SOME ESSENTIAL FACTORS IN THE PATHOLOGY AND TREATMENT OF CANCER OF THE SKIN LOUIS H. JORSTAD, M.D. (From the Department of Pathology, the Barnard Free Skin and Cancer Hospital, St. Louis, Missouri) The stimulus for this study on the pathology and treatment of cancer of the skin was twofold: first the gross and microscopic examination of a large series of laboratory animals in which a small area of skin was subjected to different dosages of x-ray (1); second, the microscopic diagnosis and clinical study of 200 cases of carcinoma of the skin. Basal-cell carcinomata of the skin were at one time called epitheliomata, the term carcinoma being used to indicate squamous-cell carcinoma. This nomenclature placed too much emphasis on the identity of the two forms. There are a certain number of tumors which are a mixture of basal-cell carcinoma and squamouscell carcinoma. This is not a new finding, but is one that cannot be over-emphasized. Since Krompecher (2) discovered this mixed form years ago it has too often been forgotten. The use of such terms as epithelioma, spinous carcinoma, and acanthoma should, I believe, be discontinued. These terms are confusing. A rearrangement of the classification of the carcinomata which we find in the skin would seem advisable. We have first the typical basal-cell carcinoma (Fig. I). In tumors of this type the basement layer of cells undergoes division but the basement membrane remains intact. Metastasis does not occur. The tumors may be multiple. The cystic basal-cell carcinomata form a second group (Fig. 2). These tumors are characteristically multiple. A third group of basal-cell carcinomata I would call the adenoid type (Fig. 3). This type is closely allied to hair follicle carcinoma and in many instances the histology of the two forms is similar. These adenoid basal-cell carcinomata have been called adenocarcinomata. From the small series which I have had opportunity 177
178 LOUIS H. JORSTAD to review it would seem that this adenoid type is more malignant than other basal-cell carcinomata. The invasion is deeper, and a certain percentage of these growths metastasize. One may group tumors of this type with the adenocarcinomata of 'sweat gland, mucous gland, and hair follicle origin (Fig. 4). A fourth group consists of the combined basal-cell and squamous-cell carcinomata. This type should be called basal-squamous or baso-squamous, as Montgomery (4) has suggested. In the cases which I have studied I have distinguished two varieties; in one the basal-cell and squamous-cell areas occur side by side on one microscopic field (Figs. 5 and 6), while in the other variety the squamous-cell areas occur within and among the basal-cell areas (Fig. 7). It is not unusual to see a tumor change in type from basal-cell carcinoma to squamous-cell carcinoma as a result of stimulation during the course of insufficient and prolonged treatment. In an insufficiently radiated or in a radio-resistant basal-cell carcinoma such a change begins with squamous anaplasia. From the standpoint of Broders' work on grading it is interesting to note that the squamous changes which I have seen in basal-cell carcinomata have usually been Grade I. It is unusual to find metastasis from Grade
Fro. 2. CYSTIC BASAL-CELL CARCINOMA
180 LOUIS H. JORSTAD I carcinoma, and it is also unusual to find metastasis from these anaplastic basal-cell carcinomata. Squamous-cell carcinoma constitutes a final group in a classification of skin carcinomata. Recently May Owen (5) has reviewed certain pathological features regarding the classification of carcinomata. The stimulus for her work came from reports that primary basal-cell carcinomata of the mucous membranes do occur. It was her experience, however, that these cases were highly malignant squamous-cell carcinomata. They resembled basal-cell carcinoma histologically, but on careful study of a number of sections taken from each tumor, the squamous-cell structure could be made out. In her review Owen cites the work of Lunford and Taussig, of Martzloff, and of Vinson, each of whom has reported a large series of carcinomata of the mucous membranes, including none of the basal-cell type. Krompecher, on the other hand, is cited as finding about one-half of the malignant tumors of the nose and larynx corresponding to the basal-cell type. The more recent studies of New and Broders mention no basal-cell carcinomata of the internal cavities of the head and neck, and Broders states that he has never seen one originating on mucous membrane. In my classification I have not in-
182 LOUIS H. JORSTAD cluded among the basal-cell carcinomata those highly malignant squamous-cell carcinomata occurring in the cervix and in the mucous membrane of the mouth mentioned by Owen as being confused with basal-cell carcinoma. It is characteristic of the basal-cell carcinoma that it is made up of small polyhedral or spindle-shaped cells which contain a large amount of nuclear material that stains deeply with a basic stain such as hematoxylin. The squamous cell has one nucleolus in contrast to the many nucleoli of the basal cell. Carcinoma developing upon keratosis is interesting from the standpoint of classification. This may be either basal-cell or squamous-cell in type, depending upon the degree of keratinization. The relationship of keratosis and hyalinization to carcinoma was clearly brought out in a study made by the author, of the reaction of the skin of animals to roentgen irradiation. In a number of patients with marked destruction of skin following irradiation the removal of these areas for therapeutic benefit has given considerable material for study. If keratosis of the superficial layer of the epithelium is present, there is a hyperplasia of the lower layers. If the keratosis is of the proper degree, atavism occurs, which may lead to basal-cell or squamous-cell carcinoma. With still deeper destruction of tissue, hair follicle carcinoma may develop. The hair follicle
being more cellular, it is stimulated to activity when located in the zone of connective tissue which has undergone hyalinization. It is usually the rule to see a more malignant carcinoma following a keratosis in a moderately young individual. Some have regarded this fact as demonstrating the development of an increasing immunity to carcinoma with advancing age. The keratosis above described is the most clearly proved precancerous lesion. To conclude, I am convinced that all skin carcinomata should be treated as if they were malignant. It cannot be determined clinically whether a tumor is a typical basal-cell, a basal-squamouscell, or a squamous-cell carcinoma. One never knows when a basal-squamous-cell carcinoma will change into a squamous carcinoma. Some clinicians apparently are not cognizant of this fact. If these factors were kept in mind when dealing with skin carcinoma, I feel certain that the percentage of recurrences and bad results would be greatly diminished. 1. JORSTAD, L. H., AND LANE, C. W.: Proc. Soc. Exper. Biol. & Med. 24: 886, 1927; Arch. Derm. & Syph. 19: 954, 1929. 2. KROMPECHER, E.: Beitr. z. path. Anat. u. z. allg. Path. 28: 1, 1900. 3. KROMPECHER, E.: Beitr. z. path. Anat. u. a. allg. Path. 44: 88, 1908. 4. MONTGOMERY, H.: Arch. Derm. & Syph. 18: 50, 1928. 5. OWEN, M.: Arch. Path. 10: 386, 1930.