OCCUPATIONAL NEOPLASTIC DISEASE

CUSHMAN D. HAAGENSEN, M.D. (From the Memorial Hospital, New York City) The extensive investigations of occupational cancer, with the resultant important contributions to the literature of the subject from England and Germany during recent years, have stimulated interest in this field of cancer research. Since the incidence of the various types of occupational cancer apparently differs greatly in different countries, and the statistics on this subject for the United States are incomplete both as regards cancer morbidity and cancer mortality, we have proposed to survey the cancer morbidity data of the Memorial Hospital, which represents, we believe, the largest group of neoplastic diseases in an industrial community in the United States. In this study we shall discuss: (1) the occupational distribution of certain types of neoplastic disease; (2) their occupational inci­ dence; (3) the anatomic distribution of the cancers in the occupa­ tional groups; (4) the average ages at which the tumors occurred in the different occupational groups.

1. THE OCCUPATIONAL DISTRIBUTION OF NEOPLASTIC DISEASE The importance, in the etiology of cancer, of various agents which produce prolonged or chronic irritation is now generally recognized. Occupational cancer produced by tar, creosote, anthracene, pitch, soot, shale oil, petroleum, arsenic, aniline dyes, radium, and roentgen rays has been observed clinically. It has been produced experimentally in animals by these and other agents. In man the association of chronic irritation due to noxious occupa­ tional agents with cancer has naturally been most often observed on the surfaces of the body-on the skin and mucocutaneous surfaces. With the exception of cancer of the bladder in aniline dye workers and cancer of the lung in the Schneeberg miners, no relationship has been shown to exist between occupation and cancer of any of the internal organs. Young and Russell, for example, found that cancer of the tongue, esophagus, and stomach occurred with somewhat less than the normally expected frequency among 641 642 CUSHMAN D. HAAGENSEN cotton-spinning employees, who are subject to the most prevalent type of occupational cancer-mule spinners' cancer of the scrotum. This inquiry has, therefore, been limited to an investigation of the occupation in cancers of the skin, mucocutaneous surfaces, bladder, and lungs. During the period from January 1917 to January 1, 1930, there were accepted at Memorial Hospital 21,510 patients with neoplastic diseases. Of these, 2,914 had malignant tumors of the skin, 678 of the lip, 104 of the penis, 11 of the scrotum, and 125 of the vulva. There were 453 carcinomas and 66 papillomas of the urinary bladder and 108 carcinomas of the lung. Among these 4,459 histories the patient's occupation was noted in 2,684, or 60 per cent. Coal Coal, from which tars and other hydrocarbons are derived, is itself apparently innocuous, although, as Ross remarks, it is hard and gritty and may well cause mechanical injury of the skin

TABLE I Cancer of the Skin and Mucocutaneous Surfaces in Occupational Groups (Male) Particularly Exposed to Coal

Occupational Group Type of Lesion Ear Eyelid Nose Cheek Lip Neck Hand Penis Total ------Coal shoveller Squamous carcinoma 1 1 ------Coal bargeman Squamous carcinoma 1 1 ------~ -- Fireman Squamous carcinoma 3 1 1 5 (unspecified) ------Basal-cell carcinoma 1 1 2 .------* Epithelioma..... 1 3 3 7

TOTAL...... , ...... 16 .. * Under epithelioma are included all cancers in which the type was not verified by biopsy. amounting almost to laceration. Coal miners, firemen, and many other workers come into intimate contact with it; yet Young and Russell found no significant 1 excess of cutaneous cancer among coal miners, according to English mortality statistics. The Memorial Hospital records are remarkable for the small number of cases of cancer of the skin and mucocutaneous surfaces with a history of exposure to coal and coal dust. These cases are listed in Table 1.

1 The word "significant" is used throughout this study in thc narrow statistical sense of significance with respect t.o errors of random sampling. OCCUPATIONAL NEOPLASTIC DISEASE 643

Tar and Pitch Coal tar may be described as concentrated coal. It is the residue after the first stage in the distillation of coal. Its composi­ tion is dependent upon the kind of coal from which it is derived and also upon the method of carbonization employed. Gas works and coke ovens produce most of it. Naphthalene, phenol, pyri­ dine, creosote oil, anthracene, and pitch are successive fractions obtained in the distillation of tar. Of all these products, pitch is probably the most highly carcinogenic. Woglom has made the most comprehensive study of the vast amount of experimental work which has been done with tar and its related substances. In 1875 Volkmann described tar cancer occurring among the lignite tar workers of Saxony. Ullmann has reported 10 cases of tar cancer which developed among 2,500 employees in Prussian briquette factories. There have been a considerable number of isolated case reports. British mortality statistics, however, have furnished the most extensive information on the subject. Indeed, British statistics have confirmed a great part of our clinical knowl­ edge of occupational cancer. From this source Henry lists 439 cases reported as due to tar between the years 1920 and 1928. The occupations in this group were:

Patent fuel manufacture (briquette making). . .. 183 Tar distilling . 118 Coal gas manufacture . 65 Pitch loading (wharves, etc.) . 22 Coke ovens . 8 Brick, tile, and pipe manufacturing . 6 Producer gas manufacture. ... 6 Cable manufacturing . 6 Creosoting timber _.. ,.,. 5 Anthracene manufacture _ 4 Net fixing and barge repairing...... 5 Felt proofing . 2 Brattice cloth, asphalt trough, electric brush, insulator, and bitumastic paint manufacturing, sailmaking, cable handling, road mending, and creosoting molds in steel works, each . 1 This list illustrates the wide variety of uses to which tar and tar products are put in modern industry and the possibilities of their carcinogenic importance. The increasing use of tar in road­ making more and more exposes the whole population. Because of the lack of occupational mortality statistics in the United States, it is difficult to estimate the frequency of tar cancer in this country. H. B. Wood, in an investigation in Pennsylvania, found a few warty 644 CUSHMAN D. HAAGENSEN conditions but no cancer among 88 workmen who handled tar in six gas works, six coke by-product plants, five briquette works, and in the largest tar products plant. The Philadelphia Gas Company, employing 750 men, reported no cases of cancer. No carcinoma was found among workmen creosoting wood. Heller has recently investigated tar distillation plants, battery manufacturing plants using pitch, wood-preserving plants, and briquette-manufacturing works. No cancer was found among the briquette workers because, Heller believes, liquid petroleum asphalt is used as a binder and because the workmen do not come into contact with it. He collected 37 cases of probable tar cancer and found that gas-works tar and pitch were responsible for 70.2 per cent of the cases. He concludes that gas-works pitch is much more highly carcinogenic than coke-oven tar and pitch. There are definite precancerous dermatoses occurring among workers with tar and pitch. Volkmann describes small red nodules corresponding to the openings of the sebaceous glands, forming on the skin of the head, arms, hands, and scrotum of workers with tar. After the acute phase the red nodules diminish, leaving a black point or comedo. The skin between the glands becomes thickened, dry, and stiff. Small warts and horns of epidermis and flat, brown scales and crusts form. Legge describes the pitch warts common to briquette workers. They begin as small nodules and almost im­ mediately begin to break down, forming an ulcer covered by a crust which gives the characteristic appearance of the so-called wart. The underlying ulcer almost always heals, leaving a small scar when the crust has fallen off. The cases of cancer of the skin and mucocutaneous surfaces with an occupational history of exposure to tar from the Memorial Hospital data are briefly as follows:

1. J. H. M., a roofer, aged sixty: Epithelioma of the skin of the cheek near the angle of the mouth. 2. A. S., a roofer, aged thirty-six: Epithelioma of the nose. 3. E. N., a roofer, aged sixty: Epithelioma of the lip. 4. J. B., a roofer, aged seventy-two: Epithelioma of the nose. 5. T. M., a painter and roofer, aged seventy-four, who remembered having been spattered with tar many times, and whose face had also been burned with powder: Multiple epithelioma of the face and keratoses of face and hands. 6. J. F., a tar roofer who had worked with tar for thirty-three years: Keratoses of the skin of the face and a squamous carcinoma of the right ear (Figs. 1 and 2). OCCUPATIONAL NEOPLASTIC DISEASE 645

7. N. P., a roofer, aged seventy: Epithelioma of the upper lip. 8. M. M., aged sixty-nine, a road mender who had worked with tar for twenty-two years: Basal-cell epithelioma of the tip of the nose. 9. D. F., a road mender who had repaired asphalt roads for seven years: Epithelioma of the hand. 10. J. M., a workman who had handled barrels of tar, frequently spilling it on himself: Epithelioma of the skin of the cheek.

FIGs. 1 AND 2. SQUAMOUS CARCINOMA OF THE EAR IN A ROOFER (J. F.) WHO HAD WORKED FOR THIRTY-THREE YEARS WITH TAR

11. E. G., aged seventy-two, who had worked with tar occasionally, was a painter in winter and worked on the beach in summer: Epidermoid carcinoma of the nose. 12. H. P., a telegraph operator, who had burned the dorsum of his left hand with hot tar: Epithelioma in the burned area. 13. H. K., aged sixty-three: From 1912 to 1917 he had worked with tar. About 1916 he burned the skin of his cheek below the inner canthus of the right eye with splashed hot tar. A sore resulted, which never healed and continued to spread. When he came to the Memorial Hospital in 1927 he had an indurated ulcer 1.5 cm. in diameter, which on biopsy proved to be a squamous carcinoma (Fig. 3). 14. D. W., a miner, aged seventy-five: About 1921 he had spilled hot tar on the dorsum of his right hand. The burn never entirely healed, and about 1922 a wart-like growth appeared in the burned area. In 1927 the growth began to increase in size rapidly and became ulcerated. When the patient came to the Memorial Hospital, four months later, there was 646 CUSHMAN D. HAAGENSEN

an indurated ulcerated area 4 em. in diameter on the dorsum of the right hand. The biopsy report was squamous carcinoma. 15. J. T., aged sixty-one: In 1900 he was burned on the hands, fore­ arms, and neck by an explosion of hot tar pitch. In 1924 he burned the

TABLE II

Cancer of the Skin and Mucoc'utaneous Surfaces in Occupational Groups (Male) Porticularlu Exposed to Tar

Fore- Occupational Group Type of Lesion head Ear Nooe Cheek Lip Arm Hand Total ------Gas works fireman .... Squamous carcinoma 1 1 ------* Epithelioma.. 1 1 ------Gas works workman .. Squamous carcinoma 1 1 ------Epithelioma.. ... 1 1 ------Gas works superin- tendent ...... Epithelioma. 1 1 . ------_. ------Squamous earcinorna Road building and re------pairing Basal-cell carcinoma. 1 1 ------Epithelioma. .. 1 1 ------. -- Roofer ..... , ...... Squamous carcinoma 1 1 ------_.- ---- _. Epithelioma. .. 2 2 2 6 ------_.- Miner working with tar...... Squamous carcinoma 1 1 ------Painter working with tar...... , ...... Squamous carcinoma 1 1 ------Telegrapher working with tar...... Epithelioma ...... 1 1 ------Workman with tar.. Squamous carcinoma 1 1 2 ------Epithelioma ... 1 1

TOTAl, ...... 20

* Under epithelioma are included all cancers in which the type was not verified Ly biopsy.

scar on the right forearm against a hot radiator. A blister formed, which developed into an ulcer. In 1928, the lesion, having extended to involve a large portion of the upper forearm, was excised and It diagnosis of carci­ noma made. Amputation was finally done. FIG. 3. SQUAMOUS CARCINOMA OF THE CHEEK FOLLOWING A BURN WITH HOT TAR (R. K.)

FIG. 4. SQUAMOUS CARCINOMA OF THE HAND IN A GAB-WORKS FIREMAN (B. B.)

647 648 CUSHMAN D. HAAGENSEN

16. T. M., aged sixty-four, a fireman in a gas works: Epithelioma of the forehead. 17. B. B., aged seventy, a fireman in a gas works: Squamous carci­ noma of the dorsum of the right hand (Fig. 4). 18. J. S., aged forty-two, a workman in a gas works: Epithelioma of the lower lip. 19. T. L., aged fifty-eight, a workman in a gas works: Squamous carcinoma of the lower lip. 20. U. B., aged forty-eight, superintendent in a gas works: Epitheli­ oma of the nose. These cases are summarized in Table II. The data are, of course, incomplete. The length of exposure is not stated in most instances, nor are the details of the physical conditions of exposure available. The histories do not specify the type of tar or tar derivative in question. Whether or not there was an associated dermatitis is not always stated. Limited as the data are, however, given the known carcinogenic properties of tar, some conclusions can be drawn. The five cases occurring in gas works employees were probably occupational in origin. In the eleven patients whose work as roofers, road menders, etc., entailed a certain amount of exposure to tar, this agent was possibly a factor in the develop­ ment of epithelioma. The carcinoma arising from a burn with tar in four patients might be attributed either to the effect of the heat or to the action of the tar. This is probably an example of the summation of different carcinogenic factors, as is so frequently the case in carcinoma of the skin. Soot Soot, the end-product of the carbonization of coal or oil, is mainly carbon, but also contains a certain amount of tar and pitch. Soot has been known as a cause of cancer since Percival Pott in 1775 identified it as the agent responsible for chimney sweeps' cancer of the scrotum. In so doing Pott became the first to show that cancer may be produced by an external agent. The disease has been almost exclusively confined to England, only a few cases being described in Germany and in other countries, despite the fact that chimneys were swept in much the same way in all European countries. Both Butlin and Bang, who studied the subject thor­ oughly, believe that the custom of heating houses by means of an open grate in which hard coal is burned, a system in use only in England, accounts for the prevalence of chimney sweeps' cancer there. In Bang's opinion the imperfect combustion of hard coal OCCUPATIONAL NEOPLASTIC DISEASE 649 in such grates produces not only more soot, but soot which is more highly carcinogenic. There have been a few isolated reports of cancers presumably due to soot in others than chimney sweeps. The cases are too rare and too poorly authenticated, however, to have much weight. Passy produced skin cancer in mice by the application of a basic ether-soluble fraction of ordinary chimney soot. The Memorial Hospital records showed no cases with a history of occupational exposure to soot. Oils The oils were associated clinically with cancer by Volkmann in 1875, when he described dermatitis and epithelioma occurring in paraffin workers. Scott collected much of the information avail­ able on this form of cancer and reported 65 cases among paraffin­ shed men and oil workers, retort men, and laborers in the Scottish shale oil industry. He described the skin changes in these workers as consisting of comedones, follicular, pustular, and papular derma­ titis, erythema simplex, dermatitis erythematosa, and a final warty stage which might terminate in the development of epithelioma after twenty or more years of exposure. About 2 per cent of all the workers in the shale oil industry developed cutaneous cancer. Cases of skin cancer in petroleum distilleries and refineries have been reported from several countries, but their number remains very small in relation to the enormous dimensions of the oil in­ dustry. Derville and Guermonprez found one case in France, Ehrlich five cases in Czechoslovakia, and Ullmann 26 cases in Hungary and Galicia. Almost all of these were on the scrotum. In the United States, Davis has described one case in a paraffin pressman occurring after twenty years' exposure. H. B. Wood investigated fifteen refineries of Pennsylvania paraffin base oils and found no epitheliomas. Heller found no skin cancer among workers in New England and New Jersey distilleries using asphaltic oils from Texas, Mexico, and Venezuela. He collected ten cases of skin cancer from two oil refineries in the Middle West, however, which used mixed paraffin and asphalt base mid-continent oils. The length of exposure in these cases varied from four to thirty­ three years. Five of these cases were in dumpers in the paraffin pressroom. In all, Heller found 21 cases of cancer caused by crude oils, and he concludes that certain kinds of unrefined oil are . . carcinogemc. 650 CUSHMAN D. HAAGENSEN

Refined lubricating oils have been recognized as a cause of cancer since Southam and Wilson first drew attention to mule spinners' cancer of the scrotum. It is now known that this disease, at least in Great Britain, is the most frequent type of occupational cancer. An official committee found records of 539 cases of skin cancer among cotton mule spinners occurring in that country be­ tween 1876 and 1925.1 Over 50 cases of scrotal cancer occur in spinners each year, approximately 2.5 per 1,000 mule spinners developing the disease. It is usually found in operatives over fifty years of age who have worked in the mill for long periods-rarely less than ten years. The growth is usually situated on the left anterior aspect of the scrotum. Southam and Wilson believe that the disease is caused by the combined effect of mechanical irrita­ tion and chemical action due to oil. The workman constantly leans over the oily faller shaft which comes into contact with the left groin and the left side of the scrotum. While the English committee found a high incidence of epi­ thelioma among mule spinners in Great Britain, inquiries in France, Germany, Russia, and Poland gave entirely negative results. Heller in a recent survey of the mill and hospital records of the New England States found only six cases. Of these, only two were positively contracted in the United States. The fact that the type of spinning machines and the working process in all its details are the same in the United States as they are in England has led Heller to the conclusion that the factor of mechanical irritation is not re­ sponsible for mule spinners' cancer, and that the difference in the type of spindle lubricating oil used in this country and in England is the decisive factor. The experimental work of Twort and Ing, who found that oils purified by the sulphuric acid method produced no tumors in mice, suggests the most plausible explanation of the rarity of cancer due to refined oils in the United States. Lubricating oils are refined from distilled oil by treatment with sulphuric acid. In this process the unsaturated hydrocarbons, which apparently are the carcino­ genic fraction, are hydrolyzed, polymerized, and converted into more stable forms. Since crude petroleum causes cancer very much more frequently than refined oil, in the United States, it would seem that some inherent feature of the process of refining in

1 Report of the Departmental Committee Appointed to Consider Evidence as to the Occurrence of Epitheliomatous Ulceration among Mule Spinners, London, H.M. Stationery Office, 1926. OCCUPATIONAL NEOPLASTIC DISEASE 651

use in this country removes the carcinogenic property to a con­ siderable extent. The question, however, appears to be more complicated. Leitch found apparent differences in the cancer-producing power of samples of crude petroleums from different countries. A sample of California oil became carcinogenic when heated, although it had been innocuous at room temperature. The Manchester Committee on Cancer 1 has found that when crude oils are applied more frequently, their carcinogenic potency is increased as much as fifty fold. In experiments with purified mineral oil of American origin, of the type used therapeutically, Francis Carter Wood has shown that it does not produce cancer in mice. With the exception of mule spinners' cancer, occupational cancer associated with the use of lubricating oil is represented only by scattered case reports in which the evidence of the oil being the carcinogenic factor is very indefinite. O'Donovan, for instance, reported the case of a gunsmith who developed multiple squamous carcinomas of the face, neck, forearm, and chest after being spat­ tered with oil for thirty-nine years. White states that folliculitis and perifolliculitis are common among workers who are exposed to lubricating oil, as in oiling machinery in shops and factories. No other skin lesions which might be construed as precancerous have been reported as occurring in workers with refined oil. Table III lists all the patients in the Memorial Hospital data with cancer of the skin and mucocutaneous surfaces whose occupa­ tions brought them into frequent contact with either crude or refined oil. The available details of the cases in which the occu­ pational nature of the disease is most apparent follow:

1. J. K., fifty-two years of age, a fireman in a petroleum refinery, who stated that his trousers were continually soaked with oil: Carcinoma on the left dependent portion of the scrotum (Fig. 5). 2. J. D., aged fifty-two, a fireman in a petroleum refinery: Squamous carcinoma of the scrotum. 3. F. P., aged fifty-three, a rigger in a petroleum refinery: Epithelioma of the lower lip. 4. S. W., fifty-three years of age, a still cleaner in a petroleum re­ finery: Carcinoma on the right anterior aspect of the scrotum. 5. M. J., fifty-six years of age, who had been a watchman for five years and previously had been for years a still cleaner in a petroleum

I Report of the Manchester Committee on Cancer for 1929, quoted in J. A. M. A. 94: 1420, 1930. TABLE III Cancer of the Skin and Mucocutaneous Surfaces in Occupational Groups (Male) Particularly Exposed to Oils Occupational Group Type Scalp ----Forehead --Ear ---Eyelid --Nose --Cheek ----Lip Neck --Hand --Leg --Penis ---Scrotum --Total Chauffeur...... Squamous carcinoma. ------1 -- -- 1 ------2 Basal-cell carcinoma. ------1 ------1 ------2 *Epithelioma ...... ------2 ---2 --2 --4-- 4 --1-- 1 -- --2 --- -- 18 Engineer, locomotive ...... Squamous carcinoma. ------1------1-- 3 --1 ------6 Basal-cell carcinoma . ------1 ------1 Epithelioma ...... ---- 1 -- 1 ------3 -- 7 ------1 --- --13 Engineer, marine ...... Squamous carcinoma. ------1 -- -- 1---- 1 ------3 c:> CJl Basal-cell carcinoma . 1 1 IV ------Epithelioma ...... ---- 1 ------1 -- -- 1 ------3 Engineer, stationary, cranemen, hoist- Squamous carcinoma. 1 1 1 3 men, etc. ------Basal-cell carcinoma . ------1 ------1 Epithelioma ...... ------1 --- --1 --2-- 2 -- --1 ------7 Engineer (unspecified) ...... Basal-cell carcinoma. ------1 ------1 Epithelioma ...... ---- 1-- 2--- 2 --3 -- -- 1 ------9 Filling station worker (gas and oil) .... Squamous carcinoma. ------2 ------2 Oiler...... Basal-cell carcinoma. ------1 ------1 Epithelioma ...... -I- 1 1 * Under epithelioma are included all cancers in which the type was not verified by biopsy. T ABLE III-Continued Occupational Group Type Scalp ----Forehead --Ear ---Eyelid --Nose --Cheek --Lip ------Neck Hand Leg --Penis ---Scrotum --Total Oil fireman ...... Basal-cell carcinoma . ------1 ------1 Epithelioma ...... ------1 ------1 Petroleum refinery rigger...... Epithelioma ...... ------1 ------1 Petroleum refinery fireman ...... Squamous carcinoma. ------2 -- 2 Petroleum refinery still cleaner ...... Squamous carcinoma. ------2-- 2 Petroleum refinery workman ...... Basal-cell carcinoma . ------1 ------1 Squamous carcinoma. ------1-- 1 ~ Plumber and steamfitter ...... Basal-cell carcinoma. ------2 ------2 Epithelioma ...... ----1 ------2 --3-- 3 -- --1-- -- 1 --- -- 11 Mechanic and machinist...... Squamous carcinoma. 2 1--- -- 1 -- 1--- 11------2 --- 3 --21 Basal-cell carcinoma. --- --3 --3 ------6 Epithelioma ...... 1 1 ---6 --5 --7 -- 3 ------1 1 ---1-- 26 Printer ...... Squamous carcinoma. ------1-- -- 2 ------3 Epithelioma ...... ----1 --1 ------3 ------1 ------6 Toolmaker...... Squamous carcinoma. 1 1 2

TOTAL...... 160 654 CUSHMAN D. HAAGENSEN

refinery: He stated that his trousers were usually soaked with dirty oil and that particles of coke frequently fell inside his clothing. He had a carcinoma of the scrotum. 6. J. S., forty-nine years old, a workman in a petroleum refinery: Carcinoma of the scrotum. 7. J. W., aged seventy, a workman in a petroleum refinery: Basal-cell epithelioma of the nose. 8. F. L., aged thirty-four, a mechanic: Carcinoma which began on the right side of the scrotum.

FIGS. 5 AND 6. CARCINOMA OF THE SCROTUM IN A PETROLEUM REFINERY FIREMAN, J. K. (LEFT), AND IN A MACHINIST, M. M. (RIGHT)

9. W. T., fifty years of age, an automatic screw machine operator in a sewing machine factory: His trousers were frequently soaked with lubri­ cating oil. The factory stated that the oil used was an "oleic base and mineral oil." This patient had a carcinoma on the right side of the scrotum. 10. M. M., aged forty, until six years previously a foreman in a woolen mill: His work was chiefly to repair machinery and in this work his clothes were occasionally soiled with oil. For the past six years his work had been to pick up large bags of wool and empty them into a hopper. For this work he wore only a pair of overalls, which were constantly soaked with oil from the wool. He had a carcinoma on the right side of the scrotum (Fig. 6). 11. D. F., aged fifty, a machinist's helper: Epithelioma of the scrotum. OCCUPATIONAL NEOPLASTIC DISEASE 655

Knowing the prevalence of cancer of the scrotum 'in workers in petroleum refineries, we may at once conclude that the five such cases listed are occupational in origin. In the two other petroleum refinery workers, one with basal-cell epithelioma of the nose and the other with epithelioma of the lip, the occupational origin can not be so definitely stated. Yet of the twenty-one cases of epitheli­ oma occurring in petroleum refinery workers collected by Heller, three were situated on the face and lip. The etiology of the four cases of scrotal cancer in mechanics and machinists, as well as the penile cancers in this occupational group, will be discussed further in studies of incidence and anatomic distribution.

Aniline Dyes Grandhomme, in 1883, noted that bladder tumors were 33 times as frequent in workers with synthetic dyes as they were in the general population. Leuenberger collected 18 cases in 1912. In one case there was cancer of the kidney as well as of the bladder. Since then over 200 cases have been registered among German chemical workers. The tumors, papillomas and carcinomas, were almost all located at the neck of the bladder. The disease is ap­ parently very chronic and first appears after from two to thirty years of exposure to dyes. The exact carcinogenic agent is not known. It may be aniline, toluidine, zylol, or anyone of the whole series of these related products. Apparently, however, the cancer-producing substance elicits a neoplastic response only in the epithelium of the urinary tract and only under particular condi­ tions common to that system. Of the 39 patients with papilloma of the bladder and the 315 patients with carcinoma of the bladder whose occupation was noted in the Memorial Hospital records, there were none who worked with synthetic dyes. The occupations of these patients are noted in Table IX. There are in the literature no reported cases of carcinoma of the skin caused by aniline dyes. In the Memorial Hospital data there were three patients with carcinoma of the skin who worked with dyes. In only one of these cases, however, was the dye specified to be aniline dye. Vegetable and mineral dyes have been regarded as innocuous. The details of these cases are as follows:

1. S. T., aged fifty-six, worked for seven years as a packer, handling cans of dyed cloth: Epithelioma of the lip. 32 656 CUSHMAN D. HAAGENSEN

2. A. M., aged fifty-one, a dyer by occupation: Squamous carcinoma of the lower eyelid. 3. C. Mc.G., aged fifty-five, by occupation a general workman. Ten years previously, for a period of three years, he had worked as a shipper in a factory where various paints, pigments, and aniline dyes were made. He could not state that his hands were soiled with the dyes to any extent. He had chronic dermatitis and keratoses of both hands and of the face. On the dorsum of the right hand there was a basal-cell epithelioma. It would seem that in these cases the exposure to dyes was not an etiological factor. Arsenic John Ayrton Paris, in 1820, recognized occupational arsenic cancer among copper smelters handling arsenic-containing ore in Cornwall. Jonathan Hutchinson first identified medicinal arsenic cancer, reporting six cases occurring in patients who had taken arsenic therapeutically for psoriasis. In later years Hutchinson attributed many other forms of cancer to arsenic. He was thus the forerunner of a modern school of oncologists who attach much im­ portance to arsenic in the genesis of cancer. Bayet, for instance, believes that practically all forms of industrial cancer are caused by arsenic, which is, of course, widely distributed in ores, tars, pitch, etc. No cancer of the internal organs has been observed, however, in persons with known arsenic cancer of the skin. This fact sug­ gests that the Schneeberg lung cancer, which occurs in miners of bismuth, cobalt, and arsenic, is not due to exposure to arsenic, but rather to the high radio-active content of the air in the mines. Pye-Smith collected some 30 cases of medicinal arsenic cancer. Usually in the form of Fowler's solution, the drug had been taken for from two to thirty years. In 50 per cent of the cases the lesions were multiple. In Great Britain three cases of occupational skin carcinoma were observed by O'Donovan in workers handling arsenical sheep-dip. Leitch and Kennaway produced metastasiz­ ing squamous carcinoma in mice by painting the skin with Fowler's solution. The precancerous changes in this disease are characteristic. Keratoses, calluses, and warts develop, chiefly on the volar and plantar surfaces of the extremities and on the face. There may also be leukoplakia of the mucosal surfaces. These lesions may remain unchanged for several decades if the exposure to arsenic is discontinued. With continued exposure rhagades and cracks form. Ulceration occurs, and finally multiple epitheliomas. The local­ ization is identical in medicinal and in occupational arsenic cancer. FIGs. 7 AND 8. MULTIPLE KERATOSES AND FISSURES OF THE PALMS OF THE HANDS AND SQUAMOUS CARCINOMA OF THE THIRD LEFT FINGER IN A PATIENT (L. S.) WHO HAD TAKEN FOWLER'S SOLUTION FOR FIFTEEN YEARS

657 658 CUSHMAN D. HAAGENSEN

There were no cases of occupational arsenic cancer III the Memorial Hospital data. The details of four cases of medicinal arsenic cancer are as follows: 1. L. S., aged fifty-five, a packer in a florist shop: Because of psoriasis he had taken Fowler's solution at irregular intervals for the last fifteen years-from 4 to 12 drops t.i.d.-until puffiness about the eyes occurred. Eleven years previously he had first noticed rough spots on the soles of his feet. Ten years ago the fifth finger of each hand had been amputated for epithelioma. The fourth and third fingers had progressively developed lesions which had been treated with paste. Examination showed multiple keratoses and fissures of the soles and palms. There were a few discrete

FIG. 9. MULTIPLE KERATOSES AND FISSURES OF THE SOLES OF THE FEET IN THE PATIENT (L. S.) SHOWN IN FIGS. 7 AND 8 areas of keratosis on the trunk. On the third left finger there was an ulcerated squamous carcinoma (Figs. 7, 8, 9). 2. M. D., aged thirty-five, elevator operator: Eight years previously he had contracted a "body itch." His physician had prescribed Fowler's solution, which he had taken ever since. There were multiple keratoses and fissures of the palms of the hands and similar but less marked changes on the soles of the feet. On the left thumb there was a squamous carci­ noma. This regressed under treatment with radium. Six months later the axillary nodes were found to be enlarged, and a dissection showed squamous carcinoma in them. 3. A. E. K., aged forty-six, a clerk, who had had psoriasis for twenty ycars: He took Fowler's solution for a period of six months sixteen years ago, and during the following years took it for four brief periods. He had not used it during the last ten years. Ulcerated areas had appeared on the left upper arm and on the left neck below the ear four years previ­ ously. Biopsy from these lesions showed basal-cell epithelioma. OCCUPATIONAL NEOPLASTIC DISEASE 659

4. F. R., aged thirty-one, clerk: In 1917 he was given Fowler's solu­ tion, 30 drops a day, for a period of six months, because of "nervousness." About that time multiple, flat warts appeared on the fingers and the palms of the hands. In May 1929, a small, ulcerated area appeared on the skin near the anus, and biopsy showed squamous epithelioma. In August 1929 numerous superficial, crusted lesions appeared on the trunk and arms and legs. One of these lesions from the trunk, on excision, showed squamous carcinoma, Grade II; others only chronic dermatitis.

Occupational Exposure to Various Other Chemicals Chromium, in various forms, is widely used in industry and is a frequent cause of dermatitis and ulceration. Painters working with lead chromate colors develop dermatitis of the hands. Tan­ ners who are exposed to sodium dichromate develop dermatitis and ulceration of the hands and feet. Caustic soda, which is also used in the leather industry, causes sharply punched out ulcers on the hands according to White. French polishers have been known to develop chrome ulcerations of the hands from the potassium di­ chromate used in staining mahogany. Wool dyers and cotton dyers, as well as "steamers" in the hat trade, develop dermatitis from the chromic oxide used. It has been the experience, however, that irritating and caustic as compounds of chromium are, the lesions which they produce do not lead to cancer. The Memorial Hospital records confirm this fact. There were no carcinomas of the hands or feet noted in these occupational groups. Lime is also a very important cause of occupational dermatitis. Plasterers, masons, and bricklayers frequently have this type of dermatitis. The lesions are said by White not to lead to the de­ velopment of cancer. In the Memorial Hospital data there were three cases of carcinoma of the hand in these occupational groups -one each of brickmaker, stone mason, and mason. Sulphuric acid is widely used in industry as a bleaching agent, in the making of iron castings, in work with copper, and in the manufacture of explosives. Burns from acid splashes are frequent. The development of cancer from such a burn is apparently an ex­ ceedingly rare occurrence, however. Mishell reported one such case-the carcinoma following an acid burn on the dorsum of the hand. In the Memorial Hospital data there was one case with a history of a burn with sulphuric acid. 1. F. T., a druggist, aged thirty-seven: In 1924 he spilled sulphuric acid on his right palm, burning it severely. About 1926 the skin in the burned area became horny. When examined in July 1929, the palm of 660 CUSHMAN D. HAAGENSEN the hand and the volar surfaces of the fingers were covered with keratoses which were 3 mm. high in places. There were several areas which were suspiciously like carcinoma. A biopsy was not obtained.

Roentgen Rays and Radio-active Substances In 1902, about five years after the discovery of roentgen rays, Frieben reported in a roentgenologist the first case of carcinoma caused by roentgen rays. Roentgenologists and their laboratory assistants, and engineers and workmen in factories making roentgen apparatus were the first to develop roentgen cancer. A few years later, after roentgen rays had been used therapeutically for a while, roentgen cancer began to appear in patients. By 1911 Hesse was able to collect 94 cases, 50 of which occurred in roentgenologists and makers of roentgen apparatus. Rowntree has reported 13 English and 4 American cases. In roentgenologists and their assistants the exposure of the dorsum of the hands and fingers incident to fluoroscopy is probably the most important factor. Palpation with the ungloved hand is certainly very dangerous. Rowntree believes that a burn plus a long continued series of small exposures is necessary to produce cancer. In his opinion cancer does not follow a single large dose or a short series of doses. Wintz and Flaskamp have never seen roentgen carcinoma follow therapeutic radiation. The interval between the first exposure and the development of true epithelioma, according to these investigators, averages four years. Often it is considerably longer. The precancerous skin changes in the classical form consist in loss of elasticity, and in thickening and loosening of the skin. The folds increase. Diffuse, small, wart-like hyperkeratoses appear. The nails become fragile, ragged, and cracked. The sweat and sebaceous glands atrophy and the skin becomes dry. Finally, on the basis of the hyperkeratoses, epitheliomas develop. Bloch suc­ cessfully produced roentgen cancer in dogs experimentally. Proved cases of skin cancer caused by radium are few. Leitch reported two cases. Ullmann observed one on the finger of a nurse who had handled radium applicators for some years. The natural history of radium cancer is apparently very similar to that of roentgen-ray carcinoma. Radium has probably not been used extensively enough, and for a long enough time, to produce many cases of skin cancer among those who handle it. Certainly we have observed, in workers with radium, thickening and roughening of the OCCUPATIONAL NEOPLASTIC DISEASE 661

skin of the fingers, brittleness of the nails, and the formation of keratoses-lesions identical with the precancerous skin changes produced by roentgen rays. The effects of radium on the hemopoietic system have been more frequently observed. In several countries studies of the blood of workers with roentgen rays and radio-active substances have shown that many develop changes in the blood picture. The earliest sign is usually a moderate leukopenia with an actual de­ crease in polymorphonuclears and a relative increase in lympho­ cytes. Occasionally there is an associated eosinophilia, or an absolute mononucleosis with leukopenia. Sufficient exposure leads to the development of anemia. Rarely erythrocytosis results. There are reports of 27 cases in which these blood changes have gone on to death. Five of these were caused by roentgen rays and 22 by radio-active substances. The distinguished radiologist Dominici was one of the earlier victims. The disease usually takes the form of a progressive aplastic anemia, death occurring in from three to six months. There is often hemorrhage, particularly from the gums. Mottram reported three such cases occurring among the personnel of the London Cancer Institute after ten, eight, and three years' exposure respectively. Leukemia has also been caused by roentgen rays and radio-active substances, but less frequently than aplastic anemia. Von Jagie and Carman each observed one case of lymphatic leukemia. Von Jagie stated that he had heard of three other cases of lymphatic leukemia appearing in radiologists. Four cases of myeloid leukemia have been observed. De Laet, and more recently Lambin, have reviewed the subject thoroughly. Martland has particularly studied the subject in relation to the noxious effects of radium-mesothorium-containing luminous paint. He reported an acute leukopenic anemia of the regenerative type occurring in one of the girl watch-dial painters who, during the seven years which she continued in the work, ingested the paint through pointing her brush with her lips. He found considerable amounts of radio-active elements in her tissues, particularly in the bone marrow, liver, and lungs. Among the 800-odd girls who did this work Martland believes that there have been an appreciable number of such deaths which have passed undiagnosed. The bone changes developing in these girls have contributed knowledge of the utmost importance in regard to the pathogenesis of bone tumors. The radio-active elements which they ingested were apparently to a large extent deposited in the osseous system. 662 CUSHMAN D. HAAGENSEN

Certainly, many of them developed bone necrosis of the maxillae and changes which were typical of radiation osteitis in many of the skeletal bones. Two known cases of osteogenic sarcoma develop­ ing in the group have been reported by Martland. Through the courtesy of Dr. Lloyd F. Craver, who has been following some of these cases at the Memorial Hospital, it is possible to report two additional cases of bone sarcoma. In this connection the cancer of the lungs in the Schneeberg miners should be mentioned. Recent investigations by Rostoski have clearly proved the extraordinarily high incidence of carcinoma of the lung in these Saxon miners. During the inquiry, which lasted three and one half years, there were 21 deaths among the 154 miners followed. Of these, 13, or 62 per cent, were proved to be due to carcinoma of the lungs. The air of the mines contains large amounts of bismuth, cobalt, and arsenic dust. It is also radio­ active, containing an emanation content as high as 50 Mache units. There have been no reports of lung carcinoma from radium and uranium mines in Bohemia and elsewhere. We have studied the occupational distribution of the malignant tumors of the lung in the Memorial Hospital data and find that the 58 cases were quite uniformly distributed among most occupational groups. In no single group was the incidence significantly high. We have one metallurgical engineer with carcinoma of the lung, but no miners. This distribution of malignant tumors of the lung is shown in Table IX. The cases of occupational neoplastic disease from the Memorial Hospital data, caused by roentgen rays and radio-active substances, are listed in Table IV. Unfortunately the details of the type and length of exposure are meager or entirely lacking in some of these histories. Such as were available follow:

1. Dr. E. C., aged forty-five: After he had worked with roentgen rays for several years keratoses appeared on his fingers and the backs of his hands in 1906. Ulceration and squamous carcinoma developed on the dorsum of one hand. Amputation of the hand was followed by axillary dissection for metastases. In 1919 there was recurrence in the axillary scar. He died in 1920. 2. Dr. J. A. L., aged forty-six: This patient began using roentgen rays in 1905 and was repeatedly burned. In 1908 an epithelioma appeared on a finger of the left hand. The finger was amputated. Axillary metas­ tases developed and a dissection was done. In 1919 there was a massive recurrence in the axillary scar and lung metastases appeared. Death occurred in 1920. OCCUPATIONAL NEOPLASTIC DISEASE 663

3. Dr. F. L. R. S., aged thirty-nine: He began roentgen-ray work in 1897. In 1899 there was a severe dermatitis on the dorsum of the right hand, and keratoses soon appeared. In 1913 squamous carcinoma de­ veloped on the third right finger. It was at first treated with radium and finally amputated. In 1919 a second carcinoma appeared on the dorsum of the right hand. Death occurred in 1921. (Fig. 10.) 4. Dr. H. R., aged sixty-nine: After prolonged exposure to roentgen rays, multiple carcinomas developed on the fingers of both hands. Axil­ lary metastases appeared. Death occurred in 1923.

FIG. 10. KERATOSES AND SQUAMOUS CARCINOMA OF THE HAND OCCURRING IN A ROENTGENOLOGIST (F. L. R. S.)

5. Dr. C. 1. E.: On the basis of old roentgen-ray burns of the hand keratoses and squamous carcinoma developed. There were metastases to the axilla. 6. Dr. E. C. K., aged seventy: After repeated exposure to roentgen rays for years keratoses appeared on the hands in 1917. In 1925 epithe­ liomas were excised from the dorsum of the left hand and fingers. A left axillary dissection was done for metastases in 1926. A year later the arm was amputated. In 1927 an epithelioma appeared on the right thumb, the right axillary nodes were found to be involved, and there was recurrence in the stump of the left arm. Death occurred in 1928. 7. Dr. L. R. E.: This patient began using roentgen rays in 1902 and continued until 1918, doing fluoroscopy and roentgenographic work an average of three or four times a week. Keratoses first appeared in 1924, on the dorsum of the first, second, and third left fingers. In 1926 the skin 664 CUSHMAN D. HAAGENSEN on the dorsum of the terminal phalanx of the second left finger broke down. In 1927 the finger was amputated, and there has been no recur­ rence to date. 8. Dr. J. 0., aged sixty-four: In 1910 this patient installed a roentgen­ ray machine and did a great deal of fluoroscopy until 1913, when he dis­ posed of the apparatus. At that time he noted dryness, scaliness, telangi­ ectases and keratoses of the skin on the dorsum of his hands. In 1928 squamous carcinomas appeared on the fingers of the right hand and a single enlarged node was felt in the axilla. The finger was amputated and the axilla treated with radium. There was no evidence of disease in 1930.

TABLE IV Malignant Disease Caused by Roentgen Rays, Radium, and Radio-active Substances

Squamous Carcinoma Occupational Group Osteogenic Lymphatic Sarcoma Leukemia Totnl Hand Foot Neck Buttock ------

Roentgenologist 0 •• 0 • 0 0 0 11 11

Radium chemist. 0 • 0 •••• 1 1 Nurse handling radium.. 1 1 Painters of watch dials with luminous radium- mesothoriurn-contain-

ing paint ... 0 0 0 0000 •• 2 2 Therapeutic roentgen-

ray carcinoma.. 0 ••••• 3 1 1 5 --

TOTAL... 0000.00.0.0 ••••••• 0 ••••••••••••••• 0 ••• 0 •• 0.0 •• 0 ••••••• o. 20

9. Dr. J. E. Mo, aged fifty-six: He began using roentgen rays in 1905 and continued until 1925. For the first fifteen years he was exposed for from five to fifteen minutes daily, doing fluoroscopy for the most part. In 1915 he first noted dryness and atrophy of the skin on the backs of both hands. Keratoses appeared in 1921. An ulcerated area developed on the dorsum of the right hand at the base of the index finger in 1923. A diagnosis of squamous carcinoma was made in 1924, by which time there were axillary metastases. The finger was amputated and the axilla dissected. Several other precancerous areas were treated with radium. There was no apparent disease in 1930. 10. Dr. W. E. Wo, a roentgenologist: In 1928 he had multiple keratoses on the backs of both hands and a squamous carcinoma on the third right finger. It was treated with radium, and there had been no recurrence by 1930. 11. Dr. D. C., aged sixty-two: He began to do roentgen-ray work in 1910. Keratoses gradually developed. In 1927 an ulcer appeared on the dorsum of the third left finger. It cleared up after fulguration. Axillary metastases appeared in 1929. Dissection was done, and there was no evidence of disease in 1930. OCCUPATIONAL NEOPLASTIC DISEASE 665

Therapeutic Roentgen-ray Cancer: 1. J. H. P., aged sixty, a building contractor: In 1908 a callus on the right foot was heated with roentgen rays. In 1919 two areas of squamous carcinoma appeared on the foot. 2. Dr. C. K., aged thirty-six: He contracted trench foot in France and on his return to the United States in 1919 was given a series of roentgen­ ray treatments. By 1922 there were marked atrophy and telangiectases of the skin of the soles of the feet. The skin broke down, and bilateral full-thickness grafts were done. In 1928 the old skin on the sole of the left foot ulcerated and squamous carcinoma was diagnosed. Metastases occurred in the groin and an inguinal dissection was done. The leg was finally amputated. The patient was well in 1930. 3. E. C., aged fifty-eight, a stenographer: Since 1913 she had had lupus erythematosis of the left face and neck. In 1919 her physician gave her a series of roentgen-ray treatments lasting over a period of eighteen months. Ulceration developed in the irradiated area in 1926 and a biopsy showed squamous carcinoma. 4. W. W., aged sixty-three: He had been given a series of roentgen-ray treatments for a fistula-in-ano. Squamous carcinoma developed on each buttock. 5. B. S., aged forty-four, a housewife: As a girl, the patient had had scaly lesions on both feet and both hands, which were diagnosed as "eczema," in Glasgow. When she was twenty-four years of age, in 1900, she was given a series of roentgen-ray treatments to the hands and feet. The treatments were given every other week over a period of months. The "eczema" improved temporarily but recurred. In 1916 an ulcer developed on the dorsum of the right foot. In 1919 it was excised and a diagnosis of squamous carcinoma made. The tumor soon recurred and the leg was amputated in 1920. In 1924 the patient returned with an extensive squamous carcinoma of the sole of the left foot. Amputation was done. An epithelioma developing on the dorsum of the fifth right finger was treated with zinc chloride paste. In 1930 there was no evi­ dence of carcinoma. (Figs. 11 and 12.)

Occupational Malignant Disease Caused by Radium: 1. Dr. C. V" a chemist, aged thirty-nine: This patient worked with radium and its associated radio-active substances from 1914 to 1928. In 1924 an ulcer appeared on the middle finger of the right hand. After considerable time had been lost in self-administered local treatment with caustics and. ointments, a diagnosis of carcinoma was made. Following numerous local removals the right hand was amputated. Axillary me­ tastases developed in 1928. There were terminal pulmonary metastases, death occurring in 1929. 2. E. H., aged forty-one, a nurse, from 1922 to 1928 night supervisor at the Memorial Hospital: It was part of this nurse's duty to handle the radium emanation pack which contained an average of 2,000 millicuries of radon. Menstruation ceased in July 1928. In November 1928 she first FlOS. 11 AND 12. THERAPEUTIC ROENTGEN-RAY CARCINOMA OF BOTH FEET (B. S.)

666 OCCUPATIONAL NEOPLASTIC DISEASE 667 noted pallor, dyspnea, edema of the ankles, and anorexia. Her blood count was found to be as follows: R. B. C., 1,000,000; W. B. C., 2,400; polymorphonuclears, 27; large lymphocytes, 8; small lymphocytes, 63. Hemoglobin was 30 per cent. There was moderate anisocytosis and poikilocytosis. Despite repeated blood transfusions her condition be­ came rapidly worse, and she died in March 1929. Her blood picture dur­ ing the latter part of her illness resembled lymphatic leukemia, with an

CHART 1 Blood Findings in Lymphatic Leukemia (E. H.) Following Prolonged and Excessive Exposure to Radium Larllll Small Red White Polymorpho- Lympho- Lympho- Transi- Eosino- Baso- Date B.C. B.C. nuclear. eytes oytea tionala phil•• philes 12--4-28...... 1,000,000 2,400 27 8 63 '2 12-5-28. Blood Transfusion~50 CC. 12-5-28 ...... 2,060,000 2,400 32 11 51 5 12-11-28 ...... Blood Tmnsfusion-800 CC. 12-15-28 ...... 3,760,000 5,000 37 18 36 7 2 12-18-28 ...... Blood Transfusion-800 CC. 12-19-28 ...... 3,360,000 3,000 38 41 14 4 3

12-22-28 ...... 4,360,000 3,200 2 53 40 5 12-27-28 ...... 4,520,000 3,000 2 60 37 1 12-31-28 ...... 4,640,000 3,200 1 36 59 4 1-7-29 ...... 4,320,000 3,600 6 37 46 9 2 1-16--29...... 3,840,000 4,000 4 41 37 16 2 1-30-29 ...... 3,200,000 16,200 7 81 12 1-31-29 ...... Blood Transfusion-700 CC. 2-1-29...... 3,808,000 12,800 7 82 12 2-11-29 ...... 3,960,000 42,400 3 74 17 3 2 2-20-29 ...... 3,570,000 58,000 87 10 3 3-1-29...... 2,992,000 41,800 2 78 17 3 3-3-29 ...... Blood Transfusion-750 CC. 3--4-29 ...... 4,040,000 45,000 5 87 6 1 3-11-29 ...... 3,656,000 35,800 6 76 17 3-11-29 ...... Blood Transfusion-800 CC. 3-14-29 ...... 3,672,000 49,000 85 10 3 2 3-16--29 ...... Blood Transfusion-SOO cc. 3-18-29 ...... 2,224,000 72,600 1 97 2 3-21-29 ...... Blood Tmnsfusion--400 cc, 3-22-29 ...... 3,160,000 73,000 8 71 18 1 2 3-27-29 ...... 2,336,000 137,100 92 4 3 1 anemia of a moderate degree. (Chart 1 illustrates the blood picture throughout the course of the disease.) At autopsy the findings were typical of lymphatic leukemia. There were diffuse lymphoid hyperplasia of the vertebral and rib marrow, lymphoid infiltration of the liver, kid­ neys, and lungs, lymphoid hyperplasia of the spleen with passive com­ pression of the malpighian bodies by large lymphoid cells of the pulp cords, and leukemic infiltration of the pulp cords of the mesenteric nodes without enlargement of the follicles. 3. Q. M., aged twenty-eight: This patient was employed marking watch dials with radium-mesothorium-containing luminous paint from 668 CUSHMAN D. HAAGENSEN

November 1917 to February 1919. In 1923 she developed pain in the legs. Changes characteristic of radiation osteitis were found in many of the bones in 1928. In September 1929 marked destruction of the heads of both femurs and pulmonary metastases were noted. Death occurred in January 1930, and the diagnosis of osteogenic sarcoma was confirmed at autopsy. (Figs. 13 and 14.) 4. C. S., aged twenty-six: This patient worked as a dial painter from 1917 to 1921. Pain in the right ankle began in 1921. Radiation osteitis

FlO. 13. OSTEOGENIC SARCOMA, WITH DESTRUCTION OF THE HEADS OF BOTH FEMURS, IN A WATCH DIAL PAINTER USING RADIUM-MESOTHORIUM LUMINOUS PAINT (Q. M.) was noted in the pelvic bones, the vertebrae, and the left tibia and fibula in 1928. A roentgenographic diagnosis of osteogenic sarcoma of the lower end of the right femur was made in September 1930.

Despite the incompleteness of our data, some facts of distinct interest emerge. For the roentgenologists who developed carci­ noma, the average interval between their first exposure and the appearance of carcinoma was fifteen and a half years, which is longer than that noted by the German investigators. Metastases OCCUPATIONAL NEOPLASTIC DISEASE 669

occurred in 63 per cent of our cases and death resulted in 35 per cent. These facts are quite in contrast to the statement of Flas­ kamp and Wintz that roentgen-ray carcinoma tends to remain localized, and to the findings of Hesse, who in his series of 94 cases reported that metastases occurred in only 26 per cent, and that the mortality was 20.3 per cent.

FIG. 14. PULMONARY METASTASES OF OSTEOGENIC SARCOMA OCCURRING IN A WATCH DIAL PAINTER USING RADlUM-MESOTHORlUM LUMINOUS PAINT (Q. M.)

The five cases of carcinoma resulting from therapeutic radiation are examples of the danger of repeated doses of inadequately filtered roentgen rays. It is unfortunate that the dosage factors in these cases are not available. The average interval between the first treatment and the development of carcinoma in these cases was eleven years. The case of rapidly fatal lymphatic leukemia developing in a nurse handling a large amount of radium emanation over a period of six years is the first of its kind to be reported in detail, that is, with 670 CUSHMAN D. HAAGENSEN

the history of exposure and the clinical and autopsy findings. A doubt may be raised as to the relationship of the exposure to radia­ tion and the development of leukemia, inasmuch as there are only two well authenticated cases of lymphatic and four of myeloid leukemia in workers with roentgen rays and radium on record. At the same time it must be remembered that the number of persons who have been exposed to large amounts of radiation over a period of years is as yet not large. In any event there is no way of arriv­ ing at a statistical solution of the question. Nor does a study of the blood findings in this case, as shown in Chart I, aid us, for a sequence such as this is sometimes seen in lymphatic leukemia. No one has succeeded in producing leukemia experimentally in animals by radiation. Viewed in the light of our knowledge of the decrease in polymorphonuclears and relative lymphocytosis produced by a certain amount of radiation, however, the development of lympha­ tic leukemia in an individual exposed to very heavy radiation might be interpreted as a lymphocytic regeneration overshooting the mark, as Amundsen has suggested. Certainly such a case is a warning of the possible danger of extensive exposure to radium. Blood counts should be done at least monthly on all workers with radium, and adequate protective measures taken when any distinct variation in the blood picture becomes apparent. Occupational Exposure to Sunlight as a Cause of Cancer Unna, in 1894, first described clinically and histologically the changes in the skin produced by prolonged exposure to sunlight. He gave the clinical entity the name of Seemannshaut. A cyanotic reddening of the skin of the face and hands, similar to that resulting from frost-bite, first appears. Areas of pigmentation develop, with intervening white atrophic spots which have lost their pig­ ment. The skin becomes rough and hard. Horny, wart-like thickenings appear. The sebaceous glands hypertrophy. Finally ulcerating carcinoma develops beneath these keratotic areas. The growth is basal-cell in type. Unna states that it never metasta­ sizes, and yet it is a more malignant form of carcinoma than rodent ulcer in that it grows more rapidly, and meets less resist­ ance in the form of mesoblastic and lymphoid reaction. Dubreuilh, some years later, re-emphasized the precancerous nature of the so-called senile keratoses, stating that these keratoses, which are strictly limited to the uncovered portions of the skin, are due to the effect of sunlight. He published statistics indicating that the type of epithelioma developing in out-door workers on the OCCUPATIONAL NEOPLASTIC DISEASE 671

basis of these keratoses is spinal-cell (squamous carcinoma) in character. Rodent ulcer (basal-cell carcinoma) is of different and unknown etiology, not related to exposure to sunlight, according to this author. In his cases it developed in otherwise normal skin and occurred in an equal proportion of in-door and out-door workers. Paul, in his monograph on cancer of the skin, agreed in a general way with Dubreuilh. He used the term dermatitis eolaris chronica to include the skin changes produced by strong sunlight which lead to the development of squamous carcinoma. He did not mention sunlight as a cause of rodent ulcer. Numerous other dermatologists have recognized exposure to sunlight as a factor in the causation of skin cancer. Lawrence be­ lieves that the relatively low humidity of the atmosphere in some parts of Australia intensifies the ultra-violet content of the sunlight. The result is a high incidence of rodent ulcers, keratoses, and epi­ theliomas, which he groups together as an "epithelial triad" of common etiology. Hazen says that "it may be clearly stated that exposure to actinic rays certainly leads to the formation of cancer of the skin." Sutton believes that long continued exposure to strong sunlight and to sudden atmospheric changes aids in the development of a peculiar quality of the skin characterized by harshness and dryness and seborrhea. The resulting seborrheic or senile keratoses are forerunners of both basal-cell and prickle-cell cancer. Darier terms the congestion, pigmentation, diffuse atrophy, telangiectasis, and keratosis of the exposed portions of the skin occurring in sailors, farmers, aviators, coachmen, and those living at high altitudes, a presenile dystrophy. Epithelioma, often multiple, may finally develop. The great rarity of cancer of the skin in negroes has frequently been cited as an example of the protective mechanism of pigmenta­ tion. Similarly, Ullmann believes cancer of the skin to be more frequent in blondes than in brunettes. It has been suggested that if exposure to sunlight causes pigment imbalance and the development of epitheliomas in the congenitally defective skin of children with xeroderma pigmentosum, it may have an analogous action in some adults who receive severe and long continued insolation. Although it thus has come to be the general opinion that sun­ light is a factor in the etiology of skin cancer, most recent writers have ignored the question of the histologic type of carcinoma thus 33 TABLE V: Cancer of the Skin and Mucocutaneous Surfaces in Occupational Groups (Male) Particularly Exposed I.QSunlight Occupational Group Type of Lesion Forehead --Ear ---Eyelid --Nose --Cheek ----Lip Neck --Arm ---Hand ---Trunk ---Penis ---Total Bayman ...... Squamous carcinoma ... ------2------2 Epithelioma ...... --- -- 1 ------1 ------2 Farmer ...... Squamous carcinoma ... 1 --6 ------1 -- 8 ------2 --- 1 ---19 I Basal-cell carcinoma. .... --3 --- --5 --- 2 -- 1 ------11 Epithelioma ...... 1 --3 ---8 --8 ---23 --22 -- --1 ------66 Fisherman ...... Squamous carcinoma ... ------1 ------1 Epithelioma ...... -- ---2 ------2 Gardener ...... Squamous carcinoma ... --2 ------7 --1 ------10 s Basal-cell carcinoma .... ------1 ------1 Epithelioma ...... --1 --- 1 -- --- 2-- 3 ------7 Huckster and peddler...... Squamous carcinoma ... 1 4 -I------1 6 Basal-cell carcinoma .... -- ---1 -- 2 --- 1 ------4 Epithelioma ...... --1 --- 3 --4--- 4 -- 5 ------17 Mail carrier...... Basal-cell carcinoma ------1 ------1 ------2 Epithelioma ...... ------2 --- 2 -- 1 ------5 Sailor and boatman ...... Squamous carcinoma ... --1 --- --1------10 2-- 2 ------16 Basal-cell carcinoma .... 1 3 1 1 ---1- 6 Epithelioma ...... 3 ------1------2 --- 2· -- 2--- 14-- 13------36 Street cleaner...... Squamous carcinoma ... I--I-I-I----I-I~I Epithelioma ...... -i--I-I-3 I: FIGs. 15 AND 16. PIGMENTATION, ATROPHY, AND KERATOSES OF THE SKIN OF THE FACE AND SQUAMOUS CARCINOMA OF THE CHEEK IN A FARMER (II. C. P.), AGED SEVENTY-BEVEN

FIG. 17. PIGMENTATION, ATROPHY, AND KERATOSES OF THE SKIN OF THE HANDS, IN THE FARMER (H. C. P.) SHOWN IN FIGs. 15 and 16 673 FlO. 18. SQUAMOUS CARCINOMA OF THE SKIN OF THE CHEEK IN A FARMER CR. C. P.)

674 OCCUPATIONAL NEOPLASTIC DISEASE 675

produced. Since the conflicting studies of Unna and Dubreuilh many years ago, no one has published data indicating whether carcinoma developing as a result of insolation is squamous or basal­ cell in type. The solution of this question would be a valuable contribution to our knowledge of the natural history of cancer. Unfortunately these Memorial Hospital data are of very little aid here, since, as will be seen from Table V, in which are grouped all patients with carcinoma of the skin whose occupations entailed

FIG. 19. CARCINOMA OF THE SKIN OF THE CHEEK DIAGNOSED CLINICALLY AS BASAI.­ CELL IN TYPE, WHlCH PROVED ON BIOPSY TO BE SQUAMOUS IN CHARACTER constant exposure to sunlight (a total of 221), biopsy was not done in a considerable proportion of these cases. (In Table V, as in the other tables, all cases in which the type was not verified by biopsy are included under Epithelioma.) We are therefore unable to supply statistics bearing on the type of skin carcinoma usually found in association with solar dermatitis in out-door workers, but it is our clinical impression that such growths are usually squamous in character. Figs. 15, 16, and 17 illustrate the appearance of solar dermatitis of the hands and face and squamous carcinoma of the cheek occurring in a farmer. Fig. 676 CUSHMAN D. HAAGENSEN

18 shows the histology of the tumor. We have seen lesions aueh as that shown in Fig. 19, which were diagnosed clinically as basal-cell carcinoma, and yet biopsy showed them to be squamous in type. Carcinoma of the face, particularly of the ear, cheek, and temple, which develops in skin showing evidence of exposure to sunlight and weather, in the form of erythema, pigmentation, atrophy, and keratosis, is commonly squamous in character.

FIG. 20. BASAL-CELL CARCINOMA OF THE EYELID IN A WORKMAN, AGED FIFTY (H. J.). Note the normal character of the skin

Basal-cell carcinoma, on the other hand, often occurred on otherwise normal skin in our series of cases; it is most frequent about the eyelids and nose. Figs. 20 and 21 illustrate the ap­ pearance and histology of such a lesion. We have not infrequently encountered mixed forms such as that shown in Figs. 22 and 23. This patient was a farmer. There were numerous pigmented areas and keratoses on his face. Below the left eye there was a small horny tumor. On biopsy the superficial portions of this tumor showed the structure of squamous carcinoma. The deeper portions were typical of basal-cell carcinoma of the FIG. 21. BASAL-CELL CARCINOMA OF THE EYELID IN A WORKMAN (R. J.)

677 678 CUSHMAN D. HAAGENSEN adenoid type. The lesion completely disappeared when treated with radium in moderate dosage, and there was no evidence of re­ currence after three years. Darier has emphasized the need of biopsy in differentiating the types of skin carcinoma. He found that 15 per cent of these tumors were mixed basal-cell and squa­ mous in type. Such mixed forms outwardly resembled basal-cell carcinoma but sometimes metastasized. They were more radio­ resistant than the basal-cell type.

Mechanical Trauma Incident to Occupation as a Cause of Cancer By mechanical trauma we mean a contusing, crushing, or lacer­ ating injury. That mechanical trauma may be an important

FIG. 22. PIGMENTATION, KERATOSES, AND MIXED SQUAMOUS AND BASAL-CELL CARCINOMA OF THE FACE OF A FARMER, AGED SEVENTY-TWO (G. D.)

factor in the causation of cancer is generally agreed. The resultant disturbance of cell grouping, the necrosis, the hemorrhage requiring absorption or organization, and the regenerative processes with hyperemia and new growth of specific cells, blood vessels, and sup­ porting tissue, are factors which at once suggest a relationship to tumor growth. The interpretation of the relation of trauma to tumors has, however, varied markedly. Ewing notes that the frequency of the traumatic origin of tumors is given as low as 2.5 per cent by Kempf and as high as 44.7 per cent by Lowenthal. He remarks that since the supposed traumatic tumors usually arise at the same age periods as the spontaneous tumors of the same type, FIG. 23. MIXED SQUAMOUS AND BASAL-CELL CARCINOMA OF THE FACE OF A FARMEK (G. D.)

679 680 CUSHMAN D. HAAGENSEN there is a definite probability that the trauma and the tumor are merely coincidental. Single Mechanical Trauma: There are a great many isolated re­ ports of cancer caused by single trauma. Ullmann believes, how­ ever, that single sharp or blunt trauma is the cause of cancer only very infrequently and under special circumstances. He found that such clinical reports were usually unreliable or inconclusive. Among the patients with carcinoma of the skin in the Memorial Hospital data there were many who ascribed the growth to a single mechanical trauma. The following histories are typical: 1. C. L. B., aged sixty: In 1922 this patient had been bitten on the back of the right hand by a fox. The wound healed without difficulty, but soon after it was noticed that there was a "scarring and scab" at the site of the bite which persisted. This increased progressively and ulceration finally occurred in 1927. Biopsy in 1929 showed basal-cell epithelioma. 2. T. M., a laborer, aged fifty-nine: About 1901 he was bitten on the left hand by a horse. A small scaly area persisted at the site of the bite. Ulceration occurred in 1922, and a diagnosis of epithelioma was made. 3. M. T., a boat builder, aged eighty-six: In 1919 his right hand was bitten by a dog. The wound was cauterized but never completely healed, crusting over at times, and gradually enlarging. In 1923 a diagnosis of epithelioma was made. 4. J. 0., aged forty-seven, a carpenter: Seven weeks previously he had been struck on the dorsum of the right hand by flying fragments of steel. A small piece of steel remained lodged in the wound and was excised by his doctor. The wound failed to heal. A diagnosis of epithelioma was made. 5. E. S., aged forty-one, an engineer: One year previously he struck the back of his left hand with a hammer. A wart-like growth appeared. Biopsy showed it to be a carcinoma. 6. W. M., a machinist, aged forty-four: One year previously, while working under an automobile, he was struck on the nose by a flying bit of metal, which caused a wound that bled profusely. It failed to heal and gradually increased in size. When he applied for treatment an epitheli­ oma was present. 7. S. J., aged sixty, a groom: In 1914 a horse stepped on his left great toe. A festering sore resulted. In 1919 the toe was amputated and squamous carcinoma found. Inguinal metastases and death occurred. 8. G. D., aged fifty-six: In March 1923, while chiseling stone, he was struck in the lower lip by flying fragments. An open wound resulted, which failed to heal. A tumor developed, which grew very rapidly. When examined in February 1924, this patient had a far advanced squa­ mous carcinoma involving the entire lower lip. It is apparent that in these histories, as was the case with all the others in the Memorial Hospital data, the evidence is too in­ complete to warrant the conclusion that cancer was caused by OCCUPATIONAL NEOPLASTIC DISEASE 681 trauma. In no case is the site of the wound described as being normal before the injury. In only six instances is it specifically stated that the growth occurred at the exact site of the trauma. In several cases the diagnosis was not proved by biopsy. Chronic or Repeated Mechanical Trauma: Stahr reported a class­ ical case in a shoemaker who frequently pricked his thumb with his awl, causing it to become thickened and deformed. A squamous carcinoma finally developed in the traumatized area. Since the shoemaker used tarred thread, exposure to tar as well as to trauma must be considered in the etiology. We found no such clear-cut case of cancer caused by repeated mechanical trauma in the Memorial Hospital records. The most suggestive finding was the rather high proportion of carcinomas of the hand in carpenters. Their hands are undoubtedly exposed to frequent and repeated mechanical trauma, not only from accidental blows with tools, but from the constant pressure and friction entailed in their use. Car­ penters thus develop hygromata or soft epithelial thickenings over the bony prominences of the palms of the hands. They acquire callosities over the right thumb and index finger from using the plane. All the epitheliomas of the hand occurring in carpenters in this series, however, were on the dorsum of the hand. In two of the eight cases of epithelioma of the hand in carpenters trauma was mentioned as a cause. The details of these cases are as follows: 1. C. C. M., aged fifty-five, a carpenter: He stated that the lesion came from a "wart" which he would repeatedly strike and tear in the course of his work. He had an epithelioma on the dorsum of the left hand over the base of the thumb. 2. F. H., aged seventy, a carpenter: For a year and a half he had noted a small, "pimple-like" growth on the back of his right hand. He had knocked it while working. He had an epithelioma on the dorsum of the hand near the ulnar border. Probably the most frequent chronic mechanical trauma causing carcinoma is that due to eyeglasses. There are numerous reports of epitheliomas of the ear and temple due to the irritation by the metal ear-pieces of glasses, and of epitheliomas on the bridge and sides of the nose caused by pressure of the nosepiece. Although this type of epithelioma is not occupational, unless one refers to those who have to wear glasses to protect their eyes in industry, it is of interest at this point. In the Memorial Hospital data there were two cases of epithelioma of the ear, one of epithelioma of the temple, and seven of epithelioma of the bridge of the nose which appeared to have been caused by eyeglasses. 682 CUSHMAN D. HAAGENSEN

It is obvious that the attitude of many authors in regard to the relationship between trauma and cancer has not been critical enough. The medico-legal aspect of the question has often con­ fused the issue. There is need of more complete and authentic case reports in which all the possible factors have been judiciously inquired into. In order to judge the causal relationship of trauma we consider that the following points must be noted in the history: 1. The condition of the site of the tumor previous to the trauma 2. The date of the trauma 3. The exact site of the trauma 4. The physical nature of the trauma 5. The detailed description of the wound 6. The condition of the injured area during the interval between the trauma and the development of the cancer 7. The date of the first appearance of the cancer 8. The exact site of the cancer when it first appeared 9. Histologic diagnosis of the cancer Occupational Extremes of Heat and Cold The development of carcinoma on the basis of burn scars is well known. Observations have not been numerous enough, however, to indicate whether such epitheliomas are due entirely to the effect of heat or are in part caused by the nature of the hot substance, 'which may itself be carcinogenic, as in the case of burns with tar or oil. Treves and Pack have discussed the subject in detail and have reviewed all the cases from the Memorial Hospital. Some of these are distinctly occupational. The following are examples: 1. E. N., aged fifty-five, a molder: This patient was burned on the forehead with molten metal. The resulting ulceration failed to heal. After treatment with various home remedies, a biopsy specimen from the lesion at the site of the burn, taken twelve years afterwards, showed basal­ cell epithelioma. (Fig. 24.) 2. A. D., aged fifty-seven, a brass turner: This patient was burned in the left lowereyelid by a hot fragment of brass. The burn healed, leaving a deformity of the lid. A year and a half later a small tumor, clinically typical of basal-cell epithelioma, appeared at the site of the burn. 3. J. F. K., aged thirty-five, locomotive engineer: He was burned on the cheek by a hot spark. A basal-cell epithelioma developed at the site of the burn. It is of interest to note that carcinoma of the skin of the lower leg is in England supposed to be the penalty of locomotive firemen and engineers. Murray states that the intense heat from the fire­ box, striking the shanks, not infrequently causes cancer. There OCCUPATIONAL NEOPLASTIC DISEASE 683

were no s~h cases in the Memorial Hospital records among the considerable number of railroad engineers with carcinoma in various locations. Francis Carter Wood has pointed out that be­ cause of the different construction of railroad engines in the United States the legs of engineers and firemen are not exposed to excessive heat.

FIG. 24. BASAL-CELL CARCINOMA DEVEU)PINa AT THE SITE OF A BVRN WITH MOLTEN METAL (E. N.)

Frost-bite has been said to predispose to the development of carcinoma of the skin. The following were the only cases in the Memorial Hospital data in which frost-bite was mentioned:

1. W. F., aged seventy-eight, a sailor: His face had been frozen several times about thirty years previously. For one year he had had a crusted lesion of the temple. It was a basal-cell epithelioma. 2. P. B., aged sixty-eight, a gardener: Fifteen years previously his ear was frozen. For twelve years there had been occasional crusting of the skin. A diagnosis of basal-cell epithelioma was made. 684 CUSHMAN D. HAAGENSEN

3. J. N., aged seventy-two, a shipping clerk: A frost-bij;e.of the ear occurring two years before had been followed by persistent scaling of the skin. A squamous carcinoma developed.

2. OCCUPATIONAL INCIDENCE OF NEOPLASTIC DISEASE It would seem worth while to study briefly the occupational incidence of cancer of the skin and mucocutaneous surfaces in the Memorial Hospital data. There has not been in the United States any previous study of the occupational incidence of cancer morbid­ ity. Nor are there in this country any official occupational mor­ tality statistics available, although beginning with 1931 these data will be collected.' Dublin and Vane analyzed the occupational mortality experience of the Metropolitan Life Insurance Company for all forms of cancer and found no remarkable variations in in­ cidence. They did not, however, consider skin cancer separately. English studies have shown that, unless skin and mucocutaneous surface cancer is considered separately, the variations in its occupa­ tional incidence become minimized and lost in the far greater num­ ber of internal cancers upon which occupation apparently has no effect. Francis Carter Wood has pointed out that cancer morbidity statistics, which have not been available, would more truly indicate the extent and distribution of cancer, and the efficacy of its treat­ ment, than do mortality statistics. He has made the timely sug­ gestion that cancer be made an officially reportable disease. It is apparent, for instance, that skin cancer is frequently cured and that many cases do not appear in mortality statistics. There are even good reasons for conjecturing that the occupational incidence of cancer of the skin and mucocutaneous surfaces in various situations differs in morbidity and mortality statistics. Carcinoma of the scrotum, for example, which is an occupational disease of petroleum refinery workers, is relatively malignant, while carcinoma of the skin of the face, an occupational disease among sailors and other workers who are much exposed to sunlight, is generally curable in a high percentage of cases. It would seem, therefore, that studies of the occupational incidence of skin and mucocutaneous surface cancer might best be made from morbidity statistics. Such a study from the Memorial Hospital data will be, of course, only relatively significant, for only a small proportion of all

1 Personal communication from Dr. T. F. Murphy. Chief of the Bureau of Vital Statistics. Bureau of the Census, Washington. D. C. OCCUPATIONAL NEOPLASTIC DISEASE 685

malignant growths occurring in the population of the area studied are treated at the Memorial Hospital. Moreover, there are other disturbing factors. Since many of the larger industrial concerns have factory surgeons who care for their employees, cases of cancer arising in certain industries may never reach oncologic hospitals. Because the patients treated at the Memorial Hospital come largely from the lower and lower middle social classes, the hospital data do not permit of generalizations as to the incidence of cancer in the social strata. Statistical studies bearing on this question have produced varying conclusions. Ullmann, after studying the findings of numerous German investigators, states that the statis­ tical data available to date do not allow of any conclusions as to the relationship between occupations in general and cancer. He recognizes, of course, isolated forms of occupational cancer. English mortality statistics, however, lead Brown and Mohan Lal to suggest that there is an association between a high cancer death rate and a low occupational status. Young and Russell, in a sub­ sequent study, found very little difference in cancer mortality be­ tween the social classes, with the exception that the three lowest classes-textile workers, miners, and agricultural workers-had a definitely smaller amount of cancer. We have used the population of New York City, Jersey City, and Newark as a basis for the calculation of the occupational inci­ dence of cancer of the skin and mucocutaneous surfaces in the Memorial Hospital data. It would be more accurate to work with the population of New York City and its suburban areas within a radius of 75 miles, for the great bulk of the hospital's patients come from this territory. In deriving these incidences we have let P represent the occupied male population ten years of age and over of New York City, Jersey City, and Newark, as given by the Four­ teenth Census of the United States. 0 stands for the number of males in a particular occupational group. P", represents the total number of males with skin and mucocutaneous cancer listed by oc­ cupation in the Memorial Hospital records. A is the actual num­ ber of patients from the occupational group in question. If the morbidity for cancer were the same in all occupational groups, the expected number of cases in the Memorial Hospital records from this particular occupational group might be derived from the formula:

po X P", = E or the expected number of cases. 686 CUSHMAN D. HAAGENSEN

E and A, the expected and the actual number of cases occurring iiil an occupational group, may then be compared, and the percentage of the actual number in excess or in defect of the expected number determined. Reference to Tables I to V will show that the number of cases of cancer in particular sites in different occupational groups is often quite small, sometimes only one or two. Percentages based on such small numbers are subject to considerable error. As a test of their significance we have used the index A ~~ E, which was em- ployed by Young and Russell under similar circumstances. If the value of this index equals two or more, the excess or deficiency is regarded as probably significant, while a value of one and five­ tenths may possibly be significant. Table VI shows those occupational groups in which the number of cases of cancer of the skin and mucocutaneous junctions in excess of what might be expected is greatest. The incidences for all the other occupational groups listed in Table IX have been calculated but are not reproduced. In a general way this table of occupa­ tional incidence of cancer morbidity resembles the similar table of cancer mortality for cutaneous cancer drawn up by Young and Russell from English statistics. Our table, of course, includes no cases of chimney sweeps' cancer and mule spinners' cancer, occupa­ tional groups which show a high excess in the English figures. Out-door workers, whose occupations entail constant exposure to sunlight, predominate in our table. In this class are the sailors and boatmen, fishermen, farmers, hostlers, gardeners, hucksters and peddlers, policemen, street cleaners, and mail carriers. The Eng­ lish statistics showed an excess of cutaneous cancer among fisher­ men, shepherds, agricultural laborers, farmers, and seamen. Habermann, from German statistics, found carcinoma of the skin to be more frequent among out-door workers. The clinical im­ pression that constant exposure to sunlight predisposes to cutane­ ous cancer is thus confirmed by studies of cancer incidence in several countries. We may postulate that exposure to sunlight is in part respon­ sible for the excess of skin cancer in locomotive engineers in our data. More apparent, however, is their constant exposure to winds of high velocity in all extremes of temperature and their liability to burns of the face from cinders. The occupational groups exposed to coal do not show an in- OCCUPATIONAL NEOPLASTIC DISEASE 687 .reaeed incidence of cutaneous cancer in either the English statis­ tics or in ours. The occupational hazard among gas works workers due to their exposure to tar is demonstrated by the excess of cutaneous cancer in this group appearing in both the English table and in ours.

TABLE VI Occupational Groups in Which the Number oj Case« oj Cancer oj the Skin and Mucocutaneo'U8 Surfaces, in EzceBB oj What Might be Expected, is Greatest

Number Expected Actual PtlI' ClllDt In ODDU' Number Number A-B Oooupatlonal Group In pa.t1onal ofC_ ofe- ~ Group B A $

• Sailor and boatman...... 15,598 11 58 420 14 Locomotive engineer ...... 2,555 2 20 900 12 Gardener...... 3,381 2 18 800 11.3 Huckster and peddler..•...... 12,569 8 27 23li 6.8 Physioian and surgeon (including roentgenologist)...... 10,238 7 25 258 6.8 Fisherman and bayman...... 473 1 7 600 6 Roofer...... 1,567 1 7 500 6 Janitor and sexton ...... 9,963 7 23 230 6 Clergyman ...... 4,569 3 13 338 5.7 t Fanner...... 213,252 58 96 66 5 Policeman...... 13,412 9 24 166 5 Carpenter...... 47,677 34 62 82 4.8 Hostler and stablehand ...... 2,535 2 8 300 4.3 Brick and stone mason ...... 11,615 8 25 213 4.2 Petroleum refinery worker...... 2,543 2 7 250 3.5 Blacksmith...... 6,167 4 10 150 3 Street cleaner ...... 4,495 3 8 166 2.9 Gas works worker...... 3,001 2 5 150 2.1 Painter, glazier, vamisher...... 38,918 24 38 37 2 Mail carrier...... 5,349 4 7 75 1.5

• As an example of this calculation: Number of cases of skin and mucocut&- Sailol'lland boatman in Metropolitan area X neous cancer in Memorial Hospital All occupations in Metropolitan area records (male) o 15,598 or p X P", or 2, 073, 528 X 1468 - 11 or E. t Calculated as for the population of the states of New York and New Jel'lleY, thus making this index untruly low. If it were calculated as for the population of the Metropolitan area, however, the index would be eJCceBIlively high. Exposure to tar possibly accounts, also, for the excessamong roofers shown in our data, although this group works out-of-doors, and ex­ posure to sunlight must also be considered. Road builders and repairers, who also frequently work with tar, do not show a high incidence in our table, while they did in the English statistics. The excess of skin cancer among petroleum refinery workers in our data is very probably due to their exposure to crude oil and the 34 688 CUSHMAN D. HAAGENSEN by-products of its distillation. The fact that the occupational groups most exposed to refined oil, the mechanics and machinists, stationary engineers, and oilers, do not show an increased incidence of cutaneous cancer would be a strong argument in favor of the harmlessness of the refined oil used in this country, were it not for a significant excess of cancer of the penis and scrotum in mechanics and machinists appearing in our data. Young and Russell's English study did not reveal a significant excess of skin cancer in general among workers exposed to lubricating oil, with the excep­ tion of an excess among mule spinners and other cotton manufac­ turing employees; yet they found a high incidence of penile cancer among millwrights, turners, and fitters (an occupational group ex­ posed to lubricating oil and comparable to our group of machinists). This question of the liability of refined oil to cause carcinoma of the penis will be discussed further when anatomical distribution is being considered. The high incidence among physicians and surgeons in our data is largely explained by roentgen-ray cancer among them. An excess of cutaneous cancer among brick and stone masons appears in both the English table and in ours. This excess might be explained on the basis of their exposure to sunlight, for their work is to a considerable extent out-of-doors, or on the basis of oc­ cupational trauma, for in our data this group contains a sug­ gestively high percentage of cases of cancer of the hand. A similar etiologic question arises in the case of carpenters, who show a high incidence in our table. A subsequent study of anatomical distribu­ tion will deal with it. Itis possible that the high incidence among janitors and sextons in our data is due to the fact that this class of workers includes many aged men unfit for other work. It is, of course, a fact that the incidence of cutaneous cancer increases with age. Since there are no tables of the age distribution of occupations available in the United States, we cannot determine the extent to whioh age influ­ ences our calculations of incidence. We are unable to suggest an explanation of the excess of skin cancer among clergymen, blacksmiths, and painters, glaziers, and vamishers appearing in our data. None of these groups showed an excess in the English statistics. OCCUPATIONAL NEOPLASTIC DISEASE 689

3. ANATOMICAL DISTRIBUTION In an effort to explain more fully the variations in incidence among the occupational groups, we have drawn up a table, ac­ cording to probable etiology, showing the anatomical distribution of cancer of the skin and mucocutaneous surfaces among the male occupational groups and some other groups. This distribution is expressed in simple percentages in Table VII. The distribution of 20 cases exposed to tar is, in the first place, remarkable for the absence of scrotal lesions. Kennaway, in reviewing the anatomical distribution of 144 English tar and pitch cancers, found them to be about equally distributed between three areas-head and neck, arm and hand, and scrotum. The preponderance of face and lip cancers in our group would suggest, therefore, that some of these at least were not caused by tar. However, the high percentage of arm and hand lesions in these workers exposed to tar, as compared to that in all male workers (25 per cent as compared to 5.1 per cent), clearly suggests that some specific carcinogenic agent is responsible, and tar is the obvious one. Our data are not detailed enough to enable us to distinguish between the anatomical distribution of tar cancer and that of pitch cancer. In such a comparison Kennaway found that the arm and hand were more affected in tar workers than in pitch workers. The striking fact about occupational cancer in petroleum re­ finery workers is that it is usually situated on the scrotum. Of our cases, 70 per cent were scrotal. The percentage of scrotal cancer was significantly high in only one other occupational group -mechanics and machinists. There were 5 petroleum refinery workers and 4 mechanics and machinists with cancer of the scrotum among the 11 patients with scrotal cancer in the Memorial Hospital records. This fact very strongly suggests that lubricating oil as well as crude oil and its distillation fractions may cause cancer of the scrotum. The incidence of skin and mucocutaneous cancer in general was not significantly high in mechanics and machinists. Reference to Table VII will further show that mechanics and machinists have the highest percentage of cancer of the penis of any occupational group. Of the 53 cases of cancer of the skin among these workers, 3, or 6 per cent, were of that organ, as con­ trasted with 2 per cent for all males. This occupational group, moreover, was perhaps the only one in our data with a significantly 690 CUSHMAN D. HAAGENSEN

TABLlD VII Anatomical Distrib'Ution oj Cancer of the Skin and Mucoc'UtaneoUi Surfaces in Male Occupational Groups, Arranged According to Presumptive Etiology, and Expre88ed in Per Cent.

All Occupational Group Face Lip Arm Penis other I I IHand I I I&rotum I areal TAB AND PITCH

Roofer (7 cases) ...... 68 32 ------Gas works worker (5 cases) ... 40 40 20 ------Road builder and repairer (2 eases) .•..•...•...... 50 50 ------Other workers with tar (6 cases)...•...... 50 33 17 ------Groups exposed to tar (20 cases)...... 55 20 20 5

OILS

Petroleum refinery worker (7 cases) .•...... •...••.•.... 15 15 70 ------Mechanio and machinist (53 cases) ...... 58 26 6 8 2

ARsENIC

Therapeutio arsenio cancer (41 oasee--all multiple) ...... 25 25 I 150 1 I I I ROENTGEN RAys AND RADIUM

Roentgenologist (11 ea-5 multiple) ...... •...... 100 ------Radium chemist (1 eaae--mul- tiple) ...... 100

(Table conlin,.", on JlGII' 691) high percentage of penile cancers. Young and Russell found an excess of cancer of the penis among turners and fitters, a sub­ sidiary group among mechanics and machinists. They attribute the excess to the fact that the organ during micturition is smeared with lubricating oil mixed with metal filings. These facts strongly suggest that lubricating oil may also cause cancer of the penis. OCCUPATIONAL NEOPLASTIC DISEASE 691

TABLE VII-Continued

An Ooaupatlonal Group Up Arm Penis othen Fa~ Hand IScrotum I I I I I I arf'U

SUNLIGHT

Sailor and boatman (58 cases) 52 44 4 ------Gardener (18 cases) ...... 33 55 12 ---- Huckster and peddler (27 cases) ...... 62 34 4 ------Fisherman (3 cases) ...... 66 34 ------Farmer (96 cases)...... 64 32 2 1 1 ------Policeman (24 cases) ...... 79 21 ------Street cleaner (8 cases) ...... 37 73 ------Mail carrier (7 cases) ...... 72 14 14 ------Groups exposed to sunlight (241 cases) ...... •..... 59.4 35.1 1.6 0.5 0.5 2.9

TRAUMA TO HANDS

Carpenter (62 cases) ...... 52 30 13 3 2 ------Brick and stone mason (25 cases) ...... 52 32 8 4 4 ------Bayman (4 cases) ...... 25 25 50 ------Diatribution of all skin and mucocutaneous cancers in males (1468 cases) ...... 56.5 29.4 4.9 0.2 2 0.7 6.3

Kennaway has particularly studied the distribution of scrotal and penile cancers. He found that cancer of the penis is fairly widely and evenly distributed through all occupational groups. Cancer of the scrotum, however, is unknown in non-industrial populations. Spittel in Ceylon, Thomson in China, and Broders in the United States, in studies of large series of surgical cases in non-industrial populations, found considerable numbers of cases of cancer of the penis but none of the scrotum. Cancer of the scrotum occurs almost exclusively in industrial populations and its incidence is highest in chimney sweeps, mule spinners, and workers especially likely to be exposed to tar, pitch, and lubricating 692 CUSHMAN D. HAAGENSEN oils. In these groups the relative immunity of the penis was remarkable. In five years there were, for instance, in English statistics, 59 deaths from cancer of the scrotum and only 2 from cancer of the penis among chimney sweeps, mule spinners, and groups exposed to tar, pitch, and oils. Kennaway found no satisfactory explanation of this particular liability of the scrotum to be the site of cancer caused by these agents. Neither the rugosity nor the abundance of sebaceous glands in the scrotum, in his opinion, sufficiently differentiated the skin of that organ from that of other parts equally exposed to the carcinogenic agents. He believes, however, that the cancer-producing substance is conveyed to the scrotum by the fingers in micturition and ad­ vocates that all workers habitually handling lubricating oils wear clean gloves when urinating. The data from the Memorial Hospital records thus lead us to conclude that occupational exposure to lubricating oil predisposes to cancer of the penis and scrotum, and that exposure to crude oil and its fractions in the process of distillation predisposes par­ ticularly to cancer of the scrotum. It occurs to us that clinical investigation as to the site of the beginning scrotal lesion might throw more light on the mode in which the oil reaches the scrotum. If it were found that in a large percentage of cases cancer begins on the anterior aspect of the scrotum where the penis comes into contact with it, one might more definitely conclude that the carcinogenic agent is conveyed by the fingers to the penis and by the penis to the scrotum in the act of micturition. This information as to where scrotal cancer begins is not available from mortality statistics. In our series of 9 cases of scrotal cancer in workers with oil, the exact location of the lesion was noted in 5. The carcinoma was on the right side of the scrotum in 4 and on the left dependent portion in one. Since the right side of the scrotum is that most exposed to and in contact with the clothing, a preponderance of right-sided lesions would suggest that the oil reached the scrotum through the clothing. We realize, of course, that our series of cases is too small to be of much weight, but we suggest that clinicians particularly inquire as to where scrotal cancer begins, so that one day the data will be available. The distribution of our cases of therapeutic arsenic cancer is characteristic. In all four cases the lesions were multiple and affected the hands, arms, legs, and trunk. The face was spared. OCCUPATIONAL NEOPLASTIC DISEASE 693

In two-thirds of Pye-Smith's large series of cases the hands and feet were involved. The marked difference in the distribution of cancers known to be caused by arsenic from those due to tar is, as Kennaway remarks, against Bayet's hypothesis that tar cancer is due to the arsenic content of tar. Hesse, and others who have studied occupational roentgen-ray cancer, have found that in roentgenologists and their assistants the lesions are almost exclusively confined to the backs of the hands. They do not usually occur above the level of the coat­ sleeve. Either the slight filtration provided by cloth is sufficient protection, or the forearms and arms are farther enough away from the tube to escape. In a very few cases the face and the V­ shaped area over the chest beneath the opening of the coat have been involved. In our group of 11 cases the lesions were on the dorsum of the hand or fingers in every instance. Five of these unfortunate physicians developed multiple epitheliomas. The percentages of facial and labial cancer in all male occupa­ tional groups exposed to sunlight were higher than in male occu­ pational groups as a whole-59.4 and 35.1 per cent as compared to 56.5 and 29.4 per cent. Since the numbers of cases are large, this excess, although small, is probably significant. Young and Russell, in the English mortality statistics, found a similar but more marked excess of facial and labial cancer in out-door workers. This excess was smaller in our (morbidity) data, probably because of the fact that our series included a great many rodent ulcers­ which occur in approximately equal proportions in indoor and out-door workers, and which are usually cured and do not, there­ fore, appear in mortality statistics. We are justified in concluding that out-door work predisposes to cancer of the face and lip. This high incidence of lip cancer in out-door workers has not been generally recognized. Itis, of course, well known that women have cancer of the lip very infrequently. Thus in our data only 3.3 per cent of all cancers of the skin and mucocutaneous surfaces in women were situated on the lip-as compared to 29.4 per cent in males. These lip cancers in males were almost all of the lower lip. Johnson has pointed out that cancer of the lip usually occurs in males with a prognathous, projecting lower lip, who work out­ of-doors. The lower lip, being a mucocutaneous surface and devoid of pigment to protect it against actinic rays, is in such individuals particularly liable to be damaged. This theory would very well explain the excess of lip cancer in out-door workers which our data reveals. 694 CUSHMAN D. HAAGENSEN Young and RUBBell point out that workers in the open air have in common unrestricted opportunities for indulging in smoking. They postulate smoking as a cause of the excess of cancer of the lip, tongue, mouth, jaw, and esophagus among males as compared with females. A final group in which the anatomical distribution of skin cancer appears significant is that composed of carpenters, brick and stone masons, and baymen, who have in common perhaps more than any other workers the opportunity for frequent and repeated trauma to the hands. Carpenters frequently knock and scratch their hands, and masons often abrade their hands against the brick and stone which they handle. The hands of baymen are often traumatized by the shellfish which they dig. If repeated trauma does lead to cancer, these occupational groups are the ones in which an increased incidence of cancer of the hand would be expected. The number of carpenters in our series is large, and,the excessof cancer of the hand among them-13 per cent as compared to 4.9 per cent for all occupied males-is probably significant. The number of hand lesions among brick and stone masons and baymen-two in each group-is too small to be statistically sig- nificant. .

4. AGE DISTRIBUTION In Table VIn are listed the average ages of the patients in each occupational group which had a significantly high incidence of skin cancer. There are rather striking differencesin these average ages. The table suggests that locomotive engineers, policemen, hostlers and stablemen, petroleum refinery workers, and mechanics and machinists, in particular, develop cancer at an earlier age than other workers. There is other fragmentary evidence which suggests that occupational cancer develops earlier than other skin cancer. Butlin found that chimney sweeps' cancer in 29 cases from St. Bartholomew's Hospital was most frequent between the ages of forty-five and fifty, and that in the climbing boys who were engaged in the work from the age of about four on, it often occurred about puberty. Pirquet, in his study of age distribution of malignant tumors in English mortality statistics, has shown that when com­ parative curves of the age at death from tumors of the skin and tumors of the scrotum and penis are plotted, the deaths from scrotal and penile tumors occur at an average of eight years OCCUPATIONA.L NEOPLASTIC DISEA.SE 695 younger than the deaths from skin tumors in general. Since scrotal cancer in England is to a large extent occupational in origin -its high incidence among shale oil workers, chimney sweeps, and mule spinners being known-the fact that it apparently occurs at

TABLE VIII AI1erage Ages oj Occupational Groups in Which the Number oj Cases oj Cancer of theSkin and Mucocutaneous Surfaces, in Ezcee« oj What Might be Expected, Was Greaiee:

Oeoupational Group 1------1-----1 Sailor and boatman. . .. 60.4 Locomotive engineer...... 52.2 Gardener...... •...... 62.7 Huckster and peddler...... 57 Physician and surgeon...... 56.3 Fisherman and bayman...... 68.2 Janitor and BeXton.. 69.2 Roofer...... M Clergyman...... 65 Policeman...... 48.5 Farmer...... M Carpenter. . 63.5 Hostler and stableman...... 55 Brick:and stone mason...... 70.3 Petroleumr8finery worker...... 55 Black:BInith , M.3 Street cleaner...... 59.2 Gas works worker...... 56.4 Painter, glazier, varnish maker...... 63.8 Mail carrier...... 65 Mechanic and machinist...... 51.3 All these occupational groups...... 60.8 All patients with cutaneous cancer (according to Pack:)...... 60 an earlier age than skin cancer in general would suggest that at least some forms of occupational cancer occur at an earlier age than skin cancer of unknown etiology. A critical evaluation of these age differences, however, must take into consideration the age distribution of occupations in the occupied population. For instance, it is a fact of common knowledge that janitors and sextons are usually old men who do such work because they are unfit for more active labor. Loco­ motive engineers, policemen, and mechanics and machinists are younger men. Men of this latter class retire on reaching the age of sixty or thereabouts, and it may be that when they come TABLE IX The Occupational Distribution, in Condensed Form, of Some Types of Neoplastic Disease in the Memorial Hospital between 1917 and 1990 Males

~ a0", 1 e lil'~ Oooupational Group .. lil~ ;g 9 '~"i .. ..0 ""':I 'tI" .. ~ "'" '8 .. ]lloo 1 :IIII 1 :I >. :i '2 .. ]0 0 ~'" ~ lloo 0 rz. I"l I"l Z 0 Z ! J 3 l III" l:ll l:ll J E-o r------All groups exposed to Coal (Table I) •.... , 3 1 1 3 5 1 1 1 16 ...... Tar (Table II) ...•. 1 1 5 4 4 1 4 20 ...... Oils (Table III) .... 2 6 11 12 25 30 43 4 8 2 8 9 160 ...... Roentgen rays and Radium (Table IV) 12 12 ...... Sunlight (Table V) . 5 20 18 28 54 81 6 1 6 1 1 221 Battery worker...... , .. 1 1 2 Barber...... 1 1 2 2 1 1 1 1 1 11 il Blaekmnith....•...... 1 1 2 6 1 1 12 co Brick and stone mason ...... , .. , .... ,,,. 2 2 4 5 8 1 2 1 1 26 Brickmaker...... 1 1 2 Carpenter...... 4 4 8 2 15 18 1 8 2 9 2 3 76 Clothing operative...... 2 2 3 2 1 1 2 13 Cha.rcoal maker.•.•...... 1 1 Chemist...... , ...... 1 1 1 1 4 Clergyman...... 1 4 5 2 1 4 1 18 Druggist and pharmacist...... 1 2 1 2 6 Dye worker ...... 1 1 1 3 Electrician.•...... 1 1 1 1 3 7 ~eer--nrlning•..•...... •...... 1 1 2 Janitor and sexton...... 1 1 2 5 5 7 2 3 26 lawyer ...•...... 1 1 2 2 1 1 1 2 11 Leather worker and tanner...... 1 1 2 1 1 6 Miner.•••...•...... 1 1 2 Molder and founder ...... 1 1 2 1 5 Painter, glazier, and varnisher...... 1 3 1 2 10 7 5 2 1 1 4 4 41 Physician and surgeon (excluding roent- genologist) ..•••...••....•...... 1 2 1 1 6 2 1 11 25 TABLE IX---"::'Continued .. 8 0 m a0 Occupational Group 0", 8 ....= 1 "'d .... Cl>" tEa . 1 8 ·il -0" 1lp., 0 :a ... ! .

Females

.. ~ Carci- Osteo- Lym- 0 8 noma genic phatic a0"- 11 ....S 0 Vulva .. 113 Sar- Leu- c- . " os:! Cl> -e "'d" "'d"- coma kemia Cl> ~ c "'dod rQ .. Z c .. -0 .. 0 ]~ :a "0 :a ... ! . ~ .. 0 ~ 0 r-. rz1 rz1 Z 0 ~ Z tx: ~ ~ r-. -< lil Il:l ! Eo< ------Total females ..... 20 2 1 21 75 18 98 234 239 26 18 3 7 13 11 8 70 4 16 884

I T~~~.~.I20 I 2 I 1 1421149/1161208143415831460 1431 7179131 127117131 111 1312137174126841 1 In the following classes, given as in the census of the United States, are condensed all other occupational groups, 698 CUSHMAN D. HAAGENSEN

to the hospital for treatment of cancer, or when they die of cancer at an age beyond sixty, their occupation is noted as "re­ tired," or, if they have taken up the lighter work of a watchman or janitor, as such. The result is that a survey of case histories such as ours contains an untrue proportion of locomotive en­ gineers, etc., under the age of sixty. This may partially or entirely explain the fact that in our data the locomotive engineers, police­ men, and mechanics and machinists appear to have developed cancer at an earlier age than janitors and sextons. Since there are no reliable tables of age distribution of occupations available in the United States, we are unable to analyze further this inter­ esting question. If, when such statistical data become available, it can be shown that definitely proved occupational cancer occurs at an earlier age than other cancer, the fact will be of great interest to oncologists.

SUMMARY AND CONCLUSIONS Summarizing briefly our findings from the Memorial Hospital records as to cancer morbidity in relation to occupation, it may be said that confirmatory evidence has been obtained of views already more or less widely accepted as to the close association of certain types of neoplastic disease with exposure to particular agents in some occupations. Thus we have found a high incidence of skin cancer among gas works workers, probably due to their exposure to tar, and among petroleum refinery workers as a result of their contact with crude oil and its distillation fractions. Our studies of incidence also lead us to conclude that occupational exposure to lubricating oil, as in the case of mechanics and machinists, predisposes to cancer of the penis and scrotum-a predilection as to anatomic site which seems best explained by the uncleanliness of the external genitalia so common in laborers. A significant excess of cutaneous cancer among out-door workers, affecting particularly the face and lower lip, confirms the importance of sunlight in the etiology of skin cancer. We have suggested further study of the pathology of this type of cutaneous cancer. Although no new types of occupational neoplastic disease have been found, some very rare forms, such as lymphatic leukemia caused by radium, have been described. The not infrequent changes in the blood picture resulting from exposure to roentgen rays and radio-active substances warrant monthly blood counts in OCCUPATIONAL NEOPLASTIC DISEASE 699 all such workers. The fact that metastases occurred in 63 per cent of our cases of occupational roentgen-ray cancer suggests that this type of carcinoma is more malignant than some authors have reported it to be. This finding may indicate that its treatment should be more radical. A study of the cases of cancer of the lung and bladder showed no apparent association with occupation. In the data examined we have found a high incidence of skin cancer in some groups-such as clergymen-where an occupational risk was not apparent. This suggests that occupational exposure is only one of the probably multiple etiological factors of cancer. Studies such as this in which we have been engaged make extra­ ordinary demands upon the record system of a hospital.' The physician who takes the history of a patient with cancer should inquire into possible occupational exposure to presumptive car­ cinogenic agents. If a history of exposure is elicited, the physical details and the length of exposure, as well as the exact nature of the noxious agent, should be gone into. In this respect, the extraordinary latency of some types of occupational cancer should be kept in mind. Bang refers to the case of a man who in his youth was a chimney sweep's climber. After going to sea and working for nineteen years, he developed a typical chimney sweep's carcinoma of the scrotum. 'White men­ tions 13 instances of mule spinners' cancer developing from one to fourteen years after the person had retired from all employment. It is apparent, therefore, that the entire life occupational history of the patient with carcinoma should be inquired into and re­ corded in the history. To facilitate studies as to occupational cancer incidence the occupation, when noted, should conform to the standard list of occupations as given by the census of the United States. The term "laborer," for instance, is too general a one. Nor is it helpful to note the patient's occupation as "retired." It is equally important that the case record contain a descrip­ tion of such occupational dermatoses as may be present. It is known that some of these lesions, such as the papules and warts occurring in shale oil workers, the pitch warts of workers with pitch, and the keratoses of roentgenologists, are precancerous. The recognition of other precancerous lesions can come about only

1 Fortunately for the purposes of our inquiry the histories of most of the patients examined at the Memorial Hospital over a period of years have been taken under the able supervision of a single individual, Dr. Lloyd F. Craver, Attending Physician. 700 CUSHMAN D. HAAGENSEN through painstaking clinical observation and careful description in case histories. Photographs are a valuable aid here. It is our opinion that our knowledge of skin cancer has not yet reached the stage where the clinical aspect of its widely varied forms is so well known as to enable their definitive diagnosis without the aid of biopsy. We believe that biopsy should be done in order to confirm the diagnosis and complete the case record. Finally, although our findings from morbidity data resemble in a general way those of English and German investigators working with mortality statistics, we suggest that morbidity statistics furnish more accurate information as to the extent and nature of occupational cancer.

BIBLIOGRAPHY Although not intended to be complete, the following bibliography includes many of the more important contributions to the subject of occupational cancer.

AMUNDSEN, P.: Blood anomalies in radiologists and in persons employed in radiological service, Acta radiol. 3: 1-7, 1924. BANG, F.: Le cancer des ramoneurs, Bull. de l'Assoc. fran9. pour l'etude du cancer 16: 656, 1927. BAYET, A., AND SLOSSE, A.: L'Intoxication houillere arsenieale, Bull. de l'Acad. Roy. de med, 29: 607, 1919. BLOCH, B.: Die experimentelle Erzeugung von Rontgenkarsinomen beim Kannichen nebst allgemeinen Bemerkungen fiber die Genese der experimentellen Karzinome, Schweiz. med. Wchnschr. 54: 857, 1924. BRIDGE, J. C., AND HENRY, S. A.: Industrial Cancers, Rep. Intemat. Conf. on Cancer, London, Wm. Wood & Co., 1928, p. 258. BRODERS, A. C.: Quoted by Kennaway, E. L.: J. Indust. Hyg. 7: 93, 1925. BROWN, J. W., AND MOHAN LAL: An inquiry into the relation between social status and cancer mortality, J. Hyg. 14: 186, 1914. BUTLIN, H. T.: Cancer of the scrotum in chimney sweeps and others, Brit. M. J. 2: 1, 1892. CARMAN, R. D., AND MILLER, A.: Occupational hazards of the radiologist with special reference to changes in the blood, Radiology 3: 408, 1924. DARIER, J.: Precis de dermatologie, Paris, Masson et Oie., 1928, p. 984. DAVIS, B. F.: Paraffin cancer, J. A. M. A. 62: 1716, 1914. DERVILLE, L., AND GUERMONPREZ: Le papillome des raffineurs de petrole, Ann. de dermat. et syph. 1: 369, 1890. DUBLIN, L. I., AND VANE, R. J.: Causes of death by occupation, Bureau of Labor Statistics, Bulletin 507, Gov't Print. Off., Washington, D. C., 1930. DUBREUILH, W.: tpitheliomatose d'origine solaire, Ann. de dermat. et syph. 8: 387, 1907. OCCUPATIONAL NEOPLASTIC DISEASE 701

EHRLICH, H.: Vber Paraffincarcinom, Arch. f. klin. Chir. 110: 327, 1918. EWING, J.: Neoplastic Diseases, Philadelphia, W. P. Saunders Oo., 1928, Ed. 3, p. 117. FLASK.AMP, W., AND WINTZ, H.: Uber Roentgenschaden und SchAden durch radioactive Substanzen, Bd. 12, Sonderbande zur Strahlen­ therapie, Berlin, Urban & Schwarzenberg, 1930, p. 71. GRANDHOMME, W.: Die Theerfarben-Fabriken der Actien-Gesellschaft Farbwerke form. Meister Lucius & Bruning zu Hochst a. M. in sanitarer und soeialer Beziehung, Heidelberg, G. Koster, 1883. HABERMANN, H.: Die in land- und forstwirtschaftlichen Betrieben vor­ kommenden beruflichen Hautschadigungen, in: Oppenheim, M., Rille, J. H., and Ullmann, K.: Die Bchadigungen der Haut, Leipzig, Leopold Voss, 1926, vol. 2, p. 448. HAZEN, H. A.: Skin Cancer, St. Louis, C. V. Mosby Co., 1916, p, 33. HELLER, 1.: Occupational cancers, J. Indust. Hyg. 12: 169, 1930. HENRY, A. S.: Cancer in relation to occupation, J. Soc. Dyers and Colour- ists 46: 61, 1930. HESSE, 0.: Das Roentgencarcinom, Fortschr. a.d. Geb. d. Rontgenstrahl. 17: 82, 1911. HUTCHINSON, J.: On some examples of arsenic keratoses of the skin and of arsenic cancer, Trans. Path. Soc. London 39: 352, 1888. HYDE, J. N.: The influence of light in the production of cancer of the skin, Am. J. M. Sc. 131: I, 1906. VON JAGIC, N., SCHWARZ, G., AND SIEBENROCK, L.: Blutbefunde bei Rontgenologen, Berl. klin. Wchnschr. 2: 1220, 1911. JOHNSON, S. C.: Personal communication. KENNAWAY, E. L.: The anatomical distribution of the occupational cancers, J. Indust. Hyg. 7: 69, 1925. DE LAET, M. : La pathologie professionnelle due aux corps radioactifs, Ann. de med. leg. 8: 443, 1928. LAMBIN, P.: Les anemies provoquees par les rayons X et les corps radio­ actifs, Rev. beIge sc, med, 2: 623, 1930. LAWRENCE, H.: The relative low humidity of the atmosphere and much sunshine as causal factor for the great prevalence of skin cancer in Australia, M. J. Australia 15: 403, 1928. LEITCH, A.: Mule-spinners' cancer and mineral oils, Brit. M. J. 2: 941, 1924. LEITCH, A.: The experimental inquiry into the causes of cancer, Brit. M. J. 2: I, 1923. LEITCH, A., AND KENNAWAY, E. L.: Experimental production of cancer by arsenic, Brit. M. J. 2: 1107, 1922. LEUENBERGER, S. G.: Die unter dem Einfluss der synthetischen Farben­ industrie beobachtete Geschwulstentwicklung, Beitr. z. klin. Chir. 80: 208, 1912. MARTLAND, H. S.: Occupational poisoning in manufacture of luminous watch dials, J. A. M. A., 92: 466, 1929. MISHELL, D.: A case of cancer following a sulphuric acid burn, J. A. M. A. 73: 1936, 1919. 702 CUSHMAN D. HAAGENSEN

MOTTRAM, J. C.: The red cell content of those handling radium for thera­ peutic purposes, Arch. Radial. & Electroth. 25: 194, 1920. MURRAY, J. A.: The biological problem of cancer, Discovery 1: 71, 1920. NUTT, W. H., BEATTIE, J. M., AND PYE-SMITH, R. J.: Arsenic cancer, Lancet 2: 210, 1913. O'DONOVAN, W. J.: Carcinoma cutis-multiple skin cancers of occupa­ tional origin, Lancet 2: 278, 1926. O'DONOVAN, W. J.: Arsenic cancer of occupational origin, Brit. J. Der­ mat. 36: 477, 1924. PACK, G. T., AND LEFEVRE, R. G.: The age and sex distribution and inci­ dence of neoplastic diseases at the Memorial Hospital, J. Cancer Research 14: 167, 1930. PARIS, J. A.: Pharmacologia. New York, F. & R. Lockwood, 1822, p, 208. PASSY, R. D.: Experimental soot cancer, Brit. M. J. 2: 1112, 1930. PAUL, C. N.: The Influence of Sunlight in the Production of Cancer of the Skin, London, H. K. Lewis & Co., 1918. . PIRQUET, C.: Allergie des Lebensalters, die bosartigen Geschw1ilste, Leipzig, G. Thieme, 1930, p. 48. POTT, P.: Chirurgieal Observations, London, Hawes, Clarke, & Collins, 1775, pp. 61-68. Ross, H. C.: Occupational cancer, J. Cancer Research 3: 321,1918. ROSTOSKI, 0.: Clinical and radiological study of Schneeberg lung cancer, Rep. Internat. Conf. on Cancer, London, Wm. Wood & Co., 1928, p. 269. ROWNTREE, C.: X-ray cancer, Brit. M. J. 2: 1111, 1922. SCOTT, A.: The occupation dermatoses of the paraffin workers of the Scottish shale oil industry, Imperial Cancer Research Fund, Eighth Scientific Report, London, 1923, pp. 85-142. SOUTHAM, A. H., AND WILSON, S. R.: Cancer of the scrotum: The etiology, clinical features, and treatment of the disease, Brit. M. J. 2: 971, 1922. SPITTEL, R. L.: Betel chewing and cancer, Brit. M. J. 2: 632,1923. STAHR, H.: Schusterdaumenkrebs, Deutsche med. Wchnschr. 47: 1452, 1921. SUTTON, R. L.: The symptomatology and treatment of seborrheic kera­ toses, J. A. M. A. 64: 403, 1915. THOMSON, J. 0.: Tumors in the south of China, Ann. Surg. 73: 212,1921. TREVE8, N., AND PACK, G. T.: The development of cancer in burn scars. Surg. Gynec. Obst. 51: 749, 1930. TWORT, C. C., AND lNG, H. R.: Mule-spinners' cancer and mineral oils, Lancet 1: 752, 1928. ULLMANN, K.: Uber das Wesen und die Verbreitung einiger die der Erdol­ gewinnung und ParafHnfabrikation entstehender Berufsdermatosen, Das 6sterreichische Sanit~tswesen, Beih. Z. Nr. 18, 1912, 112-141. ULLMANN, K.: Krebsentwicklung a.ls Folge beruflich-gewerblicher Haut­ schiidigungen, in: Oppenheim, M., Rille, J. H., and Ullmann, K.: Die Schadigungen der Haut, Leipzig, Leopold Voss, 1926, Vol. 3, pp. 202-258. OCCUPATIONAL NEOPLASTIC DISEASE 703

UNNA, P. G.: Die Histopathologie der Hautkrankheiten, Berlin, A. Hirschwald, 1894, p. 719. VOLKMANN, R.: Beitrage zur Chirurgie, Leipzig, Breitkoff & Hartel, 1875, pp. 370-381. WHITE, R. P.: The Dermatergoses or Occupational Affections of the Skin, London, H. K. Lewis & Co., 1928. WOGLOM, W. H.: Experimental tar cancer, Arch. Path. & Lab. Med. 2: 533, 1926. WOOD, F. C.: The noncarcinogenic nature of purified mineral oils, J. A. M. A. 94: 1641, 1930. WOOD, F. C.: Need for cancer morbidity statistics, Am. J. Pub. Health 20: 11, 1930. WOOD, H. B.: Skin lesions among tar workers, J. Cancer Research 13: 54, 1929. WOOD, H. B.: Paraffin not productive of cancer, J. Cancer Research 13: 97, 1929. YOUNG, M., AND RUSSELL, W. T.: An Investigation into the Statistics of Cancer in the Different Trades and Professions, Medical Research Council, Special Report Series, No. 99, London, 1926.

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