Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Attiyeh FF, Jensen M, Huvos AG, Fracchia A (1977) Axillary micrometastasis and macrometastasis in carcinoma of the breast. Surg Gynecol Obstet 144:839–842

    PubMed  CAS  Google Scholar 

  2. 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 13:1466–1473

    Article  PubMed  Google Scholar 

  3. CBO-richtlijn mammacarcinoom (2004) Nederlandse Vereniging voor Pathologie. http://www.pathology.nl. Cited Apr 2004

  4. 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):1379–1389

    Article  PubMed  Google Scholar 

  5. 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 227:645–651

    Article  PubMed  CAS  Google Scholar 

  6. 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 91:1245–1252

    Article  PubMed  CAS  Google Scholar 

  7. 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 57:695–701

    Article  PubMed  CAS  Google Scholar 

  8. Cserni G (2004) A model for determining the optimum histology of sentinel lymph nodes in breast cancer. J Clin Pathol 57:467–471

    Article  PubMed  CAS  Google Scholar 

  9. 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 55:926–931

    Article  PubMed  CAS  Google Scholar 

  10. Cserni G (2000) Mapping metastases in sentinel lymph nodes of breast cancer. Am J Clin Pathol 113:351–354

    Article  PubMed  CAS  Google Scholar 

  11. 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 89:2527–2537

    Article  PubMed  CAS  Google Scholar 

  12. Giuliano AE, Jones RC, Brennan M, Statman R (1997) Sentinel lymphadenectomy in breast cancer. J Clin Oncol 15:2345–2350

    PubMed  CAS  Google Scholar 

  13. 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 105:1–5

    Article  PubMed  Google Scholar 

  14. Huvos AG, Hutter RV, Berg JW (1971) Significance of axillary macrometastases and micrometastases in mammary cancer. Ann Surg 173:44–46

    Article  PubMed  CAS  Google Scholar 

  15. International (Ludwig) Breast Cancer Study Group (1990) Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet 335:1565–1568

    Google Scholar 

  16. Krauth JS, Charitansky H, Isaac S, Bobin JY (2006) Clinical implications of axillary sentinel lymph node ‘micrometastases’ in breast cancer. Eur J Surg Oncol 32:400–404

    Article  PubMed  Google Scholar 

  17. 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 23:7703–7720

    Article  PubMed  Google Scholar 

  18. Maibenco DC, Dombi GW, Kau TY, Severson RK (2006) Significance of micrometastases on the survival of women with T1 breast cancer. Cancer 107:1234–1239

    Article  PubMed  Google Scholar 

  19. Meyer JS (1998) Sentinel lymph node biopsy: strategies for pathologic examination of the specimen. J Surg Oncol 69:212–218

    Article  PubMed  CAS  Google Scholar 

  20. Miltenburg DM, Miller C, Karamlou TB, Brunicardi FC (1999) Meta-analysis of sentinel lymph node biopsy in breast cancer. J Surg Res 84:138–142

    Article  PubMed  CAS  Google Scholar 

  21. Richtlijn Behandeling van het mammacarcinoom (2004) Kwaliteitsinstituut voor de Gezondheidszorg CBO

  22. 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 107:467–471

    Article  PubMed  Google Scholar 

  23. Rosen PP, Saigo PE, Braun DW, Weathers E, Fracchia AA, Kinne DW (1981) Axillary micro- and macrometastases in breast cancer. Ann Surg 194:585–591

    Article  PubMed  CAS  Google Scholar 

  24. Sobin LH, Wittekind Ch (2002) TNM classification of malignant tumours, 6th edn. Wiley, Hoboken, New Jersey

    Google Scholar 

  25. Turner RR, Ollila DW, Krasne DL, Giuliano AE (1997) Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg 226:271–276

    Article  PubMed  CAS  Google Scholar 

  26. Turner RR, Giuliano AE, Hoon DS, Glass EC, Krasne DL (2001) Pathologic examination of sentinel lymph node for breast carcinoma. World J Surg 25:798–805

    Article  PubMed  CAS  Google Scholar 

  27. 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 7:983–990

    Article  PubMed  Google Scholar 

  28. 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 448:241–247

    Article  PubMed  Google Scholar 

  29. 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 92:1378–1384

    Article  PubMed  CAS  Google Scholar 

  30. 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):67–91

    PubMed  Google Scholar 

Download references

Acknowledgment

No financial support was received for this study.

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Surgery, Diakonessenhuis, Bosboomstraat 1, 3582 KE, Utrecht, The Netherlands

    Eva V. E. Madsen & Thijs van Dalen

  2. Department of Pathology, Diakonessenhuis, Utrecht, The Netherlands

    Joost van Gorp

  3. Department of Information and Decision Sciences, RSM Erasmus University Rotterdam, Rotterdam, The Netherlands

    Jan van Dalen

  4. Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands

    Inne H. M. Borel Rinkes

Authors
  1. Eva V. E. Madsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan van Dalen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joost van Gorp
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Inne H. M. Borel Rinkes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thijs van Dalen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thijs van Dalen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Madsen, E.V.E., van Dalen, J., van Gorp, J. et al. Strategies for optimizing pathologic staging of sentinel lymph nodes in breast cancer patients. Virchows Arch 453, 17–24 (2008). https://doi.org/10.1007/s00428-008-0601-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-008-0601-1

Keywords

Search

Navigation