BREAST SLIDE SEMINAR

Sheffield Histopathology Course

Abeer Shaaban MBBCh PhD FRCPath Dip Health Res

Department of Histopathology and Molecular Pathology

St James’s University Hospital,
Leeds

23/06/10
 Plan

 Case discussion
 Approach to diagnosis
 Further tests
 Difficulties
Hyperplasia vs neoplasia
ADH vs DCIS
Papillary lesions
Fibroepithelial lesions
DCIS vs LCIS including pleomorphic type
DCIS vs invasive
Hyperplasia/atypia within a structured lesion
Columnar cell lesions
Some uncommon entities
Case 1
Ck5/6

ER
Case 1 diagnosis:

Intraduct papilloma with florid

epithelial hyperplasia of usual
type
HUT

• 20-30% of women undergoing breast biopsy.

No specific clinical features. Not identified
grossly.
• Microscopy: VARIABILITY: size, shape,
arrangement.
• Mild, moderate, florid/compact florid
Risk
No increased risk (no proliferative disease)
Apocrine change
Adenosis including florid
Duct ectasia
Mild epithelial hyperplasia of usual type

Slightly increased risk (1.5-2 times)

Hyperplasia of usual type, moderate or florid
Sclerosing adenosis, papilloma

Moderately increased risk (4-5times) (AH or border line lesions)

ADH or ALH

High risk (8-10 times)

Lobular CIS and non-comedo DCIS (Page & Dupont, 1990)
 HUT
Cytology Varied nuclear shape and chromatin pattern
with round nuclei mixed with elongated,
often asymmetric nuclei
Orientation Disordered and varied in distance and
and orientation of nuclei to one another.
placement Cytoplasmic borders are indistinct,
of cells frequent streaming or swirling pattern of
parallel cell placement
Intercellular Shapes of spaces are irregular in size and
spaces shape, frequently slit-like
 Tips
 Low power assessment first

 Look for a mixed cell population

 Do not over diagnose pleomorphism

 Exclude high grade nuclei (DCIS)

 Look for involvement of adjacent lobules (DCIS)

 IHC can be helpful to support your morphological

diagnosis
Case 2
 Case 2 diagnosis

DCIS AND LCIS

 Practical Tips

 Look for dyscohesion (LCIS), architecture of DCIS (papillary,

cribriform….etc)

 Do not rely on ductal/lobular involvement.

 E-cadherin (negative in lobular neoplasia)

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

 Remember
 DCIS involving lobules

 LCIS involving ducts

 Necrosis with PLCIS

 Cals with LCIS

 Combined DCIS/ in situ lobular neoplasia

 Exclude fixation artefact

 IN SITU LOBULAR NEOPLASIA

 Most premanopausal (PLCIS might be slightly

older)
 <10% post-menopausal
 Decade earlier than DCIS
 50% other ipsilateral foci: measuring size not
required
 30% contralateral
 8X invasive risk for LCIS over lifetime
 Marker of risk ?
Pleomorphic LCIS
(DD DCIS)
 No formal accepted definition
 Larger more pleomorphic eccentrically placed
nuclei
 Apocrine differentiation
 Some more discohesive
 Central necrosis and calcification
 Immunoprofile different: high proliferation,
more likely p53+ (can be ER-, Her2+)
 DCIS
 Direct precursor

 25% of screen detected breast ca

 Calcs: most common presentation but may present

as a MASS

 Treatment: surgical excision of lesion, clear margins

Case 3
 ER

CK5/6
Case 3 diagnosis

PAPILLIMA WITH PARTIAL

INVOLVEMENT BY DCIS
How would IHC help?

 In situ vs invasive: SMM, CK5/6, CK14,p63,

laminin, type IV collagen
 Hyperplastic vs neoplastic: ER/PR, CK5/6,
CK14
 Ductal vs lobular: e-cadherin
 IHC not helpful in DD ADH from DCIS
Case 4
 Case 4 diagnosis

The so called “encysted

papillary carcinoma”
 Practical Tips

 Look for myoepithlium.

 Immunohistochemistry for myoepithelial markers:

SMM, P63 (others: CK5, CK14, collagen IV, SMA).

 Use a panel of markers.

 Look for convincing invasion

Case 5
 Case 5 diagnosis

Phyllodes tumour
 Assess: margin, stromal overgrowth, stromal
cellularity, atypia, mitoses, periglandular
stromal condensation, necrosis.

 Benign, borderline, malignant phyllodes

tumour.

 State of margin.
Case 6
 Case 6 diagnosis

Adenomyoepithelioma
Adenomyoepithelioma

 Spindle, tubular, lobulated (most common).

 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
CK14
 Case 7 diagnosis

Nipple Adenoma
 Myoepithelial hyperplasia, focal necrosis,
variable mitotic activity: do not interpret as
DCIS.

 DD Papilloma, DCIS, abscess, Paget’s

disease.
Case 8
Case 8 diagnosis

 Flat epithelial atypia and ADH

NOT HIGH GRADE NUCLEI!
Columnar cell lesions

Clinical relevance:
 Follow up studies
1. 9000 biopsies diagnosed as benign: 25 diagnosed
as clinging, one patient recurred (follow up 17.5yrs)
Eusebi et al., 1994
2. 59 clinging ca, no local rec (follow up 5.4 yrs)
EORTC 10853
3. Benign biopsies from 684 patients reviewed, ccc
with calcs or atypia : increased risk for developing
breast cancer.
(Shaaban et al 2002)
CCC with Atypia on NCB

Excision shows in situ or invasive ca

17.5% Davies et al 2006
21% Lakshmi et al 2006
23% Kunju and Kleer 2007
38.1% Kumaroswamy et al
2008 (Leeds cohort)
16.6%(20% for ADH) Darfishian et al 2009
25%-33% Abstracts Brogi et al 2002,
Harigopal 2002, Nasser 2003
Non obligate precursors?

LOH 11q, 16q, 3p (similar to associated DCIS, IC)

Moinfar et al 2000

LOH 9q, 10q, 17p and 17q Dabbs et al 2006

CGH: 5/8 cases Simpson et al 2005

Columnar Cell lesions

Classification
 Columnar cell change (without atypia)

 Flat epithelial atypia (one or more layers)

 ADH
 Management of CCC on NCB

 Non atypical (ccc, columnar cell hyperplasia:

excision not required)

 Atypical: FEA/atypical intraductal

proliferation: excision, submit all tissue, look
for ADH, DCIS
Case 9
 Case 8 diagnosis

Flat epithelial atypia with ADH

 Case 9 diagnosis

Cystic Hypersecretory DCIS

 Large distended cystic spaces, some contain
eosinophilic material resembling thyroid
colloid.

 Tumour cells are usually arranged in short

papillary structures

 DD Cystic hypersecretory hyperplasia,

clinging DCIS.
Case 10
SMM
 Case 10 diagnosis

Invasive Ductal Carcinoma

Case 11
 Case 11diagnosis

Invasive lobular ca
(pleomorphic) +
lymphovascular invasion
Case 12
 Case 12 diagnosis

Clear cell Carcinoma

Clear cell ca

 Clear cells, finely granular cytoplasm, PAS positive.

 Histology, grade 2-3, rarely grade 1.

 Reports suggest it is more aggressive, with higher

incidence of nodal metastasis.

 No analyses comparing stage for stage to other

histological types
Clear cells in breast lesions
 Myoepithelial cells: myoepith hyperplasia,
adenomyoepithelioma
 DCIS
 Primary carcinoma: DD: lipid rich ca,
histiocytoid ca, ductal carcinoma with basal
features.
 Metastatic: Metastatic clear cell ca (e.g
renal),
Case 13
 Case 13 diagnosis

Large cell neuroendocrine

carcinoma
Neuroendocrine tumours of the
breast
 Neuroendocrine differentiation is not
uncommon.
 Neuroendocrine tumours can be well
differentiated (e.g carcinoid), small cell, large
cell ne ca.
 15% of neuroendocrine breast tumours are
poorly differentiated.
Large cell neuroendocrine ca

 Large clusters of cells with moderate

abundant cytoplasm, vesicular to finely
granular chromatin, high mitotic rate (18-
65/hpf).

 The tumour has NE features similar to lung

tumours (DD).
TTF1
NSE
Large cell neuroendocrine ca

 Rare
 Where documented IHC profile is identical to
lung tumours
 Clinicopathological correlation, single/multiple
tumours
 Histologically: look for DCIS, well
differentiated NE tumours are ER pos
Case 14
Cam5.2
her2
 Case 14 diagnosis

Paget’s disease of the 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 15
SMM
p63
 Case 15 diagnosis
Tubular carcinoma
Tubular Carcinoma

 Angulated tubules (>90% of lesion)

 Apical snouts often seen
 Absent myoepithelium
 Desmoplastic stroma

 NO marked nuclear pleomorphism

DD

 Radial scar/complex sclerosing lesion:

Fibroelastotic stroma, preserved myoepithelium
Case 16
Case 16 diagnosis

 Metaplastic carcinoma (mixed epithelial and

mesenchymal with myxoid/chondroid
metaplasia)= matrix producing
carcinoma=carcinosarcoma
Metaplastic carcinoma WHO
classification
 Pure epithelial: (Sq CC, adeno with spindle
different, adenosquamous)
 Mixed epith mesenchymal: (ca with chondroid
or osseous metaplasia, carcinosarcoma)

 Metaplastic carcinoma is a variant of basal

phenotype cancer
DD

 Metastatic carcinoma
 Sarcoma (primary or metastatic)
Morphological features of basal
tumours
 Pushing margin
 Central scarring/necrosis
 Syncytial growth pattern
 Prominent lymphocytic infiltrate
Panel for basal phenotype tumours

 ER, PR, HER2

 CK5, CK14
 EGFR
 P63
 Thank you

Abeer.shaaban@leedsth.nhs.uk