Beyond conventional pathology: Towards preoperative and intraoperative lymph node staging

Accurate detection of lymph node metastases is critical for many solid tumours to guide treatment strategies and determine prognostic outcomes. The gold standard for detection of metastasis is by histological analysis of formalin-fixed paraffin-embedded (FFPE) sections of removed lymph nodes; this analysis method has remained largely unchanged for decades. Recent studies have highlighted limitations in the sensitivity of this approach, at least in its current clinical use, to detect very small metastatic deposits. Importantly, the poor prognostic outcomes associated with the presence of such small tumour deposits are now well established in a number of cancers. In addition, histological analysis of FFPE sections cannot be used practically for intraoperative node assessment. Novel lymph node staging technologies are therefore actively being developed. This review critically presents the main advances in this field and discusses why these technologies have not been able to provide a better alternative to the current gold standard diagnostic technique.