Skip to main content

Advertisement

SpringerLink
Log in

How Much is Enough? Pathologic Evaluation of Sentinel Lymph Nodes

  • Local-Regional Evaluation and Therapy (KK Hunt, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

It is well accepted that detailed analysis of sentinel lymph nodes (SLNs) may upstage breast cancer, but generally involves the identification of low-volume metastases (including isolated tumor cells and clusters). Although several guidelines recommend therapeutic interventions for micrometastases, there is also evidence supporting therapeutic interventions only for macrometastases. There is also evidence in support of means of regional disease control other than axillary lymph node dissection (ALND). The pathologic evaluation of SLNs should consider the clinical setting. Intraoperative assessment is indicated only if ALND is an immediate interventional option for SLN positivity. Generally, hematoxylin and eosin-stained sections taken at 2-mm step intervals are sufficient to disclose macrometastases, but if micrometastases are also considered in further treatment planning, smaller intervals and immunohistochemistry as well as quantitative molecular methods may also be considered.

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

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance•• Of major importance

  1. Giuliano AE, Dale PS, Turner RR, et al. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg. 1995;222:394–401.

    Article  PubMed  CAS  Google Scholar 

  2. Cserni G, Amendoeira I, Apostolikas N, et al. Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines. Eur J Cancer. 2003;39:1654–67.

    Article  PubMed  CAS  Google Scholar 

  3. Cserni G, Amendoeira I, Apostolikas N, et al. 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. 2004;57:695–701.

    CAS  Google Scholar 

  4. Cserni G. Histopathologic examination of the sentinel nodes. Breast J. 2006;12 Suppl 2:S152–6.

    Article  PubMed  Google Scholar 

  5. Schwartz GF, Giuliano AE, Veronesi U. Consensus Conference Committee: Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast, April 19–22, 2001, Philadelphia, Pennsylvania. Cancer. 2002;94:2542–51.

    Article  PubMed  Google Scholar 

  6. Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol. 2005;23:7703–20.

    Article  PubMed  Google Scholar 

  7. National Health Service Breast Screening Programme: Guidelines for pathology reporting in breast disease. NHSBSP Publication No 58. 2005. Available at http://www.cancerscreening.nhs.uk/breastscreen/publications/nhsbsp58.html. Accessed October 2011.

  8. National Breast and Ovarian Cancer Center, Australian Cancer Network: The pathology reporting of breast cancer. A guide for pathologists, surgeons, radiologists and oncologists. 3rd edn, National Breast and Ovarian Cancer Centre, Surry Hills, NSW, 2008. Available at http://www.cancer.org.au/File/HealthProfessionals/Clinical%20Guidelines/Pathology_reporting_breastcancer_3rdEd2008.pdf. Accessed October 2011

  9. Amendoeira I, Apostolikas N, Bellocq JP, et al. Quality assurance guidelines for pathology. In Perry N, Broeders M, de Wolf C, et al. editors. European guidelines for quality assurance in breast cancer screening and diagnosis, 4th edition. Luxemburg: European Comission; 2006. p. 219–311.

  10. Cserni G. Sentinel nodes, micrometastases and isolated tumor cells. In: Walker RA, Thompson AM, editors. Prognostic and predictive factors in breast cancer. London: Informa Healthcare; 2008. p. 68–87.

    Google Scholar 

  11. Hermanek P, Hutter RV, Sobin LH, Wittekind C. International union against cancer. Classification of isolated tumor cells and micrometastasis. Cancer. 1999;86:2668–73.

    Article  PubMed  CAS  Google Scholar 

  12. UICC TNM classification of malignant tumours, 6th edition. In Sobin LH Wittekind C, editors. New York: John Wiley and Sons Inc.; 2002.

  13. AJCC Cancer Staging Handbook—TNM Classification of Malignant Tumors, 6th edition. In Greene FL, Page DL, Fleming ID, et al editors. New York: Springer Verlag; 2002.

  14. Tew K, Irwiq L, Matthews A, Crowe P, Macaskill P. Meta-analysis of sentinel node imprint cytology in breast cancer. Br J Surg. 2005;92:1068–80.

    Article  PubMed  CAS  Google Scholar 

  15. Liu LC, Lang JE, Lu Y, et al. Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients. Cancer. 2011;117:250–8.

    Article  PubMed  Google Scholar 

  16. Ku NN. Pathologic examination of sentinel lymph nodes in breast cancer. Surg Oncol Clin N Am. 1999;8:469–79.

    PubMed  CAS  Google Scholar 

  17. Nahrig JM, Richter T, Kuhn W, et al. Intraoperative examination of sentinel lymph nodes by ultrarapid immunohistochemistry. Breast J. 2003;9:277–81.

    Article  PubMed  Google Scholar 

  18. Leikola JP, Tolvonen TS, Krogerus LA, von Smitten KA, Leidenius MH. Rapid immunohistochemistry enhances the intraoperative diagnosis of sentinel lymph node metastases in invasive lobular breast carcinoma. Cancer. 2005;104:14–9.

    Article  PubMed  Google Scholar 

  19. Choi YJ, Yun HR, Yoo KE, et al. Intraoperative examination of sentinel lymph nodes by ultrarapid immunohistochemistry in breast cancer. Jpn J Clin Oncol. 2006;36:489–93.

    Article  PubMed  Google Scholar 

  20. Cserni G. Effect of increasing the surface sampled by imprint cytology on the intraoperative assessment of axillary sentinel lymph nodes in breast cancer patients. Am Surgeon. 2003;69:419–23.

    PubMed  CAS  Google Scholar 

  21. Viale G, Bosari S, Mazzarol G, et al. Intraoperative examination of axillary sentinel lymph nodes in breast carcinoma patients. Cancer. 1999;85:2433–8.

    Article  PubMed  CAS  Google Scholar 

  22. Weigelt B, Verduijn P, Bosma AJ, et al. Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple mRNA markers. Br J Cancer. 2004;90:1531–7.

    Article  PubMed  CAS  Google Scholar 

  23. Blumencranz P, Whitworth PW, Deck K, et al. Sentinel node staging for breast cancer: intraoperative molecular pathology overcomes conventional histologic sampling errors. Am J Surg. 2007;194:426–32.

    Article  PubMed  Google Scholar 

  24. Tsujimoto M, Nakabayashi K, Yoshidome K, et al. One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res. 2007;13:4807–16.

    Article  PubMed  CAS  Google Scholar 

  25. • Blumencranz PW, Pieretti M, Allen KG, Blumencranz LE. Molecular analysis of breast sentinel lymph nodes. Surg Oncol Clin North Am. 2011;20:467–85. This is a review on the development of molecular tests to demonstrate SLN involvement in breast cancer, as well as a nice overview of the performance of the Veridex GeneSearch BLN Assay in practice..

    Article  Google Scholar 

  26. • Cserni G. Intraoperative analysis of sentinel lymph nodes in breast cancer by one-step nucleic acid amplification (OSNA). J Clin Pathol. 2012;65:193–9. This is a review of validation studies of OSNA as a method of analyzing SLNs intraoperatively; it suggests that this standardized quantitative molecular assay is superior not only to frozen sections or imprint cytology, but also to histology of permanent sections in identifying metastases, especially micrometastases.

  27. Daniele L, Annaratone L, Allia E, et al. Technical limits of comparison of step-sectioning, immunohistochemistry and RT-PCR on breast cancer sentinel nodes: a study on methacarn fixed tissue. J Cell Mol Med. 2009;13:4042–50.

    Article  PubMed  Google Scholar 

  28. Osako T, Iwase T, Kimura K, et al. Intraoperative molecular assay for sentinel lymph node metastases in early stage breast cancer: A comparative analysis between one-step nucleic acid amplification whole node assay and routine frozen section histology. Cancer Published Online First 22 March 2011. doi: 10.1002/cncr.26060

  29. Bernet L, Cano R, Martinez M, et al. Diagnosis of the sentinel lymph node in breast cancer: a reproducible molecular method: a multicentric Spanish study. Histopathology. 2011;58:863–9.

    Article  PubMed  Google Scholar 

  30. Laia BV, Marcos MB, Refael CM, et al. Molecular diagnosis of sentinel lymph nodes for breast cancer: one step ahead for standardization. Diagn Mol Pathol. 2011;20:18–21.

    Article  PubMed  CAS  Google Scholar 

  31. Weaver DL. Pathology evaluation of sentinel lymph nodes in breast cancer: protocol recommendations and rationale. Mod Pathol. 2010;23:S26–32.

    Article  PubMed  Google Scholar 

  32. Orr RK. The impact of prophylactic axillary node dissection on breast cancer survival—a Bayesian meta-analysis. Ann Surg Oncol. 1999;6:109–16.

    Article  PubMed  CAS  Google Scholar 

  33. Early Breast Cancer Trialists’ Collaborative Group. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet. 2005;366:2087–106.

    Google Scholar 

  34. Recht A, Houlihan MJ. Axillary lymph nodes and breast cancer: a review. Cancer. 1995;76:1491–512.

    Article  PubMed  CAS  Google Scholar 

  35. Straver ME, Meijnen P, van Tienhoven G, et al. Sentinel node identification rate and nodal involvement in the EORTC 10981–22023 AMAROS trial. Ann Surg Oncol. 2010;17:1854–61.

    Article  PubMed  Google Scholar 

  36. •• Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastasis. Ann Surg. 2010;252:426–33. This is the first report on the results of the ACOSOG Z-0011 trial, suggesting that completion of ALND may not be necessary for regional disease control in a well-described set of SLN-positive patients (those matching the inclusion criteria of the clinical trial). An important feature of these patients is that they all received whole breast irradiation, which may have contributed to the low axillary recurrence rate in the SLNB-only arm when compared to the ALND arm..

    PubMed  Google Scholar 

  37. Cserni G. Complete step sectioning of axillary sentinel lymph nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients. J Clin Pathol. 2002;55:926–31.

    Article  PubMed  CAS  Google Scholar 

  38. Huvos AG, Hutter RVP, Berg JW. Significance of axillary macrometastases and micrometastases in mammary cancer. Ann Surg. 1971;173:44–6.

    Article  PubMed  CAS  Google Scholar 

  39. Dowlatshahi K, Fan M, Snider HC, Habib FA. Lymph node micrometastases from breast carcinoma: reviewing the dilemma. Cancer. 1997;80:1188–97.

    Article  PubMed  CAS  Google Scholar 

  40. • de Boer M, van Deurzen CH, van Dijck JA, et al. Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med. 2009;361:653–63. This is a retrospective analysis of a large series of breast cancer patients with micrometastases or ITC in the axillary lymph nodes demonstrating about 10% worse disease-free survival compared to node-negative cases. The analysis showed no difference in survival for ITC and micrometastases but suggested that the survival disadvantage was not seen in patients receiving systemic adjuvant therapy..

    Article  PubMed  Google Scholar 

  41. Montagna E, Viale G, Rotmensz N, et al. Minimal axillary lymph node involvement in breast cancer has different prognostic implications according to the staging procedure. Breast Cancer Res Treat. 2009;118:385–94.

    Article  PubMed  CAS  Google Scholar 

  42. •• Weaver DL, Ashikaga T, Krag DN, et al. Effect of occult metastases on survival in node-negative breast cancer. N Engl J Med. 2011;364:412–21. This is a report from the NSABP-B32 trial demonstrating a survival disadvantage for patients with metastases remaining occult after the analysis of HE-stained histology slides taken at approximately 2-mm distance from each other; however, the magnitude of survival disadvantage was only 1.2%..

    Article  PubMed  CAS  Google Scholar 

  43. National Comprehensive Cancer Network: Clinical practice guidelines in onology—Breast cancer. Verion 2.2011. Available at http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf Accessed October 2011.

  44. Bilimoria KY, Bentrem DJ, Hansen NM, et al. Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer. J Clin Oncol. 2009;27:2946–53.

    Article  PubMed  Google Scholar 

  45. Wasif N, Maggard MA, Ko CY, Giuliano AE. Underuse of axillary dissection for the management of sentinel node micrometastases in breast cancer. Arch Surg. 2010;145:161–6.

    Article  PubMed  Google Scholar 

  46. Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 2011;22:1736–47.

    Article  PubMed  CAS  Google Scholar 

  47. Viale G. Dell’ Orto P, Biasi MO, et al.: Comparative evaluation of an extensive histopathologic examination and a real-time reverse-transcripton-polymerase chain reaction assay for mammaglobin and cytokeratin 19 on axillary sentinel lymph nodes of breast carcinoma patients. Ann Surg. 2009;247:136–42.

    Article  Google Scholar 

  48. • Castellano I, Macri L, Deambrogio C, et al. Reliability of whole sentinel lymph node analysis by One-Step Nucleic Acid Amplification for intraoperative diagnosis of breast cancer metastases. Ann Surg. 2012;255:334–42. This is a report demonstrating a novel trend in nodal metastasis detection. The SLNs are submitted in toto to OSNA, and only intraoperative imprint cytology serves as a microscopic control.

  49. • Khaddage A, Berremila SA, Forrest F, et al. Implementation of molecular intra-operative assessment of sentinel lymph nodes in breast cancer. Anticancer Res. 2011;31:585–90. This is a report demonstrating a novel trend in nodal metastasis detection. The SLNs are submitted nearly in toto to OSNA, and only one thin slice serves for histologic verification. This seems to be an acceptable compromise still allowing the detection of other gross nodal lesions.

    PubMed  Google Scholar 

  50. Cserni G. A model for determining the optimum histology of sentinel lymph nodes in breast cancer. J Clin Pathol. 2004;57:467–71.

    Article  PubMed  CAS  Google Scholar 

  51. Caudle AS, Hunt KK, Kuerer HM, et al. Multidisciplinary considerations in the implementation of the findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 study: a practice-changing trial. Ann Surg Oncol. 2011;18:2407–12.

    Article  PubMed  Google Scholar 

  52. Degnim AC, Griffith KA, Sabel MS, et al. Clinicopathologic features of metastasis in nonsentinel lymph nodes of breast carcinoma patients. Cancer. 2003;98:2307–15.

    Article  PubMed  Google Scholar 

  53. •• Cserni G. Sentinel node biopsy and nodal staging. In Kahán Zs, Tot T, editors. Breast cancer, a heterogeneous disease entity. The very early stages. Dordrecht-Heidelberg-London-New York: Springer Science+Business Media BV; 2011:149–84. This is a review on the role of nodal staging and SLNB in the earliest stages of breast cancer, including in situ carcinomas and small, screen detected carcinomas. This chapter identifies eight factors for nonsentinel node involvement in SLN-positive patients as the article by Van la Parra et al. [54••].

  54. •• Van la Parra RF, Peer PG, Ernst MF, Bosscha K. Meta-analysis of predictive factors for non-sentinel lymph node metastases in breast cancer patients with a positive SLN. Eur J Surg Oncol. 2011;37:290–9. This is a systemic review on nonsentinel lymph node-predictive tools for patients with a positive SLN. The review identifies eight important clinicopathologic features that influence the occurrence of metastases in further axillary lymph nodes..

    Article  Google Scholar 

  55. Cserni G, Bianchi S, Vezzosi V, et al. The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma. J Clin Pathol. 2006;59:518–22.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Department of Pathology, University of Szeged, Faculty of Medicine, Állomás u. 2., 6720, Szeged, Hungary

    Gábor Cserni

  2. Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyiri ut 38., 6000, Kecskemét, Hungary

    Gábor Cserni

Authors
  1. Gábor Cserni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gábor Cserni.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cserni, G. How Much is Enough? Pathologic Evaluation of Sentinel Lymph Nodes. Curr Breast Cancer Rep 4, 89–95 (2012). https://doi.org/10.1007/s12609-012-0073-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12609-012-0073-9

Keywords

Search

Navigation