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Sentinel Lymph Node procedure Sentinel Lymph Node procedure Intraoperative Examination Intraoperative Examination Belgian Breast Meeting 14/10/2006 Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Daniel Faverly MD Pathology Laboratory CMP-LabPatho Pathology Laboratory CMP-LabPatho Centre Communautaire de Référence pour le Centre Communautaire de Référence pour le dépistage du cancer du sein - Brussels, Belgium dépistage du cancer du sein - Brussels, Belgium European Community Working Group Breast Pathology European Community Working Group Breast Pathology Contact: [email protected] Contact: [email protected] Designed by Designed by www.orangeclignotant.be www.orangeclignotant.be

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Page 1: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Intraoperative ExaminationIntraoperative Examination

Belgian Breast Meeting 14/10/2006Belgian Breast Meeting 14/10/2006

Daniel Faverly MDDaniel Faverly MDPathology Laboratory CMP-LabPathoPathology Laboratory CMP-LabPatho

  Centre Communautaire de Référence pour le dépistage du Centre Communautaire de Référence pour le dépistage du cancer du sein - Brussels, Belgiumcancer du sein - Brussels, Belgium

European Community Working Group Breast PathologyEuropean Community Working Group Breast Pathology

Contact: [email protected]: [email protected]

Designed byDesigned by www.orangeclignotant.bewww.orangeclignotant.be

Page 2: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Intraoperative ExaminationIntraoperative ExaminationParadigm 1Paradigm 1

STOP

GO ON

Page 3: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Paradigm 2: Conventional AnalysisParadigm 2: Conventional AnalysisDEFINITIONSDEFINITIONS

• Metastasis pN1(sn): Metastasis pN1(sn): Tumor Tumor deposits greater than 2 mmdeposits greater than 2 mm

• Micrometastasis pN1mi(sn): Micrometastasis pN1mi(sn): Tumor deposits greater than 0.2 Tumor deposits greater than 0.2 mm but not greater than 2 mmmm but not greater than 2 mm

• Isolated tumour cells ITC pN0 Isolated tumour cells ITC pN0 (i+)(sn): (i+)(sn): Single tumor cells or Single tumor cells or small clusters not greater than small clusters not greater than 0.2 mm0.2 mm

• No Metastasis pN0 (i-)(sn):No Metastasis pN0 (i-)(sn):No No metastasis histologically, metastasis histologically, negative findings for ITCnegative findings for ITC

Page 4: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Conventional AnalysisConventional Analysis

DEFINITIONDEFINITION

Isolated tumour cells ITCIsolated tumour cells ITC

Tumor cells or small clusters not Tumor cells or small clusters not

greater than 0.2 mm, that are greater than 0.2 mm, that are

usually detected by immuno or usually detected by immuno or

molpath but which may be molpath but which may be

verified on H&E. ITC do not verified on H&E. ITC do not

typically show evidence of typically show evidence of

metastatic activity metastatic activity

(proliferation, stromal reaction,(proliferation, stromal reaction,

…)…)

Page 5: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Conventional AnalysisConventional Analysis

The WHO classification:The WHO classification:

• Qualitative and Qualitative and quantitativequantitative

analysisanalysis

• ImmunohistochemicalImmunohistochemical

investigationinvestigation

• GuidelinesGuidelines for SN analysis for SN analysis

procedures (size, serial step procedures (size, serial step

sections, immunos,…)sections, immunos,…)

Page 6: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Conventional AnalysisConventional Analysis• 382 responders; 240 units dealing with 382 responders; 240 units dealing with

SNs (63%)SNs (63%)

• 60% 60% carried outcarried out intra-operative intra-operative

assessmentassessment

• 70% use IHC in negative SN by H&E70% use IHC in negative SN by H&E

• Heterogenous interpretationHeterogenous interpretation of ITC, µM, of ITC, µM,

……

• CCL: CCL: no standardizationno standardization of technique in of technique in

EuropeEurope

Page 7: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Conventional AnalysisConventional Analysis

Disrepancies in current practice of pathological evaluation of SN in breast cancer.Disrepancies in current practice of pathological evaluation of SN in breast cancer.

Results of a EC survey. J Clin Pathol 57 (Results of a EC survey. J Clin Pathol 57 (20042004) 695-701) 695-701

No identical histological protocolNo identical histological protocol

(multilevel sectionning, IHC,…) is (multilevel sectionning, IHC,…) is

use by more than 8 pathology use by more than 8 pathology

departments departments

(out of 240!)(out of 240!)

Page 8: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Conventional AnalysisConventional Analysis

Improving the reproducibility of diagnosing micrometastasis and ITC.Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) 358-367Cancer 103 (2005) 358-367

Case 1: ITC but widespread N1mi?Case 1: ITC but widespread N1mi?

Page 9: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Conventional AnalysisConventional Analysis

Improving the reproducibility of diagnosing micrometastasis and ITC.Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) 358-367Cancer 103 (2005) 358-367

Case 2: ITC wispreading > 2 mm N1?Case 2: ITC wispreading > 2 mm N1?

Page 10: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Conventional AnalysisConventional Analysis

Improving the reproducibility of diagnosing micrometastasis and ITC.Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) 358-367Cancer 103 (2005) 358-367

Case 3: N1mi HECase 3: N1mi HE

Page 11: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Conventional AnalysisConventional Analysis

Improving the reproducibility of diagnosing micrometastasis and ITC.Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) 358-367Cancer 103 (2005) 358-367

Case 3: …but with immuno extra ITC so N1?Case 3: …but with immuno extra ITC so N1?

Page 12: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

ImprovingImproving Conventional Analysis: Conventional Analysis: ProceduresProcedures

Improving the reproducibility of diagnosing micrometastasis and ITC.Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) 358-367Cancer 103 (2005) 358-367

Gross 1 Gross 1 mmmm

4 to 6 4 to 6 levelslevels

200µ 200µ

SN intactSN intactSerial sectionningSerial sectionning

Page 13: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

ImprovingImproving Conventional Analysis: Conventional Analysis: ReportingReporting• If multiple, unevenly distributed foci, If multiple, unevenly distributed foci, only the largest should be considered.only the largest should be considered.

• If foci are separated by a few cells (2-5 If foci are separated by a few cells (2-5 cells), measure as cells), measure as one focusone focus

•Tumour in the Tumour in the capsulecapsule or growing or growing outside the capsule should be considered.outside the capsule should be considered.

• Differentiate Differentiate parenchymaparenchyma localization localization from sinuses or vascular spaces clustersfrom sinuses or vascular spaces clusters..

EC Guidelines for quality assurance in breast cancer screeningEC Guidelines for quality assurance in breast cancer screening and diagnosis. 4th edit (and diagnosis. 4th edit (20062006) )

Page 14: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

AGAINSTAGAINST

• How to differenciate N1, N1mi, ITC How to differenciate N1, N1mi, ITC

intraoperatively?intraoperatively?

• No defined procedure (frozen section, imprint or No defined procedure (frozen section, imprint or

scraping)scraping)

• EC guidelines: no frozen section on grossly EC guidelines: no frozen section on grossly

normal structurenormal structure

• Danger in case of frozen section: tissue loss Danger in case of frozen section: tissue loss

during triming to obtain slides…..etc…….during triming to obtain slides…..etc…….

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Intraoperative ExaminationIntraoperative Examination

Page 15: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Intraoperative ExaminationIntraoperative Examination

Paradigm 1 Paradigm 1 FORFOR

POSITIVE

NEGATIVE

STOP

Axill Clearance

Page 16: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Intraoperative ExaminationIntraoperative Examination

Paradigm 1 Paradigm 1 FORFOR

POSITIVE

NEGATIVE

STOP

Axill Clearance

Page 17: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Intraoperative ExaminationIntraoperative ExaminationPERFORMANCEPERFORMANCE

Accuracy 79-98%, false-negative 9-52% (FS)Accuracy 79-98%, false-negative 9-52% (FS)

Accuracy 77-99%, false-negative 5-70% Accuracy 77-99%, false-negative 5-70%

(Cytology)(Cytology)

Sensitivity FS : +/- 70-75%Sensitivity FS : +/- 70-75%

Sensitivity Cytology: 70% but sometimes less Sensitivity Cytology: 70% but sometimes less

47 to 51%47 to 51%False negative rate is not minimal False negative rate is not minimal (30%)(30%)

False positive rate is low (1 to 5%)False positive rate is low (1 to 5%)

Page 18: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Intraoperative ExaminationIntraoperative ExaminationQUESTIONS ?QUESTIONS ?

• Are all positive node significant for Are all positive node significant for conversion to axillary clearance? Benefit in conversion to axillary clearance? Benefit in

clinical outcome?clinical outcome?

• Impact of « satellite » or « sentinel + » node Impact of « satellite » or « sentinel + » node sampling on surgical and terapeutic sampling on surgical and terapeutic

strategies?strategies?

• Importance of patient selection procedures Importance of patient selection procedures and secundary medical imaging set-up and secundary medical imaging set-up (axillary node sonography & sampling)(axillary node sonography & sampling)

• Multidisciplinary approach!Multidisciplinary approach!

Page 19: Sentinel Lymph Node procedure Intraoperative Examination Belgian Breast Meeting 14/10/2006 Daniel Faverly MD Pathology Laboratory CMP-LabPatho Centre Communautaire

Sentinel Lymph Node Sentinel Lymph Node procedureprocedure

Intraoperative ExaminationIntraoperative ExaminationRATIONAL PROPOSALRATIONAL PROPOSAL

1 1 mmmm

Normal Normal STOP (CYTO?) STOP (CYTO?) NO FSNO FS

Minimally Abnormal Minimally Abnormal CYTO/FSCYTO/FS

Groosly « malignant » Groosly « malignant » FS/CYTOFS/CYTO