Sentinel node and bone marrow micrometastases and nanometastases

Step-sectioning and anti-cytokeratin immunohistochemistry allow detection of micrometastases and nanometastases down to the single cell level, but they are labor intensive and time consuming. Reverse-transcription polymerase chain reaction can be performed efficiently, but it cannot currently detect less than several thousand cancer cells per lymph node. Improvements in molecular assays are thus required for reliable use in clinical settings. Wholeaxilla dissection maximizes chances of detecting micrometastases and nanometastases. However, sentinel lymph node analysis provides an important fraction of this information in more convenient surgical and laboratory settings. Nanometastases have been shown to be a risk factor for event-free survival and for metastatic relapse. Thus, a re-evaluation of current TNM staging procedures appears needed. Corresponding therapeutic strategies should be tested accordingly in prospective clinical trials with adequate follow-up time. Microinvasion of the bone marrow is an independent prognostic indicator for disease recurrence and death from cancer, but bone marrow analyses are poorly suited to monitor disease course and response to therapy. The detection of circulating tumor cells has been shown to provide useful prognostic information, but it correlates poorly with bone marrow microinvasion, and the latter remains an independent, albeit hard to manage, prognostic determinant.