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THE AMERICAN JOURNAL OF CANCER A Continuation of The Journal of Cancer Research VOLUMEXXXVI JUNE, 1939 NUMBER2 -_________ CARCINOMA CUTIS ERIK POPPE From the General Department of the Norwegian Radium Hospital, Oslo (Chief: Rolf Bull Engelstnd, M.D.) and thc Hospital's Laboratory for Pathology (Chief: Professor Leiv Kreyberg, M.D.) Histologically three types of skin carcinoma are recognized : the squamous- cell, the basal-cell, and the intermediate. A brief review of these well known forms will suffice. ( 1) The squamous-cell carcinoma is distinguished histologically by dif- ferentiation of the tumor cells, sometimes to a considerable degree, with well marked intercellular bridges and horny pearl formation (Fig. 1). The more malignant forms are less highly differentiated, with nuclei of various sizes, hyperchromasia, and many mitoses. (2) The basal-cell carcinoma is reminiscent of the basal-cell layer in the epidermis or, even more, of the epithelium of young hair sheaths. The nucleus of the tumor cell is spindle-shaped and the cytoplasm is sparse. The appearance of the basal-cell carcinoma varies somewhat. The form most frequently seen consists of solid cords of atypical epithelium outlined by a highly differentiated columnar-cell layer with deeply staining spindle- shaped nuclei (Fig. 2). The tumor cells of the deeper layers are less dif- ferentiated and their nuclei are paler. Some tumors show an adamantinoid type of growth, the cell strands being lined by similar columnar epithelium (Fig. 3). In others there is an alveolar arrangement of the tumor paren- chyma (Fig. 4) suggesting glandular structures. In some of this group a substance resembling mucus is present in the loose connective tissue between the epithelial cords. Such cases are often designated cylindroma (Fig. 5). Less differentiated forms (Fig. 6) also occur, in which the basal-cell layer is indistinguishable, the nuclei are of equal size, ovoid, with few or no mitoses, and the connective tissue is often fibrous. As a general rule this form is not characterized by any great degree of malignancy. Occasionally a basal-cell carcinoma is seen containing pigment cells (Fig. 7), but this is unusual. (3) The intermediate forms comprise the so-called type mixte and type interme'diaire. As these designations indicate, the histologic picture is partly intermediate between the squamous-cell and basal-cell forms mentioned and partly a mixture of the two. 179 180 ERIK POPPE FIG. 1. SQUAMOUS-CELLCARCINOMA. X 35 The present paper is based upon all cases of cutaneous carcinoma (exclu- sive of carcinomas of the lip, anus, and vulva) which have been treated at the Norwegian Radium Hospital from its opening in May 1932 up to May 1935. The period of observation for the total material is at least three years from the time of treatment. The entire series consists of 198 cases. In 172 of these the tumors have been examined histologically in the hospital’s laboratory and all the sections have been reviewed by the chief of the laboratory, Professor Kreyberg, with a view to obtaining the most uniform classification possible. In 17 cases no histologic study was made; the remainder were examined at other laboratories, from which sections were unobtainable. Of the 172 tumors histologically examined and verified, 49 or 28.5 per cent were squamous-cell carcinomas, 108 or 62.8 per cent were basal-cell carcinomas, and 15 or 8.7 per cent were of intermediate type. Squamous-cell Carcinoma: Of the 49 patients constituting this group, 2 1 were women, of an average age of sixty-nine years; 28 were men, of an aver- age age of sixty-seven years. Thirty-eight of the tumors were located on the head, 34 of these being on the face; 11 were on the trunk and the extremities. The following lesions were mentioned in the case records as preceding the de- velopment of cancer : senile hyperkeratoses, scars from burns, frost-bite, chronic fistulas, and chronic leg ulcers. In several instances of tumor of the scalp the patient had for many years had a ‘( fatty tumor ” (atheroma?) at the same site. Fig. 8 shows the distribution of the individual tumors according to size. From this figure it is clear that a great number of the patients came for FIGS.2 AND 3. BASAL-CELLCARCINOMA Fig. 2 (above) X 50. Fig. 3 (below) X 220. See text. 181 182 ERIK POPPE FIG.4. BASAL-CELLCARCINOMA WITH ALVEOLARARRANGEMENT OF PAREE~CHYMA.X 80 treatment at a late stage. Tn 16 cases the tumor area exceeded 10 sq. cm. Most of these tumors were very large; in 12 there was infiltration of the deeper tissues and in 8 the regional lymph nodes were enlarged. The results of treatment, arranged according to the size of the tumor, are also shown in Fig. 8. These indicate the great bearing of tumor extension on the outcome. All of the 10 tumors measuring less than 1 sq. cm. disappeared, whereas of the 16 which exceeded 10 sq. cm. only 6 disappeared. Of the 49 patients with squamous-cell tumors, 11 had metastases. Of this group, 7 died after a period of one to fourteen months while 4 are still alive and free from recurrence. These 4 cases may be briefly described. CASEIX: A man, seventy years old, had a tumor 3 X 3 cm. in front of the right ear and a hard node about 3.5 X 2.5 cm. in the right supraclavicular fossa. Biopsy of the primary lesion showed slightly differentiated squamous-cell carcinoma with numerous mitoses. Following teleradium therapy the patient has been free of recurrence four years. CASEX: A man, sixty-three years old, had had a primary carcinoma of the right cheek radically removed a year prior to admission. Back of the angle of the jaw, on the right side, was a hard node some 4 to 5 cm. in diameter. Biopsy showed this to be a squamous- cell carcinoma. Roentgen irradiation and teleradium therapy were given and there was no recurrence three and a quarter years later. CASEVII: A man of forty-eight had a tumor in the right infraclavicular fossa, measur- ing 2 x 2 cm., and a hard node about a centimeter in diameter in the right axilla. A biopsy of the primary tumor showed a rapidly growing squamous-cell carcinoma ; the metastatic growth was of the same type. A radical axillary node operation was done and the patient was well four and one half years later. CASEXXXVI: A woman of fifty-six had had a tumor in the skin of the scalp radically removed a month before admission, This proved to be a slightly differentiated squamous- cell carcinoma. A node about 2.5 X 1.0 cm., beneath the left mastoid process, showed the same histologic picture. This was extirpated and given teleradium therapy. Five years later there was no recurrence. FIGS.5 AKD 6. BASAL-CELLCARCIKOMA Fig. 5 (above) is of the type known as cylindroma. X 200. Fig. 6 (below) is a less differ- entiated form in which the basal-cell layer is indistinguishable. 183 184 ERIK POPPE FIG.7. BASAL-CELL CARCINOMA CONTAINING PIGMENT CELLS The results of treatment in the 49 cases are as follows: Squamous-cell Carcinoma: Results of Treatment of 49 Patients Free from recurrence for more than three years ....................... 27 Symptom-free: death from intercurrent disease within three years ...................7 Symptom-free; relapse; further treatment; again symptom-free for Less than one year .................................................... 1 One year ............................................................. 0 Two years ...................................... .................... 1 Improved: death from intercurrent disease ............................. 3 Death from cancer of the skin ......................................... .I0 The patients who died of skin carcinoma will be referred to in greater detail later, as it is of interest to consider the reasons for failure of the treat- ment in these cases. Basal-cell Carcinoma: Of the 108 patients with basal-cell carcinoma, 50 were females and 58 males. The average age of the women was sixty-two years, that of the men 65.5. One hundred of these tumors were on the face; there were 4 on the scalp and 4 on the trunk or extremities. Twenty-one patients gave a history of a wart or a birthmark at the tumor site ‘(for a very long time ” or “ always.” In 7 cases the patient mentioned chronic irritation caused by spectacles or a pince-nez. A great number showed senile skin changes. Both in the present material and in that seen more recently we have ob- served that tumors which are situated in the trunk may show a clinical picture differing from that of the ordinary basal-cell carcinoma. The tumors form large or small, pink or brownish-red spots with a scaly surface and with only very superficial infiltration, or even none at all. In our more recent material CARCINOMA CUTIS 185 we have also seen multiple tumors on the trunk, resembling a restricted chronic eczema or psoriasis (Jadassohn) . Fig. 9 shows the distribution of the individual basal-cell tumors according to size, with the results of treatment in the different groups. From the dia- gram it is seen that the small tumors, less than l sq. cm., rarely infiltrate the deeper tissues and that all these tumors have been cured. Of the tumors Size of tumor Size of tumor Size of tumor :1 sq. cm. or less 1-10 sq. cm. larger than 10 sq. cm. FIG. 8. SQUAMOUS-CELLCARCINOMAS GROUPED ACCORDING TO SIZE,WITH AN INDICATIONOF THE TREATMENTRESULTS IN THE INDIVIDUALGROUPS Column I: Total number in the group. Column 11: Number of tumors in the group which infiltrated the under layer. Column 111: Number of tumors in the group with metastases. Column IV: Number cured.