The pathoanatomy of cancer: order in paradox.

The pathoanatomy of local cancer spread is approached by the ontogenetic cancer field model, deduced from aspects of evolution, development, immunity, and wound healing/regeneration in multicellular animals, postulating: (1) Cancer cells canonically respond to the disruption of tissue homeostasis caused by their uncontrolled proliferation with progressive de-differentiation, which paradoxically enlarges the cancer wound instead of healing it. (2) The de-differentiating cancer cells adhere in reverse sequence to a principle of topological order laid down during embryonic development by the metazoan cell type differentiation trajectory. The model predicts with high anatomical accuracy ontogenetic stage-dependent permissive tissue territories for local cancer propagation, i.e., cancer fields, as demonstrated for cancers of the alimentary and genital tracts. Assuming the 'export' of the local cancer field into the draining lymph nodes by tissue macrophages and regulatory T cells, the model is also applicable for regional carcinoma spread. The clinical translation into cancer field surgery has led to a marked reduction of locoregional recurrences and to increased cure rates.