Breast Pathology Flashcards by Zach Visinoni

Lesions of large ducts (4)

Duct ectasia

Squamous metaplasia of lactiferous ducts

Large duct papilloma

Paget disease

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Lesions of intralobular stroma (2)

Fibroadenoma

Phyllodes tumor

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Lesions of interlobular stroma (4)

Fat necrosis

Lipoma

Fibromatosis

Sarcoma

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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.

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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).

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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.

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What is the significance of congenital nipple inversion?

Not impressive. Acquired nipple inversion is much more concerning (cancer or inflammatory disease of the breast).

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What are the 4 most common symptoms of breast disease?

Pain

Palpable mass

“Lumpiness” without palpable mass

Nipple discharge

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What are the 3 most common palpable lesions of the breast?

Cysts, fibroadenomas and invasive carcinomas

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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.

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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

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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

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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.

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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.

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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.

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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)

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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.

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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

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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

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How is DCIS vs. LCIS detected?

DCIS - mammography most often (calcification or mass)

LCIS - incidental

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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

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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

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What loss of function mutation is found in LCIS?

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E-cadherin (CDH1 gene) - leads to discohesion of cells

Which CIS is more commonly bilateral?

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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?

1. BRCA2 mutation 2. Flat epithelial atypia 3. PIK3CA mutation 4. Atypical ductal hyperplasia 5. DCIS 6. ER+, HER2- "luminal" cancer

What is the pathway of development of breast cancer with a germline BRCA1 mutation?

1. BRCA1 mutation 2. TP53 mutation 3. DCIS 4. ER-, HER2- "basal-like" cancer

What is the pathway of development of breast cancer with a germline TP53 mutation?

1. TP53 mutation 2. HER2 amplification 3. Atypical apocrine adenosis 4. DCIS 5. 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.

Breast Pathology Flashcards

(56 cards)