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12. Breast Pathology > 5. Breast carcinoma > Flashcards

5. Breast carcinoma Flashcards

1
Q

Risk factors for breast cancer

A
  1. Race (Caucasian, Jew, Parsi)
  2. Age (perimenopausal)
  3. Socioeconomic status (high)
  4. Weight (obese)
  5. Previous breast disease
  6. Family history of breast cancer
    - BRCA1 & BRCA2 (DNA repair genes for double strand breaks) mutations account for 25% of familial breast cancers
  7. Ovarian activity (early menarche, late menopause)
  8. Exogenous estrogen (oral contraceptives, hormone replacement therapy)
  9. Nulliparity
  10. Lack of breastfeeding
  11. Proliferative diseases of the breast
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2
Q

Classification of breast cancers

A
  1. Carcinoma-in-situ
    a. Ductual carcinoma-in-situ (+ Paget’s disease)
    b. Lobular carcinoma-in-situ
  2. Invasive carcinoma
    a. Invasive ductal carcinoma
    b. Invasive lobular carcinoma
    c. Special types: tubular, mucinous, medullary
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3
Q

Clinical presentations of breast cancer

A
  1. Palpable mass
  2. Nipple discharge (serous or bloody)
  3. Mammographic density & calcifications
  4. Nipple retraction
  5. Peau d’ orange appearance
    - Lymphedema of the breast secondary to disruption of lymphatic drainage of breast by tumour deposits
    - Tethering of skin of breast by Cooper ligaments in the setting of lymphedema produces a dimpled appearance → peau d’ orange
  6. Lymph node metastates (palpable axillary metastases)
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4
Q

Prognostic factors for breast cancer

A
  1. Tumour size
    - <2 cm better, >2cm worse
  2. Tumour grade
    - Well-differentiated better
  3. Axillary nodes
    - None or few better, many worse
  4. Estrogen receptors
    - Present better
    - Can treat with estrogen antagonists (tamoxifen) or
    aromatase inhibitors
    - However, ER+ tumours are less likely to respond to
    chemotherapy
  5. HER2/neu receptor
    - Present worse
    - Can treat with tyrosine kinase inhibitors
    (trastuzumab aka herceptin or lapatinib)
  6. DNA amount
    - Diploid better, aneuploid worse
  7. Histologic type
    - Lobular & special types better, ductal worse
  8. Tumour staging
    - Lower stage better
  9. Vascular invasion
    - Present worse
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5
Q

Histological types of ductal carcinoma-in-situ

A
  1. Comedo type
  2. Cribriform type
  3. Solid type
  4. Papillary type
  5. Micropapillary type
  6. May give rise to Paget’s disease
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6
Q

Morphology of comedo type DCIS

A
  1. Solid sheets of pleomorphic cells

2. Areas of central necrosis (debris often calcify & appear on mammographs as linear & branching microcalcifications)

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7
Q

Morphology of cribriform type DCIS

A
  1. Intraepithelial spaces evenly distributed & regular in shape (cookie cutter appearance)
  2. Lumen filled with calcifying secretory material
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8
Q

Morphology of solid type DCIS

A
  1. Completely filled involved spaces

2. Not usually associated with calcifications (hence may be clinically occult)

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9
Q

Morphology of papillary type DCIS

A
  1. Grows into spaces along fibrovascular cores
  2. Lack myoepithelial layer
  3. Fibrovascular cores lined by monomorphic columnar cells
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10
Q

Morphology of micropapillary type DCIS

A
  1. Bulbous protrusions lacking fibrovascular cores (solid papillae)
  2. Narrow stalks
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11
Q

Lobular carcinoma-in-situ

A

Associated with E-cadherin mutation (also seen in invasive lobular carcinoma & signet-ring cell gastric adenocarcinoma)

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12
Q

Morphology of lobular carcinoma-in-situ

A
  1. Dyscohesive cells with round nuclei & small nucleoli

2. May have signet ring cells

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13
Q

Presentation of DCIS

A
  1. Incidental finding
  2. Mammographic density
  3. Nipple discharge
  4. Paget’s disease
  5. Palpable mass
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14
Q

Predominant location of DCIS

A

Ducts

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15
Q

Cell size in DCIS

A

Medium or large

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16
Q

Histological types of DCIS

A

Comedo, cribriform, solid, papillary, micropapillary

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17
Q

Calcifications in DCIS

A

Present or absent

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18
Q

Risk of subsequent invasive breast cancer in DCIS

A

Higher than LCIS

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19
Q

Location of subsequent invasive breast cancer in DCIS

A

Ipsilateral

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20
Q

E-cadherin expression in DCIS

A

Higher than LCIS

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21
Q

Receptor expression in DCIS

22
Q

Presentation of LCIS

A

Incidental finding (as it is not associated with calcifications or stromal desmoplastic reactions that produce mammographic densities)

23
Q

Predominant location of LCIS

24
Q

Cell size in LCIS

25
Q

Histological type in LCIS

26
Q

Calcifications in LCIS

A

Usually absent

27
Q

Risk of subsequent invasive breast cancer in LCIS

A

Lower than DCIS

28
Q

Location of subsequent invasive breast cancer in LCIS

A

Ipsilateral or contralateral

29
Q

E-cadherin expression in LCIS

A

Lower than DCIS

30
Q

Receptor expression in LCIS

A

ER+, PR+, HER2/neu-

31
Q

Definition of Paget’s disease

A

Rare manifestation of Ductal Carcinoma-In-Situ involving the nipple

32
Q

Pathogenesis of Paget’s disease

A

Extension of DCIS along ducts within the epithelial layer

to the area under the skin over nipple

33
Q

Appearance of Paget’s disease

A
  1. Unilateral
  2. Exfoliation/ulceration of nipple
  3. Erythematous eruption with a scale crust
34
Q

Definition of invasive ductal carcinoma

A

A ‘wastepaper basket’ category of invasive breast carcinomas that encompasses all breast cancers not classifiable under the other types

35
Q

Molecular classification of invasive ductal carcinoma

A
  1. Luminal A (40-55%)
  2. Luminal B (15-20%)
  3. Normal breast-like (6-10%)
  4. Basal-like (13-25%)
  5. HER2 positive (7-12%)
36
Q

Luminal A invasive ductal carcinoma

A
  1. ER+, HER2/neu-

2. Slow-growing, responds well to hormonal treatment

37
Q

Luminal B invasive ductal carcinoma

A
  1. ER+, HER2/neu+
  2. Higher grade, higher proliferative rate
  3. More likely to have lymph node metastases
  4. May respond to chemotherapy
38
Q

Normal breast-like invasive ductal carcinoma

A
  1. ER+, HER2/neu-
  2. Pattern of gene expression similar to normal breast
  3. Well-differentiated
39
Q

Basal-like invasive ductal carcinoma

A
  1. ER-, PR-, HER2/neu-
  2. Express myoepithelial markers (basal keratins, P-cadherin, p63, laminin)
  3. High grade, high proliferative rate
  4. Aggressive, metastases to brain & viscera
  5. BRCA1 associated
40
Q

HER2 positive invasive ductal carcinoma

A
  1. ER-, HER2/neu+
  2. Usually with HER2/neu gene amplification
  3. Poorly differentiated, high proliferative rate
  4. High frequency of brain metastases
41
Q

Morphology of invasive ductal carcinoma

A
  1. Grossly:
    - Hard firm mass with irregular border
  2. Histologically: (a range possible)
    - Well differentiated (tubule forming, small round nuclei)
    - Moderately differentiated (tubules & solid clusters, mitotic figures, more nuclear pleomorphism)
    - Poorly differentiated (ragged nests/solid sheets of cells with enlarged irregular nuclei)
42
Q

Associations with invasive lobular carcinoma

A

E-cadherin mutation (also seen in lobular carcinoma-in-

situ & signet-ring cell gastric adenocarcinoma)

43
Q

Morphology of invasive lobular carcinoma

A
  1. Grossly:
    - Mass with irregular border
    - In 1⁄4 of cases, tumour infiltrates diffusely & causes little desmoplasia
  2. Histologically:
    - Dyscohesive infiltrative tumour cells often arranged in a single file/loose clusters/sheets
    - No tubule formation
    - Minimal/no desmoplasia
    - May have signet-ring cells
44
Q

Clinical features of invasive lobular carcinoma

A
  1. Unique pattern of metastasis (peritoneum & retroperitoneum, leptomeninges, GIT, ovary & uterus)
  2. Rare heterozygous germline mutation of E cadherin gene resulting in genetic predisposition to:
    - Invasive lobular carcinoma
    - Signet-ring cell gastric adenocarcinoma
45
Q

Morphology of tubular carcinoma

A
  1. Small irregular masses
  2. Well-formed tubules but without myoepithelial cell layer
  3. May see cribriform pattern, apocrine metaplasia or intraluminal calcifications
46
Q

Clinical features of tubular carcinoma

A
  1. Diploid
  2. ER+, HER2/neu-
  3. Well differentiated
  4. Axillary metastases in <10%
  5. Excellent prognosis
47
Q

Morphology of mucinous carcinoma

A
  1. Well circumscribed
  2. Soft, rubbery, pale grey-blue
  3. Tumour cells arranged in clusters & small islands within large lakes of mucin
48
Q

Clinical features of mucinous carcinoma

A
  1. Usually diploid
  2. ER+
  3. Well to moderately differentiated
  4. Lymph node metastases uncommon
  5. Better prognosis than invasive ductal carcinoma
49
Q

Morphology of medullary carcinoma

A
  1. Well-circumscribed, soft, fleshy
  2. Little desmoplasia
  3. Solid syncytium-like sheets of large cells with vesicular pleomorphic nuclei & prominent nucleoli
  4. Frequent mitotic figures
  5. Lymphocytic infiltrate
  6. Pushing non-infiltrative borders
  7. Poorly differentiated
50
Q

Clinical features of medullary carcinoma

A
  1. ER-, PR-, HER2/neu-
  2. BRCA1 associated
  3. E cadherin overexpression
    - Hence increased cell-cell adhesion
    - Explains low rates of metastases, pushing non-infiltrative borders & syncytial growth pattern
  4. Lymph node metastases infrequent
  5. Better prognosis than invasive ductal carcinoma

12. Breast Pathology (6 decks)

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