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The science of histopathology revealed that like normal tissues, tumors are composed of cells. During development and in physiological contexts, proliferation is regulated by exposure of cells to soluble growth factors within their environment. Cells use a number of distinct signaling pathways to control their proliferation. A cell's decision to divide or to become quiescent is influenced by mitogenic signals in the cell's surroundings. In rapidly dividing tissues, parenchymal cells are born from asymmetric division of a stem/progenitor cell, differentiate and then undergo programmed cell death. Intact DNA damage repair systems are critical to maintain genomic stability and prevent tumorigenesis. Inactivation of the apoptotic machinery permits the survival of cells with accumulatingmutations and promotes evolution of premalignant to malignant cells. Failure in the ability of the immune system to distinguish self from non-self can result in autoimmune reactions or facilitate the development of a tumor.