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

Sentinel Lymph Node procedure Intraoperative Examination Paradigm 1 STOP GO ON

Sentinel Lymph Node procedure Paradigm 2: Conventional Analysis DEFINITIONS Metastasis pN1(sn): Tumor deposits greater than 2 mm Metastasis pN1(sn): Tumor deposits greater than 2 mm Micrometastasis pN1mi(sn): Tumor deposits greater than 0.2 mm but not greater than 2 mm Micrometastasis pN1mi(sn): Tumor deposits greater than 0.2 mm but not greater than 2 mm Isolated tumour cells ITC pN0 (i+)(sn): Single tumor cells or small clusters not greater than 0.2 mm Isolated tumour cells ITC pN0 (i+)(sn): Single tumor cells or small clusters not greater than 0.2 mm No Metastasis pN0 (i-)(sn): No metastasis histologically, negative findings for ITC No Metastasis pN0 (i-)(sn): No metastasis histologically, negative findings for ITC

Sentinel Lymph Node procedure Conventional Analysis DEFINITION Isolated tumour cells ITC Tumor cells or small clusters not greater than 0.2 mm, that are usually detected by immuno or molpath but which may be verified on H&E. ITC do not typically show evidence of metastatic activity (proliferation, stromal reaction,…)

Sentinel Lymph Node procedure Conventional Analysis The WHO classification: Qualitative and quantitative analysis Qualitative and quantitative analysis Immunohistochemical investigation Immunohistochemical investigation Guidelines for SN analysis procedures (size, serial step sections, immunos,…) Guidelines for SN analysis procedures (size, serial step sections, immunos,…)

Sentinel Lymph Node procedure Conventional Analysis 382 responders; 240 units dealing with SNs (63%) 382 responders; 240 units dealing with SNs (63%) 60% carried out intra-operative assessment 60% carried out intra-operative assessment 70% use IHC in negative SN by H&E 70% use IHC in negative SN by H&E Heterogenous interpretation of ITC, µM,… Heterogenous interpretation of ITC, µM,… CCL: no standardization of technique in Europe CCL: no standardization of technique in Europe

Sentinel Lymph Node procedure Conventional Analysis Disrepancies in current practice of pathological evaluation of SN in breast cancer. Results of a EC survey. J Clin Pathol 57 (2004) Results of a EC survey. J Clin Pathol 57 (2004) No identical histological protocol (multilevel sectionning, IHC,…) is use by more than 8 pathology departments (out of 240!)

Sentinel Lymph Node procedure Conventional Analysis Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) Cancer 103 (2005) Case 1: ITC but widespread N1mi?

Sentinel Lymph Node procedure Conventional Analysis Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) Cancer 103 (2005) Case 2: ITC wispreading > 2 mm N1?

Sentinel Lymph Node procedure Conventional Analysis Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) Cancer 103 (2005) Case 3: N1mi HE

Sentinel Lymph Node procedure Conventional Analysis Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) Cancer 103 (2005) Case 3: …but with immuno extra ITC so N1?

Sentinel Lymph Node procedure Improving Conventional Analysis: Procedures Improving the reproducibility of diagnosing micrometastasis and ITC. Cancer 103 (2005) Cancer 103 (2005) Gross 1 mm 4 to 6 levels 200µ SN intact Serial sectionning

Sentinel Lymph Node procedure Improving Conventional Analysis: Reporting If multiple, unevenly distributed foci, only the largest should be considered. If multiple, unevenly distributed foci, only the largest should be considered. If foci are separated by a few cells (2-5 cells), measure as one focus If foci are separated by a few cells (2-5 cells), measure as one focus Tumour in the capsule or growing outside the capsule should be considered. Tumour in the capsule or growing outside the capsule should be considered. Differentiate parenchyma localization from sinuses or vascular spaces clusters. Differentiate parenchyma localization from sinuses or vascular spaces clusters. EC Guidelines for quality assurance in breast cancer screening and diagnosis. 4th edit (2006) and diagnosis. 4th edit (2006)

AGAINST AGAINST How to differenciate N1, N1mi, ITC intraoperatively? How to differenciate N1, N1mi, ITC intraoperatively? No defined procedure (frozen section, imprint or scraping) No defined procedure (frozen section, imprint or scraping) EC guidelines: no frozen section on grossly normal structure EC guidelines: no frozen section on grossly normal structure Danger in case of frozen section: tissue loss during triming to obtain slides…..etc……. Danger in case of frozen section: tissue loss during triming to obtain slides…..etc……. Sentinel Lymph Node procedure Intraoperative Examination

Paradigm 1 FOR POSITIVE NEGATIVE STOP Axill Clearance

Sentinel Lymph Node procedure Intraoperative Examination Paradigm 1 FOR POSITIVE NEGATIVE STOP Axill Clearance

Sentinel Lymph Node procedure Intraoperative Examination PERFORMANCE Accuracy 79-98%, false-negative 9-52% (FS) Accuracy 79-98%, false-negative 9-52% (FS) Accuracy 77-99%, false-negative 5-70% (Cytology) Accuracy 77-99%, false-negative 5-70% (Cytology) Sensitivity FS : +/ % Sensitivity Cytology: 70% but sometimes less 47 to 51% False negative rate is not minimal (30%) False positive rate is low (1 to 5%)

Sentinel Lymph Node procedure Intraoperative Examination QUESTIONS ? Are all positive node significant for conversion to axillary clearance? Benefit in clinical outcome? Are all positive node significant for conversion to axillary clearance? Benefit in clinical outcome? Impact of « satellite » or « sentinel + » node sampling on surgical and terapeutic strategies? Impact of « satellite » or « sentinel + » node sampling on surgical and terapeutic strategies? Importance of patient selection procedures and secundary medical imaging set-up (axillary node sonography & sampling) Importance of patient selection procedures and secundary medical imaging set-up (axillary node sonography & sampling) Multidisciplinary approach! Multidisciplinary approach!

Sentinel Lymph Node procedure Intraoperative Examination RATIONAL PROPOSAL 1 mm Normal STOP (CYTO?) NO FS Minimally Abnormal CYTO/FS Groosly « malignant » FS/CYTO