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Reproductive Pathology > Breast Pathology > Flashcards

Breast Pathology Flashcards

1
Q

Where in the breast does most cancer arise from?
- What tissues compose this area?

A

terminal duct lobular unit

tissues:
1. Luminal Epithelial Cells - produces milk
2. Myoepithelial Cells Surround - propells milk

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2
Q

How do chances of a lump in the breast being malignant change as women age?

  • where are malignancies most likely to arise?
  • explain.
A

Lumps…
Under 40 - 10% chance of malignancy

Over 50 - 60% chance of malignancy

Over 80 - risk falls off

Upper Lateral Quadrant is the most common place that cancer arises because this is where most breast tissue is located

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3
Q

Fibrocystic changes

  • how do they generally present?
  • how common is this?
  • when is someone most likely to be symptomatic?
A

This is the most common breast abdnormality of premenopausal women

Symptoms are most often cyclic corresponding to hormonal changes during the ovulatory cycle

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4
Q

If you see calcification in a mammagraphy of a 39 year old woman who is still have menstrual periods, what is the most likely cause?
- what should you do next?

A

Most likely fibrocystic change is the cause, BUT you should still biopsy it

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5
Q

What are the two types of fibrocystic change?
- In general, which type has the lowest risk of progressing to cancer?

A

proliferative and non-proliferative subtypes of fibrocytsic change

NON-proliferative logically is less likely to progress to cancer, but both subtypes carry a low risk of progression

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6
Q

On gross examination of Fibrocystic Changes, what would you be likely to see?

A

a CYST that may contain brown fluid and/or white fibrosis and yellow fat

In types containing brown fluid, this is often termed a blue-domed cyst.

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7
Q

In general how is fibrocystic change treated?

A

Treatment typically involves aspiration only

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8
Q

What are the 3 subtypes of PROLIERATIVE fibrocystic changes?

A

Cysts
Fibrosis
Apocrine Metaplasia

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9
Q

Compare Cysts, Fibrosis, and Apocrine Metaplasia on the basis of histologic appearance?
- are these proliferative or non-proliferative fibrocystic change?

A

these are all non-proliferative fibrocystic change

HISTOLOGY:

  • *CYSTS**:
  • Lots of 2 layered cysts that are often dilated
  • *FIBROSIS**:
  • Bubble-gum appearance of tissue surrounding cyst on H and E
  • *Apocrine Metaplasia**:
  • Eosinophilic (pink) cells that are larger and more rounded than normal with what looks like sloughing off of the edges into the duct lumen = APOCRINE CHANGE
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10
Q

What are the 4 types of PROLIFERATIVE fibrocystic change?

A

proliferative fibrocystic change

Radial Scar
Sclerosing Adenosis
Usual Ductal Hyperplasia
Atypical Ductal and Atypical Lobular Hyperplasia

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11
Q

Compare the histology seen in:
Sclerosing Adenosis
Radial Scars

Are the proliferative or non-proliferative fibrocystic changes?

A

These are all Proliferative Fibrocystic change
**NOTE: all of these fibrocystic changes MUST have 2 layers of tissue, otherwise its cancer***

Sclerosing Adenosis
lots of collagen with glands compressed by the sclerosis (collagen) swirled in.
Ducts and Lumina often contain calcium

Radial Scars
Similar to sclerosing adenosis but in a radial pattern of sclerotic tissue

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12
Q

Compare the Histologic changes seen in:
Usual Ductal Hyperplasia
Atypical Ductal and Lobular Hyperplasia

Are these proliferative or non-proliferative fibrocystic changes?

A

These are all Proliferative Fibrocystic change
**NOTE: all of these fibrocystic changes MUST have 2 layers of tissue, otherwise its cancer***

Usual Ductal Hyperplasia
Glands often have slit-like lumina or are completely filled with proliferating cells.

  • *1Atypical Ductal Hyperplasia and 2Atypical Lobular Hyperplasia**
    1. ADH has hyperplasia (too many ducts in the boob) with very round (COOKIE CUTTER) lumina of the glands
  1. ALH has very bland cells filling the lumin of the ducts
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13
Q

What are some causes of inflammatory processes in the breast?

A
  1. Acute Mastitis
  2. Periductal Inflammation
  3. Fat Necrosis
  4. Mammary Duct Ectasia
  5. Lymphatic Mastitis
  6. Granulomatous Mastitis
  7. Inflammatory Carcinoma
  8. Paget’s Disease of the Nipple
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14
Q

Acute Mastitis

  • Presentation
  • Histo
  • Most common cause
  • Tx
A

S. aureus = most common cause

Presentation:
Breastfeeding women with inflammation and pain in her breast with purulent discharge possible and may progress to abscess if left untreated

Histo:
Neutrophils in the duct lumen and in the stroma if infection is severe

Tx:
CONTINUE BREASTFEEDING and start on ABX if necessary

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15
Q

Periductal Mastitis
Pathogenesis
Cause/Presentation

A

Pathgenesis
Squamous metaplasia of the duct epithelium leads to clogging of the duct and inflammation, this is often due to a relative Vitamin A deficiency

Cause/Presentation
Woman who smokes (causing the Vit. A deficiency) who may have a swollen breast with nipple retration (so it may look a lot like cancer)

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16
Q

Fat Necrosis
Presentation

A

Lump in the breast of a woman who may or may not remember trauma to the breast

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17
Q
  • *Mammary Duct Ectasia**
  • Pathogensis
  • Presentation
  • Histo
A

Pathogenesis
Foreign body in the duct causes an inflammatory response leading to fistulas and fibrosis with gross nipple retraction

Presentation
Nipple retraction with green-brown discharge coming from the breast

Histo
This is a foreign body reaction so we see giant cells and inflammation

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18
Q

What associations should you make with lymphocytic mastitis?

A

Associated with Diabetes and is often autoimmune (this means HLA-DR3 and HLA-DR4 could be implicated right?)

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19
Q

What are the 3 BENIGN tumors of the breast?

A

Fibroadenoma
Phyllodes Tumor
Intraductal Papilloma

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20
Q

Compare and contrast the presentations of the 3 benign tumors of the breast.

A

Fibroadenoma
Typically a lump in the breast of a woman under 35

Phyllodes Tumor
Typically a lump in the breast of a postmenopausal woman

Intraductal Papilloma
Typically a premenopausal woman with nipple retraction and bloody nipple discharge
**if after menopause you would start to think papillary carcinoma

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21
Q

Compare the Histology of the 3 benign tumors of the breast.
What feature do they all have in common?

A

These all have BOTH cell layers in tact
Fibroademoma
Lots of Fibrous Tissue compressing the glands of the breast

  • *Phyllodes Tumor**
  • Similar fibrous appearance as fibroadenomas* but is in a leaf shape. Cells here are more likely to look a bit atypical

Intraductal Papilloma
Papilla with a central fibroVASCULAR core extending into the duct from the duct wall

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22
Q

Can Phyllodes tumors be malignant?

A

Yes, sometimes they may look anaplastic and infiltrative

Once infiltrative its a malignant tumor

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23
Q

What is the most common benign neoplasm of the breast?
What part of breast tissue does this tumor arise from?

A

Fibroadenoma = most common benign lesion in the breast

BOTH fibroadenomas and phyllodes tumors are from stroma and intraductal papilloma probably is too

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24
Q

What do fibroadenomas feel like on breast exams?
*is this lesion persistent for life?
* how might these present in a juvenile patient?

A

These are typically descrete firm rubbery balls that range from 1-10cm and are mobile

Fibroadenomas often involute after menopause because they are hormonally responsive

In juvenile patients these may increase in size rapidly

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25
Q

Who most commonly gets breast cancer?
What are the risk factors for breast cancer?

A

Epidemiology:
U.S. and N. European women

Risk Factors:
Exogenous Extrogens
Radiation
Obestity (estrogen and inflammation)
Alcohol
High Fat Diet

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26
Q

What is the prevalence of breast cancer?
- what age group is at the highest risk?

A

Prevalence = 1 in 10

High Risk:
Women 45-75 are high risk

27
Q

What is the progression of mutations that lead to luminal breast cancer A and B?
**What are the corresponding histological changes?
**what will be the status of the estrogen and HER2 receptors in the luminal cancer cells?

A

**BRCA2 (Flat epithelial atypia) => PIK3A (atypical ductal hyperplasia):

=> Luminal A (ER+, HER2-)
=> Luminal B (ER+, HER+++)**

28
Q

What is the progression of mutations that is thought to lead to HER2 postive breast cancer?
**Estrogen and HER2 receptors?

A

Germline TP53 mutation => HER2 amplication => HER2 positive (ER -, HER2, +++++)

29
Q

What progression of mutations leads to basal type breast cancer?
**Final estrogen receptor and HER2 profile?

A

**BRCA1 => TP53 => BRCA1 inactivation => Basal Type (ER -, and HER2 -)

***TRIPLE NEG. Breast cancer is often associated with BRCA1*****

30
Q

What are some common mutations that are inherited leading to breast cancer?

A

BRCA 1/2
Li-fraumeni(TP53 mutation)
Ataxia telangiectasia carriers (ATM protein fixes double stranded DNA breaks)

31
Q

What features of a patient or the presentation of their cancer should lead you to think that an underlying genetic mutation may be present?

A

Bilateral, other cancers (ovarian), Family hx, Before menopause, ethnic groups (A. Jews)

32
Q

T or F: both BRCA alleles must be mutated to get cancer.

A

True

33
Q

How does a patient with BRCA 1 (chromosome 17) mutations often present?

  • Receptors on tumor (ER, HER2, PR)?
  • Prophylactic treatment?
A

BRCA1
Typically this is a woman between 45-59 (most often 50) with TRIPLE NEGATIVE breast cancer

Prophylatic Tx:

  • *Masectomy** and/or close follow-up
  • *Tamoxifen** may prevent Bilateral Cancer
34
Q

***What DISTINCTIVE HISTOLOGY defines BRCA1 mutations without even genotyping?

A

BRCA1 Histology:
Increased Rates of Ductal Carcinoma in Situ
High grade BASAL-LIKE phenotype
MEDULLARY FEATURES are often present like: PUSHING BORDERS, PERITUMORAL lymphocytes

35
Q

T or F: while BRCA 1 is associated with drug resistance, this doesn’t seem to affect death rate

A

True

36
Q

At what age does BRCA 2 (chromosome 13) often present?
*what other cancers are associated with BRCA2?

A

BRCA2
Breast cancer typically presents in BRCA2 women by age 50

Risk for Other Cancers:
Ovary, Pharynx, Prostate, Pancreas

37
Q

What histology would you expect to see in someone with a BRCA 2 mutation?

A

BRCA 2:
Usually Invasive Ductal Carcinoma
High Grade pushing margin

***NOTE: the histo is not as distinct for BRCA 2 mutations

38
Q

Why are women with early menarche and late menopause at an increased risk of getting breast cancer?

A

Having early menarche and late menopause extends the duration at which your cells are exposed to estrogen and increases the risk of breast cancer

39
Q

What are the two general Categories that we can divide breast cancers into?

A

Invasive
non-Invasive

40
Q

What are the non-invasive subtypes of breast cancer?

A

Ductal Carcinoma in Situ (DCIS)
Lobular Carcinoma in Situe (LCIS)

41
Q

What are the subtypes of Invasive Breast Cancer?

A

Invasive Ductal Carcinoma
Invasive Lobular Carcinoma
Medullary Carcinoma
Colloid/Mucinous Carcinoma
Tubular Carcinoma

42
Q

What Histological Characteristics are key to diagnosing Lobular Cell Carcinoma in Situ?
*Special Staining?

A

LCIS Histo:
Low Grade Monotonous cells with Target Mucin are KEY

LOSS of E-cadherin on IHC staining locks in the dx

43
Q

While there are several subtypes of Ductal Carcinoma in Situ, how does the histology compare to lobular carcinoma in situ in general?

A

DCIS
Many Patterns:
Solid
Comedo
Cribiform
Papillary
Micropapillary

44
Q

What subtype of Ductal Carcinoma in Situ has histology described by central necrosis and calcification?
* what is the chance of this DCIS progressing to invasive cancer?

A

COMEDO TYPE = Central Necrosis and Calcification
(this is because the central part of the duct doesn’t have enough blood supply to keep all of the cells alive)

30% chance of progressing to invasive carcinoma in 5 years

45
Q

What form of DCIS is likely to be described as a swiss-cheese like appearance of cells in the duct?

A

Cribiform

46
Q

What form on DCIS is most likely to show up as a bright lesion on mammagraphy?

A

Comedo because there is central necrosis that calcifies

47
Q

Would you expect DCIS or LCIS to present as a mass?

A

NO, it is unlikely that either of these will present as a mass in the breast

**Often these are found incidentally after doing a biopsy for fat necrosis etc.

48
Q

What is the prognosis for DCIS and LCIS?

A 
DCIS = good prognosis
LCIS = Bad?
49
Q

When is Gynecomastia physiological and not pathological?
What are some pathologic causes?

A

Physiological at puberty and Old age
**typically caused by increased estrogen

Pathologic:
Cirrhosis
Klinefelter Sydrome
Anabolic Steroids

50
Q

What do you expect to see on the histology of Gynecomastia?

A

Histology
No lobules so all you see is increased cellularity with prominant stroma and possible edema and late stage fibrosis

51
Q

What histological feature is KEY in defining all Invasive Carcinomas?

A

ALL of these have lost the underlying myoepithelial layer

52
Q

What is the most common invasive carcinoma of the breast?
What does it arise from?
Key histological Features?

A

Invasive Ductal Carcinoma (70-80% of breast CA)

Arises from the terminal Duct lobular unit but IS NOT ductal epithelium

HISTO:

  • *No Myoepithelium** when stained
  • *Interdigitation** with Surrounding Stroma
53
Q

What are some features you might see on physical exam of someone with Invasive Ductal Carcinoma?

A

May See Dimpling of the Skin or Retraction of the Nipple

54
Q

Lobular Carcinoma
Mutation in what gene essentially Defines this Cancer?
Key histological features?

A

Lobular Carcinoma

Gene: CDH1 gene for E-cadherin protein product that is essential for cell-cell adherance

Histo:
Stromal Interdigitation with “Indian Filing” of cells
Targetoid Vacuolization
Desmoplastic Response

55
Q

What is a Desmoplastic Response?

A

Desmosplastic Response = growth of fibrous tissue around cells (often neoplastic cells)

56
Q

Note: patients with lobular carcinoma of the breast with CDH1 loss are also at risk for signet ring gastric carcinoma

A

Note: patients with lobular carcinoma of the breast with CDH1 loss are also at risk for signet ring gastric carcinoma

57
Q

Medullary Carcinoma
Histo?
Risk of Recurrence?
Gene Associations?

A

Histo:
Indistinct Cell Borders (syncytial growth)
Lots of Mitotic Figures and Pleomorphic Nuclei
LYMPHOPLASMACYTIC INFILTRATE (peritumoral and Intratumoral)
Pushing Borders (well circumscribed)

Risk of Recurrence:
Low Risk of Recurrence w/o nodal involvement

Gene Association:
Associated with BRCA 1 mutation in a MINORITY of Cases

58
Q

Colloid Mucinous Carcinoma
Histo
Presentation
Prognosis?

A

Colloid Mucinous Carcinoma
Histo:
Tumor Cells Floating in pools of Mucin

Presentation
OLDER WOMEN typical ~70 y/o

Prognosis
GOOD, this cancer is really indolent with a 10 year survival rate of 90%

59
Q

Tubular Carcinoma
**Why do you HAVE to be able to recognize this?
HISTO

A
  • *Tubular Carcinoma**
  • *Favorable Px** so Recognize it

Histo:
Distinct well differentiated ANGULAR tubular structure lined by a SINGLE layer of epithelial cells

60
Q

Micropapillary Variant
***Why should you be able to recognize this histo?
HISTO?

A

Micropapillary Breat Carcinoma

  • *VERY POOR PROGNOSIS**
  • 95% have lymph node metastasis at the time of Dx
  • 70% recurr
  • 50% die of this disease

HISTO:
looks like alveolar structures on a stick

61
Q

Paget’s Disease of the Nipple
Presentation
Pathogenesis
Histology

A

Presentation
Presents as a slow growing itchy rash that can be confused as contact dermatitis or eczema
Crusted Nipple Skin

Histology
Clear looking cells that move as individuals or in small clusters up through the squamous epithelium

62
Q

Inflammatory Carcinoma
Presentation
Prognosis

A

Inflammatory Carcinoma Prognosis
Presentation
Swollen (orange peel) breast with mastitis-like appearance but no palpable mass. Patient may get tx with abx then not improve.

Prognosis:
Underlying cancer is likely poorly differentiated with Lymphocytic involvement by the time the patient presents with this
5 year survival is below 50% even if not metastatic

63
Q

TMN staging is the most important parameter used in prognosis of breast cancer patients.

  • Of these parameters, which is most useful in prognosis?
  • Which is the most important prognostic indication?
A

Most Useful:
Sentinal Node Biopsy

Metastasis:
Most important Prognostic Indicator BUT most patients present before metastasis has occured

Reproductive Pathology (6 decks)

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