Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FRCPath Histopathology Part 1 > Breast - Precursor Lesions/Proliferative Entities > Flashcards

Breast - Precursor Lesions/Proliferative Entities Flashcards

1
Q

What are the normal changes seen in the menstrual cycle?

A

1) Follicular Phase
Luminal epithelial cells with dark centrally located nuclei and eosinophilic cytoplasm

2) Luteal Phase
Vacuolation, ballooning of basal myoepithelial cells

3) Secretory Phase
Apical Snouts
Enlarged lumina
Eosinophilic secretory material

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the changes seen in pregnancy and lactation?

A

Organoid enlargement and dilation of lobular units.

Luminal epithelial cells :
Vacuolated cytoplasm
Enlarged round nuclei
Prominant nucleoli
HOBNAIL pattern — (also seen in lactating adenoma)
Can see increased mitotic activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the luminal markers for breast cells?

A

LMW cytokeratins - CK7, CK8/18, CK19
E-Cadherin (membranous) - loss is hallmark of lobular carcinoma
GCDFP-15 - gross cystic disease protein (cytoplasmic) - fairly specific, but usually patchy
Mammaglobin (cytoplasmic) - positive in 60% breast ca, but also stains gynae
GATA3 (nuclear) - highly sensitive,
**SOX10 **(nuclear) - enriched in triple negative breast Ca, but also stains melano and neuro
**ER and PR **(nuclear) - ER controls synthesis of PR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the myoepithelial markers?

A

P63 (nuclear)
P40 (nuclear)
Calponin (cytoplasmic)
SMA- smooth muscle actin (cytoplasmic)
SMMHC -smooth muscle myosin heavy chain (cytoplasmic)
CK14 (cytoplasmic)
S100 (nuclear and cytoplasmic)

**P63/P64 **and SMMHC are superior as they dont react with fibroblasts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What markers would you use to identify breast primary in a metastasis?

A

GATA3 (>90%+, but not specific)
ER/PR (60% positive)
GCDFP (~60% positive)

Consider** SOX 10** in cases of triple negative breast Ca

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Interpret ER/PR IHC

A

<1% nuclear staining - weak
1-10% nuclear staining - moderate
11%> - strong

If >1% of cells stain - positive
if <1% of cells stain - negative
1-10% is classed as low-positive - should be mentioned in the report as per ASCO/CAP 2020 guidelines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Interpret Her-2-Neu IHC

A

HER2 testing must be performed on every primary invasive carcinoma and on a metastatic site

No staining observed or incomplete faint / barely perceptible membrane staining within ≤ 10% of invasive tumor cells - Score 0 - Negative

Incomplete faint membrane staining and within > 10% of invasive tumor cells - Score +1 - Negative

Weak to moderate complete membrane staining observed in > 10% of invasive tumor cells - Score +2 - Equivocal

Tumor displays complete, intense circumferential membranous staining in > 10% of tumor cells - Score +3 - Positive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Interpret Fluoresecent in-situ hybridisation (FISH)

A

ASCO / CAP guidelines recommendations if initial HER2 testing by IHC results in equivocal values, reflex testing by FISH should be performed on the same specimen or an alternative specimen (eg lymph node).

Positive:
Single probe average HER2 copy number ≥ 6.0 signals/cell.

Dual probe HER2/CEP17 ratio ≥ 2.0 with any average HER2 copy number,
or HER2/CEP17 < 2.0 with an average HER2 copy number ≥ 6.0 signals / cell

Negative:
Single probe average HER2 copy number < 4.0 signals/cell.

Dual probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell

Borderline

Dual probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number 4.0 - 6.0 signals/cell

Count more cells or resample.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How would you differentiate Myoepithelial, myofibroblasts, and vessels?

A

SMA, Calponin, SMMHC, p63/p40

**Myoepithelial **- positive for all

Myofibroblasts - Positive for SMA, weakly for calponin

Vessels - Negative for p63/p40

This is why p63/p40 are better than SMA and calponin - less background noise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the immunoprofile of breast carcinoma (in general)?

A

CK7+
CK20-ve
GATA3
ER/PR
HER2
GCDFP-15
Mammaglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the immunoprofile of lobular carcinoma (in situ and infiltrative)?

A

Loss of E-Cadherin membranous staining
GCDFP-15

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the immunoprofile of metaplastic breast carcinoma?

A

HMWCK (CK903 or CK5/6)
CK7
p63/p40

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How can you differentiate between ALH/LCIS, ADH/DCIS, and UDH?

A

ALH/LCIS - lose e-cadherin, +ve HMWCK (CK903, CK5/6), +ve ER staining, cytoplasmic p120 catenin

ADH/DCIS- +ve e-cadherin, lose HMWCK (CK903, CK5/6), diffuse ER staining, **membranous **p120 catenin

UDH - +ve e-cadherin, +ve HMWCK, Patchy ER, Membranous p120 catenin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe Usual Duct Hyperplasia

A
  • Admixture of cell types - epithelial, myoepithelial, apocrine
  • Haphazard architecture
  • Irregular slit like spaces
  • Overlapping nuclei
  • Nuclear grooves
  • Pseudoinclusions
  • Thin bridges
  • Micropapillae with broad bases and narrow tips
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the markers for for Usual Duct Hyperplasia

A
  • Low molecular weight CKs (CK7)
  • High molecular weight CKs (CK5/6)
  • Heterogenous ER staining
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Atypical Duct Hyperplasia?

A
  • Monoclonal
  • Neoplastic proliferation of evenly spaced epithelial cells
  • Cribriform architecture
  • Bridging
  • Micropapillae
  • If >2mm or 2 duct spaces, is classed as DCIS
17
Q

What are the markers for Atypical Ductal Hyperplasia?

A
  • Low molecular weight CK - 8, 18, 19
  • Strong, uniform ER staining
  • **Negative **for High molecular weigh CK (5/6)
18
Q

What’s the treatment for ADH?

A

If found on biopsy -> surgical excision to exclude DCIS/Invasive

If found on excision -> No further treatment required

19
Q

Describe DCIS

A
  • Monoclonal
  • Neoplastic proliferation of epithelial cells of ductal origin.
  • Morphological appearance defines the grade… not architecture
  • Can involve lobules - cancerisation of the lobules
  • No specific size requirement, unlike ADH
  • Majority or non-palpable
  • Found on mammo with linear calcifications
  • High grade associated with - stromal fibosis, sclerosis, infiltrative lymphocytes
20
Q

What is the treatment of DCIS?

A

Excision with wide negative margins
+/- radiation therapy
+/- hormone therapy

21
Q

What are the markers for DCIS?

A
  • ER/PR positive in a clonal pattern (more frequently negative in high grade)
  • HER2 - variable
  • Negative for CK5/6
  • E-Cadherin retained
  • Myoepithelial cells - p40, p63, SMMS, calponin, CK5/6 and CK5

Myoepithelial cell layer surrounding ducts spaces containing DCIS is intact, but may be attenuated especially in high grade DCIS

22
Q

What are the important prognostic factors for DCIS?

A
  • Positive surgical margins
  • high nuclear grade
  • large lesion size
  • comedo necrosis
  • young age (< 45 years)
23
Q

What are the molecular mutations for DCIS?

A
  • PIK3CA (about 25%)
  • TP53 (10-15%)
  • GATA3 (about 10%)
24
Q

What are the cytogenetics for LOW GRADE DCIS?

A

LOSSES:
16q, 17p

GAINS:
1p

25
Q

What are the cytogenetics for HIGH GRADE DCIS?

A

LOSSES:
8p, 11q, 13q, 14q

GAINS:
5p, 8q, 17q

26
Q

What are the architectural growth patterns of DCIS?

A

Cribriform:
Fenestrated proliferation with multiple, round, rigid extracellular lumens with punched out appearance
Roman bridges

Micropapillary:
Papillary fronds and tufts lacking fibrovascular cores projecting into duct lumen
Papillae often have club shaped cells comprising the micropapillae are uniform in appearance

Papillary:
Papillary fronds containing prominent fibrovascular septa projecting into duct lumen, papillary cores generally lack myoepithelial cell layer

Solid:
Lumen of ducts or lobules filled with sheets of cohesive cells
Cells are evenly spaced especially in low or intermediate grade DCIS

Flat or clinging:
1 - 2 layers of generally high grade malignant cells lining a gland with a large empty lumen

Comedo:
Central expansile necrosis containing cellular debris, generally associated with high grade DCIS, frequently associated with coarse microcalcifications

27
Q

What is the Van Nuys Prognostic Index (VNPI)?

A

he VNPI was an attempt to objectively determine the aggressiveness of DCIS in terms of the likelihood of ‘local recurrence’ following ‘breast conserving’ surgeries.

28
Q

Describe Atypical Lobular Hyperplasia

A
  • small proliferation of discohesive, monomorphic epithelial cells.
  • may show pagetoid spread through ductal spaces
  • cytologically similar to LCIS… but limited to <1/2 duct
  • common in premenopausal women
  • Non-obligate precurser lesion
29
Q

Describe lobular carcinoma in situ

A

More that 50% of acini are filled with/expanded by the neoplastic cells

Non obligate precursor lesion

Most often not associated with mammographic findings

Increased incidence in owmen who are post meno-pausal on HRT

CLASSIC
* Discohesive, monomorphic epithelial cells.
* Originate from TDLU
* >50% acini are filled and expanded, moften >8 cells thick

PLEOMORPHIC
* Large epithelial cells
* Marked nuclear pleomorphism
* May see nucleoi, mitoses, intracytoplasmic vacuoles

FLORID
* Confluent, mass like lesion
* Little or no intervening stroma between distended TDLU
* often 50 cells thick

Intracytoplasmic vacuole - ** MUCICARMINE**positive (special stain)

30
Q

What is the treatment for LCIS

A

If CLASSIC on core biopsy:
No need to excise

if CLASSIC on excision:
No need for clear margins

if PLEOMORPHIC or FLORID:
excise with negative margins due to increased genomic instability and aggressive behaviour

Tamoxifen - reduced subsequent risk of ER+ by 50%

31
Q

Explain membranous IHC for normal epithelium, lobular neoplasia, DCIS

A

NORMAL EPITHELIUM:
Membrane +ve for E-cad, p120 catenin, B-catenin

DCIS:
**Membrane +ve **for E-cad, p120 catenin, B-catenin

LOBULAR NEOPLASIA:
-ve for E-cad, Cytoplasmic +ve for p120 catenin, **loses membrane **B-catenin

32
Q

What are the risks for invasive cancer with each in situ breast entity?

A

UDH:
2-fold increase risk for breast cancer

ADH:
4 to 5-fold increase risk for breast cancer

DCIS:
10x relative risk of invasive disease in ipsilateral breast
40% progress to invasive if left untreated

ALH:
4 to 5-fold increase risk for breast cancer
Life time risk is 15%
67% cancer occurs in ipsilateral breast, 33% in contralateral breast

LCIS:
8-10 fold relative risk for invasive breast cancer
remember Tamoxifen reduced risk by 50% om ER+ve LCIS

FRCPath Histopathology Part 1 (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions