Anatomically independent tumors revisited

Many malignancies exhibit a multifocal pattern of growth, which is usually attributed either to micrometastases of an original 'primary' lesion or to the presence of anatomically independent tumors that have developed close to each other by chance. However, recent advances in tumor stroma biology imply the operation of an alternative process that can be classified as in-between these two previously mentioned mechanisms. Considering that stromal fibroblasts possess the ability to stimulate malignant transformation of normal and/or benign lesions, and that these fibroblasts may persist during therapy, it is conceivable that the oncogenic pathway(s) to be followed by the epithelial cells - which will eventually grow to different and independent malignant foci - have been predetermined by the initiating events that are responsible for the transition of stromal fibroblasts into this cancer-associated state. If such a hypothesis contributes to the onset of a subset of multifocal tumors, it possesses important implications in the diagnosis, prognosis and therapy of cancer.