New insights into many pathological problems—and those of cancer in particular—are offered by the concepts we have been discussing. Let us take, for instance, the problem of just what cancer is. Classically, one is entided to speak of a condition as cancerous when cells with cancerous character are present in the body. Whether, on the one hand, only cancer in situ cells are identified or, on the other hand, the patient is dying and has almost no organ or function left untouched—the condition is considered cancerous. Yet, so long as the concept of cancer is associated implicitly with the concept of malignancy, to consider clinically healthy individuals to be cancerous only because of the presence of cells with cancerous nuclear characters, when most of them will never show further development of the disease, is entirely confusing. It is essential to separate the two concepts, the presence of cancerous entities and actual malignancy.

The fact that the hierarchic levels of the organism participate in the various manifestations of cancer puts the problem in its true light. A cancerous condition does not implicitly mean malignancy when it involves only the presence of an entity with cancerous character. Other attributes must be considered. In the hierarchic progression of cancer, malignancy begins to be manifested when the cellular level participates and induces invasive cancer. With malignancy an attribute of only some of its phases, cancer can be seen to embrace many changes, beginning with those of the lowest hierarchic entities and terminating with the systemic lethal condition.

The plurality of phases of cancer, with the broad variations in time and other factors which determine the passage from one phase to the other, logically raises several immediate questions.

In view of the multiple phases, one cannot speak of pathogenesis of cancer in general, but rather of pathogenesis of the different phases. Consequently, even postulating the existence of some specific original cancerous change, such a change would not, alone, induce the entire disease and determine the passage through successive phases. Different pathogenic factors must be considered to intervene in order to have cancer pass from one phase into another. The evolution of the cancerous condition has to be related to these different factors, some of them possibly more important than the original specific change. The passage of a cancer from the noninvasive to invasive phase, or from tissue to systemic, is surely more important than the appearance of a low level cancerous entity. An original change at a lower level appears, in fact, to be of very little importance, not only because of its ubiquity but also because it is not implicitly related to malignancy. From this point of view, then, cancer no longer can be defined as some single specific change in a cell, nucleus, chromosome, gene or other biological entity.

Carcinogenesis has to be conceived of in an entirely new way, in terms of plural factors and their relative values. Accepting the phases above invasive cancer as the only ones which correspond to clinical malignancy, they have to be regarded as the end result of a series of cancerous changes developed at progressive levels, with the intervention of many factors, not just one.