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RC > Breast > Flashcards

Breast Flashcards

1
Q

Classify papillary lesions of the breast

A

Papilloma
Papilloma with ADH or DCIS
Papillary DCIS
Encapsulated papillary CA
Solid papillary CA (in situ and invasive)
Invasive papillary CA

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2
Q

Features of solid papillary carcinoma

A

In situ or invasive carcinoma with solid growth pattern and delicate fibrovascular cores
Frequently shows neuroendocrine differentiation
ER/PR+ HER2-
Unless conventional invasion, typically indolent and staged as pTis regardless of myoeps

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3
Q

Papilloma with ADH vs papilloma with DCIS

A

Papilloma with atypia and loss of myoeps
ADH <3mm
DCIS >/=3mm

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4
Q

Intraductal papilloma vs encapsulated papillary CA

A

Papilloma - well developed fibrovascular cores, 2 cell types, often have apocrine change, myoeps present, nipple discharge
EPC - delicate fibrovascular cores, 1 cell type, atypical epithelial cells, absent myoeps, usually presents as a mass

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5
Q

IHC of encapsulated papillary CA

A

Neg for myoeps
CK5/6 neg
ER/PR+

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6
Q

Recommended management for papillary lesion diagnosed on core needle biopsy

A

If radiologic concordance and lesion appears benign on biopsy, clinical follow up
In some centres, local excision may be recommended

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7
Q

Definition of invasive papillary carcinoma

A

Invasive mammary CA with predominantly papillary morphology (>90%) and infiltrative growth pattern

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8
Q

Grading of invasive papillary carcinoma

A

Nottingham grading system

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9
Q

Differential diagnosis of mammary paget disease

A

Paget disease
Bowen disease
Melanoma in situ
Toker cell hyperplasia

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10
Q

IHC to differentiate DDx of mammary paget disease

A

Paget: CK7+ Cam5.2+ EMA+ HER2+, may express mucins
Bowen: HMWK+
MIS: MelanA+
toker cell hyperplasia: CK7+, may be Cam5.2+St

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11
Q

Staging of paget disease

A

If not associated with underlying invasive CA, then pTis
If associated with underlying invasive CA, staged by that

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12
Q

Prognosis of pagets disease

A

Determined by variables of associated carcinoma

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13
Q

Classify mesenchymal tumors of the breast

A

Fibroepithelial/biphasic: fibroadenoma, phyllodes
Fibro/myofibroblastic: myofibroblastoma, PASH, nodulart fasciitis, fibromatosis, IMT
Adipocytic: lipoma, angiolipoma, liposarc
Smooth muscle: leiomyoma, meiomyosarcoma
Neural: Granular cell tumor, neurofibroma, schwannoma
Vascular: hemangioma, angiomatosis, atypical vascular lesion, angiosarc

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14
Q

Gross and histologic characteristics of a phyllodes

A

Gross - well-circumscribed, gray-white cut surface, solid with cystic areas, fleshy leaflike processes
Histo - stromal hypercellularity, expansile stroma and benign epithelial elements, leafy architecture

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15
Q

Features that differentiate benign and malignant phyllodes tumor

A

Increased stromal mitoses (5/10hps is borderline, 10/10hpfs is significant)
Marked stromal hypercellularity
Stromal atypia
Stromal overgrowth (one 4x field without epithelium)
Infiltrating margin
Tumor necrosis
Malignant heterologous elements even in the absence of other criteria EXCEPT WDLS

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16
Q

Differentiate phyllodes tumor from fibroadenoma

A

Phyllodes - expansile, hypercellular, mitotically active stroma, leaflike architecture

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17
Q

Treatment for phyllodes

A

Malignant - local excision with wide margin
Benign - local excision preferably with wide margin
Borderline - local excision with wide margin

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18
Q

Differentiate malignant phyllodes from metaplastic CA

A

Look for epithelial lined clefts
Phyllodes stroma should be negative for epithelial markers and positive for CD34 and BCL-2
Broad panel of epithelial markers for metaplastic CA

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19
Q

Classify lymphomas of the breast

A

Primary breast lymphoma
Disseminated lymphoma with breast involvement
Recurrent lymphoma (?)
Breast implant associated anaplastic large cell lymphoma

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20
Q

Most common types of lymphomas seen in the breast

A

Most common DLBCL
Burkitt lymphoma when bilateral

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21
Q

Clinical and pathologic features of breast implant associated anaplastic large cell lymphoma

A

Rare CD30+ ALK- ALCL associated with breast implants (specifically textured ones)
Usually develops 7-10y after placement of textures surface implant, present with unilateral effusion with unremarkable or erythematous overlying skin

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22
Q

Handling of specimens from patients with clinical concern for breast implant associated anaplastic large cell lymphoma

A

Seroma fluid should be taken for cytopathology with cell block preparation, flow cytometry, C&S (if sufficient)
Capsulectomy specimens must be sampled thoroughly and mapped
Lymph nodes and capsular masses submitted fresh for lymphoma protocol

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23
Q

Which breast tumors should be tested for hormone receptors and HER2

A

All primary invasive breast CAs
All recurrent breast CAs
All metastatic breast CAs

24
Q

Optional breast biomarkers

A

Ki67
Multigene expression assays
PD-L1

25
Q

% of ER+ breast CAs

A

~80%

26
Q

% of HER2+ breast CAs

A

~10-20%

27
Q

Clinical uses for HER2 testing

A

Prognostic - associated with worse prognosis
Predictive - sensitivity to anti-HER2 therapy

28
Q

Methods for HER2 testing

A

IHC for protein overexpression
ISH to detect gene amplification

29
Q

Interpretation for IHC of HER2 testing

A

Positive 3+: complete, intense, circumferential membrane staining in >10% of invasive tumor cells
Equivocal 2+: incomplete and/or weak moderate circumferential membrane staining in >10% of invasive tumor cells or complete, intense, circumferential staining in </=10% of invasive tumor cells - reflex ISH or test new specimen
Negative 1+: incomplete, faint/barely perceptible membrane staining in >10% invasive tumor cells
Negative 0: no staining or incomplete faint/barely perceptible membrane staining in </=10% of tumor cells

30
Q

Interpretation of HER2 ISH

A

Group 1 (Positive, amplified) - HER2/CEP17 ratio >/=2 AND average HER2 copy number >/=4 signals/cell
Group 2 ( nonamplified) - HER2/CEP17 ratio >/=2 AND average HER2 copy number <4 signals per cell
Group 3 (Amplified) - HER2/CEP17 ratio <2 AND average HER2 copy number >/=6 signals per cell
Group 4 (non amplified) - HER2/CEP17 ratio <2 AND average HER2 copy number 4-6
Group 5 (negative, nonamplified) - HER2/CEP17 ratio <2 AND average HER2 copy number <4 signals per cell

31
Q

Which HER2 ISH groups require additional workup

A

Group 2, 3, 4

32
Q

Preanalytic variables for reporting biomarkers as per ASCO and CAP guidelines

A

Cold ischemia time
Duration of fixation
Type of fixative
Treatment of tissue that can potentially alter immunoreactivity (eg decal)
Status of internal and external controls
Adequacy of sample for evaluation
Primary antibody clone used
Regulatory status

33
Q

Reporting of ER and PR status

A

Positive - percentage of cells with nuclear positivity and average intensity of staining
Negative - status of internal control

34
Q

Cutoff for positivity of ER and PR biomarker testing

A

1%

35
Q

Factors that impact results of ER/PR staining

A

Exposure of tumor cells to heat
Delay in fixation
Under or over fixation
Type of fixative
Quality, freshness, concentration of antibodhy
Nonoptimized method of antigen retrieval
Decal
Method of antigen retrieval
Dark hematoxylin counterstain obscuring faintly positive staining

36
Q

Reasons for false positive ER, PR, or HER2 result

A

Use of impure antibody that cross-reacts with another antigen
Edge artifact
Misinterpretation of entrapped normal cells or in situ component
Analysis by an image analysis device that mistakenly counts overstained nuclei
Cytoplasmic positivity
Overstaining, potentially due to improper antibody titration

37
Q

Factors impact ability to obtain results for HER2 testing by FISH

A

Prolonged fixation
Fixation in nonformalin fixatives
Procedures or fixation involving acid (eg decal)
Insufficient protease treatment of tissue

38
Q

Issues to be addressed by pathologist on H&E or HER2 IHC slide prior to FISH testing

A

Identification of invasive carcinoma and area to be scored
Identification of DCIS (oftentimes will show amplification when the invasive component will not)

39
Q

Reasons Ki67 not currently recommended for breast CA

A

Lack of consensus on scoring
Lack of consensus on definition of low versus high expression
Lack of an appropriate cut point for positivity
Lack of consensus on which part of the tumor should be tested (eg leading edge, hotspot, average)
Paucity of data on effect of preanalytic variables

40
Q

Features to distinguish sclerosing adenosis from invasive ductal carcinoma

A

Lobulated clustered arrangement
Compressed and distorted tubular lumens
Fibrous stroma compressing tubules
Tubules lined by 2 cell layers
Tubules invested by basement membrane

41
Q

Describe characteristic features of microglanular adenosis

A

Haphazard proliferation of small round tubules
Tubules have open lumens
Tubules lined by single layer of epithelial cells
Lumen contains colloid-like secretory material
Dense fibrous stroma
Multilayered basement membrane on EM
Epithelial cells positive for S100 and CKs
Lack expression of ER/PR

42
Q

Clinical significance and management of MGA

A

May be mass forming or associated with microcalcs
Is a benign proliferation, but atypical forms and carcinomas arising from MGA can occur (triple negative)
May be nonobligate precursor of basal-type breast carcinoma
Should be excised with clear margins

43
Q

Benign breast lesions and relative risk of developing invasive carcinoma

A

Nonproliferative changes: 1x
Proliferative without atypia: 1.5-2x
Proliferative with atypia: 4-5x
CIS: 8-10x

44
Q

Histologic features of radial scar

A

Stellate configuration
Central elastosis and fibrosis
Entrapped distorted ductules in central scar
Dilated ductules at the periphery with various patterns of epithelial hyperplasia
Tubules lined by 2 layers of cells
IHC for some myoep markers may be aberrrant in ducts within central nidus
size < 1cm

45
Q

Clinical significance of radial scar

A

Benign mimic of cancer
Relative risk akin to proliferative without atypia
Management remains controversial

46
Q

Radial scar vs complex sclerosing lesion

A

Radial scar <1cm
Complex sclerosing lesion >1cm

47
Q

Histologic features of UDH

A

Architectural: peripheral elongated clefts, intraductal secondary spaces irregular in size, shape, location, steaming, tufts and mounds projecting into lumen, irregularly shaped/twisted bridges
Cellular: 2 cell types, lack of atypia, heterogeneous population, indistinct cell borders, apocrine metaplasia, absence of necrosis
IHC: heterogeneous expression of ER and CK5/6 mosaic

48
Q

IHC to differentiate UDH from ADH/LGDCIS

A

UDH: CK5/6 mosaic positive, ER patchy
ADH/DCIS: CK5/6 negative, ER diffuse pos

49
Q

Definition of ADH

A

Epithelial proliferative lesion with cytologic and architectural features similar to low grade CIS but less developed in extent. Partial involvement of multiple duct spaces OR uniformly involved duct spaces but no more than 2-3mm.

50
Q

Benign DDx for invasive breast CA

A

complex sclerosing lesion/radial scar
Sclerosing adenosis
Microglandular adenosis
Sclerotic papilloma

51
Q

Malignant lesions that mimic collagenous spherulosis

A

Adenoid cystic CA
DCIS, cribriform

52
Q

WHO classification of columnar lesions

A

Columnar cell change
Columnar cell hyperplasia
FEA

53
Q

Clinical significance of columnar cell lesions

A

Can be associated with calcs
Nonobligate precursors of ADH, low grade DCIS and low grade invasive CA
Clear margins for any columnar cell lesion is not required

54
Q

Clinical and histologic features of nipple adenoma

A

Clinical - nipple discharge, swelling of the nipple with or without erosion
Histologic - well circumscribed, haphazardly arranged proliferating tubular structures with myoeps, varying degrees of epithelial hyperplasia, fibrous stroma, areas of papillary architecture are possible

55
Q

Explain next steps for when a core biopsy for calcs does not show any calcs

A

Check patient ID and labels
Check radiographs for calcs
polarize to search for calcium oxalate crystals
Cut deepers
Can take X rays of the block, cut to the level of the calcs
If no calcs, have the X rays reviewed by radiology to confirm presence or absence of calcs
If no calcs in block but confirmed in patient radiographs, report as is - calcs may have fallen out of the block during trimming

56
Q
A

RC (20 decks)

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