cancers:
Herceptin - MoAb that binds and inhibits HER2
Why might a “basal-like” cancer present as a palpable mass in between mammograms?
Due to its high proliferation and rapid growth
What is the pattern of metastasis of a lobular carcinoma? (4)
Perineum and retroperineum
Leptomeninges
GI tract
Ovaries (Krukenburg tumor) and uterus
What is the most common type of breast cancer to present as an occult primary?
Lobular carcinoma
What protein is defective in lobular carcinoma?
What is the morphologic appearance?
E-cadherin
“Indian file”/linear arrays
What is the appearance of inflammatory carcinoma (AKA as..)?
What population is at an increased risk?
What is the prognosis?
Peau d’orange due to blockage of lymphatics by tumor
Higher incidence in AA
Very poor prognosis: 3 year survival is 3-10%
What is the pathogenesis of gynecomastia?
What is the appearance of the enlargement?
Estrogen/androgen imbalance leading to stimulation of breast tissue
“Button-like” subareolar enlargement (more common in puberty or very old)
Phyllodes tumor presents as…
What age does it present?
What is the most common acquired chromosomal changes?
Classic histological appearance
A palpable breast mass
Older than fibroadenoma by 10-20 years
Gain in 1q most common
“Leaf-like”
Fibroadenoma is the…
Age of onset
Presentation
Most common benign tumor of the breast
20-30 y/o
Palpable mass(es) that can often be multiple and bilateral
What is a epigenetic change occurring in medullary carcinoma?
Prognosis?
Hypermethylation of BRCA1 (downregulation)
Good prognosis
Morphology of mucinous (colloid) carcinoma
Soft or rubbery and appearance of gray-blue gelatin.
Small islands of cells found in lakes of mucin.
