Supervised automated microscopy increases sensitivity and efficiency of detection of sentinel node micrometastases in patients with breast cancer

Abstract

Aims: To investigate the practicality and sensitivity of supervised automated microscopy (AM) for the detection of micrometastasis in sentinel lymph nodes (SLNs) from patients with breast carcinoma. Methods: In total, 440 SLN slides (immunohistochemically stained for cytokeratin) from 86 patients were obtained from two hospitals. Samples were selected on the basis of: (1) a pathology report mentioning micrometastases or isolated tumour cells (ITCs) and (2) reported as negative nodes (N0). Results: From a test set of 29 slides (12 SLN positive patients, including positive and negative nodes), 18 slides were scored positive by supervised AM and 11 were negative. Routine examination revealed 17 positive slides and 12 negative. Subsequently, automated reanalysis of 187 slides (34 patients; institute I) and 216 slides (40 patients; institute II) from reported node negative (N0) patients showed that two and seven slides (from two and five patients, respectively) contained ITCs, respectively, all confirmed by the pathologists, corresponding to 5.9% and 12.5% missed patients. In four of the seven missed cases from institute II, AM also detected clusters of four to 30 cells, but all with a size ( 0.2 mm. Conclusions: Supervised AM is a more sensitive method for detecting immunohistochemically stained micrometastasis and ITCs in SLNs than routine pathology. However, the clinical relevance of detecting cytokeratin positive cells in SLNs of patients with breast cancer is still an unresolved issue and is at the moment being validated in larger clinical trials.A xillary lymph node status is one of the most powerful prognostic factors in breast cancer, despite the ongoing search for molecular markers that predict the behaviour of the primary tumour. Classic lymph node staging requires the removal of most of the axillary nodes, a procedure with the potential for considerable postoperative complications. As an alternative, sentinel lymph node (SLN) biopsy has been proposed, based on the postulate that anatomically tumour cells have to pass through one or a few lymph nodes (the ''sentinel lymph nodes'') before spreading into other nodes of the lymphatic system. This theory is strongly supported by data showing that SLNs can predict axillary status in 95% of cases.

The clinical significance of sentinel lymph node micrometastasis in breast cancer

“…Adjuncts to the conventional human assessment of specimens have been shown to be effective. Mesker et al [24] demonstrated that supervised automated microscopy can increase the sensitivity and efficiency of detection of SLN MM and Weaver et al [25] have described the utility of automated computer-assisted image analysis. [29].…”

Creation of a fully digital pathology slide archive by high-volume tissue slide scanning

“…This is the only setup that ensures that all slides are timely scanned, as opposed to postdiagnostic scanning. Furthermore, this would allow upfront digital diagnostics, for which such images are likely more than good enough [14], as well as preprocessed by image analysis algorithms, for example, finding metastases in sentinel nodes [15], mitoses [16] or microorganisms, or image analysis-supported grading and quantification of IHC [17]. Before the paradigm shift from "traditional" microscopy as the main tool for diagnostics to using digital slides, the use of digital slides needs to be validated on a large scale to make sure no information will be missed due to digitizing glass slides [5].…”

A systematic review and economic evaluation of intraoperative tests [RD-100i one-step nucleic acid amplification (OSNA) system and Metasin test] for detecting sentinel lymph node metastases in breast cancer

“…There are, however, indications that histopathologists may miss low-volume metastases. [152][153][154] Because of the low frequency of this omission relative to the occurrence of TAB, our analysis may have adopted a slightly conservative stance.…”