International Union Against Cancer. Classification of isolated tumor cells and micrometastasis

Background: Findings of isolated (disseminated or circulating) tumor cells (ITC) by immunocytochemistry and molecular pathology methods have led to varied interpretations and different applications of the TNM system.

Methods: An analysis of the relevant literature was undertaken. In addition, optional proposals for the classification of ITC, micrometastasis, and cytologic results in pleural and peritoneal washings are presented.

Results: Immunocytochemistry has a lower false-positive rate than nonmorphologic methods such as flow cytometry or the polymerase chain reaction; therefore the method(s) used always should be recorded. At the current time, the independent prognostic significance of ITC in regional lymph nodes and in the general circulation (blood, bone marrow, and other distant sites) is difficult to assess. To enable comparisons of treatment results and to avoid variation in staging, a finding of ITC should not be considered in the TNM and residual tumor (R) classifications, at least not at the current time. However, for future evaluation of their prognostic significance, the respective findings should be documented according to uniform criteria.

Conclusions: ITC should be distinguished from micrometastasis. To investigate the independent prognostic significance of ITC and of positive lavage cytology, uniform data collection according to the proposed coding schema is recommended.