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Pathology Term 5 > Week 4 - Breast Cancer > Flashcards

Week 4 - Breast Cancer Flashcards

1
Q

Describe breast anatomy.

A

• Modified sweat glands. Lobes and lobules of gland.
- Lobes and lobules join to form lactiferous ducts.
- Ducts join to form lactiferous sinuses (just below nipple).
- Sinuses open onto nipple - usually 6-10.
- Male breasts just have terminal ducts. Female breasts have glands due to effect of hormones.
• In connective tissue stroma. Glands → ducts*
• Smaller ducts join to form lactiferous ducts.
• Ducts enlarge beneath nipple to form a lactiferous sinus.
• Then individually open in nipple (6-10).

Microscopy:
• Lobule has loose areola stroma with glands and ducts inside.
Outer dense fibrous stroma.

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2
Q

Identify age-related changes in the breast.

A
  • Pre-pubertal - mostly fibrous tissue, ducts > glands (more ducts, less glands). FIBROUS.
  • Reproductive phase - plenty of glands particularly during lactation. FIBRO-FATTY.
  • Menopause - atrophy leaving behind fat tissue. FAT.
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3
Q

Outline disorders of the breast.

A

Congenital:
• Aplasia (turners), Accessory/ectopic breasts.

Inflammatory (commonest clinically):
• Mastitis - acute lactational*/chronic mastitis.
• Trauma - traumatic fat necrosis.
• Duct ectasia, abscess, galactocele.

Proliferative conditions:
• Fibrocystic disease/change - common.
• Cysts, adenosis, metaplasia and mixed.

Neoplastic:
• Benign - fibroadenoma, duct papilloma.
• Malignant - carcinoma and DCIS several types.

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4
Q

Identify the causes and diagnosis/features of breast lumps.

A
  • Fibrocystic changes - hormone induced nodularity (40%).
  • No disease (30%).
  • Miscellaneous benign (13%).
  • Cancer (10%).
  • Fibroadenoma (7%).

Diagnosis/features:
• Fibroadenoma - mobile lump, well demarcated.
• Fibrocystic disease - irregular/ill-defined lumps, cyclical pain.
• Carcinoma - firm lump, irregular, hard, lymph nodes, weight loss. Familial (younger age) or sporadic (later age).
• Clear/pus discharge - inflammation (duct ectasia).
• Bloody discharge - benign duct papilloma. Uncommon in cancer.

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5
Q

Outline acute and chronic mastitis.

A

• Infection of the breast.
• Non Lactational (central, periductal, rare).
• Lactational (periphery, common).
- First few weeks after delivery. Occurs first few weeks after delivery and usually due to crack in the nipple - allows bacteria to enter causing pyogenic inflammation, swelling, erythema, pus.
- Crack in the nipple - entry point.
- Staph. aureus, Strep. pyogenes.
- Localised inflammation, swelling erythema and pus.
- Microscopy - acute inflammatory cells.

Chronic mastitis (rare):
• Granulomatous (TB, silicone etc.)
- TB, silicone implants, foreign bodies.
• Traumatic fat necrosis - chronic granuloma, radial scar - dd Ca.
- Chronic granulomatous scarring due to trauma.
• Diabetic mastopathy - DM1 lymphocytic
- Chronic lymphocytic inflammation in diabetics.

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6
Q

Outline breast rash.

A

Intertrigo - rash between skin folds. Moisture, heat, friction, sweat, lack of air circulation → fungus, bacteria, hypersensitivity etc.

  • Atopic dermatitis (eczema)
  • Contact dermatitis
  • Sub mammary Candidiasis
  • Tinea - dermatophytes
  • Inflammatory cancer
  • Duct ectasia
  • Paget’s disease
  • Mastitis
  • Breast dermatitis
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7
Q

Outline duct ectasia.

A

• Chronic inflammatory condition.
• Later age >50y, multiparous.
- Usually in later age multiparous women due to inspissation of breast secretions.
- Drying up of the milk within the ducts leads to chronic inflammation around the ducts.
• Inspissation of breast secretions (drying) within ducts → duct obstruction/destruction, dilation → inflammation, fibrosis with fat globules and foamy macrophages in lumen.
- Fat globules due to obstructed milk - similar to bronchiectasis in the lung (plenty of pus).
• Periareolar mass with white, cheesy nipple discharge.
• Recurrent abscess/fistula.
- Prone to recurrent abscess and fistula formation.
• Scarring with nipple inversion may mimic carcinoma.
- When it is scarred → mimics carcinoma.
• Microscopy - dilated ducts with plenty of chronic inflammatory cells surrounding.

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8
Q

Outline fat necrosis.

A

• Uncommon, chronic scarring in breast.
• Usually following trauma/biopsy/surgical procedures leading to fat necrosis granulomatous inflammation → scarring and calcification.
- Leads to granulomatous inflammation first and then scarring/calcification later.
• Mimics carcinoma.
- Importance - also mimics carcinoma.
• Microscopy - dense deposits of calcification with fibrosis

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9
Q

Outline fibrocystic disease/change.

A

• Commonest (40%) cause of lumps in 20-40y. Irregular area of induration/lumps.
- Commonest cause of lumps during reproductive age. Usually regresses following menopause. Multiple lumps is a characteristic feature.
• Cyclic pain/discomfort (hormone response).
- Also causes cyclic pain/discomfort as it is hormone responsive.
• Pathology - hormone (oestrogen) induced hyperplasia of glands and stroma*
- Similar to MNG, nodular hyperplasia of prostate.

2 major types:
• Non-proliferative - cysts and fibrosis*
- When only cystic dilation of gland and fibrosis.
- Non-proliferative has less chance of malignant transformation compared to proliferative.

• Proliferative - epithelial proliferation*

  • When there is epithelial proliferation as well.
  • Plenty of epithelial cells dividing and filling up the lumen → may progress to ductal carcinoma in situ and carcinoma because epithelial cells are the precursors of malignancy.

• Gross - grey white scar tissue with cysts.
- Fibrosis with multiple cysts.
• Micro - fibrosis, cysts, hyperplastic glands.
- Fibrosis, dilation of glands - fibrocystic change.
• May progress to cancer.
• Hyperplasia → dysplasia → DCIS → carcinoma.

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10
Q

What is sclerosing adenosis and a blue dome cyst?

A

Sclerosing adenosis
Fibrocystic change - proliferative.
• Sometimes the proliferation of the epithelium can form multiple glandular structures in a fibrous stroma known as sclerosing adenosis.
• Looks like cancer on mammogram and microscopy.

Blue dome cyst
Fibrocystic change - when single large cyst - blue.
• One of the cysts only becomes very huge - blue dome cyst - type of fibrocystic disease.

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11
Q

Outline breast neoplasms.

A

Benign (round, smooth, soft, mobile):
• Fibroadenoma (stromal)
• Duct papilloma (epithelial)
• Others - rare (lipoma, fibroma etc.)

Malignant (irregular, rough, hard, fixed):
• Ductal carcinoma
• Lobular carcinoma
• Others - rare (angiosarcoma, lymphoma, melanoma etc.)

Fibrocystic disease not a neoplasm - hormone induced hyperplasia.

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12
Q

Outline fibroadenoma.

A

Types:
1. Simple fibroadenoma - solitary, few <5/breast, multiple (>5/breast).
• <5cm.
• Can be single, few or multiple.
• Small, well demarcated, greyish capsulated benign tumours.

  1. Giant fibroadenoma (>5cm) - Juvenile (<20 years, benign) & Phyllodes Tumour: Adults (benign to malignant)
    • >5cm
    • When occur in young age - benign
    • Adults - can be benign to malignant.
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13
Q

Outline simple fibroadenoma.

A

Aetiology:
• Idiopathic, benign tumour of stroma (atrophic glands).
- Tumours of stroma with atrophic glands.

Clinical features:
• Well demarcated, mobile, round/nodular (breast mouse).
- Benign, well demarcated, <5cm, smooth surface.
- AKA breast mouse.

Morphology:
• Gross - capsulated, firm grey, nodular tumour.
- No areas of haemorrhage or necrosis.
• Microscopy - compressed slit like flat glands in loose fibrous stroma.
- Compressed glandular structures in loose fibrous stroma. Covered by a capsule.

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14
Q

Outline Giant fibroadenoma/Phyllodes.

A

• Larger tumours, >5cm, on cut section appears like folded leaves (phyllodes - leafy folds), branches are branching glands. Difference between simple and giant fibroadenoma is that the giant fibroadenoma is more cellular.

Clinical features:
• Unilateral macromastia, recurrent, metastasis 15%.
- Unilateral, huge enlargement of breast.
- Can recur following removal.
- Metastasis usually in older age.

Pathology:
• Benign (juvenile) to malignant (adult) tumour of gland and stroma.
- Tumour of both gland and stroma. Simple is tumour of only stroma.

Morphology:
• Gross - large 10-15cm, with “leaf like” clefts and slits. Juvenile in young (benign) and Phyllodes tumour in adult (benign to malignant).
• Microscopy - both stroma and glands are hypercellular and pleomorphic. Glands show epithelial hyperplasia and branching (compressed in fibroadenoma).
- Glands are hypercellular rather than atrophic.
- Cells may show irregularity - atypia.
- Stroma is more cellular.

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15
Q

Outline intraductal papilloma.

A

• Clinical - middle age, bloody discharge, sub areolar lump.
- Below nipple, presents with bloody discharge.

• Gross - solitary, intra-ductal papillary proliferation.
- Intra-ductal papillary proliferation of ductal epithelium.

• Micro/path - benign papillary proliferation of lactiferous epithelium.
- Papillary structures with a stalk.

• Prognosis - recurrent, but no risk of malignancy (rare).
- Rarely can become malignant.

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16
Q

Fibroadenoma summary.

A 
• Small (<5cm) discrete mobile.
- Can be single or multiple.
• Stromal neoplasm with compressed glands.
• No malignant potential.
• Increase in pregnancy.
- Due to hormones.
• Regress/calcify in menopause.
• Microscopy - compressed glands, fibrous stroma.
17
Q

Differentiate between fibroadenoma and Giant fibroadenoma.

A 
Fibroadenoma - compressed glands, fibrous stroma.
Gross:
• Small.
• Round.
• Mobile.
Microscopy:
• Flat.
• Atrophic glands.
• Fibrous stroma.
Giant Fibroadenoma - branching glands, hypercellular glands and stroma.
Gross:
• Large.
• Round.
• Non-mobile.
Microscopy:
• Branching glands.
• Hypercellular glands and stroma.
18
Q

Differentiate between benign and malignant breast neoplasms.

A 
Benign:
• Young <35y.
• Multiple (fibrocystic disease).
• Painful.
• Soft, cystic, rubbery.
• Regular, nodular.
• Mobile.
• No lymph nodes.
• No weight loss.
Malignant:
• Old >35y.
• Single.
• Painless.
• Hard gritty.
• Irregular.
• Fixed.
• Lymph nodes.
• Weight loss.
19
Q

Outline malignant breast disorders.

A
  • Second common female cancer (lung).
  • 1 in 9 women before the age of 85 - AU (USA 1 in 8, UK 1 in 10).
  • Commonest female cancer death <55y.
  • Rare <30y, <50y familial, >50y sporadic.
  • Much less incidence in Asia, Japan.
  • Significant increasing incidence - ?lifestyle, obesity, alcohol, diet, smoking, increased oestrogen, decreased progesterone - risk factors.
  • OCT - oestrogen + progesterone therapy - known risk factor.
  • Majority - ductal carcinoma.
  • Survival is improving with therapy (96% 5y - 2006).
  • Not all breast lumps cancer - only 10%.
20
Q

Identify the risk factors for breast cancer.

A
  • Age (>30y).
  • Family history.
  • Early menarche.
  • Late menopause.
  • Nulliparity.
  • Late first pregnancy.
  • Exogenous oestrogens.
  • Oral contraceptives.
  • Obesity.
  • High-fat diet.
  • Alcohol consumption.
  • Cigarette smoking.
21
Q

Describe the aetiology of breast cancer.

A
  • Hormone, Environment & Genetics - classify into these 3 categories.
  • > 80% acquired/sporadic - only 12% familial (BRCA 1/2, RAS, MYC, HER2/NEU)
  • Still don’t know exact aetiology.
  1. Cause of breast cancer is still unknown.
  2. Aetiopathogenesis - increased oestrogens and decreased progesterone and oncogenes.
  3. Hormone receptors and respond to hormone manipulation.
  4. No good evidence for viral aetiology
22
Q

Explain the pathogenesis of breast cancer.

A
  • Normal - luminal columnar cells in breast duct, flattened myoepithelial cells on outside (contractile cells). Basement membrane and stroma on outside.
  • In response to aetiologic factors → increased proliferation of luminal cells.
  • Initially just proliferation, followed by dysplasia when develop mutations.
  • When dysplastic cells fill whole duct but don’t break myoepithelial layer or BM - known as carcinoma in situ (cancer cells within ducts).
  • When it ruptures and spreads out → invasive carcinoma.
23
Q

Identify the types of breast cancer.

A

• Commonest clinically is invasive duct carcinoma (infiltrating duct carcinoma/duct carcinoma) followed by lobular carcinoma. All other carcinomas are rare (e.g. medullary, mucinous).
• Invasive duct carcinomas are classified according to the genetic composition into 4 major types.
- Luminal A - cells are very differentiated. ER and PR +ve (normal life), HER2 -ve. Commonest type (60%). Better prognosis.
- Luminal B - ER, PR and HER2 +ve. (2 good and 1 bad) - 35%.
- HER pos - ER and PR -ve, HER2 +ve.
- Basal like - all negative (AKA triple negative) - high grade, familial. Poor prognosis.
- Unclassified.

  • ER and PR +ve = low grade.
  • ER and PR -ve = high grade.
24
Q

Outline carcinoma in situ (DCIS/LCIS).

A
  • AKA ductal carcinoma in situ or lobular carcinoma in situ - precancerous stage of the 2 common cancers.
  • Cancer cells but within duct.
  1. Precancer stage → progress to carcinoma.
  2. Hyperplasia → dysplasia → filling duct: DCIS low - high grade.
    • Hyperplasia to dysplasia and dysplastic cells filling ducts.
    • When fills duct → known as DCIS. When fills lobules → LCIS.
  3. Intact myoepithelial cells.
    • Indicate intact basement membrane.
    • Special stain for myoepithelial cells - see proliferation within duct but cells aren’t coming out.
  4. May spread throughout ductal system to produce extensive lesions.
  5. 2 types - ductal (DCIS) and lobular (LCIS).
  6. Different morphology
    • Cribriform - multiple cavity.
    - Multiple tubule or gland like structures within
    • Comedo - central necrosis (high grade).
    - High grade DCIS.
    • Paget’s disease - DCIS to skin.
    - DCIS can spread to skin → eczematous patches - Paget’s disease.

When spread beyond duct → cancer.
• When dysplastic cells spread beyond BM.

25
Q

Outline invasive duct carcinoma.

A

Infiltrating/invasive type - commonest type. Also known as Schirrhous (sclerosing/scarring), classic/typical type/NOS/NST - common type of breast cancer.

• Painless nodule/lump - felt on palpation only.
• Irregular, hard, gritty/stony.
• Upper outer quadrant* (50%).
• Central 20%
• Skin tethering/puckering.
- Tethering - fibrous tissue pulls the skin into the tumour. Because the tumour is in the tubules → gets nipple retracted inside.
• Nipple retraction, oedema.
• Painless lymphadenopathy.

Crab - radiating fibrous tissue pulling the tissues towards the cancer producing shrinkage.

NOS (not otherwise specified) or classic or typical or Schirrhous carcinoma. NST (no special type)

Cancer doesn’t show any haemorrhage or necrosis like seen in other cancers. Just dense scarring. The scar tissue gets attached to the muscles, bones and the surrounding tissue and that is why the malignant tumours of the breast are fixed/immobile.

26
Q

Outline mammograms.

A

• Mammogram density: (white areas) more white areas more risk of malignancy. >75% density = 4 fold increased risk.

  • Dusty calcification.
  • Radial scar.

Scar tissue with radiating bands (radial scar). Dusty calcification.

  • Low radiation x-ray of the breast (0.4mSv compared to 3-8mSv X-ray).
  • Light compression by plates to stabilise and spread its interior structures.
  • Detect fibrosis and calcifications <100ųm.
  • Reveals a lump 1-2y before palpable.
  • > 40y should have yearly* mammogram.
  • More for those at risk or symptoms.
  • Younger age - more fibrous tissue (fine thin white fibres)
  • Adult age - more diffuse white areas. Mammogram density - more white areas → more risk of developing malignancy.
  • Features suggestive of malignancy - dusty calcifications and radial scar.
27
Q

Outline lobular carcinoma.

A

• Multifocal, bilateral, familial (younger age).
- Tumour arises from glandular area.

• Small cells, uniform clusters.

  • Linear clusters separated by the dense fibrous tissue.
  • No ducts. Clusters and linear arrangement of cells.
  • No tubule formation.
  • ‘Indian file’ (single cell lines) between collagen bundles.
  • Pre cancer stage: LCIS lobular Ca-in-situ.
  • ER/PR neg, HER2/neu pos.
  • E-cadherin - ve (unlike IDC).
28
Q

Outline the rare types of breast cancer.

A

Medullary carcinoma:
• High grade, better prognosis.
• Expansile, no skin tethering.
- Expansile tumour unlike classic breast cancer.
• Plenty lymphocytes within tumour.
- Lymphocytes represent immune response → better prognosis.

Inflammatory carcinoma:
• Clinically erythematous breast.
• Mistaken for mastitis.
• Dermal lymphatic obstruction.
• No significant inflammation.

Others:
• Mucinous, papillary, tubular, others. Male Breast Ca ~ 1% only Duct Ca. (no lobular carcinoma).
- Males rare - always ductal carcinoma - don’t have lobules.

29
Q

Outline Paget’s disease.

A

• Spread of breast cancer cells to skin (areola) and resulting in eczematous reaction.

  • Spreading of cancer cells along the ducts into the peri-areolar skin causing eczematous patch.
  • Microscopy - clusters of malignant cells in the superficial epidermis.
30
Q

Differentiate between Paget’s disease and eczema.

A 
Paget's disease:
• Unilateral.
• Later age/menopause.
• Not itchy.
• No vesicles.
• Nipple destruction/retraction.
• Underlying lump likely.
Eczema:
• Bilateral.
• Common at lactation.
• Itchy.
• Vesicles.
• Nipple normal.
• No lumps.
31
Q

Explain the pathogenesis of Peu-de Orange in high grade carcinoma.

A
  • Tumour emboli within lymphatic vessels → obstruction → lymphedema (also radiation induced lymphangitis can cause peu-de orange).
  • Orange peel appearance of skin. Usually due to lymphedema. The malignant cells blocking the lymphatic vessels (similar to elephantitis).
  • Usually exacerbated by radiation therapy as radiation kills malignant cells causes lymphangitis and more obstruction.
32
Q

Outline the spread and prognosis of breast cancer.

A

Spread:
• Direct - also occurs to chest wall and muscles/bones.
• Lymphatic - lymphatics to surrounding lymph nodes - axillary most common.
• Haematogenous - spread to CNS, lungs, liver, bones.

Prognostic factors:
• Type of carcinoma (classic*)
• Grade and stage.
• ER and PR +ve - good.
• HER2 - bad.

Other Breast Cancers:
• Sarcoma (fibro, angio, lipo etc).
• Lymphoma.

33
Q

Outline gynaecomastia.

A

• Breast enlargement in men.
• Oestrogen excess - Klinefelter’s. Hyperthyroidism, pituitary and adrenal tumors, testicular failure, hormonal and drugs.
• Liver failure, cirrhosis, lung cancer, testicular cancer.
• Diethylstilbestrol therapy for prostatic carcinoma.
• Drugs (spironolactone, H2 antagonists (e.g. cimetidine used in PUD), Neuroactive agents (e.g. anti-depressants).
- All of the above cause enlargement of the breasts.
• Microscopy - only duct and stromal hyperplasia (no acini or lobules).
- Only ducts - hence why male breast cancers are ductal carcinomas.

34
Q

Identify the investigations for a breast lump.

A 
• History first
• Mammography
• Ultrasound
• Fine needle aspiration biopsy
• Core/needle biopsy
• Excision biopsy
• Special molecular tests on Biopsy
- Immunoperioxidase - HER2, ER &amp; PR
- Molecular techniques - Gene detection (BRCA)

*Triple assessment → clinical (assessment), imaging and biopsy

35
Q

Outline breast cytology - FNAC/FNAB.

A

• Fine Needle Aspiration Cytology/Biopsy.
- Usually ultrasound guided to locate mass → needle is then put into mass and tissue is aspirated.
• Normal cells - cohesive (few regular, uniform cells).
- Very cohesive - adherent to each other.
• Inflammation - mixture.
- Mixture of inflammatory cells.
• Neoplasm - monomorphic.
- Increased cells and monomorphic (one type of cell).
• Malignant - plenty, haemorrhagic, pleomorphic, necrotic.
- Benign - more uniform in shape.
- Malignant - plenty of cells with haemorrhage, pleomorphism and necrotic cells.

36
Q

Outline HER2 (Human Epidermal growth factor Receptor 2).

A

• The HER2 proto-oncogene is over expressed in 25-30% of breast cancers (normally 2 copies).
- 2 copies in a normal person. Over-expression → cancer.
• HER2 positive breast cancers grow quickly and spread more than others (poor prognosis).
• HER2 +ve patients benefit from the anti-HER2 antibody therapy.
• Trastuzumab (Herceptin) is the first monoclonal antibody that targets the extra cellular domain of the HER2 protein and inhibits growth of breast cancer cells that over express this protein.

37
Q

Differentiate between BRCA1 and BRCA2.

A 
BRCA1:
• 52% of genetic type (2% overall).
• Young age.
• Risk of ca - 40-90%.
• High grade, necrosis, inflam (Medullary).
• Triple -ve (ER, PR, HER2).
• F/H of ovarian, prostate, pancreas ca.
• Chromosome 17q.
BRCA2:
• 32% of genetic type (1% overall).
• Not specific.
• Risk of ca - 30-90%.
• Low grafe, NOS type. Scarring (Schirrous).
• ER +ve.
• F/H of male breast ca (ovary, prostate also).
• Chromosome 13q.

BRCAx (BRCA negative) are sporadic, ER and HER +ve, better prognosis.

Pathology Term 5 (6 decks)

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