11/19- Breast Pathology Flashcards Preview

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Flashcards in 11/19- Breast Pathology Deck (74)
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1
Q

What are the functions of the normal mammary gland?

A
  1. Newborn survival
  2. Nursing- transfer immunity, maternal bonding, post-partum uterine involution
  3. Sexual organ- implications for cancer treatment
2
Q

Describe breast anatomy

A
  • 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.
3
Q

What is seen here?

A

Breast histology

  • Close up TDLU
4
Q

Ducts and lobules are formed of what cell types? Function?

A
  • Myoepithelial cells: contractile, milk ejection
  • Epithelial cells: milk production
5
Q

Describe the makeup of the stroma

A
  • Dense fibroconnective tissue
  • Adipose tissue
  • Blood vessels
6
Q

Key fact: genes important in controlling development may be those contributing to cancer when altered

A

:(

7
Q

What is seen here?

A

Atrophy

8
Q

What is seen here?

A

Lactational changes

9
Q

What is seen here?

A

TLDU

10
Q

What are nonproliferative changes in benign breast disease?

A

Inflammatory condition:

  • Acute mastitis

(- Duct ectasia)

  • Granulomatous mastitis

Fibrocystic changes

11
Q

What are proliferative changes in benign breast disease?

A
  • May mimic cancer clinically and histologically
  • Increased risk of breast cancer
12
Q

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?
A

Granulomatous mastitis

13
Q

What is seen here?

A

Granulomatous mastitis

14
Q

What is seen here?

A

Granulomatous mastitis

15
Q

What causes acute mastitis?

A

Usually during lactation

  • Bacterial infection
  • Erythema and swelling can mimic inflammatory breast cancer
16
Q

What is seen in duct ectasia?

A
  • Dilation of ducts
  • Inspissated secretions
  • Inflammation of nlobules
17
Q

What is seen in granulomatous mastitis (process)? What causes it?

A
  • Unknown etiology
  • Immune reaction to antigens during lactation
18
Q

What are fibrocystic changes?

  • What % of women
  • Composition
  • Consequences
A
  • 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
19
Q

What is seen here?

A

Fibrocystic changes

20
Q

How can you divide proliferative breast lesions?

A
  • Without atypical cellular changes
  • With atypia
21
Q

What are some conditions that are proliferative without atypia?

A

- 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

22
Q

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?

A

Intraductal papilloma

23
Q

What is seen here?

A

Intraductal papilloma

24
Q

Case 3)

  • 28 yo female with palpable mass, 2 cm
  • Clinical: circumscribed, not fixed
  • Imaging: Round, well circumscribed

What do you expect from pathology?

A

Fibroadenoma

  • If you see someone in 20s with breast mass, THINK FIBROADENOMA
25
Q

What is seen here?

A

Fibroadenoma

26
Q

What is seen here?

A

Fibroadenoma

27
Q

What is seen here?

A

Fibroadenoma

28
Q

What are some different types/categories of hyperplasias?

A
  • Usual type ductal hyperplasia
  • Columnar cell lesions
  • Apocrine hyperplasia and apocrine adenosis
29
Q

Describe usual type ductal hyperplasia

  • Risk
  • Cells
  • Genetics
A
  • Not a precursor
  • Mixed cell population
  • No or rare random genetic alteration
30
Q

Describe columnar cell lesions

  • Risk
  • Genetics
A
  • Loss of 16q ~ FEA, ADH
  • Low grade DCIS, ALH and LCIS
31
Q

Describe apocrine hyperplasia and apocrine adenosis

  • Risk
  • Genetics
A
  • Precursor to high grade arm
  • Multiple genomic alterations
32
Q

What is seen here?

A

UDH: usual type ductal hyperplasia

33
Q

Describe proliferative lesions with atypia (premalignant lesions).

Types? Cell populations?

A
  • 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
34
Q

What is seen here? Genetics?

A

Premalignant (16q-)

35
Q

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?

A

Atypical ductal hyperplasia

  • Next: needle guided excision
  • This diagnosis requires surgical excision
36
Q

What is seen here?

A

Atypical Ductal Hyperplasia

  • Nice, round lumens
  • Can see calcifications
  • This will not require radiotherapy
37
Q

Breast cancer is the #__ cancer in women

A

Breast cancer is the #1 cancer in women

(2. lung/bronchus, 3. colon/rectal)

38
Q

Breast cancer is the #__ cause of cancer deaths in women

(__% of cancer deaths)

A

Breast cancer is the #2 cause of cancer deaths in women

(15% of cancer deaths)

39
Q

How has incidence of breast cancer changed in recent years?

A

… dunno, but stopping so much hormone replacement therapy has helped

40
Q

Look at this helpful picture for breast cancer development

A
41
Q

Describe the distribution of histologic types of breast cancer

  • In situ
  • Invasive
A
  • In situ: 15-30%
  • Invasive: 70-85%
42
Q

What are the different types of infiltrating carcinomas?

A
  • Infiltrating “ductal” carcinoma, no special type
  • Infiltrating carcinoma, special type
  • Tubular
  • Mucinous
  • Medullary
  • Lobular classic
43
Q

Describe genetic changes/risk factors for breast cancer pathogenesis

A
  • Certain growth factors
  • Hormonal changes

Process:

  • Genetic changes accumulate in ductal/lobular cells
  • E and P act as promoters
44
Q

What are the two basic types of breast cancer (in terms of inheritance)?

A
  • Hereditary: 5-10% of all cases
  • Sporadic: 90-95% of cases
45
Q

What are risk factors for breast cancer?

A
  • 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
46
Q

Sporadic breast cancer is due to what?

  • Age of onset
A
  • 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)
47
Q

Describe hereditary breast cancer

  • What % of breast cancer cases
  • Genetics?
  • Age of onset
A
  • 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
48
Q

What cancers do BRCA1 and 2 involve?

A

BRCA1:

  • Breast
  • Fallopian tube
  • Ovary

BRCA2:

  • Breast
  • Ovary
  • Pancreas
  • Prostate
49
Q

What cancers are associated with TP53 gene (Li Fraumeni syndrome)?

A
  • Breast
  • Brain
  • Sarcoma
  • Leukemia
50
Q

What syndrome does the PTEN gene cause? Associated cancers?

A

Cowden’s syndrome

  • Breast
  • Ovary
  • Thyroid
  • Colon
51
Q

Describe the histology of BRCA1 associated tumors

A
  • IDC 3/3
  • Medullary like
  • Basal
  • Triple negative in majority
  • Tumor necrosis
  • Lymphoplasmacytic infiltrate
  • DCIS and LCIS are seen less frequently
52
Q

What is seen here?

A

BRCA1 histology

53
Q

Describe the histology of BRCA2 associated tumors

A
  • IDC/pILC
  • Grade 2-3/3
  • DCIS and LCIS seen = as non-carriers
  • Luminal
  • ER+ PR+
  • Rare HER 2+
54
Q

What is seen here?

A

BRCA2 histology

55
Q

Describe the histology for the genes:

  • CDH1
  • CHEK2
  • PALB2
A

CDH1

  • Invasive lobular carcinoma CHEK2
  • Invasive lobular carcinoma PALB2
  • ER, PR, HER2: all negative
  • BASAL CK negative
  • KI67 high
56
Q

What are the two major pathways in the molecular evolution of breast cancer?

A

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
57
Q

Describe the molecular taxonomy of breast cancer

A

High throughput, microarray-based gene expression methods; to determine the molecular features of breast cancer for:

  • Histological grade
  • Metastatic propensity
  • Response to therapy
58
Q

Describe the molecular classification of breast cancer via gene profiling

  • Luminal A
  • Luminal B
  • HER2
  • Basal
A
  • Luminal A: ER+PR+, HER2-, low KI67
  • Luminal B: ER+PR+/-, HER2+/-, high KI67
  • HER2: HER2+
  • Basal: triple negative
59
Q

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 (?)

A

Pathology:

  • Ductal carcinoma in situ
  • Nuclear grade 3/3 by SBR criteria
  • Central comedo necrosis with calcifications
60
Q

What is seen here?

A

Continuum of DCIS with ER positivity/negativity

61
Q

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?

A

Surgery: Segmental mastectomy + SLN

62
Q

What is seen here?

A

Infiltrating “Ductal” Carcinoma of No Special Type

63
Q

What is the paradigm for targeted therapy?

A
  • ER+: Tamoxifen, other endocrine therapies
  • HER2+: Trastuzumab
64
Q

What are prognostic markers (major and minor)?

A

Major:

  • In Situ, invasive
  • Metastases
  • Lymph node mets
  • Locally advanced
  • Inflammatory Ca

Minor:

  • Histological types
  • Tumor grade
  • Receptors
  • LVI
  • Proliferative rate
65
Q

What are predictive markers?

A
  • Estrogen receptor
  • Progesterone receptor
  • HER2
66
Q

What is seen here?

A

Predictive markers: ER/PR positive

67
Q

What is seen here?

A

Predictive markers: HER2 negative

68
Q

What is seen here?

A

Predictive markers: HER2 positive

69
Q

What are multi-gene tests done in evaluating breast cancer/risk?

A
  1. Oncotype Dx by Genomic Health (21 gene signature).
  2. Prosigna ROR by NanoString (50 gene signature).
  3. IHC4 (ER, PR, HER2, and Ki67).
  4. EndoPredict or Epclin by Sividon, (12 gene signature plus clinical).
  5. MammaPrint by Agendia (70 gene signature).
  6. Genomic Grade Index (Qiagen Marseille, 97 gene signature).
  7. Breast Cancer Index (HoxB13/IL17 ratio + Molecular Grade Index, bio Theranostics).
70
Q

Describe Oncotype Dx RS (recurrence score)

A
  • 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.
71
Q

The 21-gene recurrence score (RS) assay predicts what?

A

Distant Relapse at 10 Years if 5 Years Tamoxifen

72
Q

What is seen here? Stage?

A

Breast cancers, stage I

73
Q

What is seen here? Stage?

A

Breast cancer, stage IV

74
Q

How to improve breast cancer mortality?

A
  • 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.