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Published in: Virchows Archiv 1/2008

01-07-2008 | Original Article

Strategies for optimizing pathologic staging of sentinel lymph nodes in breast cancer patients

Authors: Eva V. E. Madsen, Jan van Dalen, Joost van Gorp, Inne H. M. Borel Rinkes, Thijs van Dalen

Published in: Virchows Archiv | Issue 1/2008

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Abstract

Due to the extensive pathologic evaluation of the sentinel lymph node (SLN), micrometastases are frequently observed. If micrometastases are clinically relevant, the histopathologic examination of SLNs should be sensitive enough to detect them. The probability of detecting micrometastases was calculated when examining the SLN according to the current Dutch pathology protocol and strategies evaluated to optimize the chance of detection. The dimensions of 20 consecutive axillary SLNs in patients with cT1-2N0 breast cancer were measured. In a mathematical model, the probability of detecting micrometastases in a SLN was calculated. Similarly, strategies to optimize the probability of detecting micrometastases were explored. When applying the pathology guidelines, the calculated probability to detect a micrometastasis was 18% for a 200-μm micrometastasis and 69% for a 2.0-mm metastasis in a median sized SLN. To detect the smallest micrometastasis in a median-sized SLN with a 95% probability, the interval between the sections must be decreased to 200 μm, and 20 levels from both halves must be examined. Given a prognostic significance of micrometastases, our current pathology guidelines are not sensitive enough. The number of sections should be increased, while the interval between cuts should be no more than 200 μm.
Literature
1.
go back to reference Attiyeh FF, Jensen M, Huvos AG, Fracchia A (1977) Axillary micrometastasis and macrometastasis in carcinoma of the breast. Surg Gynecol Obstet 144:839–842PubMed Attiyeh FF, Jensen M, Huvos AG, Fracchia A (1977) Axillary micrometastasis and macrometastasis in carcinoma of the breast. Surg Gynecol Obstet 144:839–842PubMed
2.
go back to reference Bolster MJ, Bult P, Schapers RF, Meijer JW, Strobbe LJ, van Berlo CL, Klinkenbijl JH, Peer PG, Wobbes T, Tjan-Heijnen VC (2006) Differences in sentinel lymph node pathology protocols lead to differences in surgical strategy in breast cancer patients. Ann Surg Oncol 13:1466–1473PubMedCrossRef Bolster MJ, Bult P, Schapers RF, Meijer JW, Strobbe LJ, van Berlo CL, Klinkenbijl JH, Peer PG, Wobbes T, Tjan-Heijnen VC (2006) Differences in sentinel lymph node pathology protocols lead to differences in surgical strategy in breast cancer patients. Ann Surg Oncol 13:1466–1473PubMedCrossRef
4.
go back to reference Colleoni M, Rotmensz N, Peruzzotti G, Maisonneuve P, Mazzarol G, Pruneri G, Luini A, Intra M, Veronesi P, Galimberti V, Torrisi R, Cardillo A, Goldhirsch A, Viale G (2005) Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement. J Clin Oncol 23(7):1379–1389PubMedCrossRef Colleoni M, Rotmensz N, Peruzzotti G, Maisonneuve P, Mazzarol G, Pruneri G, Luini A, Intra M, Veronesi P, Galimberti V, Torrisi R, Cardillo A, Goldhirsch A, Viale G (2005) Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement. J Clin Oncol 23(7):1379–1389PubMedCrossRef
5.
go back to reference Cox CE, Pendas S, Cox JM, Joseph E, Shons AR, Yeatman T, Ku NN, Lyman GH, Berman C, Haddad F, Reintgen DS (1998) Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 227:645–651PubMedCrossRef Cox CE, Pendas S, Cox JM, Joseph E, Shons AR, Yeatman T, Ku NN, Lyman GH, Berman C, Haddad F, Reintgen DS (1998) Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer. Ann Surg 227:645–651PubMedCrossRef
6.
go back to reference Cserni G, Gregori D, Merletti F, Sapino A, Mano MP, Ponti A, Sandrucci S, Baltas B, Bussolati G (2004) Meta-analysis of non-sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer. Br J Surg 91:1245–1252PubMedCrossRef Cserni G, Gregori D, Merletti F, Sapino A, Mano MP, Ponti A, Sandrucci S, Baltas B, Bussolati G (2004) Meta-analysis of non-sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer. Br J Surg 91:1245–1252PubMedCrossRef
7.
go back to reference Cserni G, Amendoeira I, Apostolikas N, Bellocq JP, Bianchi S, Boecker W, Borisch B, Connolly CE, Decker T, Dervan P, Drijkoningen M, Ellis IO, Elston CW, Eusebi V, Faverly D, Heikkila P, Holland R, Kerner H, Kulka J, Jacquemier J, Lacerda M, Martinez-Penuela J, De Miguel C, Peterse JL, Rank F, Regitnig P, Reiner A, Sapino A, Sigal-Zafrani B, Tanous AM, Thorstenson S, Zozaya E, Fejes G, Wells CA (2004) Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology. J Clin Pathol 57:695–701PubMedCrossRef Cserni G, Amendoeira I, Apostolikas N, Bellocq JP, Bianchi S, Boecker W, Borisch B, Connolly CE, Decker T, Dervan P, Drijkoningen M, Ellis IO, Elston CW, Eusebi V, Faverly D, Heikkila P, Holland R, Kerner H, Kulka J, Jacquemier J, Lacerda M, Martinez-Penuela J, De Miguel C, Peterse JL, Rank F, Regitnig P, Reiner A, Sapino A, Sigal-Zafrani B, Tanous AM, Thorstenson S, Zozaya E, Fejes G, Wells CA (2004) Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology. J Clin Pathol 57:695–701PubMedCrossRef
8.
go back to reference Cserni G (2004) A model for determining the optimum histology of sentinel lymph nodes in breast cancer. J Clin Pathol 57:467–471PubMedCrossRef Cserni G (2004) A model for determining the optimum histology of sentinel lymph nodes in breast cancer. J Clin Pathol 57:467–471PubMedCrossRef
9.
go back to reference Cserni G (2002) Complete sectioning of axillary sentinel nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients. J Clin Pathol 55:926–931PubMedCrossRef Cserni G (2002) Complete sectioning of axillary sentinel nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients. J Clin Pathol 55:926–931PubMedCrossRef
10.
go back to reference Cserni G (2000) Mapping metastases in sentinel lymph nodes of breast cancer. Am J Clin Pathol 113:351–354PubMedCrossRef Cserni G (2000) Mapping metastases in sentinel lymph nodes of breast cancer. Am J Clin Pathol 113:351–354PubMedCrossRef
11.
go back to reference Farshid G, Pradhan M, Kollias J, Gill PG (2000) Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma. Cancer 89:2527–2537PubMedCrossRef Farshid G, Pradhan M, Kollias J, Gill PG (2000) Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma. Cancer 89:2527–2537PubMedCrossRef
12.
go back to reference Giuliano AE, Jones RC, Brennan M, Statman R (1997) Sentinel lymphadenectomy in breast cancer. J Clin Oncol 15:2345–2350PubMed Giuliano AE, Jones RC, Brennan M, Statman R (1997) Sentinel lymphadenectomy in breast cancer. J Clin Oncol 15:2345–2350PubMed
13.
go back to reference Groen RS, Oosterhuis AWJ, Boers JE (2007) Pathologic examination of sentinel lymph nodes in breast cancer by a single haematoxylin–eosin slide versus serial sectioning and immunocytokeratin staining: clinical implications. Breast Cancer Res Treat 105:1–5PubMedCrossRef Groen RS, Oosterhuis AWJ, Boers JE (2007) Pathologic examination of sentinel lymph nodes in breast cancer by a single haematoxylin–eosin slide versus serial sectioning and immunocytokeratin staining: clinical implications. Breast Cancer Res Treat 105:1–5PubMedCrossRef
14.
go back to reference Huvos AG, Hutter RV, Berg JW (1971) Significance of axillary macrometastases and micrometastases in mammary cancer. Ann Surg 173:44–46PubMedCrossRef Huvos AG, Hutter RV, Berg JW (1971) Significance of axillary macrometastases and micrometastases in mammary cancer. Ann Surg 173:44–46PubMedCrossRef
15.
go back to reference International (Ludwig) Breast Cancer Study Group (1990) Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet 335:1565–1568 International (Ludwig) Breast Cancer Study Group (1990) Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet 335:1565–1568
16.
go back to reference Krauth JS, Charitansky H, Isaac S, Bobin JY (2006) Clinical implications of axillary sentinel lymph node ‘micrometastases’ in breast cancer. Eur J Surg Oncol 32:400–404PubMedCrossRef Krauth JS, Charitansky H, Isaac S, Bobin JY (2006) Clinical implications of axillary sentinel lymph node ‘micrometastases’ in breast cancer. Eur J Surg Oncol 32:400–404PubMedCrossRef
17.
go back to reference Lyman GH, Giuliano AE, Somerfield MR, Benson AB III, Bodurka DC, Burstein HJ, Cochran AJ, Cody HS III, Edge SB, Galper S, Hayman JA, Kim TY, Perkins CL, Podoloff DA, Sivasubramaniam VH, Turner RR, Wahl R, Weaver DL, Wolff AC, Winer EP (2005) American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23:7703–7720PubMedCrossRef Lyman GH, Giuliano AE, Somerfield MR, Benson AB III, Bodurka DC, Burstein HJ, Cochran AJ, Cody HS III, Edge SB, Galper S, Hayman JA, Kim TY, Perkins CL, Podoloff DA, Sivasubramaniam VH, Turner RR, Wahl R, Weaver DL, Wolff AC, Winer EP (2005) American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23:7703–7720PubMedCrossRef
18.
go back to reference Maibenco DC, Dombi GW, Kau TY, Severson RK (2006) Significance of micrometastases on the survival of women with T1 breast cancer. Cancer 107:1234–1239PubMedCrossRef Maibenco DC, Dombi GW, Kau TY, Severson RK (2006) Significance of micrometastases on the survival of women with T1 breast cancer. Cancer 107:1234–1239PubMedCrossRef
19.
go back to reference Meyer JS (1998) Sentinel lymph node biopsy: strategies for pathologic examination of the specimen. J Surg Oncol 69:212–218PubMedCrossRef Meyer JS (1998) Sentinel lymph node biopsy: strategies for pathologic examination of the specimen. J Surg Oncol 69:212–218PubMedCrossRef
20.
go back to reference Miltenburg DM, Miller C, Karamlou TB, Brunicardi FC (1999) Meta-analysis of sentinel lymph node biopsy in breast cancer. J Surg Res 84:138–142PubMedCrossRef Miltenburg DM, Miller C, Karamlou TB, Brunicardi FC (1999) Meta-analysis of sentinel lymph node biopsy in breast cancer. J Surg Res 84:138–142PubMedCrossRef
21.
go back to reference Richtlijn Behandeling van het mammacarcinoom (2004) Kwaliteitsinstituut voor de Gezondheidszorg CBO Richtlijn Behandeling van het mammacarcinoom (2004) Kwaliteitsinstituut voor de Gezondheidszorg CBO
22.
go back to reference van Rijk MC, Peterse JL, Nieweg OE, Oldenburg HS, Rutgers EJ, Kroon BB (2006) Additional axillary metastases and stage migration in breast cancer patients with micrometastases or submicrometastases in sentinel lymph nodes. Cancer 107:467–471PubMedCrossRef van Rijk MC, Peterse JL, Nieweg OE, Oldenburg HS, Rutgers EJ, Kroon BB (2006) Additional axillary metastases and stage migration in breast cancer patients with micrometastases or submicrometastases in sentinel lymph nodes. Cancer 107:467–471PubMedCrossRef
23.
go back to reference Rosen PP, Saigo PE, Braun DW, Weathers E, Fracchia AA, Kinne DW (1981) Axillary micro- and macrometastases in breast cancer. Ann Surg 194:585–591PubMedCrossRef Rosen PP, Saigo PE, Braun DW, Weathers E, Fracchia AA, Kinne DW (1981) Axillary micro- and macrometastases in breast cancer. Ann Surg 194:585–591PubMedCrossRef
24.
go back to reference Sobin LH, Wittekind Ch (2002) TNM classification of malignant tumours, 6th edn. Wiley, Hoboken, New Jersey Sobin LH, Wittekind Ch (2002) TNM classification of malignant tumours, 6th edn. Wiley, Hoboken, New Jersey
25.
go back to reference Turner RR, Ollila DW, Krasne DL, Giuliano AE (1997) Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg 226:271–276PubMedCrossRef Turner RR, Ollila DW, Krasne DL, Giuliano AE (1997) Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg 226:271–276PubMedCrossRef
26.
go back to reference Turner RR, Giuliano AE, Hoon DS, Glass EC, Krasne DL (2001) Pathologic examination of sentinel lymph node for breast carcinoma. World J Surg 25:798–805PubMedCrossRef Turner RR, Giuliano AE, Hoon DS, Glass EC, Krasne DL (2001) Pathologic examination of sentinel lymph node for breast carcinoma. World J Surg 25:798–805PubMedCrossRef
27.
go back to reference Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, Intra M, Veronesi P, Maisonneuve P, Gatti G, Mazzarol G, De Cicco C, Manfredi G, Fernandez JR (2006) Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study. Lancet Oncol 7:983–990PubMedCrossRef Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, Intra M, Veronesi P, Maisonneuve P, Gatti G, Mazzarol G, De Cicco C, Manfredi G, Fernandez JR (2006) Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study. Lancet Oncol 7:983–990PubMedCrossRef
28.
go back to reference Viale G, Mastropasqua MG, Maiorano E, Mazzarol G (2006) Pathologic examination of the axillary sentinel lymph nodes in patients with early-stage breast carcinoma: current and resolving controversies on the basis of the European Institute of Oncology experience. Virchows Arch 448:241–247PubMedCrossRef Viale G, Mastropasqua MG, Maiorano E, Mazzarol G (2006) Pathologic examination of the axillary sentinel lymph nodes in patients with early-stage breast carcinoma: current and resolving controversies on the basis of the European Institute of Oncology experience. Virchows Arch 448:241–247PubMedCrossRef
29.
go back to reference Viale G, Maiorano E, Mazzarol G, Zurrida S, Galimberti V, Luini A, Renne G, Pruneri G, Maisonneuve P, Veronesi U (2001) Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma. Cancer 92:1378–1384PubMedCrossRef Viale G, Maiorano E, Mazzarol G, Zurrida S, Galimberti V, Luini A, Renne G, Pruneri G, Maisonneuve P, Veronesi U (2001) Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma. Cancer 92:1378–1384PubMedCrossRef
30.
go back to reference Wilkinson EJ, Hause LL, Hoffman RG, Kuzma JF, Rothwell DJ, Donegan WL, Clowry LJ, Almagro UA, Choi H, Rimm AA (1982) Occult axillary lymph node metastases in invasive breast carcinoma: characteristics of the primary tumor and significance of the metastases. Pathol Annu 17(Pt 2):67–91PubMed Wilkinson EJ, Hause LL, Hoffman RG, Kuzma JF, Rothwell DJ, Donegan WL, Clowry LJ, Almagro UA, Choi H, Rimm AA (1982) Occult axillary lymph node metastases in invasive breast carcinoma: characteristics of the primary tumor and significance of the metastases. Pathol Annu 17(Pt 2):67–91PubMed
Metadata
Title
Strategies for optimizing pathologic staging of sentinel lymph nodes in breast cancer patients
Authors
Eva V. E. Madsen
Jan van Dalen
Joost van Gorp
Inne H. M. Borel Rinkes
Thijs van Dalen
Publication date
01-07-2008
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 1/2008
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-008-0601-1

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