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Isolated tumour cells and micrometastases represent two different staging categories and are often dealt with differently when identified in sentinel lymph nodes of breast cancer patients. The reproducibility of these categories was found to be suboptimal in several studies. The new edition of the TNM (Tumour Node Metastasis) is expected to improve the reproducibility of these categories. Fifty cases of possible low-volume nodal involvement were represented by one to four digital images and were analysed by members of the European Working Group for Breast Screening Pathology (EWGBSP). The kappa value for interobserver agreement of the pN (TNM) staging categories and of the isolated tumour cells category were 0.55 and 0.56 reflecting moderate reproducibility, and the kappa of the micrometastatic category (0.62) reflected substantial reproducibility. This is an improvement over the results gained on the basis of the previous edition of the TNM. Maximal adherence to the category definitions supplemented by explanatory texts in the staging manual should result in more homogeneous nodal staging of breast cancer.

Item does not contain fulltext Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.

Tibor Tot1,*, James Going2, Maria Pia Foschini3, Gyula Pekar1, Lee Tucker4, Anna Sapino5 1 Uppsala University, Central Hospital Falun, Department of Pathology and Clinical Cytology, Falun, Sweden 2 Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK 3 Department of Biomedical and Neuromotor Sciences, Section of Anatomic Pathology “M. Malpighi”, University of Bologna at Bellaria Hospital, Bologna, Italy 4 Virginia Biomedical Laboratories, Wirtz, VA, USA 5 Department of Medical Sciences, University of Turin, Turin, Italy

Because of the important therapeutic implications, a crucial issue in breast cancer pathology is the correct identification of true HER2 positivity in tissue specimens. The relevance of such assessment on HER2-positive breast cancer patients will be further enhanced if trastuzumab is administered to patients in monotherapy, such as trastuzumab emtansine (i.e. trastuzumab-DM1, T-DM1), an antibody–drug conjugate consisting of trastuzumab linked to the cytotoxin mertansine (DM1). T-DM1 is designed to target and inhibit HER2 signaling and to deliver the chemotherapy directly inside HER2-positive cancer cells. As a consequence, it will be of utmost importance for pathologists to recognize HER2-positive carcinomas with precision, because patients will not be administered any other chemotherapeutic agents and response to treatment will rely strictly on the pathological assessment of HER2 [1]. Activation of HER2 may be driven not only by HER2 gene amplification; indeed, in terms of the biology of HER2-positive tumors, a “brand new” topic is the recent demonstration by next-generation sequencing studies of the presence of HER2 mutations in breast cancer [2]. Bose and colleagues [3] have functionally characterized 13 HER2 mutations, and seven of these mutations were activating mutations sensitive to the irreversible HER2/EGFR tyrosine kinase inhibitor neratinib [3]. Estrogen-receptor(ER-)positive breast carcinomas, either HER2-negative (score 0/1+) or showing equivocal HER2 expression (score 2+), seem to be putative candidates for HER2 mutations. Here we discuss some of the “hot topics” concerning HER2 assessment.