The causative factor in cancer of the skin is that of cancer in any other portion of the body, and is still unsolved. Dermatologists have not done their share toward the elucidation of the carcinoma riddle, although they have had better opportunities than any other type of clinician, inasmuch as they are sometimes able to trace the development of cutaneous cancer from the various precancerous dermatoses, of which xeroderma pigmentosum forms such a beautiful example. Ewing* has recently treated exhaustively of the different theories as to the etiology of cancer, and Loeb* has published a number of excellent papers.

Cohnheim's Theory

Cohnheim* believed that cancer arose from congenitally displaced epithelium, beginning to grow riotously. As Unna has well pointed out, this certainly takes place in the neoplasms arising from congenital moles and from other nevi. At least three objections may, however, be placed against this theory- first, that cancer often starts where no congenital rests can be demonstrated, and where it is extremely improbable that any such rests would exist; second, that the theory does not explain why the rests become malignant; and, third, as pointed out by Welch, that even in very deep burns, where all of the surface epithelium is destroyed, a carcinoma may later develop. It may be added that the known congenital malformations do not very frequently become malignant.

Changes In Cell Type Or Metaplasia

While an epithelial cell of one type may be changed into an epithelial cell of another type, there is no proof that one type of cell may turn into a radically different type. It seems certain that metaplasia in epithelial tumors is confined within narrow limits. Of course, it is known that a benign papilloma, so-called, that has existed for years may later become malignant. But, again, this theory is not satisfying, for it gives no explanation why these changes take place.

*Ewing: Arch. Int. Med., 1908, i, 175.

*Loeb and Sweek: Jour. Med. Research, 1913, xxiii, 2, July. 18 Cohnheim: Vorlesungen iiber allg. Pathologie, Berlin, 1877, i.

Regression

By this term Ribbert indicated a condition of cell change where cells become atavistic, or less differentiated. It is generally stated by pathologists that tumors arising from the less differentiated cells and showing the structure of the primitive cells are the most malignant, and yet in carcinoma of the skin we find that the basal-celled (or primary) tumors are much less malignant than the tumors arising from the prickle cells and to some extent retaining their structure. It is true that in the latter the prickles arc short, or entirely lost, and that the cells are smaller than normal, but these changes may largely be due to pressure.

Atypical mitotic figures have been studied by many, and by some believed to be responsible for the abnormal proliferation of the cells, but the majority of pathologists believe that these abnormalities are the result and not the cause of bewildered growths.

Changes In Tissue Balance

Thiersch held that in carcinomata the primary change was in the connective tissue, that there was a weakening of it which allowed the epithelial cells to expand and penetrate into it. He thought that there was an antagonism between the epithelial cells and the connective tissue cells, a totally unjustified assumption. It is well known that in many conditions, as in x-ray cancer, the primary change is in the connective tissue, but there are no facts to justify the belief of Thiersch. Hertzler has shown that in very early cases of cancer the connective tissue does not take acid stains in a normal way, but nothing practical has developed out of this interesting demonstration.

Microorganisms

Ewing gives the following list of parasites that have at some time been held to be responsible for cancer:

Bacteria

Bacillus of Rappin, 1886; Scheurlen, 1887; Francke, 1888; Lampiasi, 1888; Koubassof, 1889; Micrococcus neoformans, Doyen, 1902.

Coccidia

Cocidium of Darier, 1889; Albarran, 1889; Thoma, 1889; Sjobring, 1890; Coccidium sarcolytum, Adamkiewicz, 1892; Soudakiewitsch-Metchnikoff, 1892; Monsarrat, 1905.

Sporozoa (unclassified).-Birdseye inclusion, Foa, 1891; Plim-mer's bodies, 1892; Sporozoon, Ruffer, 1892; Sawtschenko, 1893; Ameba-sporidium, Pfeiffer, 1893; Rhopalocephalus canceromatosus, Korotneff, 1893; Sporozoon, Kourloff, 1894; Bose, 1897; Hemato-zoon, Kahane, 1894; Cancriameba macroglossa, Eisen, 1900; Ley-denia gemmipara, Schaudinn, 1896; Intranuclear parasite, Schuller, 1901-4.

Blastomycetes

Saccharomyces neoformans, Sanfelice, 1896; Plimmer, Leopold; Roncali, Bra; Russell's fuchsin bodies; Mucor racemosus, Schmidt, 1906.

Mycetozoa

Plasmodiophora brassicae, Behla, Podwyssoski, Fein-berg, Gaylord, Robertson and Wade.

Spirochete

Gaylord, Calkins, 1907; Cyanid-fast bodies, Robertson, 1907.

This list is of special value as showing two things-first, the enormous amount of work that has been devoted to the subject, and, second, the frailties of human judgment. Practically none of these men published their results until they were sure that they had confirmed them, and many had the advice of distinguished protozoologists. From all of these results there has come only one thing of value- namely, a healthy skepticism on the part of other workers. Almost, however, this identical situation held for syphilis until Schaudinn and Hoffman demonstrated its cause only a few years ago, and it is by no means inconceivable that some modern Pasteur will prove to us that cancer is a disease that is caused by a micro-organism.

Contagiousness

There are certain factors that speak for the fact that cancer may be more or less contagious. These facts are:

Cancer of the thyroid gland is probably epidermic in the fish of certain hatcheries. Recent articles stating that these were not true cancer, but only adenomata, refer merely to local conditions in certain hatcheries. It must, however, be admitted that a systematic investigation should again be made in order to settle this point definitely.

Cancer seems to be more prevalent in certain localities than in others; in some it has been almost endemic for a certain length of time.

Nurses who have nursed cancerous patients for a number of years, whether or not they are related to the victim, seem to be especially liable to suffer from cancer.

Cancer is certainly inoculable, though usually within very narrow limits; mouse cancer is not inoculable from a white mouse to a gray one, so it would be unreasonable to expect human cancer to be inoculable to the lower animals. Again, this condition is somewhat similar to that pertaining in syphilis.

Sarcoma can be transmitted by a filterable virus according to a late publication by Rous and Murphy.16

In transplanted epithelial tumors in animals the connective tissue has been stimulated to neoplastic formation, as already mentioned earlier in this chapter.

Carcinoma or sarcoma usually develop at points of lowered resistance, so often spoken of in dermatology as precancerous dermatoses.

Malignant neoplasms in plants may be due to the Bacterium tume-faciens, according to the recently published researches of Erwin Smith.17 This seems to be the most definite work so far published.

And yet it must be admitted that cancer of the penis has never been proven to cause cancer of the uterus in the wife of a patient, nor has cancer of the lip ever been shown to cause another cancer.