The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma

Background: Cytokeratin immunohistochemistry (IHC) reveals a higher rate of occult lymph node metastases among lobular carcinomas than among ductal breast cancers. IHC is widely used but is seldom recommended for the evaluation of sentinel lymph nodes in breast cancer patients. Objective: To assess the value of cytokeratin IHC for the detection of metastases in sentinel lymph nodes of patients with invasive lobular carcinoma. Methods: The value of IHC, the types of metastasis found by this method, and the involvement of non-sentinel lymph nodes were analysed in a multi-institutional cohort of 449 patients with lobular breast carcinoma, staged by sentinel lymph node biopsy and routine assessment of the sentinel lymph nodes by IHC when multilevel haematoxylin and eosin staining revealed no metastasis. Results: 189 patients (42%) had some type of sentinel node involvement, the frequency of this increasing with increasing tumour size. IHC was needed for identification of 65 of these cases: 17 of 19 isolated tumour cells, 40 of 64 micrometastases, and 8 of 106 larger metastases were detected by this means. Non-sentinel-node involvement was noted in 66 of 161 cases undergoing axillary dissection. Although isolated tumour cells were not associated with further lymph node involvement, sentinel node positivity detected by IHC was associated with further nodal metastases in 12 of 50 cases (0.24), a proportion that is higher than previously reported for breast cancer in general. Conclusions: IHC is recommended for the evaluation of sentinel nodes from patients with lobular breast carcinoma, as the micrometastases or larger metastases demonstrated by this method are often associated with a further metastatic nodal load.

[1]  The pathology reporting of breast cancer A guide for pathologists, surgeons, radiologists and oncologists National Breast and Ovarian Cancer Centre and Australian Cancer Network 3rd edition , 2008 .

[2]  R Holland,et al.  European guidelines for quality assurance in breast cancer screening and diagnosis. Fourth edition--summary document. , 2008, Annals of Oncology.

[3]  G. Cserni Evaluation of sentinel lymph nodes in breast cancer , 2005, Histopathology.

[4]  Diethelm Wallwiener,et al.  A concept for the clinical implementation of sentinel lymph node biopsy in patients with breast carcinoma with special regard to quality assurance , 2005, Cancer.

[5]  S. Bianchi,et al.  Improving the reproducibility of diagnosing micrometastases and isolated tumor cells , 2005, Cancer.

[6]  A. Sapino,et al.  Meta‐analysis of non‐sentinel node metastases associated with micrometastatic sentinel nodes in breast cancer , 2004, The British journal of surgery.

[7]  C. Hudis,et al.  Cytokeratin‐positive cells in sentinel lymph nodes in breast cancer are not random events , 2004, Cancer.

[8]  J. Peterse,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 , 2004, Journal of Clinical Pathology.

[9]  A. Giuliano,et al.  Manipulation of the primary breast tumor and the incidence of sentinel node metastases from invasive breast cancer. , 2004, Archives of surgery.

[10]  M. Fiche,et al.  Validation of axillary sentinel lymph node detection in the staging of early lobular invasive breast carcinoma , 2004, Cancer.

[11]  H. Thaler,et al.  Immunohistochemically detected tumor cells in the sentinel lymph nodes of patients with breast carcinoma , 2004, Cancer.

[12]  J. Peterse,et al.  Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines. , 2003, European journal of cancer.

[13]  G. Pruneri,et al.  Ectopic Breast Tissue as a Possible Cause of False-Positive Axillary Sentinel Lymph Node Biopsies , 2003, The American journal of surgical pathology.

[14]  I. Chandler,et al.  Invasive lobular carcinoma and cytokeratin immunohistochemistry: an audit , 2003, Journal of clinical pathology.

[15]  Ch. Wittekind,et al.  TNM supplement : a commentary on uniform use , 2003 .

[16]  J. Buckingham,et al.  The clinical significance of cytokeratin-positive cells in lymph nodes at the time of mastectomy from patients with ductal carcinoma-in-situ , 2002, Annals of surgical oncology.

[17]  G. Cserni Complete sectioning of axillary sentinel nodes in patients with breast cancer. Analysis of two different step sectioning and immunohistochemistry protocols in 246 patients , 2002, Journal of clinical pathology.

[18]  A. Giuliano,et al.  Tumor characteristics predictive of sentinel node metastases in 105 consecutive patients with invasive lobular carcinoma. , 2002, American journal of surgery.

[19]  I. de Mascarel,et al.  Prognostic significance of immunohistochemically detected breast cancer node metastases in 218 patients , 2002, British Journal of Cancer.

[20]  A. Giuliano,et al.  Proceedings of the Consensus Conference on the role of sentinel lymph node biopsy in carcinoma of the breast, April 19–22, 2001, Philadelphia, Pennsylvania , 2002, Cancer.

[21]  S. Edge,et al.  AJCC Cancer Staging Handbook, 6th edition , 2002 .

[22]  S. Robboy TNM Supplement: A Commentary on Uniform Use, 2nd Edition. , 2002 .

[23]  R. Zarbo,et al.  Cytokeratin Immunostaining Patterns of Benign, Reactive Lymph Nodes: Applications for the Evaluation of Sentinel Lymph Node Specimen , 2001, Applied immunohistochemistry & molecular morphology : AIMM.

[24]  P. V. van Diest,et al.  Sentinel node investigation in breast cancer: detailed analysis of the yield from step sectioning and immunohistochemistry , 2001, Journal of clinical pathology.

[25]  J. Connolly,et al.  ADASP recommendations for processing and reporting of lymph node specimens submitted for evaluation of metastatic disease. , 2001, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[26]  X. Xu,et al.  Undesirable cytokeratin immunoreactivity of native nonepithelial cells in sentinel lymph nodes from patients with breast carcinoma. , 2009, Archives of pathology & laboratory medicine.

[27]  J. Connolly,et al.  Updated protocol for the examination of specimens from patients with carcinomas of the breast. Cancer Committee. , 2000, Archives of pathology & laboratory medicine.

[28]  P. Lilleng,et al.  'Missed' Micrometastases: The Extent of the Problem , 2000, Acta oncologica.

[29]  E. Kubista,et al.  Classification of isolated tumor cells and micrometastasis , 2000, Cancer.

[30]  L. Venta,et al.  Are malignant cells displaced by large-gauge needle core biopsy of the breast? , 1999, AJR. American journal of roentgenology.

[31]  B. Gusterson,et al.  Role of immunohistochemical detection of lymph-node metastases in management of breast cancer , 1999, The Lancet.

[32]  A. Giuliano,et al.  Sentinel node biopsy in breast cancer. , 1999, Journal of the American College of Surgeons.

[33]  A. Giuliano,et al.  Improved Axillary Staging of Breast Cancer with Sentinel Lymphadenectomy , 1995, Annals of surgery.

[34]  J. Coindre,et al.  Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. , 1992, British Journal of Cancer.

[35]  R. Gelber,et al.  Occult axillary lymph-node micrometastases in breast cancer , 1990, The Lancet.

[36]  R. Blamey,et al.  Occult axillary lymph-node micrometastases in breast cancer , 1990, The Lancet.

[37]  D. Jones,et al.  Comparison of the detection of breast carcinoma metastases by routine histological diagnosis and by immunohistochemical staining. , 1988, European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes.

[38]  J. Coindre,et al.  Micrometastases to axillary lymph nodes from carcinoma of breast: detection by immunohistochemistry and prognostic significance. , 1987, British Journal of Cancer.

[39]  E. Berardengo,et al.  The immunohistochemical detection of lymph node metastases from infiltrating lobular carcinoma of the breast. , 1986, British Journal of Cancer.

[40]  D. Mason,et al.  The immunocytochemical detection of axillary micrometastases in breast cancer. , 1984, British Journal of Cancer.

[41]  J. Pickren Significance of occult metastases. A study of breast cancer , 1961, Cancer.

[42]  O. Saphir,et al.  Obscure axillary lymph-node metastasis in carcinoma of the breast. , 1948, Cancer.