Breast Pathology - Dr. Abeer Shaaban - February 2025

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BREAST SLIDE SEMINAR

Manchester FRCPath Course

Professor Abeer Shaaban

MBBCh PhD FRCPath Dip Health Research

Queen Elizabeth Hospital Birmingham & University of Birmingham

Outline

ā—¼ Case discussion

ā—¼ Approach to exam cases

ā—¼ Role of immunohistochemistry

ā—¼ Brownie points!

Exam cases

ā—¼ Tiny malignant tumour: lobular

ā—¼ pseudo infiltrative benign lesions: papilloma, radial scar

ā—¼ Uncommon entities

ā—¼ Hot topics: basal phenotype cancer

ā—¼ Two pathologies

ā—¼ Borderline lesions/DD

ā—¼ Calcification in core biopsy

Case 12

ā—¼ Diagnostic excision

Diagnosis

ā—¼ Flat epithelial atypia with calcification

Current Classification

ā—¼ Columnar cell change without atypia: columnar cell change/columnar cell hyperplasia

ā—¼ Flat epithelial atypia

Note: Architectural complexity: ADH/DCIS

High grade nuclei: DCIS

Immunohistochemistry: not helpful

Columnar cell change

FEA

ā—¼ Uniform rounded nuclei resembling cells of low/intermediate grade DCIS

ā—¼ Nuclear pleomophism (not high grade)

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 nuclei/ pleomorphism present

Management of CCC on NCB

ā—¼ Examine cores at multiple levels (at least 3)

ā—¼ Non atypical (CCC, columnar cell hyperplasia): B2excision not required.

ā—¼ Atypical: FEA/atypical intraductal proliferation:B3 further tissue examination, submit all tissue, look for ADH, DCIS, invasion.

ā—¼ High grade cytological atypia: DCIS (flat type), B5a

New B3 Management guidelines

ā—¼ Second line VAB (VAE =Vacuum Assisted Excision) is the method of choice for further sampling of B3 lesions.

ā—¼ This applies to all B3 lesions except: papilloma with atypia, cellular fibroepithelial lesions and other rare B3 lesions (spindle cell lesions, vascular lesionsā€¦etc).

Third International Consensus

ā—¼ Swiss Minimal-Invasive Breast Biopsy (MIBB) Working Group

ā—¼ Voting by experts: 11 pathologists, 12 radiologists, and 10 specialist gynecologists/specialist medical oncologists/breast surgeons from seven European countries.

ā—¼ If a core-needle biopsy (CNB) returned as B3 lesion on histology, should the lesion be excised?

ā—¼ If so, should it be excised using vacuum-assisted biopsy (VAB) or open surgical excision (OE)?

ā—¼ If the VAB returned a B3 lesion on histology and if the lesion was completely removed on imaging, is surveillance acceptable or should a repeat VAB or OE be performed?

Elfgen et al Virchows Archives 2023 483, pages5ā€“20 (2023)

Summary of atypia follow up

ā—¼ Current UK guidelines, a yearly mammographic follow up for 5 yrs, still apply.

ā—¼ Consult with colleagues and audit your B3 rate.

ā—¼ ? Effect of digital reporting on atypia diagnosis.

ā—¼ Ongoing work to refine follow up strategies.

ā—¼ Various guidelines available for management

Columnar cell lesions in surgical excision

ā—¼ With atypia: good sampling to exclude more advanced lesions.

ā—¼ Part of low nuclear grade neoplasia lesions.

ā—¼ Associated lesions

FEA and Lobular insitu neoplasia

Key diagnostic points

ā—¼ FEA with relevant calcifications.

ā—¼ No ADH, DCIS or invasive carcinoma.

Case 4

ā—¼ Intraduct papilloma with florid epithelial hyperplasia

and fibrosis

Useful Immunohistochemistry

Papilloma Papillary DCIS CK5

ER Patchy pos

Uniformly pos

SMM present absent

Tips

ā—¼ Assess the overall architecture of the lesion

ā—¼ Look for myoepithelium

ā—¼ Examine solid areas in detail

ā—¼ Look for involvement of adjacent lobules (DCIS)

ā—¼ IHC can be helpful to support your morphological diagnosis

Case 9

ā—¼ sclerosed papilloma/Duct adenoma

ā—¼ Papillomas may undergo sclerosis leading to distortion and pseudo infiltrative growth pattern DD carcinoma.

ā—¼ Duct adenoma: solid occlusive adenosis growth pattern within a duct. Focal papillary architecture may be seen.

ā—¼ Look for focal papillary pattern

ā—¼ Look for myoepithelium

ā—¼ IHC for myoepithelium: SMM, p63

Case 13

ā—¼ DCIS in a papilloma/papillary DCIS, with post surgical changes

Case 15

ā—¼

Atypical lobular hyperplasia (ALH), fibrocystic change

Tips

ā—¼ Look for discohesion (lobular neoplasia).

ā—¼ E-cadherin: negative in lobular neoplasia

ā—¼ Beta catenin: negative in lobular neoplasia

ā—¼ P120: Cytoplasmic in LCIS

Case 3

ā—¼ Adenomyoepithelioma with calcification

Adenomyoepithelioma

ā—¼ Spindle, tubular, lobulated (most common).

ā—¼ Well circumscribed/infiltrative lesion

ā—¼ Fibrous septa with central hyalinization/infarction : common in lobulated lesions.

ā—¼ Cells: clear, eosinophilic, plasmacytoid.

ā—¼ Satellite nodules can be seen.

ā—¼ Mitotic activity 2 or less/10hpf.

ā—¼ Both epithelial and myoepithelial components can undergo malignancy.

Case 7

ā—¼ Invasive ductal NST carcinoma, grade 1

ā—¼ Sclerosing adenosis

Case 11

ā—¼ Radial scar.

ā—¼ No atypia or malignancy.

ā—¼ Radial scar/complex sclerosing lesion:

Architecture

Fibroelastotic stroma preserved myoepithelium

No epithelial atypia

DD

Tubular Carcinoma/grade 1 carcinoma

ā—¼ Absent myoepithelium

ā—¼ Desmoplastic stroma

ā—¼ Epithelial atypia

Radial scar

ā—¼ On core biopsy: B3

ā—¼ Comment on presence/absence of atypia

ā—¼ Second line VAB (VAE)

Case 1

ā—¼ Mixed ductal NST and lobular carcinoma with DCIS and LCIS/PLCIS

ā—¼ E-cadherin can be helpful.

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

ā‘ Beta catenin and p120 can help in difficult cases.

Beta catenin

Case 8

ā—¼ Invasive mixed lobular and mucinous carcinoma with DCIS

Case 10

ā—¼ Invasive no special type (NST) carcinoma with basal like features.

ā—¼ Lymphovascular invasion

Morphological features of basal tumours

ā—¼ Pushing margin

ā—¼ Central scarring/necrosis

ā—¼ Syncytial growth pattern

ā—¼ Prominent lymphocytic infiltrate

Basal cytokeratins

ā—¼ CK5 (or CK5/6)

ā—¼ CK14

ā—¼ Others : p63, EGFR

Medullary carcinoma

ā—¼ This terminology was dropped in the Blue WHO Book (published Dec 2019).

ā—¼ Invasive ductal carcinoma with medullary like features to be used.

ā—¼ UK guidelines being updated.

ā—¼ Metaplastic carcinoma, grade 3

DCIS

Current WHO Classification for Metaplastic ca

ā—¼ Squamous cell carcinoma

ā—¼ Spindle cell carcinoma

ā—¼ Carcinoma with mesenchymal differentiation

ā—¼ Low grade adenosquamous ca

ā—¼ Fibromatosis like ca

ā—¼ Mixed

All have a basal phenotype

Case 6

ā—¼ Invasive lobular carcinoma invading muscle

Case 2

ā—¼ Melanoma

ā—¼ Squamous cell carcinoma in situ

ā—¼ Clear cell change/Toker cell hyperplasia

ā—¼ Pagetā€™s disease of nipple with DCIS

Pagetā€™s cells

ā—¼ Positive for EMA, low molec wt cytokeratin

ā—¼ Majority Her2 positive

ā—¼ May express ER, PR

ā—¼ Negative for HMB45, Melan A (and also S100)

Clues

ā—¼ Look for underlying DCIS/invasion.

ā—¼ Pagetā€™s cells may lie singly in all layers of epidermis or as basal clusters

ā—¼ Look for melanin, junctional activity, full thickness dysplasia

Case 5

ā—¼ Invasive micropapillary carcinoma

Case 16

ā—¼ Mammotome core biopsy for calcs, R3

ā—¼ Invasive tubular carcinoma (B5b).

ā—¼ Look for calcification and comment on its presence/absence

ā—¼ Angulated tubules without conspicuous myoepithelium: suspect invasion, do myoepithelial markers to confirm.

Case 17

ā—¼ Increasing calcifications from previous screen, history of WLE for DCIS

ā—¼ Fat necrosis, haemosiderin deposition, scarring

ā—¼ Calcification of appropriate size

ā—¼ No DCIS or invasive carcinoma

ā—¼ Dystrophic calcification- B2

Case 18

ā—¼ U/S guided core biopsy of a solid mass

ā—¼ Myxoid fibroadenoma

ā€“ B2

ā—¼ A minority can be associated with Carneyā€™s syndrome: Familial condition of cutaneous and cardiac myxomas, spotty cutaneous pigmentation, endocrine overactivity and melanotic schwannoma.

ā—¼ Most patients with myxoid fibroadenomas, however, do not have a systemic abnormality: discuss at the MDT meeting

Case 19

ā—¼ Fibroepithelial lesion

ā—¼ Stromal overgrowth

ā—¼ Stromal cellularity

ā—¼ Leaf-like pattern

ā—¼ Stromal atypia

ā—¼ Infiltrative margin

ā—¼ Phyllodes tumour (borderline)

ā—¼ Cellular fibroepithelial lesion and benign phyllodes are managed similarly.

ā—¼ Borderline and malignant phyllodes: excision with margin.

DD: Spindle cell lesion on core biopsy

ā—¼ Look for biphasic pattern

ā—¼ Look for DCIS

ā—¼ A panel of cytokeratins (including basal cytokeratins) to exclude metaplastic carcinoma

Technical considerations

B coding

Benign lesions mimicking malignant

Malignant lesions mimicking benign lesions

Metastases

Non epithelial lesions

Pitfalls in hormone receptors

Birmingham Breast Pathology Update Course

ā—¼ Friday 7 November (first week of November each year)

ā—¼ One day virtual with slide seminar

ā—¼ 7CPD credits

ā—¼ https://birminghambreastpathology.co.uk/ bbpuc-register/ Thank you

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