breast - pinder - path · " fibroadenoma vs benign phyllodes tumour " phyllodes tumour...
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What Do Breast Pathologists Find Difficult?
Learning from My Referral Practice
Sarah E Pinder
• Approximately 2300 cases
• Epithelial proliferations (237)• Sub-typing invasive carcinoma (236)• Fibroepithelial lesions (206)• Papillary lesions (203)• Sclerosing lesions (166)
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Commonest lesions referred = epithelial proliferations
• FEA vs ADH vs DCIS; UEH vs DCIS; DCIS vs LCIS (PLCIS)
• Invasion vs DCIS vs seeding
• Apocrine lesions• Atypia in papillary lesions• Etc• Etc
CCC
FEA
FEA
FEA
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ADH LG DCIS
Features of UEH & of low gradeDCIS
Punched-out spaces, rigid bars, micropapillae
Cells as in low grade DCIS.Microfocal; < 2 duct spaces with complete involvement (mixed with UEH) (or < 2mm)
Evenly-spaced.Small, regular cells.Round nuclei.
Intraductal Epithelial Proliferations
Low grade DCIS
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Epithelial proliferation
CK5 (5/6), CK14, ER
Ck5 +ve Ck5 -ve, Ck14 -ve, ER +ve
(Intermediate or) high grade
morphology
UEH DCIS ADH, LG DCIS, LISN, FEA,
Ck5, Ck14 & ER
mosaicism
CK5
CK14
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CK5
CK14
Learning from my referral practice =
Confusion and variation in use of term ‘basal’ in the breast- Basal position;- Myoepithelial;- Cells expressing 'basal'
cytokeratins
Flat high grade DCIS Nuclear Grade of DCIS
Arch Pathol Lab Med 2009;133:15-25; UK Guidelines 2016
Feature Low grade Intermediate High
Pleomorphism Monotonous Intermediate Markedly pleomorphic
Size 1.5x to 2x RBCs or normal duct
epithelial nucleus
Intermediate >2.5 RBCs or normal epithelial
nucleusChromatin Usually diffuse,
finely dispersedIntermediate Usually vesicular,
regular chromatin distribution
Nucleoli Only occasional Intermediate Prominent, often multiple
Mitoses Only occasional Intermediate May be frequent
Orientation Polarized Intermediate Usually not polarized
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Atypical pregnancy-like hyperplasia Learning from my referral practice = HER2 can be helpful
Inter-observer variability in diagnosis• Retrospective study of original diagnostic reports vs
later review by specialist in breast pathology • 610 specimens sent for consultation and/or 2nd opinion • Poor agreement for diagnoses of pleomorphic LCIS
(κ=0.22)• Weak correlations for diagnoses of columnar cell
change (κ=0.38) & columnar cell hyperplasia (κ=0.32)• Moderate agreement (κ=0.47) for FEA; ADH (κ=0.44),
low-grade DCIS (κ=0.47), intermediate-grade DCIS (κ=0.45) and DCIS with microinvasion (κ=0.56)
• Good agreement for ALH (κ=0.62) & LCIS (κ=0.66) and high-grade DCIS (κ=0.68)Gomes DS et al. Diagn Pathol. 2014;9:121
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LCIS – classical type
Learning from my referral practice =Some cases are just very difficult……..
• All of 25 ILCs harboured an in-frame deletion in exon 7 (867del24) of E-cadherin gene & loss of wild type allele
• Even when E-cadherin is expressed, cadherin-catenin complex maybe nonfunctional
Learning from my referral practice =Don’t overinterpret E-cadherin
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Referral PracticeFibroepithelial lesions
• Classification of phyllodes tumour• Fibroadenoma vs benign phyllodes tumour• Phyllodes tumour with another element –
liposarcoma, carcinoma, melanoma
• 76 cases of benign or borderline PT • Mean age 37.9 years & median follow-up 58 months• 75 patients (99%), mean tumour size 27 mm, had BCS• Margins considered positive (tumour at ink) in 7 of 76
cases (9%) & negative in 65 of 76 (86%)• Small negative margins (<10mm) in 89%; <1mm in 71%;
no re-excision• No increase in local recurrence (4%) compared literature • “Systematic revision surgery for close or positive
surgical margins for benign PT should not be systematically performed”Moutte A et al. 2016. DOI: 10.1111/tbj.12623
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Phyllodes TumoursBenign Borderline Malignant
Mitoses 0-2/10HPF 2-5 >5, usually >10
Margins Circumscribed
(>90%)
Focally
infiltrative
Infiltrative (>50%)
Stromal
overgrowth
Mild Moderate Marked
Stromal atypia/
pleomorphism
Mild Moderate Marked
Heterologous
elements
No No Yes - Sometimes
Necrosis No No Yes - Sometimes
Tumour ?type• Metaplastic?• Metastasis or primary• Neuroendocrine• Salivary gland-like
(adenoid cystic; collagenous spherulosis; cylindroma; acinic cell)
• Histiocytoid/signet ring• Secretory• Thyroid-like• Mucinous
cystadenocarcinoma
Learning from my referral practice =Pathologists love to pigeon-hole Always remember clinical relevance
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MNF116
CAM5.2
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Learning from my referral practice =
All spindled cell lesions are metaplastic carcinomas, until proven
otherwise……
• Papillary lesions +/- invasion• Adenomyoepithelioma – diagnosis and classification• Granular cell tumour - classification• Classification of nodal disease – micromet vs ITCs• Squamous metaplasia, squamous cysts
Other referral cases - miscellany
Summary • Epithelial proliferations are lesions most commonly
referred & cause most major diagnostic discrepancies• We sometimes over-rely on IHC (E-cadherin) and
sometimes do not request the best markers• Difficulties include:
• Entities where reliance for diagnosis is heavily on one feature alone (e.g. flat high grade DCIS, PLCIS)
• Lesions with poorly described cut-points for classfication or difficulty in predicting clinical behaviour (e.g. PT classification, adenomyoepithelioma, some granular cell tumour)
• Rare lesions we see uncommonly, or have never seen before, or don’t know exist………
Cases for opinionPlease provide
• Background – patient & clinical details• Local opinion (+ provisional report)• Relevant slides – not necessarily all• IHC performed (avoids repeat)• Representative block (or unstained slides) for any
additional IHC• Level of urgency - but allow time for case to arrive
and be booked in ……• Any specific questions – diagnosis, clinical
management etc.• Be prepared for delay if IHC, additional
‘molecular’ tests, third opinion, needed
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