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Management of Papillary Lesions Diagnosed at Rad‐Path Concordant Core Biopsy (CNB)
Edi Brogi MD PhDAttending PathologistDirector of Breast PathologyISBP symposium @USCAP meeting ‐March 5, 2017
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Papilloma ???
Atypical papilloma EXCISIONPapillary DCIS EXCISION Papillary Carcinoma EXCISION
Management of Papillary Lesions Diagnosed at Rad‐Path Concordant CNB
Evaluation of a papillary lesionRULE OUT EPITHELIAL ATYPIA
Evaluate epithelial proliferation between two adjacent fibrovascular cores as if within a duct space
No atypia Atypia
Evaluation of papillary proliferations
• Pathologist’s expertiseupgrade rate to atypia/ carcinoma at EXC of benign papilloma at CNB
breast pathologists – 16.3% upgrade
non‐breast pathologists ‐ 26.3% upgrade
Jakate et al. Am J Surg Pathol 2012
• Use of IHC to rule out ADH or DCIS– ER
– CK5/6
– ADH5 cocktail
In an analysis of 204 benign papillary proliferations, IHC increased the identification of atypia/ carcinoma in CNB material, and reduced the rate of upgrade to carcinoma at EXC (7.4% vs 4.7%)
Koo JS et al. Breast Cancer Res Treat 2013
Strong and diffuse ER(+) and CK5/6(‐) support the diagnosis of ADH/ DCIS
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• Type and size of the imaging target– mass lesion– Ca2+– MRI mass or non‐mass enhancement
• Fragmented vs non‐fragmented cores– Fragmentation more common for
larger and more complex lesions– The nature of the epithelium may be
more difficult to evaluate in a fragmented specimen
• Complete removal by CNB– Small papillomas and/or vacuum
assisted CNB
Factors affecting upgrade at EXC of papilloma w/o atypia at CNB
Upgrade at EXC of papilloma w/o atypiaVacuum Assisted Biopsy (VAB) vs 14G CNB
Seely J The Breast Journal 2015
Papilloma @CNB: Upgrade rates to carcinoma or atypia in F/U EXC
author year ## carcinoma at EXC
atypia predictors recommendtotal invasive DCIS
Mercado 2006 36 2 (6%) 0 2 (5%) 8 (22%) none EXC
Bernik 2009 47 4 (9%) NS NS 13 (28%) none EXC
Lu 2012 66 4 (6%) 0 4 (6%) 8 (12%) none EXC
Fu 2012 203 34 (6%) 0 12 (5.9%) 41 (20%) none EXC
Tseng 2012 24 7 (29%) 2 (8%) 6 (25%) 0 none EXC
Rizzo 2012 234 21 (9%) 2 (0.9%) 19 (8.1%) 42 (17.9%) none EXC
Foley 2015 18827
(14.3%)7 (3.7%) 20 (10.6%) 21 (11%) older age EXC
Glenn 2015 146 7 (4.7%) NS NS 25 (17%) none EXC
Ahmadiyeh 2009 29 1 (3%) 0 1 (3%) NS none No EXC
Li 2012 370 7 (2%) 1 (0.3%)5 (1.3%)
1 P‐LCIS (0.3%)48 (13%) calcifications*
No EXC (except*)
Swapp 2013 77 0 0 0 0 none No EXC
Hong 2016 234 14 (6%) 5 (2%) 9 (4%) NS age >54 y; size >1 cm No EXC
Kim 2016 141 6 (2.6%) 2 (0.8%) 4(1.8%) 8 (5.6%) none No EXC
Nakhlis 2015 45 3 (6.6%) 1 (2.2%) 2 (4.4%) NS palpable mass No EXC
Pareja 2016 171 4 (2.3%) 2 (1.1%) 2 (1.1%) 39 (22.8%)synchronous carcinoma
No EXC
TOTAL 2011 141 (7%)22/ 1818 (1.2%)
86/1818 (4.7%)1 PLCIS
253/ 1703 (15%)
Papilloma @CNB: Upgrade rates to carcinoma or atypia in F/U EXC
author year ## carcinoma at EXC
atypia predictors recommendtotal invasive DCIS
Mercado 2006 36 2 (6%) 0 2 (5%) 8 (22%) none EXC
Bernik 2009 47 4 (9%) NS NS 13 (28%) none EXC
Lu 2012 66 4 (6%) 0 4 (6%) 8 (12%) none EXC
Fu 2012 203 34 (6%) 0 12 (5.9%) 41 (20%) none EXC
Tseng 2012 24 7 (29%) 2 (8%) 6 (25%) 0 none EXC
Rizzo 2012 234 21 (9%) 2 (0.9%) 19 (8.1%) 42 (17.9%) none EXC
Foley 2015 18827
(14.3%)7 (3.7%) 20 (10.6%) 21 (11%) older age EXC
Glenn 2015 146 7 (4.7%) NS NS 25 (17%) none EXC
Ahmadiyeh 2009 29 1 (3%) 0 1 (3%) NS none No EXC
Li 2012 370 7 (2%) 1 (0.3%)5 (1.3%)
1 P‐LCIS (0.3%)48 (13%) calcifications*
No EXC (except*)
Swapp 2013 77 0 0 0 0 none No EXC
Hong 2016 234 14 (6%) 5 (2%) 9 (4%) NS age >54 y; size >1 cm No EXC
Kim 2016 141 6 (2.6%) 2 (0.8%) 4(1.8%) 8 (5.6%) none No EXC
Nakhlis 2015 45 3 (6.6%) 1 (2.2%) 2 (4.4%) NS palpable mass No EXC
Pareja 2016 171 4 (2.3%) 2 (1.1%) 2 (1.1%) 39 (22.8%)synchronous carcinoma
No EXC
TOTAL 2011 141 (7%)22/ 1818 (1.2%)
86/1818 (4.7%)1 PLCIS
253/ 1703 (15%)
Papilloma @CNB: Upgrade rates to carcinoma or atypia in F/U EXC
author year ## carcinoma at EXC
atypia predictors recommendtotal invasive DCIS
Mercado 2006 36 2 (6%) 0 2 (5%) 8 (22%) none EXC
Bernik 2009 47 4 (9%) NS NS 13 (28%) none EXC
Lu 2012 66 4 (6%) 0 4 (6%) 8 (12%) none EXC
Fu 2012 203 34 (6%) 0 12 (5.9%) 41 (20%) none EXC
Tseng 2012 24 7 (29%) 2 (8%) 6 (25%) 0 none EXC
Rizzo 2012 234 21 (9%) 2 (0.9%) 19 (8.1%) 42 (17.9%) none EXC
Foley 2015 18827
(14.3%)7 (3.7%) 20 (10.6%) 21 (11%) older age EXC
Glenn 2015 146 7 (4.7%) NS NS 25 (17%) none EXC
Ahmadiyeh 2009 29 1 (3%) 0 1 (3%) NS none No EXC
Li 2012 370 7 (2%) 1 (0.3%)5 (1.3%)
1 P‐LCIS (0.3%)48 (13%) calcifications*
No EXC (except*)
Swapp 2013 77 0 0 0 0 none No EXC
Hong 2016 234 14 (6%) 5 (2%) 9 (4%) NS age >54 y; size >1 cm No EXC
Kim 2016 141 6 (2.6%) 2 (0.8%) 4(1.8%) 8 (5.6%) none No EXC
Nakhlis 2015 45 3 (6.6%) 1 (2.2%) 2 (4.4%) NS palpable mass No EXC
Pareja 2016 171 4 (2.3%) 2 (1.1%) 2 (1.1%) 39 (22.8%)synchronous carcinoma
No EXC
TOTAL 2011 141 (7%)22/ 1818 (1.2%)
86/1818 (4.7%)1 PLCIS
253/ 1703 (15%)
Papilloma @CNB: Upgrade rates to carcinoma or atypia in F/U EXC
author year ## carcinoma at EXC
atypia predictors recommendtotal invasive DCIS
Mercado 2006 36 2 (6%) 0 2 (5%) 8 (22%) none EXC
Bernik 2009 47 4 (9%) NS NS 13 (28%) none EXC
Lu 2012 66 4 (6%) 0 4 (6%) 8 (12%) none EXC
Fu 2012 203 34 (6%) 0 12 (5.9%) 41 (20%) none EXC
Tseng 2012 24 7 (29%) 2 (8%) 6 (25%) 0 none EXC
Rizzo 2012 234 21 (9%) 2 (0.9%) 19 (8.1%) 42 (17.9%) none EXC
Foley 2015 18827
(14.3%)7 (3.7%) 20 (10.6%) 21 (11%) older age EXC
Glenn 2015 146 7 (4.7%) NS NS 25 (17%) none EXC
Ahmadiyeh 2009 29 1 (3%) 0 1 (3%) NS none No EXC
Li 2012 370 7 (2%) 1 (0.3%)5 (1.3%)
1 P‐LCIS (0.3%)48 (13%) calcifications*
No EXC (except*)
Swapp 2013 77 0 0 0 0 none No EXC
Hong 2016 234 14 (6%) 5 (2%) 9 (4%) NS age >54 y; size >1 cm No EXC
Kim 2016 141 6 (2.6%) 2 (0.8%) 4(1.8%) 8 (5.6%) none No EXC
Nakhlis 2015 45 3 (6.6%) 1 (2.2%) 2 (4.4%) NS palpable mass No EXC
Pareja 2016 171 4 (2.3%) 2 (1.1%) 2 (1.1%) 39 (22.8%)synchronous carcinoma
No EXC
TOTAL 2011 141 (7%)22/ 1818 (1.2%)
86/1818 (4.7%)1 PLCIS
253/ 1703 (15%)
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papilloma w/o atypia at CNB: MSKCC Study
• MSKCC in‐house CNBs obtained 2003‐2013
• All CNB modalities
• CNB dx: “papilloma” or “papillary” lesion
• EXCLUDED: atypia, DCIS and/or invasive carcinoma
• All imaging studies and slides of CNB and EXC specimens re‐reviewed
• Rad‐path concordance reassessed for all cases
Pareja et al. Cancer. 2016;122(18):2819‐27.
MSKCC Study
196 rad‐path concordant CNB DX papilloma w/o atypia
171/196 (87%) cases with F/U EXC
25/196 (13%) cases No EXC‐ stable F/U
4 (2.3 %) cases withUPGRADE
167/171 (97.7%) cases with NO UPGRADE
Pareja et al. Cancer. 2016;122(18):2819‐27.
Clinical characteristics of patients with upgrade
Case 1 Case 2 Case 3 Case 4
Age (years) 50 51 52 58
Personal Hx BrCa No Yes Yes Yes
laterality - Ipsilateral Ipsilateral Ipsilateral
time - 2 yrs prior Concurrent Concurrent
histology - IDC IDC IDC
Pareja et al. Cancer. 2016;122(18):2819‐27.
Clinical characteristics of patients with upgrade
Case 1 Case 2 Case 3 Case 4
Age (years) 50 51 52 58
Personal Hx BrCa No Yes Yes Yes
laterality - Ipsilateral Ipsilateral Ipsilateral
time - 2 yrs prior Concurrent Concurrent
histology - IDC IDC IDC
Pareja et al. Cancer. 2016;122(18):2819‐27.
Patient undergoing excision for concurrent carcinoma; consider excision of papilloma
Cases with UpgradeCase 1 Case 2 Case 3 Case 4
Imaging target massnon-mass
enhancementmass Ca2+
Carcinoma in EXC DCIS DCIS ILC, DCIS ILC
Size of carcinoma 2 mm 2 mmILC 1 mm
DCIS 1.5 mm2 mm
Nuclear Grade 1 2-3 1 2
Residual IDP (mm) 7 mm 0.7 mm 8 mm 4 mm
Involves IDP Yes No No No
Distance of carcinoma DCIS involves ILC: 8 mmPareja et al. Cancer. 2016;122(18):2819‐27.
Cases with UpgradeCase 1 Case 2 Case 3 Case 4
Imaging target massnon-mass
enhancementmass Ca2+
Carcinoma in EXC DCIS DCIS ILC, DCIS ILC
Size of carcinoma 2 mm 2 mmILC 1 mm
DCIS 1.5 mm2 mm
Nuclear Grade 1 2-3 1 2
Residual IDP (mm) 7 mm 0.7 mm 8 mm 4 mm
Involves IDP Yes No No No
Distance of carcinoma from IDP
DCIS involves IDP
11 mmILC: 8 mm
DCIS: >10 mm15 mm
Pareja et al. Cancer. 2016;122(18):2819‐27.
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Cases with UpgradeCase 1 Case 2 Case 3 Case 4
Imaging target massnon-mass
enhancementmass Ca2+
Carcinoma in EXC DCIS DCIS ILC, DCIS ILC
Size of carcinoma 2 mm 2 mmILC 1 mm
DCIS 1.5 mm2 mm
Nuclear Grade 1 2-3 1 2
Residual IDP (mm) 7 mm 0.7 mm 8 mm 4 mm
Involves IDP Yes No No No
Distance of carcinoma from IDP
DCIS involves IDP
11 mmILC: 8 mm
DCIS: >10 mm15 mm
Pareja et al. Cancer. 2016;122(18):2819‐27.
Cases with UpgradeCase 1 Case 2 Case 3 Case 4
Imaging target massnon-mass
enhancementmass Ca2+
Carcinoma in EXC DCIS DCIS ILC, DCIS ILC
Size of carcinoma 2 mm 2 mmILC 1 mm
DCIS 1.5 mm2 mm
Nuclear Grade 1 2-3 1 2
Residual IDP (mm) 7 mm 0.7 mm 8 mm 4 mm
Involves IDP Yes No No No
Distance of carcinoma from IDP
Type of UPGRADE
DCIS in IDP
TRUE
11 mm
Incidental
ILC: 8 mm DCIS: >10 mm
Incidental
15 mm
Incidental
Papilloma size – wide range
lobule
Some studies: no EXC for imaging target size up to 1 cm or 1.5 cm
At present, no lowest size cutoff for the DX of papilloma
Morphologic mimics of micropapilloma at CNB
myoepithelial hyperplasia papillary usual ductal hyperplasia
(Micro)papilloma completely excised at rad‐path concordant
CNB No EXCISION
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• The decision to excise a papillary lesion without atypia needs to be individualized based on risk, including such criteria as size; symptomatology, including palpability and presence of nipple discharge; and breast cancer risk factors. Those not excised should be followed closely with imaging. Palpability alone is not an absolute indication for excision.
CNB Dx of papillary lesion w/o atypiaGuidelines for management of high risk lesions American Society of Breast Surgeons
https://www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/Concordance_and_High%20RiskLesions.pdf
Papillary lesions
Excision OR
clinical and imaging F/U
‐ Excise palpable lesions and those with atypia ‐ Incidental, benign papillary lesions can be followed
Patient Management following CNB Dx of papilloma without atypia @MSKCC
No excision required
• Rad‐path concordant findings
• No clinical symptoms
• Routine radiologic F/U planned
• (micro)papilloma completely removed by CNB
Excision Recommended
Rad‐path discordant findings
Patient is symptomatic (nipple discharge/ palpable mass)
Patient undergoing surgery for synchronous breast cancer
Guidelines for management of high risk lesions –Am Society of Breast SurgeonsLesion Recommendation Exceptions/ Notes
ADH EXCSmall volume ADH if completely excised on CNB may be observed based on risk factor assessment and multidisciplinary input
LCIS/ ALHEXC or observation with clinical and imaging F/U
Excision is necessary if pathology is discordant, limited sampling, or other high lesion present
Pleomorphic LCIS EXC Similar for necrosis and other non‐classical lesions
Pure FEA or CCHObservation with clinical and imaging F/U
EXC if concurrent ADH
Papillary lesionsEXC or clinical and imaging F/U
EXC palpable lesions and those with atypiaIncidental, benign papillomas can be followed
CSLs EXC Small, adequately sampled CLSs may be observed
Fibroadenoma EXC or clinical observation
FEL with concern for phyllodes
EXCConcerning features include stroma mitoses, overgrowth, pleomorphism, fragmentation, adipose tissue infiltration or other path concerns
Mucocele‐like lesion
EXC or F/UBenign MLLs can be observed if atypia would not alter pt management
Fibromatosis Wide local EXC High risk local recurrence
PASH Clinical observation
https://www.breastsurgeons.org/new_layout/about/statements/PDF_Statements/Concordance_and_High%20RiskLesions.pdf