BREAST PATHOLOGY

BREAST SLIDE SEMINAR Manchester FRCPath Course Abeer Shaaban MBBCh PhD FRCPath Dip Health Research Queen Elizabeth Hospital, Birmingham

Outline    

Case discussion Approach to exam cases Role of immunohistochemistry Brownie points!

Exam cases  

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Tiny malignant tumour: lobular pseudo infiltrative benign lesions: papilloma, radial scar Uncommon entities Hot topics: basal phenotype cancer Two pathologies Borderline lesions/DD Calcification in core biopsy

Case 12

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Diagnostic excision

Diagnosis 

Flat epithelial atypia with calcification

Current Classification 

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Columnar cell change without atypia: columnar cell change/columnar cell hyperplasia Flat epithelial atypia

Note: Architectural complexity: ADH/DCIS High grade nuclei: DCIS Immunohistochemistry: not helpful

Columnar cell change

FEA 

Uniform rounded nuclei resembling cells of low/intermediate grade DCIS

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Pleomorphic cells (not high grade)

CCC

CC hyperplasia

FEA

ADH

Int contour

irregular

irregular

smooth

variable

Nuclei

columnar

columnar

Col/cuboidal

cuboidal

Cell layers

2

>2

variable

variable

architect

flat

hyperplastic

Flat/tufts Not complex

complex

N/C ratio

normal

normal

increased

increased

Atypia

Absent

absent

Present (uniform present nuclei/ pleomorphism

Management of CCC on NCB 

Examine cores at multiple levels (at least 3)

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Non atypical (CCC, columnar cell hyperplasia): B2excision not required.

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Atypical: FEA/atypical intraductal proliferation:B3 further tissue examination, submit all tissue, look for ADH, DCIS, invasion.

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High grade cytological atypia: DCIS (flat type), B5a

New B3 Management guidelines 

Second line VAB (VAE =Vacuum Assisted Excision) is the method of choice for further sampling of B3 lesions.

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This applies to all B3 lesions except: papilloma with atypia, cellular fibroepithelial lesions and other rare B3 lesions (spindle cell lesions, vascular lesions…etc).

Columnar cell lesions in surgical excision 

With atypia: good sampling to exclude more established lesions.

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The concept of low nuclear grade lesions.

Key diagnostic points 

FEA with relevant calcifications.

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No ADH, DCIS or invasive carcinoma.

Case 4

Ck5/6

ER

CK5

ER

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Intraduct papilloma with florid epithelial hyperplasia and fibrosis

Useful Immunohistochemistry Papilloma

Papillary DCIS

CK5

mixed

Neg

ER

Patchy pos

Uniformly pos

SMM

present

absent

Tips 

Assess the overall architecture of the lesion

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Look for myoepithelium

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Examine solid areas in detail

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Look for involvement of adjacent lobules (DCIS)

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IHC can be helpful to support your morphological

diagnosis

Case 9

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sclerosed papilloma/Duct adenoma

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Papillomas may undergo sclerosis leading to distortion and pseudo infiltrative growth pattern DD carcinoma.

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Duct adenoma: solid occlusive adenosis growth pattern within a duct. Focal papillary architecture may be seen.

Tips   

Look for focal papillary pattern Look for myoepithelium IHC for myoepithelium: SMM, p63

Case 13

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DCIS in a papilloma/papillary DCIS with post surgical changes

ER

Case 15

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Atypical lobular hyperplasia (ALH), fibrocystic change

Tips 

Look for dyscohesion (lobular neoplasia).

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E-cadherin (negative in lobular neoplasia)

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34E12 typically positive in lobular neoplasia (negative in DCIS)

Case 3

CK14

p63

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Adenomyoepithelioma with calcification

Adenomyoepithelioma  

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Spindle, tubular, lobulated (most common).

Well circumscribed/infiltrative lesion Fibrous septa with central hyalinization/infarction : common in lobulated lesions.

Cells: clear, eosinophilic, plasmacytoid.

Satellite nodules can be seen.

Mitotic activity 2 or less/10hpf.

Both epithelial and myoepithelial components can undergo malignancy.

Case 7

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Invasive ductal NST carcinoma, grade 1 Sclerosing adenosis

p63

Case 11

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Radial scar

DD Radial scar/complex sclerosing lesion: Architecture Fibroelastotic stroma preserved myoepithelium No epithelial atypia 

DD Tubular Carcinoma/grade 1 carcinoma   

Absent myoepithelium Desmoplastic stroma Epithelial atypia

Case 1

E-cadherin

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Mixed ductal NST and lobular carcinoma with DCIS and LCIS/PLCIS

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E-cadherin can be helpful. 

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Note: e-cadherin can show heterogeneous/aberrant expression.

Beta catenin and p120 can help in difficult cases.

Beta catenin

Case 8

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Invasive mixed lobular and mucinous carcinoma with DCIS

Case 10

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Invasive ductal carcinoma with basal like features.

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Lymphovascular invasion

Morphological features of basal tumours   

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Pushing margin Central scarring/necrosis Syncytial growth pattern Prominent lymphocytic infiltrate

Basal cytokeratins   

CK5 (or CK5/6) CK14 Others : p63, EGFR

Medullary carcinoma 

This terminology will be dropped in the pending Blue WHO Book.

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Invasive ductal carcinoma with medullary like features will be used.

Case 14

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Metaplastic (basal phenotype) carcinoma, grade 3 DCIS

Current WHO Classification for Metaplastic ca     

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Squamous cell carcinoma Spindle cell carcinoma Carcinoma with mesenchymal differentiation Low grade adenosquamous ca Fibromatosis like ca Mixed

All have a basal phenotype

Case 6

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Invasive lobular carcinoma invading muscle

ER

Case 2

Cam 5.2

Her2

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Paget’s disease of nipple with DCIS

Paget’s cells    

Positive for EMA, low molec wt cytokeratin Majority Her2 positive May express ER, PR Negative for HMB45, Melan A (and also S100)

DD   

Melanoma Squamous cell carcinoma in situ Clear cell change/Toker cells

Clues  

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Look for underlying DCIS/invasion.

Paget’s cells may lie singly in all layers of epidermis or as basal clusters Look for melanin, junctional activity, full thickness dysplasia

Case 5

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Invasive micropapillary carcinoma

Case 16

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Mammotome core biopsy for calcs, R3

p63

SMM

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Invasive tubular carcinoma (B5b).

Tips 

Look for calcification and comment on its presence/absence

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Angulated tubules without conspicuous myoepithelium: suspect invasion, do myoepithelial markers to confirm.

Case 17

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Increasing calcifications from previous screen, history of WLE for DCIS

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Fat necrosis, haemosiderin deposition, scarring Calcification of appropriate size No DCIS or invasive carcinoma

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Dystrophic calcification- B2

Case 18

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U/S guided core biopsy of a solid mass

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Myxoid fibroadenoma – B2

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A minority can be associated with Carney’s syndrome: Familial condition of cutaneous and cardiac myxomas, spotty cutaneous pigmentation, endocrine overactivity and melanotic schwannoma.

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Most patients with myxoid fibroadenomas, however, do not have a systemic abnormality: discuss at the MDT meeting

Case 19

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Fibroepithelial lesion Stromal overgrowth Stromal cellularity Leaf-like pattern Stromal atypia Margin

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Phyllodes tumour (borderline)

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Cellular fibroepithelial lesion and benign phyllodes are managed similarly.

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Borderline and malignant phyllodes: excision with margin.

DD: Spindle cell lesion on core biopsy  

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Look for biphasic pattern Look for DCIS A panel of cytokeratins (including basal cytokeratins) to exclude metaplastic carcinoma

Birmingham Breast update course 1 November 2019

www.breastpathologyupdate.com

Thank you