3s: Breast Pathology Flashcards

1
Q

What is the triple test for breast conditions

C1-5 what is the gold-standard

structure of breast

A
  • Clinical examination
  • imaging = sonogrpahy, mammography, MRI (MRI only for small lesions missed by previous two)
  • pathology

Cytopathology (FNA) = cells spread across slide and stains

  • C1 = inadequate sample
  • C2 = benign
  • C3 = atypia
  • C4 = suspicious of malignancy
  • C5 = malignant

Histopathology (Core biopsy, GOLD-STANDARD) = intact tissue removed, normal is ductal-lobular system lined by inner glandular epithelium

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2
Q

Terminal duct lobular unit (TLDU)

A
  • Stained purple is the breast’s glandular tissue
  • Pink area around the glands is the stroma
  • Large pink circle in the middle of the top left image is the duct with the acini around the duct
  • This unit is called the terminal duct lobular unit (TDLU)
  • Blue arrows are pointing towards myoepithelial cells (this helps to pump milk)
  • Epithelial (luminal) cells are on the inside of myoepithelial cells
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3
Q

give 3 inflammatory breast diseases

A

Duct ectasia

Acute mastitis

Fat necrosis

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4
Q

Duct ectasia = inflammation and dilatation of large breast ducts, benign

A
  • Aetiology unclear = multiparous, 40-60 yo women, smoking (BIGGEST RF)
  • nipple discharge = thick, white nipple secretions
  • breast pain, breast mass, nipple retraction
  • can lead to mastitis, abscess, fistula

Cytology = proteinaceous material and neutrophils ONLY

Histology

  • duct distension with proteinaceous material in it
  • foamy macrophages
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5
Q

Acute mastitis = acute inflammation in breast

A
  • often in lactating women due to cracked skin and milk stasis
  • may complicate duct ecstasia
  • organism = staphylococci (lactational)
  • non-lactational = keratinising squamous metaplasia
  • painful (tender), red breast
  • mx = drainage and abx
  • cytology = neutrophils
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6
Q

Fat necrosis = inflammatory reaction to damaged adipose tissue

A
  • causes = trauma, surgery, radiotherapy
  • breast mass
  • cytology = fat cells surrounded by macrophages
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7
Q

Give 5 benign breast conditions

A
  • Fibrocystic disease = group of alterations which reflect normal, albeit exaggerated, responses to hormonal influences
  • Fibroadenoma = benign fibroepithelial neoplasm of breast
  • Phyllodes (leaf-like) tumour = a group of potentially aggressive fibroepithelial neoplasms of the breast
  • Intraductal papilloma = a benign papillary tumour arising within the duct system of the breast
  • Radial scar = benign sclerosing lesion characterised by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue (mimics breast cancer on radiology
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8
Q

Fibrocystic disease – group of alterations which reflect normal, albeit exaggerated, responses to hormonal influences (e.g. menstrual cycle)

A
  • Very common
  • Presentation: breast lumps
  • No increased risk for subsequent breast carcinoma
  • Histology → ducts dilated; ducts calcified (seen on mammogram)
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9
Q

Fibroadenoma ‘breast mouse’ – benign fibroepithelial neoplasm of breast

A
  • Common
  • Presentation: well circumscribed mobile breast lump [young women; 20-30yo]
  • Treatment: ‘shell out’
  • Histologyglandular and stromal cells
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10
Q

Phyllodes (‘leaf-like’) tumour – a group of potentially aggressive fibroepithelial neoplasms of the breast

A
  • UNCOMMON
  • Presentation: enlarging mass in women >50 years
  • Some may arise within pre-existing fibroadenomas
  • Vast MAJORITY are BENIGN (but a small proportion can behave aggressively (malignant phyllodes))
  • Histology → overlapping cell layers, cellularity
    • Level of malignancy determined on cellularity of the stroma
    • High cellularity + stromal overgrowth → malignant
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11
Q

Intraductal papilloma – a benign papillary tumour arising within the duct system of the breast

A

Arises within the:

  • Small terminal ductules (peripheral papilloma)
  • Large lactiferous ductules (central papilloma)

COMMON (mainly in 40-60 years)

Central papillomas present with bloody nipple discharge

Peripheral papillomas may remain clinically silent

Treatment: excision of duct

Cytology = clusters of cells, potential increased risk with multiple papillomas of carcinoma

Histology = dilated ducts; polypoid mass in the middle

  • Fibrovascular core (which nourished the polyp)
  • Blood vessels within the stroma
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11
Q

Intraductal papilloma – a benign papillary tumour arising within the duct system of the breast

A

Arises within the:

  • Small terminal ductules (peripheral papilloma)
  • Large lactiferous ductules (central papilloma)

COMMON (mainly in 40-60 years)

Central papillomas present with bloody nipple discharge

Peripheral papillomas may remain clinically silent

Treatment: excision of duct

Cytology = clusters of cells, potential increased risk with multiple papillomas of carcinoma

Histology = dilated ducts; polypoid mass in the middle

  • Fibrovascular core (which nourished the polyp)
  • Blood vessels within the stroma
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12
Q

Radial scar – benign sclerosing lesion characterised by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue (mimics breast cancer on radiology)

A
  • Range in size from microscopic to large / clinically apparent
  • Lesions >1 cm = complex sclerosing lesions
  • Thought to be due to exuberant reparative phenomenon in response to areas of tissue damage in the breast
  • Presentation: stellate masses on screening mammograms (may closely resemble carcinoma)
  • Excision is curative
  • Histology = two distinct areas:
    • Central stellate area
    • Peripheral proliferation of ducts and acini
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13
Q

what are proliferative breast diseases?

A

a diverse group of microscopic intraductal proliferative lesions of the breast associated with an increased risk of subsequent development of invasive breast carcinoma → produce no symptoms (found on biopsy)

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14
Q

Give 3 examples of proliferative breast diseases

A

(1) Usual epithelial hyperplasia [LEFT] – not a true pre-malignant change

  • Marker of slightly increased risk of breast cancer
  • The lumens are quite irregular (but this is a benign feature)
  • glandular tissue and epithelial cell growth forming fronds

(2) Flat epithelial atypia/atypical ductal carcinoma [MIDDLE] – the first likely low-grade malignant change

  • FEA may represent the earliest morphological precursor to low grade ductal carcinoma in situ
  • 4 x increased risk of developing cancer
  • There are multiple layers of epithelial cells and the lumens are becoming more regular

(3) In situ lobular neoplasia [RIGHT]

  • Associated with an increased risk of invasive breast carcinoma
  • It occurs within the acinar unit of the breast
  • You get a very solid proliferation of cells within the acinus
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15
Q

Ductal Carcinoma in situ = neoplastic intraductal epithelial proliferation with risk of progression to breast cancer

A
  • COMMON (Incidence has INCREASED since screening programmes came into effect)
  • 85% are detected on mammography (areas of microcalcification)
  • 10% will produce clinical features (lump, Paget’s disease); 5% diagnosed incidentally
16
Q

DCIS histological classification: low, intermediate or high grade

A

LOW → cribriform/punched-out DCIS

  • lumens compact/regular
  • calcification (cells rapidly dying and regenerating)
  • overlapping cells

HIGH

  • central lumen necrotic material (large cells)
  • pleomorphic cells occlude the duct (few limens)
17
Q

How do we treat DCIS

A
  • Treatment: surgical excision (chemotherapy is hardly ever given)
  • Recurrence is more likely with high grade or extensive disease
18
Q

Invasive breast carcinoma (the breast cancer you know)= a group of malignant epithelial tumours which infiltrate within the breast and have the capacity to spread to distant sites

RFs

A
  • MOST COMMON cancer in women (1 in 8 risk); Incidence increases with age

Risk factors

  • Early menarche
  • Late menopause
  • Obesity
  • Alcohol
  • OCP
  • FHx (5% inheritance)
  • Genetics → BRCA mutations (up to 85% increased lifetime risk)
19
Q

TWO distinct genetic pathways for invasive carcinomas

A

Low Grade – arise from low grade DCIS or in situ lobular neoplasia and show 16q loss

High Grade – arise from high grade DCIS and show complex karyotypes with many unbalanced

20
Q

4 types of invasive breast carcinoma

A

Invasive ductal carcinoma = pleiomorphic cells with large nuclei

  • AKA: Non-specific type
  • E-cadherin +ve

Invasive lobular carcinoma = linear (‘Indian File’ pattern), monomorphic (look similar)

Invasive tubular carcinoma [MIDDLE] = elongated tubules invading the stroma

Invasive mucinous carcinoma [RIGHT] = empty spaces contain lots of mucin

21
Q

Two types of carcinoma in situ

A
22
Q

What do we use to differentiate between invasive ductal carcinoma and invasive lobular carcinoma?

A

E-cadherin +ve = invasive ductal carcinoma

E-cadherin -ve = invasive lobular carcinoma

23
Q

Basal-like carcinoma = carcinoma type discovered following genetic analysis of breast carcinomas

A
  • Histology = sheets of markedly atypical cells, prominent lymphocytic infiltrate, central necrosis
  • Immunohistochemistry = +ve for “basal” cytokeratins CK5/6 and CK14
  • Associated with BRCA mutations
  • Propensity to… vascular invasion and metastasis
24
Q

Histological grading of breast cancers: name and scoring

A

Nottingham Modifications of Bloom-Richardson System (NMBRS)

Grading is dependent on:

  • Tubule formation 1, 2, 3
  • Nuclear pleomorphism 1, 2, 3
  • Mitotic activity 1, 2, 3

Graded up to score from 3→9

  • 3-5 = grade 1 = well differentiated
  • 6-7 = grade 2 = moderately differentiated
  • 8-9 = grade 3 = poorly differentiated
25
Q

Receptor status: which ones do we assess for and what does this tell us about the grade of the cancer

A

All invasive breast cancers are assessed for:

  • Oestrogen receptor (ER)
  • Progesterone receptor (PR)
  • Her2 receptor
26
Q

What factors shape prognosis of breast cancer, which is the most important one

A
  • The status of the axillary lymph nodes is the MOST IMPORTANT PROGNOSTIC FACTOR
  • Other factors: size, histological type, histological grade
27
Q

NHS Breas tscreening programme, aim and when

A

NHS Breast Screening Programme = aim to pick up DCIS and early invasive carcinomas

Women aged 47-73 years are screened every 3 years

  • The screening test is a mammogram
  • 5% will have an abnormal mammogram and are recalled for further investigation
  • Further investigation may include FNA/biopsy or further scans
28
Q

Coding biopsies B1 to B5b

A
  • B1 = normal breast tissue
  • B2 = benign abnormality
  • B3 = lesion of uncertain malignant potential
  • B4 = suspicious of malignancy
  • B5 = malignant
  • B5a = DCIS
  • B5b = invasive carcinoma
29
Q

Male breast disease = gynaecomastia

A

enlargement of the male breastBENIGN

  • Affects pubertal boys and men > 50 years
  • Idiopathic or associated with drugs (therapeutic and recreational)
  • Histology = epithelial hyperplasia of ducts with finger-like projections extending to duct lumen + periductal stroma often cellular and oedematous [similar to fibroadenoma]
30
Q

Male breast cancer

A
  • RARE
  • Median age: 65 years
  • Presentation: palpable lump
  • Histologically similar to female breast cancers
31
Q

Tamoxifen and herceptin/trastuzumab

A

Tamoxifen = mixed agonist/antagonists of oestrogen at its receptor.

Herceptin/trastuzumab = monoclonal Ig to Her2 (direct toxic effect on myocardium, must monitor LVEF)