Many authors think that a carcinoma springs from one center, but Petersen's11 work would seem to show that the multicentric origin of malignant epithelial tumors is far from uncommon. As Bloodgood well observes, Petersen's demonstrations apply to the basal-celled type, a form of tumor that is frequently multiple. Petersen's work appears to have been very carefully done after the "Platten-modellen-Methode" of Born.12 The early tumors were cut into serial sections, and from these sections a wax model was built up. This is, of course, the only positive way in which the question as to the unicentric or multicentric origin of cancer can be settled. As bearing on this point, Gilchrist has recently had a very early basal-celled carcinoma of the face, in which, at a distance of about 3 mm. from the main tumor mass, there was a distinct new and exceedingly early carcinoma developing. Serial sections showed that there was no connection between the two. If these tumors are really of multicentric origin, the point has a great practical bearing, for it means that a wider incision is necessary at the time of operation. This fact, or rather theory, may explain why basal-celled carcinomata so often recur after operations in which but a small margin is given them. On the other hand, it must always be remembered that metastases may have taken place by a lymph channel, and that an apparently separate growth is in reality simply a metastasis.

At first it was thought that cancer spread by apposition, that the cancer cell caused the neighboring cells to also become cancerous, and later observation has shown that to some extent this belief is correct. Hertzler says: "In transplanted epithelial tumors in animals the connective tissue has been stimulated to sarcoma formation, showing that the power of growth may be transmitted to other kinds of tissue. Still more conclusive are the experiments of Bor-rel and Lewin, in which epidermis was stimulated to the formation of squamous epithelioma by the transplantation of glandular tumor beneath it, showing that the proliferating stimulus may be conveyed by cells possessed of the power of unlimited growth. In both these instances there can be no confusion between the normal and the tumor cells. The proliferation excited by Scharlach R. and Sudan III. likewise show clearly that epithelial cells can be made to proliferate and invade surrounding tissue by the action of certain extrinsic stimuli. It may be regarded as proven, therefore, that normal epithelial cells, under certain conditions, may be made to proliferate by close contact with malignant cells or by other stimulation." And yet it is generally conceded that tumor growth comes from the multiplication of the tumor cells, rather than from the conversion of other cells to a malignant type.

*Petersen: Beitr. z. klin. Chir., 1902, xxxii, 543.

*Born: Bohm-Oppel Taschenb. d. Mikr. Technik., 74.

Growth takes place by the cancer cells either invading between the connective tissue fibers through the lymphatics or otherwise, or by bodily pushing the connective tissue aside, or more usually by a combination of both methods. These invading cells may or may not retain connection with the main body of the tumor. In the more malignant types of tumors, cells may escape to the lymphatic glands, or may be carried by blood vessels to remote portions of the body, or they may spread out and form separate masses in the proximity of the parent neoplasm. In cancer the growth usually takes place through the lymph spaces and lymph vessels. On account of this spread through the lymphatic system, it is often impossible to differentiate between metastasis and local infiltrative growth; in fact, it is desirable not to attempt to distinguish between them, for they are essentially the same. The superficial spread may be so great as to form cancer en cuirasse, where practically the whole subcutaneous tissue becomes cancerous. The lymph glands affected are usually the nearest glands draining the cancerous area, but rarely these are skipped and more remote ones are involved. Extension by contact is rarely seen in tumors of the skin, and many excellent clinicians deny its existence. It is very important to note that cancer cells may lie dormant for many years, and then suddenly take on great activity. We no longer speak of cancer patients as cured when an interval of three years has elapsed without recurrence.

Occasionally adenomata of the suprarenal or thyroid glands form metastases, and the author has observed one case where a histologically benign adenoma of the sweat glands metastasized to the neighboring glands. It seems reasonable, however, to suppose that there are true area of malignancy in these neoplasms.

Recurrence after operation depends on the factors already discussed. Recurrence means that all tumor cells were not removed by the surgeon, either because they had escaped to other organs, or because of a wide local spread.

Toxins

It has not been proven that epithelial tumors have a specific toxin. What absorption there is probably comes from the endotoxins of bacteria which are secondary invaders.

Immunity

There is probably no authentic instance where an epithelial neoplasm, microscopically proven to be malignant, has spontaneously healed, and failed to recur. The central portion of a rodent ulcer may heal and form scar tissue, and may likewise scab over and apparently heal for a year or even more, but not permanently; in fact, we know nothing of true immunity.