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
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
Diagnostic excision
Diagnosis
Flat epithelial atypia with calcification
Current Classification
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
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)
Non atypical (CCC, columnar cell hyperplasia): B2excision not required.
Atypical: FEA/atypical intraductal proliferation:B3 further tissue examination, submit all tissue, look for ADH, DCIS, invasion.
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.
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.
The concept of low nuclear grade lesions.
Key diagnostic points
FEA with relevant calcifications.
No ADH, DCIS or invasive carcinoma.
Case 4
Ck5/6
ER
CK5
ER
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
Look for myoepithelium
Examine solid areas in detail
Look for involvement of adjacent lobules (DCIS)
IHC can be helpful to support your morphological
diagnosis
Case 9
sclerosed papilloma/Duct adenoma
Papillomas may undergo sclerosis leading to distortion and pseudo infiltrative growth pattern DD carcinoma.
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
DCIS in a papilloma/papillary DCIS with post surgical changes
ER
Case 15
Atypical lobular hyperplasia (ALH), fibrocystic change
Tips
Look for dyscohesion (lobular neoplasia).
E-cadherin (negative in lobular neoplasia)
34E12 typically positive in lobular neoplasia (negative in DCIS)
Case 3
CK14
p63
Adenomyoepithelioma with calcification
Adenomyoepithelioma
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
Invasive ductal NST carcinoma, grade 1 Sclerosing adenosis
p63
Case 11
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
Mixed ductal NST and lobular carcinoma with DCIS and LCIS/PLCIS
E-cadherin can be helpful.
Note: e-cadherin can show heterogeneous/aberrant expression. Beta catenin and p120 can help in difficult cases.
Beta catenin
Case 8
Invasive mixed lobular and mucinous carcinoma with DCIS
Case 10
Invasive ductal carcinoma with basal like features.
Lymphovascular invasion
Morphological features of basal tumours
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.
Invasive ductal carcinoma with medullary like features will be used.
Case 14
Metaplastic (basal phenotype) carcinoma, grade 3 DCIS
Current WHO Classification for Metaplastic ca
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
Invasive lobular carcinoma invading muscle
ER
Case 2
Cam 5.2
Her2
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
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
Invasive micropapillary carcinoma
Case 16
Mammotome core biopsy for calcs, R3
p63
SMM
Invasive tubular carcinoma (B5b).
Tips
Look for calcification and comment on its presence/absence
Angulated tubules without conspicuous myoepithelium: suspect invasion, do myoepithelial markers to confirm.
Case 17
Increasing calcifications from previous screen, history of WLE for DCIS
Fat necrosis, haemosiderin deposition, scarring Calcification of appropriate size No DCIS or invasive carcinoma
Dystrophic calcification- B2
Case 18
U/S guided core biopsy of a solid mass
Myxoid fibroadenoma – B2
A minority can be associated with Carney’s syndrome: Familial condition of cutaneous and cardiac myxomas, spotty cutaneous pigmentation, endocrine overactivity and melanotic schwannoma.
Most patients with myxoid fibroadenomas, however, do not have a systemic abnormality: discuss at the MDT meeting
Case 19
Fibroepithelial lesion Stromal overgrowth Stromal cellularity Leaf-like pattern Stromal atypia Margin
Phyllodes tumour (borderline)
Cellular fibroepithelial lesion and benign phyllodes are managed similarly.
Borderline and malignant phyllodes: excision with margin.
DD: Spindle cell lesion on core biopsy
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