Columtiia ®nibers;itp 
 m tije Citp of iSeto ^orfe 
 
 COLLEGE OF PHYSICIANS 
 AND SURGEONS 
 
 Reference Library 
 
 Given by 
 
THE SURGICAL TREATMENT OF X-RAY CARCINOMA 
 
 AND OTHER SEVERE X-RAY LESIONS. BASED UPON 
 
 AN ANALYSIS OF FORTY-SEVEN CASES 
 
 C. A. PORTER, M.D. 
 
 (Assistant Professor of Surg-ery, Harvard Medical School; Surgeon to the 
 Massachusetts General Hospital, Boston, Mass.) 
 
 THE PATHOLOGICAL HISTOLOGY OF CHRONIC X-RAY 
 DERMATITIS AND EARLY X-RAY CARCINOMA 
 
 S. B. WOLBACH, M.D. 
 
 (Director of the Pathological Laboratory, Montreal General Hospital, Montreal) 
 
 Reprinted from 
 
 The Journal of Medical Research, Volume XXI., No. 3 
 
 (New Series, "Vol. XVI., No. 3), pp. 357-449, October, 1909 
 
 BOSTON 
 
 MASSACHUSETTS 
 
 U.S.A. 
 
'RJ)I3S' 
 PS3 
 
 Digitized by tine Internet Arciiive 
 
 in 2010 witii funding from 
 
 Open Knowledge Commons 
 
 http://www.archive.org/details/surgicaltreatmenOOprot 
 
THE SURGICAL TREATMENT OF X-RAY CARCINOMA AND 
 OTHER SEVERE X-RAY LESIONS, BASED UPON AN 
 ANALYSIS OF FORTY-SEVEN CASES.* 
 
 C. A. Porter, M.D. 
 
 {Assistant Professor of Surgery, Harvard Medical School ; Surgeon to the 
 
 Massachusetts General Hospital, Boston, Mass.) 
 
 In the Annals of Surgery for November, 1907, 1 published 
 the account of two cases of severe X-ray lesions ; one of 
 possible sarcoma of the finger, the other of an X-ray 
 operator who, since 1896, in addition to the severer forms of 
 dermatitis and ulceration, had developed, between 1902 and 
 
 1907, numerous carcinomata, requiring many operations, 
 amputations, excisions, and skin graftings. At the time, I 
 was able to gather the records of ten other cases making, 
 with my own, eleven undoubted X-ray cancers, of which six 
 had been fatal. 
 
 Since that time occasional reports of cases have appeared, 
 and three notable papers by E. Schumann ^ in the Beitrage 
 fUr Klinische Chirurgie, 1907, LXXXIV., Heft 3, page 355 ; 
 by Karl Lindenborn,^ in the same journal, 1908, LXXXIX., 
 Heft 2, page 385 ; and by Dr. Cecil Rowntree^ of London 
 in the Archives of the Middlesex Hospital, XHI., July, 
 
 1908. In all of these papers new cases have been pre- 
 sented, and the etiological relation between X-ray lesions 
 and carcinoma, possibly also sarcoma, has been thoroughly 
 discussed and, in the case of the former at least, definitely 
 proved. In the German literature especially, the subsequent 
 development of cancer upon lupus tissue treated with X-rays 
 has aroused considerable interest; though Steinhans has col- 
 lected eighty-three cases of carcinoma following lupus, with- 
 out X-ray treatment, it seems, after a careful perusal of the 
 histories, at least probable that the X-ray had a definite 
 influence upon the subsequent development of the cancer. 
 The cases can be studied in detail in the contributions of 
 Schiimann and Lindenborn. 
 
 * Received for publication July 26, 1909. 
 
 (357) 
 
358 PORTER. 
 
 I propose in this paper to omit all consideration of the 
 lupus cases, and to limit myself, with very few exceptions, to 
 a consideration of the severer lesions which have resulted 
 from the prolonged action of the X-ray upon previously 
 healthy skin, and I should like to emphasize the fact that not 
 only was the skin healthy, but the wearer of it was almost 
 without exception young. 
 
 As a result of my former publication, I have had, so far as 
 I know, a unique experience, having operated upon eleven 
 other cases in addition to further operations upon both of 
 the cases previously reported. Thirteen in all : of these 
 three were non-malignant, two beginning carcinoma, six 
 carcinoma, one sarcoma(?), another carcinomia or sarcoma. 
 The distinctions between the phrases precancerous and 
 beginning epithelioma must of course be a matter of opinion, 
 but the clinical histories of other similar cases in this X-ray 
 series seem to show that tissues which presented a precan- 
 cerous condition or commencing epithelioma at the time 
 of excision would, unless adequately treated, subsequently 
 develop into squamous celled carcinoma. From my experi- 
 ence it seems almost assured that, given lesions of a sufficient 
 duration and severity without adequate treatment, the future 
 development of cancer can be predicted. 
 
 Though the harmful results of continuous exposure to the 
 X-rays were unknown to the early workers in this field, it would 
 seem that unwittingly they have given us the best demon- 
 stration yet known of the artificial or experimental produc- 
 tion of cancer. It is unlikely that old age itself, with its 
 accompan}-ing skin atrophies, even if combined with expos- 
 ure to such various noxious influences as sea life, raw winds, 
 powerful actinic rays, soot or paraffin, would give such an 
 example of malignant skin degeneration as seems so fre- 
 quently to result from protracted exposure to the X-ray. 
 When it is remembered that these lesions have been pro- 
 duced in young men at an age when skin cancer is extremely 
 rare, its occurrence is all the more striking. 
 
 I have gathered from the literature, and especially through 
 the kindness of physicians whose names will be mentioned 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 359 
 
 with their personal communications, combined with my own 
 experience, the records of forty-seven cases of severe X-ray 
 lesions. This number in no way represents the actual 
 figures, for there are surely very many cases both of serious 
 damage and also of carcinoma which have . not been 
 reported, and are therefore not available. For example. 
 Dr. Pusey of Chicago states : 
 
 "I have seen many cases of this kind; certainly more than a score. 
 They are all of one kind and may be briefly characterized in a group. As 
 a result of either an acute or more frequently of a chronic long continued 
 X-ray dermatitis, the skin becomes atrophic, thinned, and harsh, with a 
 number of dilated blood vessels coursing through it and many keratoses 
 forming upon it. These keratoses very frequently become the site of 
 epithelioma. In my judgment, the condition is analogous to senile 
 atrophy of the skin and on the basis of this analogy I prophesied, before 
 the report of any epithelioma in these cases, that epithelioma would 
 develop in them. At the start these X-ray epitheliomata ought theoreti- 
 cally to be very easily handled, just as the superficial epitheliomata 
 beginning in senile keratoses are very easily handled and this has proved 
 true in my experience. In my judgment these epitheliomata should be 
 handled in exactly the same way as epitheliomatous senile keratosis, either 
 by excision or by some other destriictive procedure. Many such lesions 
 have been excised upon my advice with good result. Many others that 
 were very superficial I have treated by destruction, usually with carbon 
 dioxide snow. The reason for this sort of procedure is that it does not 
 require the destruction of as much tissue as a thorough excision and some- 
 times, of course, this is a matter of importance." 
 
 Dr. Hyde, in addition to the cases recorded, says that he 
 has seen at least six other patients in a precancerous stage. 
 The experience of these dermatologists is, no doubt, equalled 
 by some in this and other countries, so that the cases 
 reported are by no means an index of the number of persons 
 who are now suffering from early exposures. From France, 
 so far as I am aware, there has been no report of serious 
 X-ray lesions. 
 
 Of these forty-seven cases, four of my own were not 
 unusual and are reported simply for record. Four were 
 described as in a precancerous stage or beginning epithe- 
 lioma; thirty-six were undoubted epidermoid cancer, and 
 two of my own, questionable sarcomata. Had it not been for 
 
360 PORTER. 
 
 the reports of sarcomata by other observers, especially in con- 
 junction with the X-ray treatment of lupus, these two cases 
 would be open to more question. As it now stands, it seems 
 probable that the X-rays may be a factor in the production not 
 only of cancer, but of sarcoma. Of the thirty-six cases of 
 epidermoid cancer, nine have died; a mortality of twenty- 
 five per cent, showing I think quite clearly that these X-ray 
 carcinomata are as malignant, if not more so, than the 
 epitheliomata which ordinarily grow in the skin of older 
 persons, and are, if allowed to advance beyond a certain 
 stage, prone to early metastasis. 
 
 In the histories of these cases, the reader will be struck by 
 the period of incubation, if so it may be called, which dates 
 from the occurrence of the original severe lesions, or early 
 unprotected exposures to the rays, during which time 
 characteristic changes have taken place in the skin and 
 underlying tissues, which precede the development of a 
 cancer. This period varies from three to eleven years 
 (Case XXII.), usually from five to seven, and is dependent 
 no doubt upon the number of the exposures and the vulner- 
 ability of the individual. 
 
 While progressive and characteristic lesions have developed 
 siiice the dangers of the X-ray were recognized, and some 
 precautions were taken, it is among those who did the earliest 
 work that we have had the greatest number of fatalities and 
 the most severe lesions ; and this without regard to the middle 
 age or youth of the individuals. It has seemed that the 
 development of the photographic plates combined with X-ray 
 work has led to earlier and more serious lesions than when 
 X-ray work was done alone. We have, then, quite clearly 
 differentiated from other skin diseases a definite occupation 
 dermatosis which can be diagnosed at a glance, and in the 
 chronic form resembles no other skin afTection known to me. 
 The dry thickened skin, without hairs, the telangiectases, the 
 ribbed nails, the keratoses on the backs of the hands in young 
 men are together pathognomonic, and show the results of the 
 specific action of the X-ray; in a more advanced stage, 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 36 1 
 
 paronychia, more numerous keratoses, rhagades and ulcera- 
 tions which alternately heal and break down, until finally 
 there comes, as inevitably as fate, the development of epi- 
 thelioma at the base of a persistent or inflamed keratosis, or 
 in. a chronic ulcer. While the keratoses in no way differ from 
 the usual senile condition, the combination of juvenile kera- 
 toses with ulceration of the skin of the dorsum of the hands 
 and fingers seems peculiar to X-ray dermatoses. I have not 
 yet seen an X-ray lesion of the palmar surface of the hands 
 or fingers. Either the thickened skin offers some immunity, 
 or what is more probable, the dorsum, from the position of 
 the hands in work either with the fluoroscope or otherwise, is 
 more exposed. The base of the middle finger seems to be 
 the place most universally affected. This knuckle is obviously 
 most exposed and nearest to the tubes. The thumb, while 
 the nail and the ulnar border is occasionally affected, is to 
 some degree protected in most exposures by the thick palmar 
 skin. The nails suffer relatively early, and the changes are 
 to some degree permanent. An accidental discovery in the 
 case of J. G., Case XVIII., seems to show the value of pro- 
 tection during the early years of work, and the lack of harm- 
 ful influence to recent exposures with proper precautions. A 
 broad gold ring was worn during the first two years of work 
 on the ring finger of the left hand. This was subsequently 
 removed. The whole dorsum of the hand shows the character- 
 istic changes, while the skin protected by the ring remains to 
 this day perfectly normal. The immunity which even light 
 clothing offers is shown by the rarity or slight degree of 
 dermatitis above the cuffs, and in those parts of the body 
 protected by clothing. It would seem, therefore, in view of 
 this immunity from slight covering, that not the X-ray 
 themselves, but other emanations from the tube are to be 
 held chiefly responsible for the burns and the chronic der- 
 matitis. With these few general remarks, I shall proceed to 
 record the cases, with the pathological reports when avail- 
 able, and to give after each one a brief summary in which 
 any interesting feature will be mentioned. 
 
362 PORTER. 
 
 Case I. — Miss A. Personal communicafion fiiom physidan. Owing 
 to slight tabercolons disease of the anUe, patient was subjected to vigor- 
 oos X-rar treatment for a year and a half. Extensive X-ray bum resulted 
 in an intractable deep ulceration 3x2 inches in extent, just above the 
 ankle on the inner side of the leg. Pain was extreme. Amputation at 
 point of election, wound healing, but pain in stump persisting a year after 
 operation. No evidences of carcinoma in the ulcer. 
 
 Comment: Exdsion and skin grafting mi^t have been done in this 
 instance bat. owing to the tabercolosis of the tarsus, amputation seemed 
 preferable. 
 
 Case II. — ?er=o::a'.. Dr. VVolbach, Case I. F. M. : age 55: was 
 operated upon :':- aze- ::ar:iiionia of the s:: — ;:- v.ith partial gastrec- 
 tomy, Dec. 19. :;'.': re:- very was perfec: ' :Iy 23, 1908, after 
 swallowing bisrr.-;:-. . .e i; - ;.'.;aed for t:: :/:- :-an twenty minutes 
 with the fluoro5:::e. -.>.e v_.e .eiDg suppose:^ a: a distance of fifteen 
 inches. In three we e /: s - e r e 1 : : : =-. 'I : : rr. :. ! ;. : - i r. 'c '. : - e . e re pain an d an area 
 of erythema about tr.e =ize .: a z:.:.:.-- \\^.-. ir. :.e rr:d die of the back. 
 This was treated wi:' :r.e :. t: len:. ;:r..' :! ■ a;- . .- :- extreme suffer- 
 ing, the skin broke c: r. . :::-; .^ ar. :-, .a; u :t- \ : -: .rree inches by 
 two, which was resJsia- : :. a . rta.v- .. ar. - .a: r.:rea--I in size. 
 
 Operation under ether, i«iov. 18, 1900, M;. ;ac . .se.:- e era' Hospital. 
 In the center of the back, over an area i,t. '•'- ih :r.:r.es, is a superficial 
 ulcer, surrounded by an irr^^ular margin of reddened skin, situated over 
 the last two dorsal and first two lumbar vertebrae. The base oi the ulcer 
 is slightly depressed, showing no evidence of granulation tissue, but the 
 sur&ce is covered with firmly adherent fibrin. There are several roundish, 
 moundlike elevations, varying in diameter from a quarter to a half inch. 
 After careful preliminary cleansing, the whole area, with a margin of 
 three-quarters of an inch, was excised down to the imdeiiying muscle. 
 The choice then arose as to a plastic operation or a skin graft ; the former 
 was chosen. A flap was made with the base uppermost, extending down- 
 ward and. to the right. This was dissected up and turned over, and 
 sutured without tension to the margins of the wound. Another flap was 
 swung from below into the denuded area; appronmation was almost 
 complete. In a few days the wound became infected fi-om a nearby fiirun- 
 culosis and, in spite of vaccines, there occurred some sloughing of the distal 
 part of the flap. Healing took place slowly, but without fever. Super- 
 ficial necrosis of the surrounding sldn is still taking place, and raw sur- 
 faces being covered with a characteristic fibrinous membrane. On Decem- 
 ber 22, the patient was temporarily discharged fi'om the hospital, the 
 depth of the wound granulating healthily, but the skin still undergoing 
 superficial necrosis. 
 
 Summary : X-ray bum after long exposure, July 23, 1908. Ulceration 
 began six weeks afterwards, steadily progressing with g^reat pain in spite 
 of treatment. Excision of large ulceration on back on Nov. 18, 1908. 
 Operation brought about immediate and permanent relief fi'om pain, but 
 
SURGICAL TREATMENT OF X-RAY CARCINOi\L\. 
 
 0"0 
 
 subseqaent necrosis of the edges of the wound raised the question as to 
 whether the excision had been adequate. Whether the sloughing 
 of the flap was due to infection or to inadequate blood supply, on 
 account of the obiiterative endarteritis present, is an open question. 
 There are other instances of the sloughing of flaps where the .^^kin has 
 been for a long time exposed to X-rays. This at least would sene as 
 a warning in the performance of plastic surgery in these cases, and were I 
 to operate again I should simply excise such an ulcer with primary skin 
 grafting. The mounds mentioned on the surface of the ulcer were shown 
 by microscopic examination to be blisters in the deep layers of the 
 epidermis. 
 
 Pathological report by Dr. Wolbach. Material consists of Zenker hard- 
 ened tissue representing a large ulcer about lo centimeters in diameter 
 surrounded by a border of epidermis i to i^ centimeters in thickness. 
 
 Microscopic description: paraffine sections: phosphotungstic and 
 hematein stain. 
 
 The portions covered by skin are very similar in appearance to the tissue 
 from the cases 6f IVfiss H. and Mr. S., that is, we have the same rarefica- 
 tion of the corium immediately beneath the epidermis. The papillje 
 are absent, so that the epidermis presents a perfectly smooth under sur- 
 face. The portion denuded of epithelium shows a slight fibrinous exudate 
 overlying the corium. In a few places there is granulation tissue beneath 
 thick layers of coarse meshed fibrin. The epidermis in places is mark- 
 edly thinned and the ordinary arrangement of the basal layer is lost. 
 The cells of the epidermis in the thin portions are larger, somewhat ves- 
 icular in character and stain less deeply than those of normal epidermis. 
 There is nowhere any evidence of invasion of the corium by epidermis. 
 The deep vessels of the corium show very slight changes. There are 
 many coil glands which are practically normal. Others are atrophic and 
 are surrounded by new formed connective tissue and masses of lymphoid 
 and plasma cells. No hair follicles or sebaceous glands found in the sec- 
 tion. Irregular areas and tracts throughout the corium filled with 
 lymphoid and plasma cells are probably spaces once occupied b}^ coil 
 glands and ducts. 
 
 In brief, this tissue sho^i^ the same processes found in Case VIII. 
 and Case IV., but to a less advanced degree. The characteristic changes 
 of the corium are present. Vessels show very slight thickening of the 
 intima. Epidermis, however, does not show irregular downgrowth sug- 
 gesting beginning carcinoma. 
 
 Case III. — Personal. Dr. Wolbach, Case II. E. R. ; 28 years 
 (female) ; referred to me by Dr. Reeves of Boston. Patient con- 
 sulted Dr. R. first for ulcerations of elbow and knee on March 18, 
 1908. X-ray treatment until the end of April at the Emergency Hos- 
 pital, when they broke down and she went to the Emergency as a 
 patient for three weeks, as ulcers formed on both knee and elbow. 
 Under treatment, the acute dermatitis subsided, but since then the ulcers 
 
364 PORTER. 
 
 have never healed. While at hospital the ulcer diminished on the knee 
 from 5x3 inches to 2^ x i ; that on the elbow from 2^x1^ to the size of a 
 •' quarter." Patient worked for two weeks, and although the ulcerations did 
 not increase in size, the skin surrounding them became irritated. Was 
 again admitted to hospital for three weeks in June ; improvement under 
 rest and treatment. Reentered August 18, where she remained until 
 Nov. 7, 1908, when she was discharged. Daily dressing since then. 
 
 Examination Dec. 4, 1908. Over inner aspect of flexure of elbow are 
 characteristic X-ray changes ; evidences of old ulceration about 4x3 
 with cicatricial tissue and telangiectases. Just above the inner condyle is 
 an ulceration about size of a dime which is covered with a yellow, fibrin- 
 ous scab. The skin about it is atrophic; causes pain on motion ; no der- 
 matitis. Examination of left leg : dermatitis from middle of thigh to 
 top of boot ; a great deal of irritation and itching. There is some 
 edema. On the outer side of the knee over an area 6x5 inches the skin is 
 reddened, pigmented and shows scars peripherally to the old healed 
 ulcerations ; also telangiectases. Ulceration at present is 2^ x i inches ; 
 sore and tender to touch. Pain and sensitiveness, however, are less now 
 than during acute inflammation. Patient says boric acid, aristol, corro- 
 sive wash, as well as ichthyol all irritated the skin. The edges of the skin 
 show little evidence of healing ; there is fibrin at the margin of the grow- 
 ing epithelium. The whole skin of this area is indurated and is two or 
 three times the normal thickness. There is already some tendency to 
 cicatricial contraction, but this is on the outside of the knee, not in the 
 popliteal space. The dermatitis of the rest of the leg can be properly 
 called medicamentosa. 
 
 Operation, Jan. 21, 1909, N. E. Baptist Hospital. Since last visit, 
 the patient has been comparatively free from pain, as the dermatitis has 
 subsided, but the ulceration shows no evidence of healing or of growing 
 smaller. Its base is very much indurated. Under ether, thorough exci- 
 sion down to fat, with half-inch margin. After bleeding had stopped raw 
 surface was covered with Thiersch grafts from the left thigh. Protective 
 tissue ; firm pressure ; splint. 
 
 Jan. 28, 1909. First dressing. Little maceration; five-sixths of the 
 grafts have taken, but here and there in the edges, and in one or two 
 places in the center, there have been small hemorrhages with resulting 
 necrosis. 
 
 Jan. 30, 1909. Grafts exposed to air and apparently doing well. 
 
 Feb. 24, 1909. Almost all of the grafts took, but here and there, one' 
 or two small areas subsequently broke down and showed a tendency to 
 spread. It would seem to me as if excision had been inadequate and 
 further operation was advisable. This proves to me quite clearly, in con- 
 nection with the S. case, that it is hard to gauge how much devitalized 
 tissue should be removed ; although my excisions have appeared at the 
 time free enough, I think in general they may have been inadequate. 
 
 March 25, 1909. As there had been a previous history of specific dis- 
 ease in this case. I decided to try the effects of internal treatment before 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 365 
 
 resorting to further grafting. After ten days of mixed treatment and the 
 local application of black wash, the broken-down areas were entirely 
 healed over. It would thus seem as if the original ulcerations, for which 
 the X-rays had been applied, were undoubtedly specific, and that in spite 
 of grafting the disease progressed from a lower level. 
 
 April I, 1909. Patient is entirely free from pain. Grafts are beginning 
 to be mobile ; the leg is soundly healed. 
 
 For pathological report see Dr. Wolbach's paper under Case II. 
 
 Case IV. — Personal. Dr. Wolbach, Case III. F. H. S. ; 40 years; 
 referred to me by Dr. C. J. White Nov. 16, 1908. Treatment with 
 X-rays five years ago, for eczema of both legs, with marked improvement. 
 After subsequent, rather frequent treatments, extending over a period of 
 a year, there developed a rather severe dermatitis which healed slowly 
 with complete desquamation of the superficial layers of the skin from the 
 middle of the thighs downward. Four years ago there appeared on the 
 inner side of the left calf a small ulcer, which from that time has never 
 completely healed. On the right shin there was also an ulcer which took 
 months to heal. Both popliteal spaces showed characteristic telangiec- 
 tases. There has been no pain. In August, 1908, the ulceration of the 
 left leg began to spread rapidly and refused to yield to any treatment ; 
 radium was twice applied. Examination on Nov. 16, 1908, shows about 
 the middle of the left leg an ulceration, 3 x 2| inches. The edges are 
 irregular, slightly indurated ; in some parts there are islands of growing 
 epidermis, and in others fairly healthy areas of granulation — in still 
 others, there is an unhealthy surface covered with adherent fibrin. The 
 skin is undermined and shows no evidence of repair. Operation was 
 advised and accepted. 
 
 Operation under ether, Nov. 19, 1908. Leg was disinfected with 
 extreme care and the whole ulcer excised with a margin of half an inch 
 down to the subcutaneous fat and under the old ulceration to the sheath 
 of the gastrocnemius muscle itself. After bleeding had ceased the 
 wound was again disinfected and moderately thick skin grafts were taken 
 from the left thigh. These were stitched to the edges and wound covered 
 with protective and a firm bandage. On the evening following operation 
 the temperature rose to loi, but he had no pain. At noon on the follow- 
 ing day the wound was dressed, the temperature being at that time 100. 
 It was found that infection had taken place, and that the periphery of 
 the grafts had sloughed with some hemorrhagic infiltration into the 
 central portion. In spite of exposure to air, alternating with antiseptic 
 fomentations, all of the grafts separated, except for an irregular area 
 about three-fourths of an inch in diameter, in the very center of the 
 wound. At the end of two weeks the wound became healthy, and granu- 
 lation was well established. Small Thiersch grafts from another patient 
 were placed on the surface, but in two days all of these except two had 
 likewise sloughed ; in the meantime there had been an unusual amount of 
 suppuration of the thigh from which the grafts had originally been removed. 
 
366 PORTER. 
 
 The lower edge of the wound, where the skin was twice the normal thick- 
 ness, showed no evidence of healing. While infection probably played 
 the chief role in this failure, it seemed to me not unlikely that the tissues 
 both of the thigh and of the leg were less resistant owing to the previous 
 X-ray injuries. On several occasions, small strips of skin were placed 
 upon the wound and covered with cr^pe lisse. These grafts with the 
 rapid growth of the original Thiersch graft in the middle allowed the 
 patient to return to his home on Dec. 22, 1908, with the wound four-fifths 
 healed. 
 
 Pathological report by Dr. S. B. Wolbach. A large piece of Zenker 
 hardened tissue consisting of an ulcer with surrounding skin. Microscopic 
 examination : Zenker fixation ; paraffine sections ; phosphotungstic acid- 
 hematein stain. 
 
 The tissue is very similar to that from the case of Miss H. The ulcer- 
 ated surface shows typical granulation tissue springing from a base of 
 rarefied corium. On the surface are small islands of epithelium which 
 present no striking or unusual characteristics. The most striking changes 
 found in the sections are in the corium just beneath the epidermis sur- 
 rounding the ulcer and in the vessels throughout the sections. The con- 
 nective tissue cells of the corium just beneath the epidermis are widely 
 separated and of embryonic type in appearance ; they are surrounded by 
 very few delicate collagenous fibrils. In this rarefied corium are many 
 large blood vessels lined with a single layer of endothelium. A few of 
 these vessels lie in direct contact with the basal layer of the epidermis, 
 some are completely surrounded by epidermis and a few are filled with 
 fibrin thrombi. 
 
 In the deep layers of the corium there is marked thickening of the walls 
 of both arteries and veins. The thickening is due chiefly to an increase 
 in the connective tissue of the intima. The endothelium of some vessels 
 is swollen. There is also an increase of connective tissue in the muscular 
 coats. There are numerous completely obliterated arteries. 
 
 The coil glands are nearly completely absent. A few atrophic tubules 
 are found in areas of new formed connective tissue. No hair follicles or 
 sebaceous glands are to be found. The epidermis surrounding the ulcer 
 is slightly thickened. The horny layer is strikingly narrow and in places 
 absent. There are many irregular downgrowths of epidermis into the 
 rarefied corium, but these processes all present an orderly layer of colum- 
 nal basal cells. At the edge of the ulcer are downgrowths of atypical 
 epithelium, not however more striking than in the case of any chronic 
 ulcer. 
 
 There is nowhere any suggestion of malignancy or actual invasion of 
 the corium. 
 
 Subsequent history: Feb. i, 1909. Upon returning to his home, the 
 wound was completely healed in three or four days, but on January 2 the 
 grafts which had been taken from another patient .slowly broke down 
 with the formation of blisters, and upon his arrival in Boston had entirely 
 disappeared. The under surface, however, was healthy, and in two days 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 367 
 
 snips were applied from liis arm and covered witti crepe lisse. Tliese 
 grafts rapidly coalesced by January 20, and he was discharged home 
 entirely healed and has so remained until the present time. 
 
 Case V. — Personal. W. H. M. (physician), Lawrence, Mass.; 43 
 years. Patient's hands have been treated by the X-rays for seven years, for 
 eczema; exposures ten to fifteen minutes — both coil and static machines. 
 Extensive, rather superficial burns of both hands in January, 1906; the 
 skin sloughed off but was replaced. Later exposures in May, 1906, followed 
 by slight dermatitis. Last exposure, Dec. 10, 1906, static machine, five 
 inches, twelve minutes, followed by swelling of hands, and in four days, 
 with small cracks at knuckle of index finger of right hand. Black spots on 
 all sides of the fissure. Continual, though gradually increasing ulceration 
 with no tendency to heal. Pain has been excessive, cutting down his 
 sleep to an average of two hours a night ; unrelieved by anything except 
 morphia. 
 
 Examination of right hand shows characteristic X-ray lesions, few kera- 
 toses and many telangiectases. Over the knuckle of index finger is an 
 ulceration with slightly indurated edges, about 3x4 centimeters. On the 
 dorsum of the first phalanx, same finger, is another ulceration about the 
 size of the little finger nail. There are several extremely tender points in 
 both ulcerations. Owing to immobilization of the hand, there is some 
 edema and little flexion of the first and second fingers. (See Plate 
 XXXV., Fig. I.) 
 
 Patient was operated upon by me at the Massachusetts General Hospi- 
 tal May 2, 1907. With a wide margin, both ulcers were thoroughly 
 excised, removing all of the skin down to the tendons, and the dorsal 
 aponeurosis, and the skin grafted in the usual manner. Treated with pro- 
 tective for thirty-six hours, and then exposed to air under a cage. The 
 grafts healed soundly, except for one or two small areas at the edge. 
 Patient was discharged from the hospital in ten days. Pain entirely 
 ceased from the time of operation. 
 
 Pathological examination showed no definite carcinoma, but in certain 
 spots the epithelium was clearly in a precancerous stage. The papillary 
 layers were depressed below the surface, mitosis was well marked, and 
 there was slight round cell infiltration. 
 
 In August, 1907, for the first time, the slight ulceration at the edge of 
 the graft, near the base of the middle finger, was completely healed. 
 There has been no pain, and flexion in the fingers is rapidly returning. 
 By Jan. i, 1908, there was final and permanent healing; flexion normal; 
 no pain. 
 
 March 11, 1908. Fingers could be flexed normally, the graft was mov- 
 able on the underlying tissues, and appeared to be the most normal skin' 
 on the back of the hand. He still suffers from eczema of other parts of 
 the skin. 
 
 Summary : Treatment with X-rays for seven years for eczema of right 
 hand. Extremely painful ulceration at base of first and middle fingers. 
 
368 PORTER. 
 
 Average sleep for past six months, without morphia, only two hours. 
 Deep excision ; grafting. Complete freedom from pain. Sore at edge of 
 graft unhealed for several months. Present condition : complete healing ; 
 normal motion. Precancerous condition, but no definite epithelioma. 
 
 Case VI. — B. S. B.; X-ray manufacturer; personal communication 
 from Dr. M. M. Johnson, of Hartford, Conn. Patient had severe X-ray 
 burn of back of left hand, and over the middle of the sternum. The skin 
 of the back of the hand was thickened, and cut like leather. There were 
 many small nodules and one large open sore, the result of sloughing. A 
 circular incision was made around the open sore, and the metacarpal bone 
 and the tissues were curetted and thoroughly cleaned. A Wolf graft was 
 taken from the arm and stitched in position. At one time there was indi- 
 cation of sloughing at the border of the transplanted tissue, but eventually 
 the result was perfect. The small nodules were excised and but few have 
 returned. The ulcer over the sternum was excised and closed by granula- 
 tion. Microscopic examination showed chronic inflammatory tissue, with- 
 out any trace of epithelioma. 
 
 Case VII. — Personal. Dr. Wolbach, Case VI. W. W. G. (physi- 
 cian), of St. Louis; 42 years. Began using the X-ray in his practice in 
 1897; a static machine. May, 1900, had an itching dermatitis on the 
 dorsal surface of the left hand ; this healed in the course of a few weeks. 
 He next noticed, within a short time, trophic changes about the nails, 
 especially that of the index finger. There was alopecia ; the skin became 
 dry and reddened. In December, 1900, infection about index finger 
 caused excruciating pain, and in March, 190 1, the nail was removed. In 
 1903 patient was in Berlin, and at that time had numerous telangiectatic 
 areas on the dorsum of hand and fingers, as well as several keratoses. 
 Owing to persistent ulceration about the matrix of the first finger nail, the 
 finger was amputated through the middle phalanx by Professor Sonnen- 
 berg. Since then other ulcerations have developed, the most annoying at 
 the base of the middle finger. This remained open until January, 1905, 
 when it was excised by Dr. Bernays, and a Krause graft implanted ; the 
 graft healed well. Following this operation he had but little pain but was 
 frequently annoyed by superficial ulcerations about the fingers. For a 
 year or more, prior to December, 1907, he suffered from a slight ulcera- 
 tion near a keratosis at the base of the ring and little fingers. There was 
 also painful ulceration about the matrix of the little finger nail. On Dec. 
 22, 1907, Dr. Willard Bartlett operated under ether. The middle finger 
 was amputated, through the second phalanx, several ulcerations at the 
 base of ring and little fingers excised and the skin sutured. An attempt 
 was made to extirpate the matrix of the radial half of the little finger nail. 
 At the same time, Thiersch graft was implanted, after excision of a painful 
 fissure over the distal portion of the proximal phalanx of the ring finger; 
 the Thiersch graft was a success. Except for frequent slight injuries to 
 the dorsal surfaces of the fingers, which healed promptly, the hand 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 369 
 
 remained practically free from further ulceration until April, 1908, when 
 an ulcer developed beneath a keratosis near the proximal end of the 
 middle phalanx of the ring finger which, like all the other ulcerations, was 
 exceedingly painful at times. The skin about the thumb remained 
 throughout practically free from lesions, except for a horny growth over 
 the inner surface of the proximal phalanx. There had never been serious 
 trophic disturbances of the thumb nail, but the finger nails, in order of 
 severity, from index to little finger, were profoundly affected. The kera- 
 totic spots have invariably been the seat of the ulcerations, excepting that 
 on the amputated index finger which arose from retention of some of the 
 nail-producing membrane. 
 
 Patient consulted me Aug. 17, igo8. The left hand is typical in appear- 
 ance ; telangiectases are numerous ; there are several thickened papules 
 over the base of the thumb ; the ends of two fingers have been amputated ; 
 the nail of the ring finger is irregular and thickened ; the nail of the little 
 finger has in part been removed, but there has been persistent ulceration 
 on the radial side of the matrix which is extremely sensitive. There is 
 an open ulceration, without indurated margins, over the first interphalangeal 
 joint of the ring finger. There is moderate motion in this joint ; the 
 last joint is hyperextended and somewhat stiff. On the backs of the 
 other three fingers are areas of keratoses, scar tissue, and occasional 
 petechiae. At the base of the cleft, between the thumb and first finger, 
 is an ulcerated papule with somewhat indurated edges. 
 
 Operation under ether, Aug. 19, 1908. Several small papules were 
 excised ; the wound sutured with horse hair. The ulcerated area on the 
 ring finger was carefully excised with a wide margin down to the dorsal 
 aponeurosis ; the edges were bevelled as usual ; bleeding was profuse. 
 The ulcerated hemorrhagic and keratotic areas on the backs of the other 
 fingers were also excised, as were several keratoses in other parts of the 
 hand. The entire matrix of the little finger was thoroughly removed and 
 a graft applied. Moderately thick grafts were cut from the arm and 
 sutured in position after the bleeding had ceased. Hand was carefully 
 strapped to a well-padded splint, rubber tissue placed in an imbricated 
 fashion over the grafts. Firm pressure with large gauze dressing applied. 
 The operation lasted about two hours and a quarter. 
 
 At the end of thirty-six hours the protective was removed, the hand 
 greased with a mixture of benzoated lard, lanolin, and ichthyol. All the 
 grafts, except one on the forefinger, looked well. August 23, grafts 
 looked fairly well ; that on fourth finger improving in appearance. Graft on 
 terminal phalanx of little finger dead. Some sloughing of portions of 
 grafts on first and middle fingers. August 26, large part of graft on fore- 
 finger is sloughing, and part of that on the middle. Grafts on the ring 
 and little fingers and dorsum have taken well. August 29, grafted areas 
 thoroughly clean and all portions of unattached skin were removed. 
 September 12, all granulating areas are cicatrizing rapidly from the edges. 
 Discharged on Sept. 15, 1908. 
 
370 PORTER. 
 
 Letter from patient, dated Oct. 22, 1908 : 
 
 " It is just a few days more than a month since I took leave of you, and 
 since that time my hand has shown continuous improvement. The scabs 
 have fallen from index and middle fingers, and the slight cicatrization 
 about these in no way interferes with the free mobility of the joints. There 
 is a certain elasticity about the skin of these two fingers which I have 
 not hitherto felt. The grafts on the other fingers and at the base of ring 
 finger are simply perfect. Even the slight ' V ' shaped defect of graft on 
 ring finger has filled in, so that the entire surface is now uniform. There 
 has been no sign of activity in little finger matrix, and this more than two 
 months since the operation, so that I am not anticipating any further 
 trouble at this point. The dorsal surface of the hand, with the exception 
 of one little point, is entirely free from keratoses, and the places where 
 such were shaved are now smooth and pliable cicatrices : indeed, the 
 appearance of the whole hand shows a vitality which I had not dreamed to 
 be possible."" 
 
 Pathological report by Dr. S. B. Wolbach. The sections show approx- 
 imately normal epidermis and corium, except in the middle portion where 
 the epidermis is markedly thickened, the cerium infiltrated with lymphoid 
 and plasma cells and without papillae. There is a marked heaping up of 
 the horny layer of the epidermis, and in one place in the center, where the 
 section is tangential to a hair follicle, there is a downgrowth of the epi- 
 dermis into the infiltrated corium. These processes from the epidermis 
 are atypical in that the columnar regularly arranged basal layer of cells is 
 absent, and because of included collagen fibrils. The corium just beneath 
 the epidermis does not show the rarefication found in many other sections 
 of X-ray keratoses. The hair follicles and glands are practically normal. 
 
 Siimviary : Marked hypertrophy of epidermis with keratosis and begin- 
 ning invasion of corium by epithelium. 
 
 Case VIII. — Personal. Wolbach, Case IV. Plate XXXV., Figs. 2 
 and 3. Miss H., 40 years, is one of extreme interest from many points of 
 view. In brief, the previous history is as follows : seven years ago, 
 patient was operated upon by Dr. Boothby for a so-called fibroid of the 
 uterus, the operation being an abdominal hysterectomy. She was well 
 for a year, when there formed, to the right of the incision, in the abdomi- 
 nal wall, a slowly growing tumor, which was. however, characteristic of a 
 sarcoma, and pronounced inoperable by Dr. Maurice H. Richardson, by 
 whom she was sent to Dr. W. B. Coley of New York for treatment by 
 toxins. He excised a portion of the growth, and found it to be a fibro- 
 sarcoma. At first the growth diminished under toxins, but after ten 
 months it was decided that further treatment was not warrantable as the 
 growth was increasing rapidly. The patient was losing flesh, markedly 
 cachectic, very weak, and complained bitterly of pressure symptoms. I 
 am quoting from the report of this case by Dr. Clarence E. Skinner of 
 New Haven, Conn., to whom she was referred by Dr. Bevan of West 
 
SURGICAL TREATMENT OF X-RAV CARCINOMA. 37 1 
 
 Haven, for roentgenization. At this time, he states that the mass 
 covered ten inches from side to side at the level of the anterior superior 
 spines of the ilia, eight inches vertically in the median line, and 
 about five inches antero-posteriorly. Treatment was begun by him on 
 Jan. 28, 1902. and during the next four months she received forty-six 
 applications. The general condition began to improve at once, but the 
 tumor showed little change. Patient went home for a visit, and upon her 
 return it was noted that the tumor had diminished about one-fifth in 
 size. From June 17 to September 3 she received thirty-one roentgeniza- 
 tions. Her general health continued to improve, and the tumor steadilv 
 decreased in size, and at the end of this period she resumed her school 
 teaching. 
 
 In brief, then, the patient was under treatment for two years and three 
 months, receiving, however, the majority of her applications during the 
 first eight months. The last treatment was given on May 20, 1904, at 
 which time no trace of the tumor was discoverable at examination by Dr. 
 C. A. Bevan of West Haven, and in July by Dr. W. B. Coley of New 
 York. The patient remained perfectly well until August, 1907, though 
 she had noticed that the skin of the hypogastric region was irregularly 
 mottled and much thicker than normal, especially on the right side. 
 Pain, from which she had been free, began to be severe and ulceration 
 commenced. No treatment seemed of avail, the ulcerative process 
 gradually spreading, undermining the skin, which subsequently necrosed. 
 She lost weight and strength, becoming anemic, and suffered severely 
 from the pain. She was referred to me by Dr. Dennett of Winchester, 
 and I first saw her at the Baptist Hospital on March 7, 1908. Examina- 
 tion at this time showed in the hypogastric region more on the right than 
 on the left, an irregular, undermined ulcer about the size of the palm of 
 one's hand, roughly an equilateral triangle, extending to the right side of the 
 pubis, then nearly to the right iliac spine, the other angle approaching the 
 umbilicus. The base of this ulceration is sloughing in parts ; in others 
 presenting poorly vascularized granulation tissue, in which necrosis is 
 advancing rapidly. Several areas in the surrounding skin show charac- 
 teristic appearances. The irregular undermined ulceration with a firmly 
 adherent fibrinous base is surrounded by a very bright scarlet red areola, 
 which bleeds on the slightest touch. Certain points in the ulceration are 
 exquisitely painful on pressure. There is slight fever. After attempt- 
 ing to cleanse wound with antiseptics for a few days on March 16, the 
 whole ulcerated area, with a margin of about an inch, was excised down to 
 the underlying tissue. This excision left apparently normal fat. except 
 over an area two by three inches to the right of the median line, where 
 extremely firm scar tissue marked the site of the original growth. The 
 skin at the periphery, however, was very tough- and three times the normal 
 thickness. The whole wound was thoroughly disinfected with carbolic 
 acid, ninety-five per cent alcohol and salt solution, and an attempt was 
 made by tension sutures to diminish the gaping wound. It was dressed 
 with protective tissue, gauze, and swathe. The tissue was given to Dr. 
 
372 PORTER. 
 
 Wolbach of the Harv-ard Medical School for examination. His report 
 was as follows : 
 
 " The specimen consists of a large, irregularly triangular piece of skin 
 and subcutaneous tissue, its ' base' is 9 centimeters, and the sides are 10 
 and 1 1.5 centimeters respectively; it is from 2 to 2.5 centimeters in thick- 
 ness, except at the central portion where it is .5 to .7 centimeter thick. 
 The skin surface shows a large, irregularly triangular ulcer (5.2 x 7.5 x 8 
 centimeters) conforming in general to the shape of the specimen. The 
 base of the ulcer is depressed from .2 to .6 centimeter below the rough, 
 irregular, ragged, overhanging, and undermined non-indurated edges 
 which are necrotic, reddish gray in color, and bathed in bright yellow 
 purulent exudation. 
 
 " The base of the ulcer is bright red to grayish red in color ; it is rough 
 and ragged and is irregularly covered with purulent exudate. 
 
 " The lower surface of the specimen consists of bright yellow fat tissue 
 through which is a delicate tracery of grayish-white fibrous tissue. In the 
 central part of this surface of the specimen (the thinner area above 
 referred to) there is an area (3.5 x4 centimeters) of firm, dense, grayish- 
 white glistening elastic fibrous tissue. On section this fibrous ' disc ' is 
 seen to be in places in continuity with the base of the ulcer ; in other 
 places it is connected by fine and coarse fibrous strands. 
 
 " The margin of skin surrounding the ulcer is from i to 3 centimeters 
 in width : it is thicker and firmer than normal skin ; it is diffusely red- 
 dened with a deep punctate erythema, except for numerous, slightly 
 elevated, rounded, whitened areas (.3 to .6 centimeter in size) which 
 have a distinct nodular, almost ' shotty ' feel. On section, these areas 
 are .4 to .6 centimeter in thickness ; the surrounding skin is .2 to .3 centi- 
 meter thick. The bright punctate appearance in the diffuse erythema 
 of the skin surrounding the ulcer is apparently due to marked injection of 
 very small blood vessels. 
 
 "Microscopic examination: I. Disc of fibrous tissue, from deeper 
 tissue of lower portion of tissue, forming floor of ulcer. 
 
 " This tissue is dense fibrous tissue poor in cells, composed of bundles 
 which run in all directions. There are numerous small arteries and veins 
 and capillaries, all of which are surrounded by narrow zones of lymphoid 
 and plasma cell infiltration. The amount of elastic tissue is small, and 
 that present is in small masses, usually composed of clumps of thick fibers, 
 most abundant in the neighborhood of the larger vessels. 
 
 "II. Section of nodules or elevated areas of skin found at the periph- 
 ery of ulcer. 
 
 "The epidermis for the greater partis markedly thin. There are no 
 hair follicles or glands of any sort. The corium is composed of dense 
 fibrous tissue continuous with the deeper tissues so that its normal rela- 
 tions and appearances are gone. There are no papillae so that the 
 epidermis lies evenly upon dense white fibrous tissue. The corium imme- 
 diately beneath the epidermis in places stains very poorly. There is 
 marked diminution of collagen fibrils and there are many connective 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 373 
 
 tissue cells of embryonic type. There are many large spaces filled with 
 blood and lined by a single layer of endothelium, which on one side may 
 lie directly in contact with the epidermis. The corium is composed of 
 dense fibrous tissue continuous with the subcutaneous tissue so that there 
 is one compact layer between the skin and fat tissue. This fibrous tissue 
 contains areas with excessive amounts of elastic tissue resembling the 
 masses of elastic tissue found in the stroma of carcinomata. In a few 
 places there is a marked downgrowth of epithelium between dilated 
 vessels. A few areas show branching stalks of epithelium with character- 
 istic pearls or onion bodies. There is marked lymphoid and plasma cell 
 infiltration about the epithelial downgrowths. The atypical character of 
 the epithelium, the presence of pearls and many mitoses and the relation- 
 ship of epithelium to connective tissue in these downgrowths warrant the 
 diagnosis of epidermoid carcinomata. 
 
 "The ulcers: All show similar appearances. The floor is usually 
 covered with fibrin and pus, underlying which is granulation tissue. The 
 epidermis at the edges shows slight downgrowths which do not suggest 
 malignancy. The deep connective tissue contains areas of elastic tissue 
 increase like those described above. Completely and partially obliterated 
 arteries are common in the subcutaneous fibrous tissue. The obliteration 
 is caused by a proliferation of intimal connective tissue. A few nerve 
 trunks are found showing increased connective tissue and compressed 
 nerve fibers. The fat tissue below and adjacent to the ulcers show 
 absorption with organization. The newly-formed tissue contains many 
 large, occasionally multinucleated and grotesquely shaped cells, which 
 are derived from connective tissue as shown by the presence of fibroglia 
 fibrils when stained by Mallory's methods." 
 
 The operation was followed by. marked reaction, pain, temperature of 
 102, rapid pulse, exhaustion, and at the end of three or four days con- 
 tinuous sloughing of the edges of the wound, involving the skin more 
 than the fat. The wound at first was dressed with dry gauze, but this 
 was soon replaced, on account of pain, by ichthyol lanolin ointment on 
 bandage cloth. By March 15 necrosis stopped temporarily, and granu- 
 lation was beginning. The constitutional symptoms were distinctly 
 better, though fever in the afternoon still persisted. On March 20, the 
 condition was as follows : the edges of the skin, in the right groin, had 
 ceased sloughing and granulation was fairly well established. On the 
 left, however, necrosis still proceeded involving only the skin, whereas the 
 fat was granulating healthily. There are new areas of necrosis, varying 
 in size from a dime to a split pea in the thickened skin, near the margin 
 of the wound. There is not much discharge, no enlargement of the 
 glands in either groin, and the general condition of the patient is slowly 
 but steadily improving. Her chief complaint is of pain in the right loin, 
 the lightest contact over the old scar causing extreme shooting pains. 
 This cicatrix is covered with an adherent diphtheritic membrane which is 
 extremely tough. If a portion of it be peeled off, bleeding is free. Cult- 
 ures were made and sent to Dr. Wolbach, and he reported that bacilli, 
 
374 PORTER. 
 
 morphologically similar to diphtheria, were present; inoculation however 
 showed that they were inactive. 
 
 April 25 : For the past two weeks the wound has been granulating 
 healthily throughout its greater part. The central zone which comprised 
 the old scar is behaving in a most unique fashion. The area, which a 
 month ago was covered by a diphtheritic membrane, is now changed to a 
 smooth, glistening surface, which bleeds on the slightest touch. From 
 the periphery, granulation is slowly stealing in. The skin in the right 
 pubic region is healing soundly, and the epithelium is growing normally 
 over the granulations. Just above the right iliac spine is an irregular dirty 
 fibrin-covered ulcer, about the size of the end of the thumb. The deeper 
 layers of the skin are necrotic. In the central portion, above the umbil- 
 icus are a number of similar radiating ulcerations. There are some lymph- 
 angitis about the wound. The undermining at the left-hand side of the 
 wound is less marked. From her morning headaches, nervous feelings, 
 and poor pulse, it would seem as if there was continuous, slight infection 
 from the wound, though the temperature is now almost normal. During 
 the summer she lived in a tent, the wound being dressed twice daily. 
 Granulation was slow and epithelium once formed frequently broke down, 
 but over the pubic region, and in the right groin, epidermization con- 
 tinued satisfactorily but slowly and gradually the ulcerations starting in 
 the skin spread, the size of the wound was continually increasing, by their 
 confluence, in all directions. In view, however, of her marked prostra- 
 tion, after her iirst operation, it seemed better to allow the tissues to 
 slough rather than to remove them. During September her general con- 
 dition improved very markedly, and with this the central granulating 
 wound took on a more normal appearance. On September 28, I decided 
 upon another operation, at which, under ether, I removed the remaining 
 skin of the anterior abdominal wall, as far out on both sides as the ante- 
 rior superior spines and upwards to a level of four inches above the umbil- 
 icus. At this operation, I only removed the skin, leaving behind as much 
 as possible of the fat tissue. The wound was dressed with protective. 
 Reaction was well marked but was less severe than after the previous 
 operation, and the temperature became normal in ten days. 
 
 By Dec. 5, 1908, the patient had gained in general strength and color, 
 and was walking about. Healing has taken place rapidly from the edges, 
 and with the exception of some painful ulcerations in the remaining skin 
 of the left groin the whole wound is granulating for the first time, in a 
 perfectly normal manner. On this date, three long, narrow Thiersch 
 grafts were taken from the arm of a friend, cut into fourteen pieces about 
 three-quarters of an inch square, and scattered over the granulating sur- 
 face. They were held in position by broad strips of cr6pe lisse, covered 
 with protective tissue. After twenty-four hours, salt solution fomenta- 
 tions were applied frequently, and at the end of ten days twelve had 
 healed soundly in position, thus greatly diminishing the denuded area. 
 Dec. 24, 1908. All of the grafts have grown vigorously during the 
 past week. It seems as if no further grafting would be necessary, as 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 375 
 
 three-fourths of the huge granulating wound is now covered with appar- 
 ently healthy epithelium. There is in the left groin, outside the edge of 
 the wound, an irregular, unhealthy ulceration, which is extremely sore and 
 tender. This must be grafted at a later period. 
 
 Feb. 24, 1909. After three or four weeks all of the grafts taken from 
 her friend were raised by blisters and slowly disappeared. Two weeks 
 ago the left end of the wound was grafted with snips from her thigh ; of 
 nine, eight took and have grown well. In view, however, of the slow 
 progress it seemed to me best to operate this morning, February 23. 
 Accordingly, under gas and ether, the wound was thoroughly cleaned 
 with green soap and water, and the granulations vigorously scrubbed with 
 salt solution, followed by a copious saline irrigation. Moderately thin 
 Thiersch grafts were removed from the right thigh, and the whole wound 
 covered. One could not but be surprised by the copious serous discharge 
 from the whole granulating surface. I have never seen anything like it. 
 Whether this was due to some peculiar condition, or possibly to the irrita- 
 tion of the green soap, I do not know. The grafts were covered with 
 protective, gauze was then placed carefully over the uneven surfaces, and 
 held in place by adhesive plaster. The thigh was covered with protective 
 and bandage. A snug swathe was then evenly fitted over the whole 
 abdomen, making all possible pressure. 
 
 April I, 1909. With a few exceptions, all of the Thiersch grafts took, 
 and, with their continued growth, at present the huge wound is continuously 
 covered with sound, thick, and somewhat movable skin, except for an 
 area on the right hand upper margin, 2x3 centimeters. There is no 
 tenderness in the scar, and no pain. Patient has been up and about for 
 three weeks, having been in the hospital thirteen months. Owing to con- 
 tinued flexion of the thighs there is some subluxation of both knee 
 joints, and she walks clumsily and somewhat in a stooping manner, owing 
 to the contraction of the anterior muscles of the body. There is no 
 evidence of recurrence of the sarcoma. Her general condition is excellent. 
 
 Summary : This patient, after unsuccessful treatment of ten months 
 with Coley's serum for a fibrosarcoma of the abdominal wall, was entirely 
 cured of this condition by one hundred and thirty-six X-ray treatments, 
 covering a period of two years and three months. She was well for four 
 years, except for some thickening of the skin and telangiectases, when 
 severer and characteristic X-ray lesions developed, not only in the scar 
 of the shrunken tumor, but in the skin over the whole anterior abdomen. 
 In addition to the ulcerations of the skin, which not only refused to heal 
 under all treatment, but steadily increased in depth and area, there were 
 numerous papules of undoubted epidermoid cancer. At the first opera- 
 tion the ulcerated areas of the lower abdomen were thoroughly excised 
 with wide margins, down to the scar of the tumor and the anterior aponeu- 
 roses. The operation was followed by marked infection, which was 
 questionably diphtheritic. The wound was extremely sluggish and granu- 
 lations very slowly formed, covered by unhealthy fibrin. General con- 
 dition poor. After months of convalescence, granulation gradually 
 
376 PORTER. 
 
 established, and epidermization slowly took place from the pubic and 
 inguinal regions, but the thickened skin ulcerated upward and laterally, 
 with great pain and some fever. Six months after the first operation I 
 decided under ether to remove the remaining thickened skin of the 
 anterior abdominal wall for a distance of four inches above the umbilicus, 
 and laterally to a level with the anterior superior spines. The skin and 
 upper half of the subcutaneous fat alone was removed. The wound was 
 dressed with protective. After two months, the wound at that time granu- 
 lating healthily, a number of Thiersch grafts were removed from the arm 
 of a friend and applied over the large surface. In three weeks, healing 
 was almost complete, but in two more the apparently healthy grafts began 
 to blister and come away. In three weeks more, patient was etherized 
 and grafts from her own thigh placed in position. These at the present 
 time, thirteen months after the first operation, have grown soundly and 
 the whole wound is healed. This case should serve as a warning not to 
 use Thiersch grafts from other people, unless the condition of the patient 
 contraindicates ether. 
 
 Case IX. — M. K. K. (physician); 40 years; X-ray operator, Phila- 
 delphia. Began work in 1899. In 1901, hands showed usual early 
 lesions ; telangiectases, ribbing of the nails and thickened fissured skin. 
 In 1903 the superficial ulcerations and keratoses shown in the photo- 
 graphs, involving the lower parts of the hands and fingers. By January, 
 
 1908, there was general improvement of the dorsum of the hands and 
 fingers of the right hand, but an extensive and suspicious keratosis at the 
 base of the fourth finger. For two years there has been ulceration of 
 the two terminal phalanges of the middle finger of the left hand, and for 
 eighteen months a similar condition over the first phalanx and distal 
 joint of the fourth finger. By December, 1908, the large keratosis on the 
 right hand, under treatment, has almost disappeared, but the ulcerations 
 on the end of the middle finger of the left hand were typically malignant. 
 The ulcerations and a keratosis on the ring finger became infected, and 
 an exuberant growth appeared increasing rapidly in size. On April 4, 
 
 1909, the middle finger was amputated at the end of the first phalanx, 
 and the ring finger at the knuckle. There were no glands in the axilla. 
 (Pathological diagnosis: epidermoid carcinoma; Plate XXXV., Figs. 
 4, 5, 6.) 
 
 Case X. — M. N. ; 35 years; Swede. Personal communication from 
 Dr. A. D. Bevan of Chicago. In April, 1902, had abscess of obscure 
 nature in left lower quadrant of abdomen. This was opened and found 
 to be fecal and drained. A fecal fistua resulted, which was closed at 
 operation August, 1902. He returned again October, 1902, with symp- 
 toms of intestinal obstruction and an exploratory laparotomy was per- 
 formed and a tumor-like mass found in the descending colon. The 
 operation was purely exploratory. December, 1902, he again had symp- 
 toms of obstruction ; another operation was performed ; some adhesions 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 377 
 
 between the small intestine and descending colon separated, and a 
 Meckel's diverticulum was found and removed. This apparently had 
 nothing to do with his illness. The tumor-like mass in the colon was of 
 uncertain diagnosis ; we regarded it as either carcinoma, syphilis, or 
 tuberculosis. He was given antispecific treatment and was given a large 
 number of X-ray exposures over the mass. This resulted in rather an 
 extensive X-ray burn, which healed slowly. The swelling in the abdomen 
 disappeared and the man made an apparently complete recovery. 
 
 October, 1908, he returned to the hospital with several irregular ulcers 
 in the scar of the X-ray burn. It was thought that they were suspicious 
 of carcinoma and a large area about 6x6 inches containing the scar of 
 the old X-ray burn and these ulcers were dissected off, and the surface 
 covered with skin grafts. The microscopical sections from the margin of 
 the ulcers show a suspicion of beginning carcinoma. There is prolifera- 
 tion of the epithelial cells with processes extending a moderate depth in 
 the subcutaneous tissue, in several portions of the section, but only at 
 these points is the basement membrane broken. There is some round 
 cell infiltration ; nowhere is there a separate island of epithelial cells or 
 epithelial pearls. From the microscopical section I am inclined to regard 
 it as a beginning epithelioma. 
 
 Summa?y : Large number of X-ray exposures for abdominal tumor ; 
 extensive burn which healed slowly. Latent period at least five years, 
 when several irregular ulcers developed in the scar. A large area 6x6 
 inches dissected off with successful skin grafting. Pathological report : 
 beginning epithelioma. 
 
 Case XI. — Personal, E. W. C. ; aged 37 years ; admitted to the 
 Massachusetts General Hospital Sept. 3, 1907, with the following history : 
 Shortly after beginning work with the X-rays, ten years ago, patient 
 noticed desquamation and ulcerative areas appearing on the dorsum and 
 knuckles of left hand. He also developed telangiectases of left thigh and 
 lower abdomen. Although he has long since ceased to expose himself, 
 the parts have continued to ulcerate, until some of them have taken on a 
 more deep-seated epitheliomatous character. He has tried all sorts of 
 washes and ointments, exposure to sunlight, arc light, with and without 
 screens, and the so-called luecodescent light. In his case, all of these 
 agents were harmful ; the relief reported by some, he explained, as due 
 entirely to the heating effect, for the pain, which prevented sleep, would 
 often yield to treatment for fifteen or twenty minutes, with an electric 
 heating pad. 
 
 Examination of left hand shows the usual telangiectases, atrophy of the 
 skin, with numerous keratoses and papules, and several ulcerated areas ; 
 two in particular appearing most suspicious — one at the base of the first 
 finger, and another in the cleft between it and the thumb. There were 
 superficial ulcerations with keratoses over the interphalangeal knuckles of 
 the first two fingers, and another rather extensive keratosis at the base of 
 the ring finger. 
 
378 PORTER. 
 
 Under ether, Sept. 4, 1907, all of these areas were excised, the suspi- 
 cious ones down to the subcutaneous tissues ; the others well into the 
 corium. Skin grafts of moderate thickness were applied to the wound, 
 after bleeding had ceased. Protective tissue, just outside the periphery of 
 the grafts, with firm pressure applied by a gauze roller, the hand having 
 previously been immobilized upon a well-padded splint. On the 5th, 
 rubber tissue removed, and grafts exposed to air, covered with ointment. 
 On the 7th, grafts looked finely. On the 8th, grafts were all looking well, 
 except one over the fourth metacarpo-phalangeal joint, which is a little 
 white in the center, where a small necrotic area has developed. On the 
 9th, all grafts had taken, except the one previously mentioned over the 
 knuckle of the ring finger. Discharged on September 12, eight days after 
 operation. 
 
 Pathological examination showed that ulceration at the base of the fore- 
 finger was undoubtedly epithelioma. In two other places, a precancerous 
 condition was present ; the tissues from other parts showed superficial 
 ulcerations or keratoses. 
 
 Quotation from letter dated Sept. 15, 1908 : "For your records, I have 
 to report that all the grafts grew successfully, and most of them have con- 
 tracted much more than I expected. They are all in splendid condition, 
 except that there is a tendency to the formation of keratoses at some of the 
 margins. It seems to me that this condition, so common in all X-ray 
 hands, nearly always starts from a small abrasion, and that the trauma at 
 the margin of the incision for the skin graft is just the sort of injury 
 which has produced this kind of growth. I have been able to improve the 
 condition very much by having these spots treated with liquid air, after 
 which there is no tendency toward recurrence. There are no signs of 
 metastatic involvement of the epitrochlear or axillary glands." 
 
 SiDiimary ; Characteristic X-ray hands. For several years, intermittent 
 healing and ulceration ; finally persistent ulceration in spite of treatment 
 by various forms of light, in addition to the usual treatment. Eight 
 excisions ; all grafts successful. One undoubted carcinoma ; two pre- 
 cancerous lesions. All keratoses which formed at margins of graft suc- 
 cessfully treated with liquid air. No return of ulcerations or of disease. 
 Satisfactory result. 
 
 Case XII. — S. L. (physician), New York. Personal communication 
 in regard to his own case. " Frequent excisions of epitheliomatous areas, 
 which broke down from time to time, has reduced them to a definite 
 number; five on my left hand of very small size. Of course I have abso- 
 lutely given up the use of the X-ray, and have even had my machine 
 removed from the office. I still find that the left hand resists chemicals 
 very badly. Too strong or too frequent use of bichlorid will give me an 
 eczematous condition, which immediately lights up the spots from which 
 the epitheliomata have been removed." 
 
 Case XIII. — C. L. L. (physician). Several years ago developed an 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 379 
 
 epithelioma of his forefinger, and fearing excision or even amputation, lest 
 metastases result, applied the X-ray very vigorously, with the intention of 
 destroying all malignant cells before operation. He produced a slough 
 which extended to the bone, after which the finger was amputated and 
 healed by primary union. There are a few suspicious areas over the 
 fingers of the same hand ; no glandular involvement. 
 
 Case XIV. — Mr. S., New York, radiographer. Amputation of one 
 finger for epithelioma developing in an X-ray lesion. Now well. 
 
 Case XV.— Personal. Wolbach, Case V. Plate XXXVI., Figs. 7 to 
 II (inclusive). F. H. S. Patient sent to me by Dr. Percy Brown. 
 First used X-ray apparatus in the spring of 1897; static machine. 
 Received acute dermatitis on back of left hand, which after healing 
 showed characteristic pigmentation. He has had a few attacks of acute 
 processes since then, but not until three years ago did an ulcer form on 
 the back of the left hand between the knuckles of the first and second 
 fingers. This healed up several times and broke down again. Over the 
 backs of the hands in various places keratoses have formed which became 
 black and then spontaneously fell off. Sometimes has scraped them off 
 with pumice stone. Except for the inconvenience of dressing the ulcera- 
 tion he has had practically no pain in his hand since the original derma- 
 titis. For many years he has noticed that the skin on the front of his 
 chest has become thickened ; here and there are somewhat more indurated 
 spots; the whole chest is covered with the characteristic venules. For a 
 number of months he has noticed that the pores of the tip of his nose have 
 filled up, occasionally discharging sebaceous matter. For two months 
 and a half he has noticed a warty growth on tip of nose about the size of a 
 pea. 
 
 Examination : On the tip of the nose is a warty growth on which a scab 
 has formed of the size before mentioned. This discharges some serum, 
 no pus ; is not sore. The chest presents the characteristic appearance of 
 chronic X-ray dermatitis with telangiectases and some pigmentation. 
 There is thickening of the skin in plaques, but no ulceration. The skin 
 of the back of the left hand is thickened in some places, especially over 
 the joints where it is atrophic and cracked. As shown in the photograph, 
 there are about half a dozen keratoses, the skin about them being 
 thickened to twice normal. At the cleft between the first and second 
 fingers is a well-marked induration with a keratosis growing on the distal 
 part. Above this are three open ulcerations, the distal one having 
 slightly raised indurated edges. The proximal one is flat, non-indurated, 
 appearing like smooth granulation tissue. Diagnosis of the distal ulcera- 
 tion probably beginning epithelioma ; of the proximal one, simple ulcer. 
 
 Operation under ether March 29, 1908. Ulcerated area on back of 
 hand carefully excised with broad margin down to underlying veins, fat 
 and tendon of middle finger. Edge of thickened skin bevelled. Several 
 Indurated areas and keratoses were either excised or shaved down to the 
 
380 PORTER. 
 
 deep skin. All of the raw places were skin grafted from the left arm. 
 The growth on the tip of the nose was shaved off deeply. All of the 
 wounds were covered with protective and the hand firmly bandaged on a 
 splint and elevated. No dressing applied to nose. 
 
 For purposes of microscopic examination, an indurated superficial 
 ulcerated papule in the cardiac area of the chest was removed by an 
 elliptical incision, and the skin approximated with silkworm gut sutures. 
 
 Convalescence : the usual protective dressing remained in position for 
 twenty-four hours, then ointment and cage. Patient discharged in a 
 week. 
 
 Pathological examination by Dr. Wolbach. 
 
 1. Keratosis from nose. (Plate XXXVI., Fig. ii.) 
 
 The epidermis is greatly thickened and irregular and the horny layer is 
 heaped up, forming a thick layer of keratinized cells. The cells of the 
 stratum germinativum are large, vesicular, and present mitoses. In some 
 by high power fields as many as ten mitoses are found. The processes 
 extending into the corium for the most part present an orderly arranged 
 basal layer except in a few places where the epidermis is infiltrated with 
 lymphoid and plasma cells. The corium immediately beneath the 
 epidermis is thinned in places. Some of the smaller vessels are filled 
 with polynuclear leucocytes. There is everywhere extensive infiltration 
 with lymphoid and plasma cells beneath the epidermis. The epidermis 
 on either side of the keratosis is practically normal. 
 
 The most striking feature of this tissue is the extraordinary number of 
 mitotic cells in the epithelial processes and the change in the character of 
 the cells from the compact, basic-staining appearance of the normal 
 epidermal cells to the large vesicular neutral-staining cells found in the 
 processes beneath the keratosis. 
 
 2. Large ulcer from hand. (Plate XXXVI., Fig. 8.) 
 
 The ulcerated surface is practically the exposed surface of a vascular 
 new growth of epithelium, atypical in type and containing many whorls of 
 keratinized cells. This tissue is microscopically a typical epidermoid 
 carcinoma and there is definite evidence of invasion of the corium. The 
 epidermis on each side of the central mass is irregularly thickened in 
 places and thinned in others. The corium immediately beneath the 
 epidermis is rarefied. A few arteries show thickened walls. No sweat 
 glands or hair follicles found in the sections. 
 
 3. Keratosis of hand between index and middle fingers. 
 
 The same general picture is found here as in the tissue removed from 
 the nose. The rarefication of the corium beneath the surrounding 
 approximately normal epidermis is more striking than in the case of the 
 nose. There is less infiltration beneath the keratosis, and the epithelium 
 shows comparatively few mitoses. No positive evidence of malignancy. 
 
 4. Tissue from the chest. (Plate XXXVI., Fig. 10.) 
 
 Consists of a semicircular piece of tissue the convex border of which is 
 covered by epidermis. The central portion of the tissue is very similar to 
 that from the ulcer of the hand in that we have a new growth of epidermis 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 38 1 
 
 supplied with many blood vessels and having no definite epidermal cover- 
 ing. The projecting stalks of the central mass contain many whorls of 
 keratinized cells, and the relationship to the connective tissue of the 
 corium leaves no doubt that the tissue is that of a new growth, epider- 
 moid carcinoma in type. The corium beneath the surrounding epidermis 
 shows the same rarefication noted in other cases. 
 
 General Note : A description of the new growths from the hand and 
 from the chest hardly seems necessary. In both locations the picture is 
 that of typical epidermoid carcinoma. Mitoses are numerous and the 
 masses of epithelium enclose remnants of elastic fibers and collagenous 
 connective tissue. In the corium, immediately beneath the new growth, . 
 there is more increase in elastic tissue, otherwise the changes in the deeper 
 tissue are similar to those noted in the cases of H. and S. 
 
 April 22, 1908. Patient visited me the day before yesterday. All of 
 the skin grafts have healed and now show the usual increase in vascularity 
 and are raised above the surrounding skin. The large graft on the back 
 of the hand shows a slightly hypertrophic condition, but is beginning to be 
 movable on the underlying tissues. Several areas of keratoses are slowly 
 reforming. 
 
 May 30, 1908. The pathological report that the papule excised from 
 the chest was carcinoma came as a complete surprise. This fact was 
 explained to the patient, and on May 29, under cocaine, the scar of the 
 former operation was excised with a wide margin down to the subcu- 
 taneous fat; wound closed with sutures. 
 
 December, 1908. Present condition: the nose is slightly flattened at 
 the tip and shows a slight scar. Grafted area upon the hand shows no 
 evidence of recurrence of the carcinoma, and is quite freely movable upon 
 the underlying structures. There are several cracks and fissures, as well 
 as keratoses on the various parts of the hand, but nothing suggesting epi- 
 thelioma. There is no return of the cancer at the site of the excision over 
 the breast. 
 
 Su7n)nary : Early acute dermatitis in 1897; innumerable exposures of 
 chest for fluoroscopic examination of heart. Characteristic lesions of 
 chest and left hand ; ulceration of hand persisted for three years ; no pain. 
 Operation : excision of keratosis on tip of nose, of ulceration of hand and 
 keratoses ; successful skin graft. Excision of papule on chest for examina- 
 tion, which proved to be undoubted epithelioma. Prognosis doubtful, as 
 the remains of the indurated tissues of chest may develop carcinoma. 
 Very satisfactory graft. 
 
 Case XVI. — G. W. D. ; 32 years ; radiographer and salesman. Patient 
 of Dr. F. E. Pinkham, Providence, R.I. Patient began work in 1896. 
 Had amputation of ring finger of left hand at the Worcester City Hospital 
 in 1905, on account of ulceration and exuberant growth which had been 
 microscopically examined and pronounced to be an epithelioma. He 
 entered the Massachusetts General Hospital April 7, 1908, having noticed, 
 six weeks ago, a hard lump in the axilla which, though slightly tender, 
 
382 PORTER. 
 
 was not painful. In the past three weeks there had been rapid growth of 
 this tumor. No loss of weight. 
 
 Examination of left hand : ring finger amputated at the metacarpo 
 phalangeal joint. On the dorsum of back of hand are several small kera- 
 totic areas which have been present since 1899. Skin of dorsum of hand 
 is hard and indurated. No enlargement of left epitrochlear gland. In 
 the left axilla is a tumor about the size of a hen's egg, which is slightly 
 elastic and tender, and more or less fixed to the surrounding tissues. No 
 palpable glands above clavicle. 
 
 Operation, April 7, 1908. Incision made through center of axilla over 
 the mass, parallel to the lower border of the pectoralis major muscle. 
 Skin dissected back ; axillary fascia opened ; gland found to be very hard, 
 possibly slightly fluctuating in the center. Incision made into it, speci- 
 men given to Drs. Kidner and Wright for examination. Frozen section 
 showed undoubted epithelioma. The center of the gland was softened 
 and about a teaspoonful of pus or epithelial debris escaped. An incision 
 was then made upward from the other, at right angles to the collar bone. 
 The pectoralis major muscle was divided and retracted, and the pectoralis 
 minor divided at its insertion into the coracoid process. By blunt dis- 
 section the fascia covering all of the muscles forming the axillary triangle 
 was removed with the inner portion of the pectoralis major, minor, and 
 axillary third of the latissimus dorsi, and some of the subscapularis ; bleed- 
 ing was quite profuse. The long thoracic nerve was preserved, but some 
 of the branches of the subscapular and the latissimus dorsi were cut. A 
 part of the axillary vein in contact with the gland was resected for a dis- 
 tance of two inches, but the collateral branches of the brachial veins, 
 entering above, carried on the circulation adequately. With the arm 
 flexed and brought forward, the nerves, axillary artery and vein were 
 held forward with retractors and with great care, the whole mass of gland- 
 bearing fat was removed well above the clavicle. It was obvious that in 
 order to get good motion in the arm, a plastic would be necessary. The 
 sternal portion of the pectoralis major muscle was therefore freed from its 
 attachment, and brought downward over the axillary vessels and sutured 
 to the insertion of the muscle. A "U" shaped flap of skin was left 
 attached to it, and utilized to close in the axillary opening. 
 
 Convalescence : Some infection occurred from the pus in the broken- 
 down gland, accompanied by fever for several days. Several stitches 
 were removed and a portion of the pectoral muscle sloughed, but patient 
 was discharged with a granulating wound May 4, twenty-five days after 
 operation. 
 
 Letter dated Dec. 7, 1908 : " I thank you very much for your enquiry, 
 and am greatly pleased to report that I am enjoying excellent health. 
 After leaving the hospital, the wound granulated very nicely and closed 
 up beautifully within three weeks. I have now a fairly good use of the 
 arm." 
 
 Summary: X-ray work begun in 1896; ring finger aniputated in 1905 
 for an epithelioma of over a year's duration. Patient well until February 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 383 
 
 1908 (three years) when malignant disease appeared in the axillary glands ; 
 epitrochlear not involved. Very radical dissection of axilla ; some infec- 
 tion of wound. Sound healing in six weeks; good use of arm. At 
 present well. 
 
 Pathological report by Dr. Wolbach. " Microscopic description : 
 methylene blue and eosin ; Mallory's connective tissue stain, phospho- 
 tungstic-hematein stain. Paraffine sections. Tissue consists of large 
 lymph node infiltrated with new growth consisting of anastomosing 
 stalks of epithelial cells containing many whorls of cornified cells. The 
 whole is supported by a fairly dense connective tissue reticulum. The 
 picture is that of typical rapidly-growing epidermoid carcinoma. Mitoses 
 are extremely numerous." 
 
 Case XVII. — Personal. (Plate XXXVIII., Figs. 22 and 23 ) H. G. ; 
 48 years. Consulted me first in January, 1908. He had been working 
 since the very beginning in the manufacture of X-ray tubes. The first 
 indication of any trouble appeared in the shape of a red, itching rash, of 
 which he took very little notice, supposing it to be caused by acid fumes. 
 This condition was succeeded, the latter part of 1898, by the appearance 
 of a number of callosities on the back of the hand, which about the 
 spring of 1899 had changed into warty growths, which he tried to remove 
 by pulling them off". The removal was attended by severe pain, and free 
 bleeding, and seemed to cause them to increase in size and multiply. 
 These warts and other scaly areas were removed frequently by means of a 
 live cautery, only to reappear in increased size. His physician used 
 almost every known salve but the only result was to allay the pain some- 
 what. " No pen can describe the sensitiveness or the pain of these burns." 
 " One peculiarity of my case is that from the frequent examination of my 
 body with the fluoroscope by hundreds of doctors, the skin of my chest 
 became black and hard, like parchment, giving me, however, no incon- 
 venience and never becoming sore ; in less than a year, this blackened 
 skin all came off" in one piece, leaving the chest clean, without a scar, but 
 of course removing all hair." For seven years, then, there has been 
 ulceration, induration, and keratosis over an area about 3 x it inches on 
 the back of the left hand. This had been treated in various ways, and 
 during the past six months has shown signs of improvement, under a 
 dressing of vaseline, turpentine, and creosote. The backs of both hands 
 show many keratoses, but the usual telangiectases are remarkable for their 
 absence. On the back of both wrists is an area about the size of a pea, 
 which is hard, not sore, ulcerated in the center, with indurated edges, 
 presenting the characteristic appearance of an epithelioma. A similar 
 growth started three months ago on the left forehead. This soon 
 acquired raised and everted edges and was operated upon by a surgeon 
 in Hartford, but in a month had recurred, and was larger than before. 
 It was again excised, but rapidly returned. On examination of the fore- 
 head there appeared a growth about the size of a quarter, gangrenous in 
 the center, with palisaded edges. There was induration about it, and the 
 
384 PORTER. 
 
 growth was firmly fixed at the center to the underlying tissues. No 
 glands could be made out in the parotid region or at the angles of the jaw. 
 
 Operation Jan. 17, 1908; ether. After thorough disinfection with 
 pure carbolic acid, the growth on the forehead was excised with an ample 
 margin, removing a circle of tissue about two inches in diameter. The 
 incision was carried down to the periosteum, which was removed with the 
 growth. Section of the tumor showed that it involved the periosteum. 
 On this account, the outer table was chiselled away for an area the size of 
 a half dollar, and the inner table was also removed, over an area the size 
 of a quarter, exposing the dura and the mucous membrane lining the 
 frontal sinus. A complicated plastic operation was done, and the wound 
 closed without drainage. The two epitheliomata over the wrists were 
 excised and the skin sutured. Next, with considerable margin, the 
 ulcerated and thickened skin over the back of the hand was removed down 
 to the veins, subcutaneous tissue, and tendons. A rather thick Thiersch 
 graft was applied and sutured in position with firm pressure. The graft 
 grew by primary union, except for a small area at the base of the little 
 finger, which healed within a few weeks. Patient discharged at the end 
 of ten days. 
 
 The two discrete epitheliomata from the wrist were lost. The micro- 
 scopical examination from the skin of the back of the hand by Dr. J. H. 
 Wright was as follows : The surface of the portion of skin removed 
 is covered with crusts, scabs, and discrete and confluent wart-like eleva- 
 tions. After fixation in Zenker's fluid, paraffine sections were prepared 
 from six different places. The lesions found in these may be summarized 
 as follows : " The stratum corneum is very much thicker than normal, and 
 shows cyst-like cavities of varying size containing hyaline material. The 
 stratum germinativum in places is either thicker or thinner than normal, 
 and the interpapillary processes are irregularly variable in size and shape or 
 are wanting. In a few places the cells of this stratum show atrophy with 
 exaggeration of the intercellular spaces and there is infiltration with leu- 
 cocytes. The cells of this stratum also show some imperfect cornification. 
 In one section two circular masses of cornified epithelium, like the 
 " pearls " of epidermoid carcinoma, are present in interpapillary processes. 
 In another section over a small area, the stratum germinativum is pro- 
 longed into small columns of atypical epithelial cells which lie in the 
 superficial portions of the corium. In the corium about the cell masses 
 is some infiltration by cells of the lymphoid series. I am inclined to 
 interpret these appearances as indicating an incipient carcinoma at this 
 point. The corium generally shows an increase of its connective tissue 
 over the normal, and this connective tissue in places is in the condition of 
 hyaline degeneration. The papillie vary considerably in size and in 
 places contain greatly dilated capillaries. Some papillns are in a condition 
 of myxomatous degeneration and some others show more or less transfor- 
 mation of the connective tissue into hyaline material. In places, small 
 areas of the corium are infiltrated with cells of the lymphoid series. 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 385 
 
 Examination of the recurrent tumor on the forehead brings out a differ- 
 ence of opinion between Dr. Wolbach and Dr. Wright. 
 
 (See Plate XXXVIII., Fig. 22.) Pathological report by Dr. Wolbach. 
 Tissue from forehead. The sections consist of tumor tissue with adjoin- 
 ing necrotic tissue. No normal tissue in sections, except for a narrow 
 strip of dense fibrous tissue on one edge of a few sections. The micro- 
 scopic picture is that of invading cells or of cells having proliferated in situ, 
 distending the meshes of connective tissue. There are bands of dense 
 collagen fibrils separated by large, irregularly shaped cells, many in stages 
 of mitosis. That the connective tissue present is not wholly the product of 
 the tumor is shown by the presence of normal nerve bundles. Between 
 the tumor cells and between small groups of cells there is in places only 
 a small amount of collagen fibrils (Mallory connective tissue stain). The 
 tumor cells are very irregular in shape and in size. Many are multinu- 
 cleated. There is no definite arrangement of cells and in places the appear- 
 ance suggests that these cells may have arisen in situ by multiplication of 
 preexisting cells. In other places, the picture is definitely that of a 
 tumor. The nuclei are large, and each contains a large nucleolus. Where 
 numerous nuclei exist in a single large cell, the nucleoli are unusually con- 
 spicuous in each nucleus. Mitoses are abundant in all portions of the 
 sections. Multipolar mitoses are common. The smaller tumor cells are 
 round, oval, and spindle-shaped. The larger very irregular in outline 
 and usually have many slender processes. A few tumor cells show deli- 
 cate fibrils (Mallory fibroglia stain) running parallel to the long diameter. 
 For this reason and because of the arrangement of the tumor and the 
 apparent presence of intercellular collagen fibrils the tumor should be 
 classed as a sarcoma of connective tissue origin. 
 
 Pathological report by Dr. J. H. Wright: "In accordance with your 
 request I confirm my verbal report to you made some time ago upon my 
 views as to the nature of the tumor of the forehead in the case of Mr. G . 
 Although the histological character of this tumor is very suggestive of 
 sarcoma, I believe that the essential cells are of epidermal origin, and 
 that the tumor should be regarded as carcinoma originating from the 
 epithelium of the skin of the forehead. I am led to this belief for the 
 following reasons : the situation of the tumor, the presence of fibrillation 
 in some of the cells reminiscent of the fibrils of the cells of the epidermis, 
 and the existence at the periphery of some of the cells of structures 
 strongly resembling the characteristic 'prickles' of the epidermal cells." 
 
 Quotation from letter, March 6, 1908: " My hand has healed in good 
 shape and most of the thickened spots on my fingers are disappearing. I 
 can about half shut my hand. My forehead is all right except for some 
 tightness of the skin and absence of normal sensation. The spot, where 
 the growth had been, is tight and does not move." 
 
 Examination, Aug. 5, 1908. Sensation has been gradually coming 
 back to forehead, which he can wrinkle almost normally. There is very 
 slight thickening on the inner side of right eyebrow where the flap was 
 reflected. The scars are hardly visible. There is no induration or pain 
 
386 PORTER. 
 
 suggesting any recurrence of the disease. The back of the left hand is 
 entirely healed ; the graft is movable over the underlying structures. The 
 backs of the fingers still show keratoses, which he is cutting and paring 
 off. He can flex and extend fingers normally. In every respect a most 
 excellent result. 
 
 Sinmnary ; Intermittent ulceration of back of left hand for seven years, 
 improving for the past six months ; excision down to aponeuroses and 
 tendons ; successful skin grafting. Microscopic examination showed com- 
 mencing epithelioma. The longest case of persistent ulceration, without 
 cancer, in the series. Thrice recurrent growth of forehead, which involved 
 the periosteum : removal of bone down to dura and frontal sinus : com- 
 plicated plastic operation. Opinions differ as to the nature of the growth ; 
 Dr. Wolbach classifying it as a sarcoma ; Dr. Wright believes it to be a 
 carcinoma. One year after operation, no evidence of recurrence. 
 
 Case XVIII. — Personal. (Plate XXXVII., Figs. 13, 14, and 15.) J. 
 G. ; 34 years ; X-ray operator. Patient has suffered for several years from 
 the milder forms of X-ray lesions, atrophy of the sweat glands, eczema, rib- 
 bing of the finger nails, telangiectases and keratoses. During the winter 
 he has a great deal of pain and trouble from fissures over the extensor 
 surfaces of the joints. In May, 1906, numerous excoriations and fissures 
 were excised and successfully grafted. On Sept. 15, 1906, there was a 
 recurrence of ulceration near the radial border of the terminal phalanx of 
 the ring finger. On October 18 this ulceration was freely excised, and 
 the radial fourth of the nail with its matrix extirpated. The skin at the 
 margin of the nail was approximated with plaster and another graft 
 applied: sound healing in ten days. 
 
 Pathological report by Prof. F. B. Mallory of the Harvard Medical 
 School: "The section shows a small mass of actively proliferating con- 
 nective tissue cells, covered with epidermis, which is edematous and 
 contains fairly numerous mitotic figures. At one or two points the 
 epidermis is lacking, and a little granulation tissue has formed. In these 
 areas, and beneath the epidermis, is a small amount of infiltration with 
 cells (chiefly lymphocytes) of inflammatory origin. The proliferating 
 connective tissue cells occur diffusely scattered among the bundles of 
 collagen fibrils of the corium. Mitotic cells are numerous and often 
 multiple. Many of the resulting cells are large and often contain large 
 lobulated or multiple nuclei. The lesion is an active, in some ways 
 atypical, proliferation of connective tissue cells.'' 
 
 The finger remained healed until the middle of March, 1907, when the 
 distal part of the graft on the radial side began to increase in size and 
 show well marked vascularity. After two weeks there was a slight dis- 
 charge near the edge of the nail. By April 23, 1907, the growth had 
 become decidedly larger and was apparently extending backward into the 
 proximal graft. The terminal joint was accordingly amputated under gas 
 and ether ; primary union. 
 Pathological report by Prof. F. B. Mallory of the Harvard Medical 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 387 
 
 School (see Plate XXXVII., Fig. 15) : " The section shows an oval, cell- 
 ular mass of tissue, partially surrounded by more or less normal fibrous 
 tissue. The cellular mass at its outer end is ulcerated and covered with 
 fibrin, cells, and dried necrotic tissue. The more normal tissue is covered 
 with epidermis. The oval cellular mass of tissue is quite sharply defined 
 and is limited by a layer of dense, fibrous tissue. It is composed of 
 rapidly-growing connective tissue cells and of a small number of thin- 
 walled blood vessels. The connective tissue cells are typical, that is, they 
 have flat, oval nuclei, and contain one to three coarse chromatin masses. 
 The cytoplasm is made out with difficulty. In places the cells are 
 bordered by very delicate fibroglia fibrils. Everywhere the cells are sepa- 
 rated from each other by a relatively large amount of ordinary (collage- 
 nous) fibrils. The cells and their fibrils tend to form small bundles which 
 run in all directions. Mitotic figures are numerous, one to three showing 
 in nearly every oil immersion field. While the cellular mass of tissue at 
 its base is sharply defined, on both sides, it gradually blends with the 
 adjoining connective tissue. The adjoining tissue of the finger shows 
 infiltration with numerous groups of lymphocytes. Otherwise there 
 appears to be no change in it. It is difficult to give a positive diagnosis 
 in this case. The rapidly-growing mass of connective tissue may be either 
 an unusual form of reparative action on the part of connective tissue or it 
 may be a connective tissue new growth, namely, a rather slow-growing 
 spindle cell sarcoma. Personally I favor the former view, owing to the 
 lack of any definite evidence as yet of invasion." 
 
 The finger remained well until August, 1908, when on the ulnar side of 
 the same there appeared an induration in the skin which was neither 
 tender nor painful, but gradually grew until it was the size of an old- 
 fashioned three-cent piece. There was no ulceration, the tumor had slight 
 vascularity and was movable to some extent upon the underlying struct- 
 ures. In view of the doubt as to the true pathology of the recurrent 
 growths on this finger, amputation at the interphalangeal joint was per- 
 formed in November, 1908 ; primary union. 
 
 Pathological report by Prof. F. B. Mallory of Harvard Medical School : 
 " This lesion, like No. 2, is quite definitely outlined. In places at the 
 periphery, however, the cells extend among the bundles of old collagen 
 fibrils of the corium. The tissue is fairly cellular and contains mitotic 
 figures, but they are not so numerous as in lesions i and 2, and are rarely 
 atypical. The cells and fibrils are separated by a small amount of fluid 
 (edema). The sections from these lesions show masses of rapidly-prolif- 
 erating connective tissue cells. In numbers i and 2, especially, the cells 
 are often atypical. The mitoses are frequently multiple and large multi- 
 nucleated cells result from them. All these lesions suggest the possibility 
 of being fibrosarcomata. It seems wisest for the present, however, to 
 regard them as more or less atypical growths of connective tissue cells 
 under conditions not fully understood. If later it should be proved that 
 X-rays cause similar connective tissue growths which give rise to metas- 
 tases or to evident invasion of other tissues (true fibrosarcomata), these 
 
388 PORTER. 
 
 lesions might be regarded as of a similar nature, but at present such an 
 assumption is not justifiable." 
 
 Pathological report by Dr. Wolbach. Amputation of middle pha- 
 langeal joint of ring finger, left hand. Beneath the skin of the distal 
 portion on the ulnar side of dorsal surface is a firm, resilient, yellowish, 
 ovoid nodule, .8 x .6 centimeter in diameter. This nodule is completely 
 covered by epidermis and is not attached to the bone or tendon. 
 
 Microscopic examination : The nodule is composed of loose cellular con- 
 nective tissue, the cells of which form bundles and whorls running in all 
 directions. The amount of collagenous intercellular substance is much 
 greater than that in the first specimen removed and examined by Dr. 
 Mallory. The collagenous fibrils are more widely separated than in 
 normal connective tissue, suggesting a slight amount of edema. The 
 cells resemble those of normal connective tissue. The nodule is fairly 
 sharply demarcated from the immediately surrounding practically normal 
 connective tissue of the corium by means of the concentric flattened 
 arrangement of the cells and fibrils of the latter. There is no definite 
 capsule. There is no evidence of invasion. There are numerous mitotic 
 figures throughout the nodule, all of them normal in type. The tissue is 
 supplied with numerous small, thin-walled vessels and capillaries, uni- 
 formly distributed. The epidermis covering the nodule consists of a 
 smooth thin layer lying directly upon the tissue described and which pre- 
 sents an unbroken convex surface. The horny layer of this covering epi- 
 dermis is thin. The stratum germinativum is poorly differentiated ; it 
 consists mainly of slightly swollen pale-staining prinkle cells of fairly 
 uniform size. The deepest layer is regularly apposed to the underlying 
 tissue in the manner of normal epidermis. Where the nodule adjoins the 
 normal tissue there is a deep downgrowth of epidermis in the form of 
 slender stalks partially embracing the new tissue. The surrounding epi- 
 dermis is slightly hypertrophic and shows slight irrelevant changes. A 
 positive diagnosis is not possible in this case, as the same discussion used 
 by Dr. Mallory in his description of the tissue removed applies here. 
 Against the view that the tissue is granulation tissue is the lack of signs of 
 active inflammation, the presence of unbroken epidermis and the absence 
 of a vascular arrangement. Favoring the view that we are dealing with a 
 slowly-growing connective tissue tumor (fibrosarcoma) is the presence of 
 numerous mitoses, and against this view is the lack of evidence of invasion. 
 
 Suminary : Mild chronic X-ray lesions, numerous skin grafts for kera- 
 toses and fissures over knuckles. Primary union. Recurrent growth of 
 the matrix of ring finger nail, left hand ; amputation. Occurrence of a 
 fibrous tumor on the ulnar side of stump one year afterwards ; amputation 
 through first phalanx. Pathologists differ as to the character of this 
 growth, some believing it to be an unusual form of granulation tissue ; 
 others classifying it as a sarcoma. 
 
 Case XIX. — Personal. (Plate XXXVII., Figs. i6, 17, 18.) W. J. D. 
 (physician) ; 32 years. X-ray operator. Began work with a large static 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 389 
 
 machine in March, 1896; in October of same year a powerful twelve-inch 
 coil was used. In November, 1896, the first severe dermatitis took place. 
 This subsided under treatment, but was followed in April, 1897, by an 
 extremely severe general dermatitis with pain beyond description. All 
 kinds of washes, ointments, and powders were used with orthoform to 
 relieve the pain. My first graft was applied to an ulcer on the tip of the 
 left forefinger on July 10, 1897. On Aug. 13, 1897, fourteen different 
 grafts were applied after excision of as many ulcerated areas. The 
 extreme pain ceased at once and the great majority of the grafts healed 
 soundly. Between this date and 1902 there were seven other similar 
 operations under ether. Most of the grafts were successful, but in spite 
 of several attempts failure was constant over ulcerations on the ends of 
 the ring finger of both hands. 
 
 In July, 1902, another attempt at excision and grafting was made; it 
 failed. In October, extremely painful, angry looking ulcers with indurated 
 edges had formed upon the ends of both ring fingers, these were 
 amputated. The report from the pathologist was unmistakable carci- 
 noma. In consequence, on Oct. 31, 1902, both of the ring fingers 
 were amputated at the knuckles. From October, 1902, until June, 1905, 
 a dozen or more operations consisting of partial amputations, excision 
 of growing ulcerations and keratoses were performed. In May, 1905, 
 for the first time in eight years, the patient was free from pain and 
 no dressings had to be worn. In June, the left hand was practically well, 
 but keratoses broke down on the base of the middle finger of the right 
 hand, and there was some ulceration near the matrix of the thumb nail. 
 In November, 1905, an undoubted epithelioma was excised from the base 
 of the third finger of the right hand, and numerous other ulcerations were 
 skin grafted ; some of these showed a precancerous stage. 
 
 By April, 25, 1907, after ten years of treatment, and twenty-five opera- 
 tions under ether, the condition of the hands was as follows : Left hand : 
 amputation of little finger through the interphalangeal joint ; amputation of 
 ring and middle fingers at knuckles ; fourth finger shows slight ulceration at 
 its base, and a small ulcer in the middle of the back of the hand ; there are 
 numerous keratoses, but no ulcerations. Right hand : the thumb is use- 
 ful, but its ulnar side is covered with thickened epithelium at the base of 
 which is a small ulceration. For two months there has been ulceration 
 over the joint between the first and second phalanx of the forefinger, with 
 flexion of this joint ; this ulceration strongly suggests malignant disease. 
 The middle finger is stiff, the fourth is lacking, as is also the end of the 
 fifth. The hand shows the presence of numerous grafts which have taken, 
 and a few keratoses. The patient was at work at a medical school, and 
 did not submit to an operation until July 5, 1907, at which time it was 
 evident that the forefinger must be amputated, for undoubted epithelioma- 
 tous ulcerations were forming in several parts of the dorsum of the finger, 
 notably about the opening into the joint before mentioned. Under ether, 
 the forefinger was amputated at the middle of the first phalanx, a palmar 
 flap of sound skin being reflected backward. Several suspicious areas 
 
390 PORTER. 
 
 were exxised in other parts of both hands, and skin grafted. Microscopic 
 examination of the amputated forefinger showed five diiTerent areas of 
 carcinoma, which owing to delayed operation had infiltrated deeply the 
 subcutaneous tissues, surrounded the digital nerves on the radial side, and 
 caused the extreme pain (see Plate XXX VII., Fig. i6). The columns of 
 epithelial cells had penetrated to the periosteum. As aresult of this examina- 
 tion it was decided on July 15 to amputate higher up. The head of the first 
 metacarpal bone was removed and a large flap reflected onto tiie dorsum of 
 the hand, thus forming a sound stump for approximation of the thumb. 
 
 In September, 1908, after eating lobsters, there occurred a general 
 urticaria and both hands became much swollen and the serous discharge 
 was extreme. The patient was confined to bed for ten days, then 
 very gradually the exudate dried up and there followed desquamation. 
 This, however, did not affect the keratotic areas. There have been one 
 or two injuries to the base of the forefinger of the left hand, and to the 
 base of the middle finger of the right hand, which set up extremely pain- 
 ful and obstinate excoriations. For several months there has been an 
 inflamed warty growth over the stump of the little finger of the left hand. 
 
 Examination and operation Dec. 7, 1908 (see Plate XXXVII , Fig. 18). 
 Over the head of the ulna, on the left, are two irritated thickened exco- 
 riated areas, which are being continually injured by the cuff Over the 
 center of the hand there is a small, tender, deep ulceration about the 
 size of a split pea. Over the base of the forefinger, and along the ulnar 
 side of the thumb are keratoses cracks and fissures. The left hand was 
 the first operated upon. The warty growth on the little finger was 
 excised down to the aponeurosis and submitted to Dr. Whitney, who 
 reported epithelioma. The question arose as to whether the finger 
 should be amputated at the knuckle or whether more conservative meas- 
 ures were justifiable, owing to the usefulness of this finger. I decided to 
 remove a slightly larger margin down to the aponeurosis, which was then 
 thoroughly cauterized with the Paquelin cautery. The other areas 
 described were deeply shaved, and skin grafted just back of the first 
 interphalangeal joint, and another about the center of the middle phalanx 
 were also excised and grafted. After this operation the remainder of the 
 left hand seemed in good condition. There was, of course, atrophy of 
 the hair, some telangiectases, large areas covered by grafts and cicatricial 
 tissue. The condition of the right hand was as follows : the middle 
 finger is partially flexed and there is hyperextension at the first interpha- 
 langeal joint. There is, however, flexion at the knuckle. The worst 
 lesion seems to be excessive hypertrophy and keratosis of the skin, over 
 knuckle of little finger, as shown in the photographs. This spot is fie- 
 quently subjected to slight trauma. There are similar inflamed and tliick- 
 ened areas on the radial side of the first knuckle, and along the ulnar 
 side of the thumb. The nail of the thumb is deformed and split on the 
 ulnar side of the median line, where granulation tissue and hypertrophied 
 matrix keep up a chronic sore. There exists over the ulnar bone, 
 similar to the left hand, an area of thickened epithelium which is irritated 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 39 1 
 
 by the cuff. At the base of the middle finger there are several keratoses. 
 The ulnar half of the thumb nail was removed, and with curette and knife 
 the matrix was thoroughly eradicated. The area over the base of the 
 middle finger was excised down to the cicatricial tissue, exposing a small 
 part of the tendon in the median line. All of the keratoses were shaved 
 off with a knife and grafted. It was quite remarkable at this operation 
 to see the hemostatic action of the grafts. Once placed in position, 
 bleeding quickly diminished, and in a few moments practically ceased. 
 Both hands were placed upon splints, the forearm held in position by 
 adhesive plaster, and the grafts covered with small strips of protective 
 tissue. Two keratoses were excised, one from the forehead and the 
 other from the inner part of the upper eyelid. 
 
 Dec. 20, 1908. The large and important graft over the knuckle of 
 the middle finger has healed soundly, as have five other grafted areas on 
 the right hand ; grafts upon two small keratotic areas failed. The grafts 
 placed on the left hand, however, have not been so successful, owing to 
 hemorrhages underneath them. Only two out of five have taken. The 
 base of the little finger, which was cauterized, has been extremely painful, 
 and is granulating very slowly. 
 
 A more careful pathological report showed epithelioma at the site of 
 the excision on the little finger of the left hand, and commencing epithe- 
 lioma over the knuckle of the right middle finger. All of the other areas 
 excised were negative. 
 
 Jan. 20, 1909. In spite of various sorts of dressing the ulceration 
 after cauterization of the little finger has been persistently and exquisitely 
 sensitive and painful, causing loss of sleep and necessitating opiates 
 and, locally, Schleich's solution. To-day egg membrane was tried, and 
 gave such marked relief that several skin grafts were applied as a dress- 
 ing, though from the character of the granulations it seemed unlikely 
 that they would grow. The pain was immediately relieved, and much to 
 our surprise part of the grafts "took" and slowly extended downward 
 over the ulcer. Progress ceased, however, by February 10, and in view 
 of the extreme pain and danger of recurrence it seemed as if the attempt 
 to save the finger had been a mistake. It was decided, therefore, that if 
 the next attempt at grafting proved unsuccessful that amputation 
 should be done. On Feb 19, 1909, under ether, the ulceration was 
 thoroughly disinfected and carefully shaved down to a smooth base. 
 Thin grafts were used and held in position by protective strips. Several 
 other areas were excised and similarly treated, the majority of which 
 grew, but at the end of two days infection occurred in the little finger, 
 and all of the grafts came away. Pain, however, has been distinctly less 
 after the last operation and, in a few days, epidermis began to grow from 
 the former grafts and the edges of the wound, so that by March i, 1909, 
 spontaneous healing was complete. 
 
 Suinmary : Commencing with July 10, 1S97, I have operated upon this 
 patient under ether thirty-two times, the operations varying in duration 
 from one hour and a half to three hours. At present there remains of his 
 
392 PORTER. 
 
 left hand two joints of the little finger, the forefinger and thumb ; of the 
 right hand, the thumb, the middle finger, barring part of the terminal 
 phalanx, and one and a half phalanges of the little finger. More than half 
 of the skin of the backs of both hands consists of Thiersch grafts. From 
 the initial dermatitis there has been continual, though slight enlargement 
 of the axillary glands, but no evidence of recent increase in size, or any 
 suggestion of metastases. There was undue and dangerous delay in am- 
 putating the cancerous forefinger of the right hand. With this exception, 
 epitheliomatous ulcerations have been excised early. For two months it 
 seemed as if the attempt to save the stump of the little finger was a failure, 
 but in spite of the severe pain the patient seemed unwilling to sacrifice it, 
 owing to the damaged forefinger and the fear that with its possible loss in 
 the future the thumb would have nothing to press against in grasping 
 small objects. 
 
 The number of different carcinomata in this one case has been over a 
 score. I have no doubt that general metastases would have taken place 
 long ago had it not been for timely excisions and amputations. 
 
 Case XX. — Personal. F.J. B. (physician) ; 34 years, Baltimore, Md. 
 Began X-ray work in 1900 and suffered at the start from an acute derma- 
 titis. When this subsided, all finger nails, with the exception of those on 
 the thumbs, came off. After six months' rest the dermatitis cleared up, 
 and all of the nails grew again, except that on the right forefinger ; this 
 never reformed. In the spring of 1902, after resumption of work with the 
 X-ray, there was no active dermatitis, but keratotic patches formed on the 
 hands with the appearance of the usual telangiectatic areas. Gradually 
 the nails became deformed. Up to this time there was little pain but 
 considerable stiffness in the hands. The keratoses increased up to 1905, 
 when the first ulcer appeared on the dorsum of the left hand and one on 
 the right forefinger at the junction of the second and third phalanges. 
 These ulcerations were excised and numerous keratoses were removed. 
 The ulcer on the right forefinger returned in a few months and remained 
 about the size of a pea. Numerous attempts were made to heal it as it 
 was exceedingly painful, but these were not successful. The keratosis on 
 the base of the right finger returned after excision and has persisted up to 
 the present time, without ulceration. In 1906, ulceration began in a small 
 keratosis which had been present for several years, situated on the external 
 side of the nail of the ring finger of the right hand. This has since 
 gradually increased in size, extending along the outer edge of the nail, and 
 then upwards upon the dorsum of the finger almost to the first inter- 
 phalangeal joint. The pain in this ulcer for the last nine months has been 
 very intense, so that for many nights no rest could be obtained. In the 
 fall of 1907 the matrix of the right forefinger nail broke down and assumed 
 the character of a sluggish ulcer, exquisitely tender and painful. The 
 whole matrix was destroyed. At present the dorsum of the forefinger, 
 almost to the joint between the first and second phalanges is occupied by 
 a raw, beef red ulceration without induration. This resembles in a striking 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 393 
 
 degree the ulcerations which occurred on the ring fingers of Case XIX. 
 " The pain is most intense and is best described as a sharp shooting neu- 
 ralgic pain of the worst character. It lasts two or three seconds and 
 occurs from eight to ten times every minute. When the pain was of this 
 character the ulcer always appeared raw and the granulations very red. 
 Next would come the formation of a slough, when the more intense pain 
 would disappear." 
 
 Patient entered the Massachusetts General Hospital on Jan. 19, 1909. 
 Both hands presented typical X-ray dermatoses extending up to the wrists. 
 There were numerous keratoses and a few crusted spots The chief lesions 
 have already been described — the raw ulcerations on the distal phalanx 
 of the first and ring fingers of the right hand. The nail of the middle 
 finger is deformed and there is considerable suppuration about the thin 
 and cracked edges of this nail. 
 
 Operation Jan. 20, 1909, under ether. As I feared malignant disease 
 of the forefinger and the ring finger, a small portion from the forefinger 
 ulceration was first removed and given to Dr. Whitney for rapid exami- 
 nation. Though nothing malignant was found, I determined upon amputa- 
 tion of the ends of both of these fingers, owing in part to questionable 
 malignancy, but chiefly because I believed that the grafts, even if success- 
 ful, would ultimately break down. Accordingly a transverse incision was 
 made down to the bone, through the skin, just below the first interphalan- 
 geal joint. The skin was carefully dissected downward, and the bone 
 divided at the middle of the second phalanx ; a long palmar flap of healthy 
 tissue being turned backward and sutured in position. This gave a rough 
 resemblance to the crescent of the finger nail. Numerous keratoses and 
 minor ulcerations were deeply shaved from various parts of both hands 
 and skin grafted. All wounds were dressed with protective, and carefully 
 applied pressure held the grafts in firm apposition. There occurred at the 
 site of both amputations a slight degree of infection which delayed healing. 
 By making two parallel incisions at the angle of the nail an attempt was 
 made to extirpate the matrix of the middle finger nail ; the pulp of the 
 finger was grafted ; of twenty other grafts, eighteen took. The patient 
 was discharged on February 14, with sound union in the amputations 
 and all grafted areas looked well. 
 
 On April i, patient stated that he had been entirely free from pain 
 since leaving the hospital, for the first time in years. About the matrix 
 of the middle finger there is slight suppuration, and from the sides there 
 has been some reformation of soft nail. The grafts are looking very well. 
 After consultation it was decided that this patient should be allowed to 
 continue the use of the X-rays provided he never exposed himself unpro- 
 tected. 
 
 Pathological examination by Dr. Whitney. More careful examination 
 of the tissues removed from this case showed that in both forefinger and 
 ring finger there was undoubted superficial carcinoma ; the other areas 
 excised were negative. 
 
394 PORTER. 
 
 Case XXI. — Personal communication from Dr. L. L. McArthur, of 
 Chicago, 111. S. C. G. (physician), who combined electrical therapeutics 
 from a static machine with X-ray pictures ; he developed his own plates. 
 Chronic dermatitis ; ulceration of the terminal phalanges of first and 
 middle finger of left hand; amputation of terminal phalanges. Later, 
 there developed a typical epithelioma on the remains of the left index fin- 
 ger, and numerous keratoses. The finger was amputated and found to be 
 carcinomatous. Keratoses excised and grafted; axilla thoroughly dis- 
 sected. No glands found to be involved. Patient well one year after. 
 
 Summary : Epithelioma of left index finger ; amputation ; dissection 
 of axilla. No glands involved. At present no evidence of recurrence 
 Prognosis good. 
 
 Case XXII. — Personal communication from Dr. L. L. McArthur, of 
 Chicago, 111. W., of Chicago; probably the first X-ray burn on record. 
 Eleven hours' exposure within a period of three days. Huge burn extend- 
 ing from the symphysis to the chin, the healing of which required several 
 plastic operations. In July, 1908, having been well in the interim, he was 
 thrown from his pony and injured the cicatrix. The ulcer refused to heal 
 and carcinoma rapidly developed, until an area 10 x 4 inches had become 
 involved. At operation, with a wide margin, the cancerous skin was 
 removed, as well as the anterior sheath of the rectus, part of the rectus 
 muscle, and in parts even its posterior sheath. By undermining the skin 
 laterally, beyond the axillary line, the wound was closed anteriorly, and 
 though infection occurred, healing is now nearly completed, Dec. 11, 1908. 
 
 Su)n7>iary : Severe X-ray burn in 1896, involving the chest and abdo- 
 men ; plastic operations. Latent period "eleven years;" extensive car- 
 cinoma of abdominal wall ; radical excision. 
 
 Case XXIII. — Personal communication from Dr. Charles H. Bowen, of 
 Columbus, O. L. M. E (physician) ; has been doing X-ray work for the 
 last ten years. Nine years ago he developed a dermatitis which gradu- 
 ally increased in severity until ulcers developed. These ulcers were 
 curetted from time to time, and skin grafts were tried, but seemed of no 
 permanent benefit. The grafts would take, but in a few months would 
 break down, and the ulcerations would be as painful as ever. His phalan- 
 ges were amputated on a number of occasions, until he finally lost three 
 fingers from his left hand and two from the right. Several months ago 
 he developed an ugly ulcer on the back of his left hand, which gradually 
 became an epithelioma. This was curetted on several occasions, but 
 without effect. The remains of the right hand is so painful that it has to 
 be kept continually covered in a layer of cotton in order to avoid the 
 slightest injury. In April, 1908, the left forearm was amputated at the 
 middle. In December, 1908, no evidence of recurrence on the left. 
 The right hand, which had quite a number of very suspicious looking 
 ulcers, has been gradually getting better, under large amounts of iodine, 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 395 
 
 though not necessarily caused by it. X-ray work and medicine have been 
 given up. There is no evidence of metastases. 
 
 Siimmary : X-ray worker ; persistent ulcerations and deep epithelioma 
 necessitating amputation of left forearm at the middle. Persistent 
 ulcerations of right hand required amputation of two fingers. Recently, 
 ulcerations on the back of the hand have improved, while taking iodine 
 and giving up work. 
 
 Case XXIV. — M. W. ; X-ray manufacturer ; static machines ; has suf- 
 fered for years with the severer grades of dermatitis ; recently multiple 
 epitheliomata have developed on the hands and fingers. After several 
 operations there remains on the right hand the thumb and forefinger ; 
 on the left hand the thumb, index, and middle fingers — the fourth and 
 little fingers, with their metacarpal bones, have been removed. There are 
 other lesions on the face and back. 
 
 Case XXV. — F. D. A. (physician); radiologist, Rochester, N.Y. 
 Amputation of left hand ; X-ray carcinoma ; Journal American Medical As- 
 sociation, Dec. 12, 1908. Personal communication from Dr. J. Kevins 
 Hyde and Dr. Ormsby of Chicago ; two private patients never reported. 
 
 Case XXVI. — O. R. ; severe X-ray lesions after treatment for plantar 
 keratodermia : epithelioma ; excisions of soles of both feet ; Krause graft- 
 ing successful. 
 
 Case XXVII. — P. J. S. ; epithelioma of back of hand, following 
 X-ray lesions. 
 
 Cases XXVIIL, XXIX., XXX., XXXI. —Four cases of carcinoma, 
 operated upon by Dr. Sick of Hamburg, abstracted from an article by Dr. 
 E. Schumann in Archiv. fur Klinische Chirurgie, 1907, Band 84, page 
 860. 
 
 Case XXVIII. — X-ray operator; cracks and fissures of fingers and on 
 dorsum of hands, which were excessively painful and did not yield to any 
 conservative treatment. These warty growths of epithelium were finally 
 excised and sutured. Unna examined the specimens and pronounced 
 them as beginning epitheliomata. The tissue was so friable that the 
 sutures did not hold, and it was difl^cult to make satisfactory sections. 
 The wounds healed by second intention and remained well thereafter. 
 
 Case XXIX. — Patient, X-ray tube maker. Usual pigmentations of 
 the skin of face and arms; typical changes of finger nails. In addition, 
 two prominent keratotic growths on the back of one hand. These were 
 excised and pronounced by Dr. Fraenkel to be epidermoid carcinoma. 
 
 Case XXX. — Young physician; severe lesions on fingers and backs of 
 hands. On the right forefinger a chronic paronychia, and on the back of 
 the hand a small ulceration. Usual treatment without avail. The pain 
 was extreme, often keeping the patient awake all night. Evulsion of the 
 
396 PORTER. 
 
 nail was not beneficial. The terminal phalanx was amputated and the 
 ulcer excised and skin grafted. The graft died, but satisfactory healing 
 took place eventually. Pathological examination showed typical skin 
 cancer. 
 
 Case XXXI. — Man, 32 years, who after three years of X-ray work 
 suflFered from severe lesions on both arms, breast, neck, and face. In 1901 
 there began a slowly growing ulceration of the back of the right hand? 
 which by the middle of 1902 had become a gangrenous epithelioma; 
 glands enlarged at the elbow and in the axilla. Amputation at the 
 shoulder ; axillary glands removed, and found full of squamous celled 
 carcinoma. Sound healing. In December, 1904, a typical cancer of the 
 lower lip and another of the angle of the mouth were excised, as was a 
 suspicious lesion on the back of the left hand. In March, 1905, a growth 
 of the cheek was removed, which was pronounced by Unna to be a 
 sarcoma. In September, 1905, excision of the right lower jaw for carci- 
 noma. Recurrence involving the tongue and the adjacent cheek was 
 present in February, 1906. Death soon followed. 
 
 Case XXXII. — Patient operated upon by Professor Trendelenburg. 
 The specimen was carefully studied by Dr. Schumann. Man, 39 years ; 
 unusually exposed since 1896 to the X-rays — he used his own hands to 
 test the tubes — four years later, developed a dermatitis of both hands. 
 The skin became rigid, dry, and swollen ; the nails brittle with chronic 
 onychia. This condition lasted two years. In 1902 he became worse. 
 On the right hand there developed yellowish, horny growths, particularly 
 over the knuckle of the third finger. In 1906 the removal of this keratosis 
 left behind an ulcer, which in two months grew to the size of a mark piece 
 with indurated edges. The epitrochlear glands were enlarged ; the axillary 
 glands not palpable. In February, 1907, the ulcer was radically excised 
 and skin grafted; healing uncomplicated. No mention is made of the 
 treatment of the enlarged epitrochlear glands. Examination of the ulcer 
 showed typical epidermoid cancer. 
 
 Cases XXXIIL, XXXIV., XXXV., XXXVI., XXXVII.— The fol- 
 lowing cases occurring in Great Britain are abstracted from a paper by 
 Mr. Foulterton in the Transactions of the Pathological Society, July, 
 1906, and from personal communication from Dr. Cecil W. Rowntree, and 
 a paper by him, published in the Archives of the Middlesex Hospital, 
 Volume XIII., July, 1908. 
 
 Case XXXIII. —X-ray work in 1897, at the age of 38. In two years, 
 loss of tactile sensation in fingers. In May, 1903, severe dermatitis. 
 Resulting ulcers took four months to heal. Warty bodies next developed 
 on the dorsal aspect of index and second fingers. A similar acute attack 
 in December, 1903. An ulcer on the index finger refused to heal and 
 increased in area and depth ; in September, 1904, the finger was ampu- 
 tated. In 1906, a small superficial ulcer on the middle phalanx of the 
 middle finger persisted, and was excised and grafted. Examination of 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 397 
 
 the ulceration, for which amputation was done, showed a typical epithe- 
 lioma with cell-nest formation, which invaded the underlying bone. Exam- 
 ination of the ulcer excised in 1906 shows absence of elastic tissue, 
 thickening of the epithelium, early keratinization and plasma cell infil- 
 tration ; a precancerous condition. 
 
 Case XXXIV. — Man, 60 years ; engaged for some years in the manu- 
 facture of X-ray tubes. For painful fissure over the last interphalangeal 
 joint of the first finger, excision was performed. Microscopic examination 
 showed early but undoubted squamous cell carcinoma. 
 
 Case XXXV. — Man, 40 years. The third finger showed a glossy 
 appearance of the skin, which was thin and adherent to the underlying 
 structures. The nail had entirely disappeared, except for a small portion 
 at one edge. There were no cracks nor warts, nor any actual ulceration 
 anywhere, but at the base of the finger was an area where the surface 
 epithelium showed a slight irregularity. This finger was amputated at 
 the metacarpo phalangeal joint, and the metacarpal bone subsequently 
 dissected out. Examination of the indurated skin showed the presence 
 of a malignant growth, infiltrating the deeper structures ; a typical squa- 
 mous cell carcinoma, with well-marked cell-nest formation. The axilla 
 was cleaned out, but the enlarged glands showed no evidence of 
 metastases. 
 
 Case XXXVI. — Man, 42 years ; engaged for several years in the manu- 
 facture of X-ray apparatus. For two years the left hand had been 
 affected, and eighteen months previously a growth had appeared on the 
 middle finger ; surgical treatment had been refused. Finally the left 
 middle finger became very greatly enlarged by an irregularly lobed new 
 growth, which was ulcerating on the surface and very foul. There were 
 a number of irregular, pigmented warts ; no enlarged glands. The finger 
 was amputated through the proximal end of the shaft of the third meta- 
 carpal bone; good recovery. Since this operation in 1905 there has 
 been no evidence of recurrence in the hand, but there are persistent 
 ulcerations upon the chin and over the upper part of the sternum. 
 Microscopic examination of the growth shows that it is composed of 
 small and slender columns of eyelets of squamous cells, irregularly dis- 
 tributed and separated from one another by a well-marked connective 
 tissue stroma, composed of large cells with large nuclei. Mitotic figures 
 are present. " Of special interest in this ulceration is the striking 
 appearance of the connective tissue stroma, the individual cells being of 
 a size and character not usually met with. Their large size and great 
 number produce the appearance as if the small eyelets of epithelial cells 
 were dispersed throughout granulation tissue, and suggesting the view 
 that the connective tissue cells themselves are endowed in these instances 
 with a special activity.'" None of the cells were found to be multinu- 
 cleated. An X-ray of the finger removed showed a total disappearance of 
 the bony tissue of the first and second phalanges and suggested further 
 study by the X-rays of such hands. In other instances, also, marked 
 atrophy of the bony tissue was noted, and in one case absorption had 
 
398 PORTER. 
 
 taken place, giving tlie appearance of a punched-out area in the middle 
 phalanx. 
 
 Case XXXVII. — Man, 38 years; seen in July, 1905. Had been work- 
 ing with the X-rays for six years. On account of trouble with his hand 
 gave up work in 1902. The skin of both hands was thin, glossy, and 
 pigmented; usual telangiectases. On the proximal phalanx of the right 
 middle finger was a growing ulcer about one inch in diameter. There 
 were two other smaller ulcers, which showed no evidence of healing. Xo 
 enlargement of glands. The finger was amputated with nearly the whole 
 metacarpal bone, and the ulcer over it. The other ulcer was excised 
 and grafted. Patient remained well for a year, when a small ulcer 
 appeared in the scar; this healed, however, eventually. A few months 
 later a scab formed over the scar, which was gradually raised by a 
 prominent growth about the size of half a cherry, which rose dome-like 
 above the skin. This growth was bright red in color : of firm consistenc}'. 
 It was removed, and the resulting wound covered with a Thiersch graft. 
 At present, May, 1908, there is no recurrence. Microscopic section of 
 the original ulcer revealed a keratinization and a squamous cell carcinoma, 
 in which the cell nests are numerous and well developed. Examination 
 of the second growth showed that it consisted entirely of young granula- 
 tion tissue, which replaced the epidermis and corium for a limited area, 
 the epidermis gradually merging into and disappeanng in the granula- 
 tion tissue. "The cells composing the granulation tissue are unusually 
 large and well developed, and possess large, round, oval nuclei, contain- 
 ing much chromatin and staining deeply ; in fact the appearance of these 
 cells are strikingly similar to that of the cells which formed the stroma of 
 the new growth in the previous case. The elastic tissue is disappearing 
 in a narrow zone below the epithelium with moderate plasma cell infil- 
 tration. 
 
 Sujnniary ; Five cases of carcinoma, developing with a long latent 
 period, in cases of chronic X-ray dermatitis. In all but one, early opera- 
 tion. One case neglected, but no involvement found in the axillary glands. 
 In two instances, attention is called to an unusual form of granulation 
 tissue in which the cells are unusually large and contain large, round, or 
 oval nuclei, and stain deeply. 
 
 Case XXXVIII. — H. E. (physician); amputation of arm for epithe- 
 lioma of hand. 
 
 Case XXXIX. — At Leeds, England; amputation of arm for car- 
 cinoma. 
 
 Fatal cases, X-ray carcinoma. 
 
 Case XL. — B. (physician), England; X-ray carcinoma of hands; 
 general metastases and death. 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 399 
 
 Case XLI. — W. C. E. (physician). Personal communication from 
 Dr. Nevins Hyde of Chicago. X-ray cancer of hand; general metastases 
 and death. 
 
 Case XLII. — W. (physician), Rochester, N.Y. Personal com- 
 munication from Dr. W. B. Coley of New York. For five years, had 
 been using X-rays continuously. Ulcerations present for six months on 
 the backs of both hands, specimens from which were examined by Pro- 
 fessor Welch of Johns Hopkins Hospital and found to be undoubted 
 epithelioma. The carcinoma had deeply involved the metacarpal bones 
 of the index and middle fingers. Amputation of right hand above wrist, 
 and thorough excision of ulceration on the left hand, Oct. 10, 1904 
 Subsequent recurrence in axilla and liver; death. 
 
 Case XLHI. — C. D. Personal communication from Dr. Samuel 
 Lloyd of New York and Dr. W. B. Graves of East Orange, N. J. This 
 patient was very seriously burned on both hands years before in working 
 with X-ray tubes. He was treated at many different hospitals. Skin 
 grafting was tried without result, until finally' epithelioma developed on 
 the right hand and on the base of the little finger of the left hand. At 
 the time of Dr. Lloyd's first examination the right hand was infiltrated 
 with carcinoma and the axillary glands were involved. The arm was 
 amputated at the shoulder joint, and the glands above and below the 
 clavicle removed. Amputation of the left hand was advised but refused. 
 This was Aug. 8, 1902. The ulceration gradually increased in size and 
 depth and the left a.rm was amputated by Dr. Graves on March 16, 1904. 
 Death followed from mediastinal recurrence in October, 1904. 
 
 Case XLIV. — B. F. (female), of San Francisco, Cal, Personal 
 communication from Dr Childs Macdonald. Patient was a pioneer in 
 X-ray work. In 1903 her hands commenced to show signs of X-ray der- 
 matitis, the nature of which was not understood, and attributed to chem- 
 icals used in developing the plates. Patient worked twelve hours a day, 
 without protection. In the early part of 1904 she came for the first 
 time under treatment The fingers of both hands were badly ulcerated ; 
 chiefly the tissues over the middle phalanges and the middle joints ; all 
 the nails were affected, the surfaces presenting ulcerated, warty condition, 
 the warts assuming the form of necrogenica, healing alternating with 
 ulceration. All the secreting glands and hair follicles were destroyed, so 
 that the skin was hard and dry, and cracked easily. All sorts of treatment 
 of ointments and washes were without permanent benefit. In November, 
 1904, a wart appeared on the index finger, near the terminal phalanx, 
 which was very raw, and grew with great rapidity. A portion was removed, 
 under cocaine, and submitted to Dr. Rifkogel, who reported a branching 
 papilloma, with a tendency to downward growth, and advised amputation. 
 This the patient refused, so the growth was freely excised and healed 
 healthily. A few weeks afterwards, however, a nodule appeared near the 
 
400 PORTER. 
 
 scar, which pushed up through the epithelium, broke through it and 
 appeared exactly the same as growth No. i. The glands in the axilla 
 were found somewhat enlarged. Radical operation was again refused, 
 until after Christmas, when axilla was freely opened and the whole space 
 cleared of glands. Pathological examination of these showed undoubted 
 involvement with epidermoid carcinoma. In the course of a week, more 
 nodules appeared just below the acromioclavicular articulation. It was 
 decided that the only chance of recovery lay in amputation at the shoulder. 
 Accordingly on Jan 27, 1905, after preliminary ligation of the subclavian 
 in the third part, the arm and scapula with the clavicle were removed. 
 The patient rallied well from the operation, and the wound healed rapidly, 
 but about the end of April, 1905, a recurrence took place at a point rep- 
 resenting the position of the inferior angle of the removed scapula. This 
 was excised and found to be carcinoma. Slowly, and then rapidly, other 
 nodules appeared, until ultimately the whole of the vertical scar, corre- 
 sponding to the vertebral border of the scapula, became involved. Metas- 
 tases took place in the pleura and lungs, and the patient died on Aug. 3, 
 
 1905- 
 
 On reading this history it is obvious that the patient by refusing early 
 radical surgical treatment jeopardized her life, though it is of course 
 possible that metastases had occurred early. 
 
 Case XLV. — F. (physician). Personal communication from Dr L. L. 
 McArthur of Chicago, dated April 26, 1907. Patient was the first photog- 
 rapher to develop X-ray plates in America. " He early developed the 
 chapped and fissured hands which go with the exposure to the ray, espe- 
 cially in those who combined the development of their plates with their 
 X-ray work. For the last three years he has been having, from time to time, 
 minor surgical procedures in the way of removal of a phalanx now and 
 then, until three fingers of the right hand and two on the left had been 
 sacrificed. After various plans of local treatment and a trip to Europe 
 in search of remedial agents, he came to me for the first time with an 
 enormous axillary involvement. This was indubitably squamous celled 
 carcinoma. The radical operation with removal of portions of the pecto- 
 rales and a dissection of the axilla en bloc failed to effect an arrest of the 
 trouble. Recurrence took place very promptly, and within three months 
 again filled the axilla, and involved the supraclavicular glands. Deeming 
 it hopeless to subject him to further surgical interference, trypsin injec- 
 tions were given, with a resulting liquefaction of the axillary mass to a 
 nonpurulent, sero-sanguinolent fluid, containing immense masses of epithe- 
 lial cellular detritus, as was shown on opening and draining the same. 
 After lingering for six weeks he finally succumbed to a multiple metastasis 
 on April 23, 1907. 
 
 Case XLVI. — R. V. W. (physician); X-ray machine manufacturer; 
 has used both static and coil machines continuously from their beginning, 
 subjecting himself to countless fluoroscope examinations. His skin, both 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 4OI 
 
 front and back, for a number of years, has been covered with characteristic 
 lesions, many of which have recently become epitheliomata. He was 
 operated upon for a carcinoma of the cheek, by the actual cautery, down 
 to the mucous membrane, and a thorough removal of epitheliomatous 
 glands on both sides of the neck. He had also epitheliomata of both 
 hands and some on the back. Patient died in April, igo8, of extensive 
 metastatic carcinoma of the liver. 
 
 Case XLVH. — J. B. Personal communication from Dr. Russell S. 
 Fowler and his house surgeon, Dr. C. H. Criley, of the Brooklyn Hospi- 
 tal, New York. Man, 33 years; a glass worker by occupation, since the 
 age of fourteen. Soon after the discovery of the X-ray, patient became 
 interested in the manufacture of the tubes. His work was chiefly in the 
 testing-room, where he worked over a bench, waist high exposed for one 
 to four hours a day. In 1900 he noticed a few small, warty growths on 
 the fingers, knuckles, and backs of hands. In 1904 patient gave up 
 business on account of general poor health, at which time he noticed a 
 peculiar erythem.a with a slight tendency toward hard, warty nodules over 
 the face, neck, and anterior trunk, above the waist line. The keratoses 
 were still very small, the largest not more than a quarter of an inch in 
 diameter. He has some on the face removed with the actual cautery and 
 silver nitrate. The growths rapidly recurred and increased in size, becom- 
 ing soft and slightly ulcerated. 
 
 Examination, April 19, 1907. Marked erythema and mottling of the 
 skin of face, trunk, and arms. Many scattered, hard, flat papules. A 
 small cutaneous horn on the forehead and several smaller ones on the 
 chest. Large epithelioma over the metatarso phalangeal joints of index 
 and middle fingers of left hand. Deep ulceration and small ulcerations 
 over some of the joints of the right hand. 
 
 Operation : amputation of first and second fingers with heads of meta- 
 carpal bones of left hand. Removal of numerous epitheliomata. Patient 
 refused more radical treatment and would only allow curetting of the 
 carcinomata on the right hand. 
 
 Nov. II, 1907. The growths on the right hand had increased in size 
 and fused, but were not deep. Rapid recurrence at site of amputation of 
 fingers of left hand ; only curettage was permitted, followed by an unsuc- 
 cessful attempt at skin grafting. 
 
 March 11, 1908. Since last examination, rapid progress of the disease, 
 involving the base of the thumb and the metatarsal bones of the third 
 and fourth fingers ; no evidences of glandular enlargement. Amputation 
 at junction of middle and lower thirds of left forearm ; amputation healed 
 by primary union. Another curettage of the right hand. 
 
 April 20, 1908. Another attempt was made to benefit right hand by 
 curettage and skin grafting ; unsuccessful. Discharged on June 14, with 
 cancer slowly spreading on right hand. No evidence of granular enlarge- 
 ment anywhere. By Aug. 8, 1908, however, the general condition had 
 become poor, with marked loss of weight; epitrochlear and axillary lymph 
 
402 PORTER. 
 
 nodes on the left enlarged; no recurrence in stump. Epithelioma of 
 right hand had begun to spread rapidly, and had involved deeply the 
 metacarpo phalangeal areas of the first and second fingers. These fingers 
 were accordingly amputated on August ii,and the wound skin grafted. 
 The left epitrochlear and axillary glands increased very rapidly in size, 
 forming great masses which were extremely painful. On Sept. 25, 1908, 
 interscapulo thoracic amputation was performed, and a small epithelioma- 
 tous ulcer removed in the region of the umbilicus. The amputation 
 wound healed very slowly, showing evidence of recurrence. Patient died 
 Nov. 7, 1908, of general carcinosis. 
 
 Pathological report. Glands above clavicle carcinomatous. The lymph 
 nodes in the mediastinum and about the bronchi were enlarged to about 
 the size of a fist. There were nodules in both the parietal and visceral 
 layers of each pleura. Some nodules in both lungs. Nodules also in 
 kidneys and adrenals. Numerous carcinomatous areas in the liver and 
 one in the wall of the stomach. 
 
 SiDiiinary I In 1897 began work with the X-rays, testing the tubes for 
 several hours a day. First noticed erythema and warty growths in 1900. 
 In 1905, keratoses and warts had formed on both hands, chest, and face. 
 First carcinoma developed and required amputation of two fingers of the 
 left hand in April, 1907; similar growth curetted on right hand. By 
 March, 1908, rapid extension of the disease necessitating amputation of 
 left forearm; curettage of epithelioma on right hand. August, 1908, 
 involvement of epitrochlear and axillary glands. Aug. 11, 1908, ampu- 
 tation of fingers of right hand. Sept. 25, 1908, amputation at shoulder. 
 Death on Nov. 7, 1908 ; general carcinosis. 
 
 On reading this history it is obvious that death was caused by the 
 patient's refusal to subject himself to early and radical operation. The 
 amputation at the shoulder was not performed until after general metas- 
 tases had taken place. 
 
 While on reading the histories of these cases one cannot 
 fail to be struck by the inevitable and progressive evolution 
 of the disease from the milder grades of inflammation to 
 ultimate carcinomatous degeneration, there appear, fortu- 
 nately, a few exceptions to the general rule, which careful 
 inquiry from my own and other cases have developed ; where 
 through the years, in spite of persistent lesions, there has 
 been a gradual improvement in the general condition of the 
 hands, as if the natural reparative power of the skin had 
 begun to assert itself. This is analogous to a few recent 
 cases of improvement in the genital glands, after protracted 
 loss or abeyance of function. The degree to which this 
 return toward normal may develop must depend upon the 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 403 
 
 presence or absence of continued irritations, and the depth 
 or degree of the original damage to the skin and subcuta- 
 neous tissues. 
 
 Pain. — The amount of pain which these patients suffer is 
 variable, though usually extreme. From my experience and 
 personal communications from patients I believe that the 
 agony of inflamed X-ray lesions is almost unequalled by any 
 other disease. Its character has been described, and varies 
 with individuals. While morphia has been used in some of 
 the cases, it is really surprising to find how man}' have borne 
 their pain without resorting to its habitual use. The pain 
 seems to be due, in some instances, to the exposure of 
 irritated nerve endings in a raw ulcer, like the " erethystic " 
 varicose ulcer of the leg, to suppurating nail beds, irritated 
 by small pieces of nail, and, in acute burns, very probably 
 to a definite neuritis. In the more chronic cases I believe 
 that the microscopic sections show quite clearly that the pain 
 is caused by the cicatricial contraction in the thickened corium, 
 compressing the nerves. In one case of mine (XIX.) 
 the nerves were shown to be actually involved in an infil- 
 trating cancer. At another time, the lateral digital nerve of 
 the little finger was exposed at the base of a slowly-healing 
 sore ; sensitiveness and pain were intolerable, but ceased as 
 soon as the bare nerve was covered with granulation tissue 
 and skin. Without regard to the particular cause of the 
 pain, in either the acute or chronic cases, adequate excision 
 of the lesions has invariably given immediate relief. In 
 Cases IV. and XV., though dirtering so far as one could see 
 in no respect from other very painful ulcerations, pain was 
 remarkable for its absence throughout the whole course of 
 the disease. Rupture of the dilated capillaries is of frequent 
 occurrence and always accompanied by extreme, radiating 
 pain, until the extravasation works to the surface, forms a 
 black spot, and is thrown off" in the process of desquamation, 
 when the pain ceases. Not infrequently, these minute 
 hemorrhages form the sites of subsequent ulcerations. 
 
 Acute infections arising in the fissures or inflamed nail 
 beds, keratoses or ulcerations, or coincident injuries are 
 
404 PORTER. 
 
 responsible for much of the disability associated with such 
 hands, always rendering more painful lesions which were 
 painful enough before. 
 
 The palliative treatment of these chronic X-ray lesions 
 must be left in a great measure to the personal experience 
 of the individual. Relief from pain and improvement often 
 take place under remedies which in another patient are most 
 painful and harmful. In general, dry treatment, when it 
 can be borne, combined with protection has seemed to be 
 most beneficial. Maceration should be avoided. Pure ben- 
 zoinated lard I have found the most valuable ointment; 
 ichthyol combined with lanolin occasionally useful. At 
 times, local anesthetics must be used; preferably a weak 
 solution of cocaine upon two layers of compress cloth. 
 Orthoform I am convinced should never be used, owing to 
 its tendency to produce ulcerations. Of the washes, simple 
 salt solution or aluminum acetate are valuable. If infec- 
 tion is present, citrate of silver (i-6,000) has been very 
 useful in most of my cases. Alumnol (1-200) has proved a 
 most satisfactory antiseptic and astringent. The keratoses 
 may be softened with a solution of caustic soda and shaved 
 down with a sharp knife or pumice stone. If they are 
 scratched off, bleeding is profuse, and ulceration not rare. 
 The actual cautery which several have used, while tempo- 
 rarily destroying the condition, seems to invite recurrence 
 on a larger scale. Sparking with high tension current has 
 been tried by various radiographers with temporary improve- 
 ment, but no permanent benefit. With the non-surgical 
 methods of destroying keratoses, I have had no personal 
 experience, Dr. Whitehouse of New York prefers liquid air, 
 while Dr. Pusey of Chicago is well satisfied with carbon 
 dioxide snow. Both of these milder methods have the 
 advantage over excision of causing no detention from busi- 
 ness, and possibly of acting only upon the abnormal cells, 
 without affecting normal tissues. 
 
 After months or years of treatment, or neglect of treat- 
 ment, carried out with more or less relief upon various lines, 
 the early X-ray worker usually finds that while the general 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 405 
 
 condition of the hands may have improved somewhat, either 
 certain keratoses recur after removal, or the nail beds are 
 afifected, or that after healing and breaking down several 
 times a particular ulceration finally refuses to heal. The 
 lesions are chronic, moderately severe, recurring, eventually 
 persistent. The first question usually asked is, " Should 
 X-ray work be given up? " While it is obvious that to do 
 this would be conservative, I feel personally convinced that 
 no harm results from X-ray work carried out with all modern 
 precautions. It is easy to give this advice, but only in 
 exceptional instances is the advice conscientiously carried out. 
 The second question, "What is the danger of cancer?" 
 Provided ulcerations have not persisted for more than three 
 months, or have not occurred at the site of an inflamed 
 keratosis, I believe it to be slight. 
 
 The surgical treatment of X-ray lesions. — Acute and 
 sub-acute burns : By this I mean the results of one or at the 
 most a few protracted exposures such as occurred in Case 
 II. The severe symptoms develop from a few hours to a 
 few weeks after the injury, and are accompanied by extreme 
 pain. The area apparently involved gradually shrinks, 
 leaving behind, eventually, evidence of the actual damage 
 done. Depending upon the depth of the lesion there is 
 desquamation, blistering, ulceration, or deeper death of the 
 tissues. In all degrees we have the abundant formation of a 
 very tough and adherent fibrin with great pain upon its 
 removal ; this condition is well shown in Case VIII., and is 
 peculiar to X-ray lesions. For a time, at least, the deterio- 
 rated tissues seem to be in unstable equilibrium, unable to 
 slough or to repair themselves. Pain is extreme and for its 
 relief the tendency is to perform an early excision, but it is 
 most difficult to determine how much tissue should be 
 excised. While in Case II. immediate relief of the pain 
 followed operation, and the excision at the time seemed 
 adequate, the wound failed to heal and further necrosis 
 occurred in the margins and base of the wound. In general, 
 then, except for the pain, I would advise conservative 
 
406 PORTER. 
 
 treatment of these acute or sub-acute lesions until what would 
 correspond to a " line of demarcation " has been established. 
 Excision with skin grafting should be preferred to plastic 
 operations. If the graft fails to grow owing to continued 
 necrosis, later grafting may be done after the wound has ' 
 granulated. 
 
 Fissures and thin skin over the knuckles. — The treatment, 
 whether conservative or operative, must depend upon the 
 individual experience of the operator and the choice of the 
 patient. If skin grafting is successful, there can be no doubt 
 that the result will be most satisfactory, and to my mind 
 should be advised. 
 
 Keratoses. — Until recently, my personal experience led 
 me to believe that simple, uninflamed, non-ulcerating kera- 
 toses were benign, but I am now convinced that there are 
 exceptions, and that all keratoses which show a tendency to 
 dip below the level of the surrounding skin should be 
 regarded as suspicious. Microscopical examination of many 
 of those which I have removed showed all stages from a 
 perfectly harmless condition to beginning invasion of the 
 corium. I have had no experience with liquid air or carbon 
 dioxide snow, but have found their removal by operation 
 very satisfactory. If situated upon the dorsum of the hand 
 where the skin is lax, excision and suture is satisfactory. 
 If upon the fingers, especially over the knuckles, excision 
 and skin grafting should be practised. If superficial, 
 excisions well into the corium will be adequate when a thin 
 Thiersch graft can be applied. If primary grafting fails, I 
 am convinced from several observations that thorough 
 removal of the diseased tissue promotes spontaneous healing 
 from the edges. It has been suggested that the irritation of 
 the graft excites the surrounding skin to the formation of 
 thickened epithelium, but it has seemed to me that if 
 recurrence of the keratoses takes place at .the margins of the 
 graft that this is more reasonably explained by inadequate 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 407 
 
 excision. If the keratosis suggests malignancy, the whole 
 thickness of the skin should certainly be removed. 
 
 Pachydermia with telangiectasis. — The proper treatment of 
 this condition is extremely difficult to determine. In Case 
 XV., where the whole front of the chest was affected, and in 
 VIII. where the anterior abdominal wall was in a similar con- 
 dition, with undoubted epithelioma in certain unsuspicious 
 localities, treatment must depend upon the individual indica- 
 tions. In a case like XV. the patient must be watched with 
 care; in one like Case VIII. it soon became obvious that all 
 of the damaged tissues would gradually slough unless 
 removed by operation. The histological examination of such 
 tissue shows that the main arteries are pervious, but that 
 there is both marked endarteritis and endophlebitis, which 
 unless collateral circulation is formed will probably lead to 
 subsequent anemic necrosis. 
 
 Paronychia and onychia. — Probably the most painful of 
 the X-ray lesions, and one of the most persistent. If disin- 
 fection and dry treatment does not bring about healing in a 
 reasonable length of time, extirpation of the nail is clearly 
 indicated. If healing then does not take place, the whole 
 nail bed, both at the base and on the sides should be 
 destroyed. Owing to the difficulty of distinguishing between 
 nail-forming membrane and the insertion of the extensor 
 tendon into the terminal phalanges, subsequent re-formation 
 of portions of the nail is not uncommon. Amputation with 
 certain cure is often too long delayed in this condition. 
 
 Ulcers. — I have learned to dread a slowly developing 
 ulcer, in chronic X-ray lesions, which may or may not be 
 painful ; the edges may be slightly raised and a little indu- 
 rated, or soft and flat. Nothing but the persistence of the 
 lesion really suggests malignancy. In Case XVII., though an 
 intermittent ulceration, never completely healed, had persisted 
 for seven years, only beginning carcinoma was shown by the 
 microscope, while a very malignant tumor, either cancer or 
 
408 • PORTER. 
 
 sarcoma on the forehead progressed very rapidly within half 
 a year. I have been informed that ulcerations have been 
 open for years in the same spot in two cases, and then 
 entirely healed. Such variations in the tendency to malig- 
 nancy must be taken into consideration in advising radical 
 treatment. On the other hand, pain and disability, not the 
 fear of malignancy, is often an indication for operation. 
 Even rapid histological examination may be unreliable, for 
 twice I have found undoubted cancer, after amputation on 
 the clinical evidence, when a small piece microscopically 
 examined was negative. 
 
 Treatment of ulcers, benign and malignant. — If an ulcera- 
 tion becomes exquisitely sensitive and painful, raw and beefy 
 red, whether or not the base is indurated, such as occurred in 
 1902 in Case XIX., and recently in Case XX., early amputa- 
 tion should be done. As a rule amputation at the knuckle 
 of a finger, upon which a carcinomatous ulcer has developed, 
 will be found to be sound and conservative treatment ; but 
 when one finds that multiple lesions upon both hands have 
 been treated, and more will probably occur in the future, in 
 view of the possible reparative power of the skin, and the 
 relatively benign character of these epitheliomata, if treated 
 early, it seems, so far as my experience goes, that conserva- 
 tive treatment (by which I mean local excisions or minor 
 amputation) will probably be adequate to control metastases. 
 Although since 1902 Case XIX, has developed very many 
 carcinomata, and twice at least operation has been too long 
 delayed, there is as yet no evidence of increasing glandular 
 enlargement, which surely would have occurred long ago, 
 except for the timely operations. It is not unlikely that this 
 relative immunity may be partially explained by the oblitera- 
 tion of the adjacent lymphatics, which has been induced by the 
 X-rays. It must become a question, finally, as to how close to 
 the wind the patient and surgeon are willing to sail. For ex- 
 ample: this same Case XIX. developed an epithelioma on the 
 stump of the little finger. This he did not wish to sacrifice, as 
 the forefinger was maimed, so after thorough excision, down to 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 4O9 
 
 the aponeurosis, the actual cautery was thoroughly applied. 
 Healing was most painful and slow, yet at present, six months 
 after operation, there is no evidence of recurrence and the 
 finger is soundly healed. One case has remained well for 
 two years and a half, after thorough dissection of the axilla 
 for cancerous involvement; one of my patients is well a year 
 and a half after a similar operation. In those cases, where 
 there have been many epitheliomata on the hands and fingers, 
 it must be a serious problem as to whether amputation at the 
 wrist, which would practically guarantee a cure, would not be 
 sound surgery; yet I know of no X-ray operator in my 
 experience who would make this deliberate choice. 
 
 Skin grafting. — I have been so successful in the treat- 
 ment of these cases by Thiersch grafting that I personally 
 advise it in all of the more severe X-ray lesions. I have not 
 used Wolff" grafts, although some of the Thiersch transplan- 
 tations have been so thick as to practically amount to the 
 same thing. After two failures in using skin for these 
 grafts from parts to some degree affected, I am convinced 
 that sound skin never subjected to the X-rays has more 
 vitality. Heterogeneous grafts, in the few instances in which 
 I have employed them, have been failures. The disinfec- 
 tion of these cases before operation is a difficult problem, 
 for as open ulcerations invite sepsis in the grafts we would 
 prefer thorough germicidal treatment; but this, if thoroughly 
 carried out, usually results in so much irritation that the 
 subsequent discharge of serum is excessive. I have pre- 
 ferred, therefore, mechanical rubbing with a sponge and 
 salt solution, followed by carbolic acid solution (1—50) for 
 a few moments. If the skin is unbroken, ordinary methods 
 are applicable. A tourniquet should always be used, for 
 bleeding is free and dissections must be delicate when made 
 over the joints, tendons, or aponeuroses. After the removal 
 of the diseased tissues, the tourniquet should be removed, 
 and the hands elevated until bleeding has stopped spontane- 
 ously. I have seen little benefit from peroxide, and have 
 never dared to use adrenalin. In some cases the hemostatic 
 
410 PORTER. 
 
 action of grafts quickly placed upon an oozing surface has 
 been remarkable. If possible, excisions should have bevelled 
 edges, and the graft should be cut thick in the middle, thin- 
 ning out towards the periphery, so that it will accurately fit 
 the wound. Firm pressure must be applied for the first 
 twenty-four hours to prevent oozing and hemorrhage. In 
 order to insure even pressure after operation, and to avoid 
 danger of detachment of the grafts by slight motions of the 
 etherized patient, the. hand and fingers must be firmly fixed 
 to a well-padded splint by adhesive plaster before any of 
 the grafts are applied. This is often a painstaking proced- 
 ure, owing to the various deformities and irregularities in 
 the lengths of the fingers between which gauze must be 
 placed to make them comfortable. The grafts are dressed 
 with small pieces of protective placed in an imbricated fash- 
 ion, and stuck by blood to the palmar surfaces of the fingers ; 
 the protective should be perforated. After sufficient gauze 
 has been placed over the protective to make an elastic 
 dressing, firm pressure should be made directly downwards 
 by series of opened gauze sponges which are tied on the 
 palmar surface of the splint. By this manoeuvre, detach- 
 ment of the grafts is prevented, as I have frequently seen 
 when a roller bandage was used, causing gradual lateral 
 creeping of the grafts. After twenty-four hours the pro- 
 tective should be removed with great care, and if the pain 
 is not too severe the grafts should be exposed to the air in 
 a cage. If such exposure cannot be borne, benzoinated lard 
 is the least macerating ointment which I have found. Blisters 
 are punctured as fast as they are formed. If these punctures 
 scab, and serum accumulates under the graft, dry treatment 
 is contraindicated. At the end of three days the hands are 
 bathed in warm salt solution or citrate of silver; while under 
 water small tabs of skin, etc., may be very readily removed, 
 as in making a wet dissection. In ten days the grafts are 
 soundly healed, when dry treatment with occasional lanolin 
 ointment is all that is necessary. The patient must be kept 
 in bed for four or five days with the hands elevated. If the 
 grafts owing to infection or from lack of blood supply do 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 4 II 
 
 not take over the aponeuroses, a subsequent grafting may be 
 done when the wound granulates, provided spontaneous heal- 
 ing does not take place. 
 
 SUMMARY. 
 
 With the more general recognition of the existence of 
 these X-ray carcinomata, it seems clear that such early con- 
 servative treatment as I have outlined will be adequate to 
 prevent metastases, for a careful study of the fatal cases 
 shows that in eight of them inadequate treatment, either in 
 point of time or extent of operation, due almost always to 
 refusal of the patient to submit to the treatment suggested, 
 was the cause of the fatal issue. In the case of Sick, and 
 also of Wagner, coincident development of epithelioma on 
 the face or other parts of the body made adequate surgical 
 treatment more difficult. 
 
 [In my former paper I was indebted to Dr. J. H. Wright, Director of 
 the Clinical Laboratory, and to Dr. W. F. Whitney, Pathologist at the 
 Massachusetts General Hospital, for the microscopical reports of my 
 cases. Dr. C. J. White, Dermatologist to the Hospital, made an exhaus- 
 tive study and report of the numerous sections removed from Case XIX., 
 while both Dr. Wright and Dr. Whitney have examined the material from 
 many of my subsequent cases, and Professor Mallory of the Harvard 
 Medical School has given me his valuable opinion on two cases. Most 
 of the pathological specimens have been sent to Dr. S. Burt Wolbach of 
 the Bender Hygienic Laboratory in Albany, who is making a special 
 study of X-ray lesions and their causative relation to carcinoma. As his 
 contribution will be published in conjunction with this paper, I devote 
 myself chiefly to the clinical side of the subject, leaving to him a more 
 careful description of the pathological lesions found in the less advanced 
 cases, and an estimate of their value in a theoretical attempt to explain 
 the etiology of cancer, or at least the conditions which immediately precede 
 its development.] 
 
 REFERENCES. 
 
 1. E. Schumann. Beitrage fiir Klinische Chirurgie, 1907, Ixxxiv, 
 Heft 3, 855. 
 
 2. Karl Lindenborn. Same journal, 1908, Ixxxix, Heft 2, 385. 
 
 3. Dr. Cecil Rowntree. Archives of the Middlesex Hospital, xiii,july, 
 
 lL,OS. 
 
412 PORTER. 
 
 DESCRIPTION OF PLATES. 
 Plate XXXV. 
 
 Fig. I. — Case V. Precancerous ulceration. Dr. W. H. M. Condition 
 before and ten days after operation. 
 
 Fig. 2. — Case VIII. Miss H. Huge X-ray ulceration with epitheli- 
 omatous nodules, as marked in ink square; after first operation. 
 
 Fig. 3. — Miss H. Condition after second operation with outline of 
 extent of excision with subsequent healing. 
 
 Fig. 4. — Case IX. M, K. K. 1901 ; note pachydermia. 
 
 Fig. 5. — Same, 1903. Note ribbing of nails, rhagades, and superficial 
 ulcerations. 
 
 Fig. 6. — Same, January, 1908. Carcinoma base of ring finger, and 
 over terminal phalanx of middle finger of left hand. Keratosis right 
 hand. 
 
 Plate XXXVI. 
 
 Fig. 7. — Case XV. F. H. S. Epitheliomatous ulcer back of hand, 
 with numerous keratoses and telangiectases. 
 
 Fig. 8. — Same. Low power; carcinoma of hand. 
 
 Fig. 9. — Same. Telangiectases of chest with carcinomatous nodule 
 outlined in ink circle. 
 
 Fig. 10. — Same. Low power; nodule chest; epidermoid carcinoma. 
 
 Fig. II. — Same. Keratosis nose, high power. Note extraordinary 
 number of mitotic cells. 
 
 Fig. 12 — X-ray ulcer leg. Case III. 
 
 Plate XXXVII. 
 
 Fig. 13. — J- G. Case XVIII. Recurrent growth of finger, pushing 
 through skin graft. 
 
 Fig. 14. — Section same case, low power. Note encapsulated growth 
 and small carcinoma on right. 
 
 Fig. 15. — High power of same growth. Pathology described by Pro- 
 fessor Mallory, under Case XVIII. 
 
 Fig. i6. — W. J. D. Case XIX. Condition of hands, June, 1905. 
 Epithelioma base middle finger, right hand. 
 
 Fig. 17. — Same case. Condition of hands July, 1907. Epitheliomatous 
 ulceration forefinger. Flexion owing to destruction of extensor tendon 
 over head first phalanx. 
 
 Fig. 18. — Same case. Condition November, 1908. Epithelioma base 
 little finger, left hand. Malignant keratosis base middle finger, right hand. 
 
 Plate XXXVIII. 
 
 Fig. 19. — W.J. D. Case XIX. March, 1909. Present condition 
 after thirty-four operations. 
 
SURGICAL TREATMENT OF X-RAY CARCINOMA. 413 
 
 Fig. 20. — X-ray same case, March, 1909, showing no osteoporosis, in 
 spite of long duration of disease. 
 
 Fig. 21. — Photomicrograph, Case XIX., showing in center, nerve sur- 
 rounded by carcinoma, causing intense pain. 
 
 Fig, 22. — H. G. Case XVII. Hand one year after operation. Graft 
 is outlined; note thickness of skin, keratoses and characteristic nail 
 changes. 
 
 Fig. 23. — Case XVII. Recurrent growth on forehead, low power. 
 Question of sarcoma or carcinoma. See pathological description. 
 
 The Journal of Medical Research, Vol. XXI., No. 3, October, 1909. 
 
, Journal of Medical Research. 
 
 Vol. XXI. Plate XXXV. 
 
 ^f 
 
 % 
 
 ^: 
 
 > 
 
 4 
 
 C. A. Porter. 
 
 X ray lesions. 
 
Journal of Medical Research. 
 
 Vol. XXI. Plate XXXVI. 
 
 9 
 
 1 
 
 ]0 
 
 11 
 
 C. A. Porter. 
 
 12 
 
 X ray lesions. 
 
Journal of Medical Research. 
 
 Vol. XXI. Plate XXXVll 
 
 14 
 
 
 :%^ 
 
 %.^ 
 
 
 J.11 ^^. 
 
 7,5 
 
 16 
 
 77 
 
 7^9 
 
 C. A. Porter. 
 
Journal of Medical Research. 
 
 Vol. XXI. Plate XXXVIII. 
 
 19 
 
 ^^ 
 
 I A .11'^ 
 
 20 
 
 m^. 
 
 22 
 
 '■^0^^^^ 
 
 'i!^^^, •^ 
 
 21 
 
 C. A. Porter. 
 
 X ray lesions. 
 
THE PATHOLOGICAL HISTOLOGY OF CHRONIC X-RAY DER- 
 MATITIS AND EARLY X-RAY CARCINOMA.* 
 
 S. B. WOLBACH, M.D. 
 
 {^Director of the Pathological Laboratory, Montreal General Hospital, Montreal.^ 
 
 The development of multiple carcinomata in the skin of 
 patients and operators who have suffered repeated injuries 
 from exposures to the X-rays has occurred so many times 
 that the causal relationship has been generally accepted in all 
 countries. The tumors have made their appearance in each 
 instance reported, several years after the establishment of 
 severe chronic changes in the skin, characterized by great 
 thickening, telangiectases, ulceration, hyperkeratosis, and loss 
 of the epidermal appendages. 
 
 The tumors which have developed in the permanently 
 altered skin have been epidermoid carcinomata almost invari- . 
 ably, and microscopically cannot be distinguished from 
 similar carcinomata of ordinary occurrence. 
 
 Striking features of the carcinomata following X-ray 
 injuries, already brought forth in numerous publications, 
 are the occurrence in young individuals and the malignant 
 nature of the tumors as shown by the high mortality. The 
 article of Dr. C. A. Porter in this issue describes the clinical 
 features of these cases and presents a summary of those from 
 this country. 
 
 The opportunity to make a careful histological study of 
 early X-ray carcinomata and of skin from cases showing 
 varying degrees of the chronic changes which precede the 
 occurrence of these tumors has been a great privilege for 
 which I am indebted to Dr. C. A. Porter. His interest and 
 care has also made it possible to obtain tissues fixed immedi- 
 ately after removal from the patient. In every instance a 
 general anesthetic was employed so that the tissues obtained 
 were not injured by local injections. 
 
 All of the material studied for this report was fixed in 
 
 * Received for publication July 26, 1909. 
 (415) 
 
41 6 WOLBACH, 
 
 Zenker's fixative, and in every instance immediately after oper- 
 ation. The staining methods employed were the methylene 
 blue and eosine stain, Mallory's phosphotungstic acid hema- 
 tein, Mallory's connective tissue stain and Verhoeff's elastic 
 tissue stain (all are described in the Pathological Technique 
 of Mallory and Wright, fourth edition). 
 
 The descriptions were made chiefly from sections stained 
 by the phosphotungstic acid hematein stain, though the 
 other stains were used for corroborative evidence when neces- 
 sary. This stain proved to be especially useful in the study 
 of the collagenous fibrils of connective tissue because it 
 brings out differences in staining properties which are 
 not demonstrable by the other methods or any ordinary 
 stain. 
 
 As the use of Mallory's phosphotungstic acid hematein 
 stain has not yet become general a brief account of its stain- 
 ing qualities is desirable. Nuclear material and protoplasm 
 are stained blue, collagenous fibrils are stained brownish red. 
 Epidermal, neuroglia, myoglia, and fibroglia fibrils are 
 stained a deep blue. Elastic fibers are stained either a deep 
 purple or purple with a brownish periphery. In the epider- 
 mis the superficial layers of cells stain purplish to brownish 
 red. Most cell inclusions stain brownish. 
 
 The advantages of this stain in a histological study of skin 
 lesions are : 
 
 I. Differential staining of connective tissue. 
 
 II. Differences in staining of normal and degenerated 
 collagenous material. 
 
 III. The demonstration of fibrils of all sorts and of elastic 
 
 fibers. The arrangement and development of 
 epidermal fibrils is of importance in the study of 
 altered function of epidermal cells. Myoglia and 
 fibroglia fibrils assist in the identification of 
 smooth muscle and connective tissue cells. 
 
 IV. The ease by which products of cell degeneration are 
 
 recognized when within the cell. 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 417 
 
 V. The general excellence of the cell pictures, which is 
 largely due to the deep staining of the protoplasm, 
 an especially valuable feature in the study of con- 
 nective tissue cells in dense fibrous tissue. Eosin- 
 ophilous cells may be recognized by the presence 
 of deep blue stained granules. Mast cells are not 
 demonstrated, owing to the fixative necessarily 
 employed. 
 
 The effects of X-ray exposures upon human and animal 
 tissues have been incompletely determined. Studies from 
 cases similar to those forming the basis for this paper have 
 been (ew in number, and although the most important of the 
 constant changes have been described, no single observer 
 has had the opportunity of comparing the cases from a series 
 as large as the present one. Many important changes have 
 been overlooked owing to the employment of inferior staining 
 methods. 
 
 Case I. (Case II., Dr. Porter). — R. M., a man aged' 55 
 years was exposed July 23, 1908, for not more than twenty 
 minutes during a fluoroscopic examination. In three weeks 
 a painful area of erythema the size of a dinner plate appeared 
 in the site of the exposure. The edges of the erythema grad- 
 ually subsided, though the patient continued to have severe 
 pain. The skin broke down and a superficial ulcer 3x2 
 inches resulted, which resisted treatment and steadily 
 increased in size. On Nov. 18, 1908, the whole of the 
 ulcer was excised with a wide margin of surrounding skin. 
 
 The material received for examination consisted of tissue 
 hardened in Zenker's fixative, representing a large ulcer 
 about ten centimeters in diameter surrounded by a border of 
 epidermis one to one and a half centimeters in width. The 
 tissue includes the skin and subcutaneous tissues for a depth 
 of one-half to one centimeter. 
 
 ■ Description, under the microscope, from sections stained 
 with phosphotungstic acid hematein. The most striking 
 lesions, aside from the ulceration, are found in the connective 
 
41 8 wo LB AC H. 
 
 tissue of the corium and subcutaneous tissues. The corium 
 everywhere, beneath the ulceration and where covered with 
 epidermis, is of great density. Immediately beneath the 
 epidermis, however, it has a delicate structure, and is the seat 
 of an active process. The subcutaneous connective tissue 
 exhibits marked degenerative changes, including deposits 
 of fibrin and reparative processes evidenced by the presence 
 of young connective tissue cells. 
 
 The deeper layers of the corium are composed of very 
 dense connective tissue, poor in cells, with thick bundles of 
 deeply-staining collagenous fibrils. The latter are stained a 
 deep red and form bundles many times thicker than occurs 
 in the normal corium. The fibrils are coarse in texture 
 and have a more hyaline refractive appearance than those in 
 normal skin. In places there are bundles in which the 
 collagenous fibrils are fused into homogeneous refractive 
 masses. Elastic fibers are very numerous, they run parallel 
 to the collagenous fibrils, in great numbers at the periphery 
 of bundles, but often imbedded within. The elastic fibers 
 vary greatly in thickness, many can be easily resolvd'd only 
 with the highest oil immersion objective (Zeiss 1.5 mm. 
 apo.). All show a central bluish stained core with a 
 brownish outer zone. The connective tissue cells show no 
 abnormalities. 
 
 The corium immediately beneath the epidermis for a con- 
 siderable depth is of loose texture, contains little collagenous 
 material but many young connective tissue cells. The 
 papillae are absent. These changes are most marked, near 
 the ulceration and gradually diminish in the direction of the 
 periphery of the excised tissue. Still every part of the 
 material examined shows absence of papillje and rarefication 
 of the collagenous material. The collagenous fibrils in this 
 part of the corium are very delicate and stain less deeply 
 than normal, taking a pale brownish color. The individual 
 fibrils or small bundles of them are widely separated. The 
 tissue is infiltrated with polymorphonuclear leucocytes, 
 lymphoid and plasma cells and eosinophiles. There are 
 numerous large, many processed connective tissue cells 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 419 
 
 having extraordinarily large nuclei. There are many dilated 
 capillaries in this rarefied corium, made conspicuous by the 
 large endothelial cells lining them. Migrating endothelial 
 cells are easily found, and there are occasional clusters of 
 them surrounding capillaries. A few capillaries are filled 
 with free endothelial cells, occasionally one contains a single 
 giant cell. In places greatly dilated capillaries lie imme- 
 diately beneath the epidermis. The epidermis is separated 
 from the corium by a basement membrane, usually well 
 defined, but in places composed of an extremely delicate 
 hyaline brownish stained material. In the connective tissue 
 below the corium are large areas containing deposits of 
 fibrin. The collagenous fibrils are faintly stained and in 
 places changed into a hyaline material. Young connective 
 tissue cells are numerous. There are very few polymorpho- 
 nuclear leucocytes, lymphoid and plasma cells except about 
 the remains of coil glands. The fat lobules show little 
 change. In places the cell walls are wrinkled and there are 
 accumulations of lymphoid and plasma cells between the fat 
 cells and surrounding capillaries. 
 
 The epidermis is uniformly thickened. The horny layer 
 is very thin. The layers of prickle cells and granular cells 
 are of increased thickness. In a few places the epidermis is 
 separated from the basement membrane by spaces filled 
 with finely granular material. The layer of basement or 
 cylindrical cells in general is orderly arranged, but in places 
 there are groups of deeply-stained cells which are irregularly 
 arranged upon the basement membrane. These cells are of 
 the prickle cell type, while elsewhere the basement cells are 
 of the normal type. In these atypical groups the cells are 
 often separated by narrow clear spaces. The prickle fibrils, 
 which are stained a deep blue, run vertically at the base into 
 the basement membrane and here, in places, form a delicate 
 blue line by a series of contiguous arches. 
 
 The ulcerated surface is covered with a layer of coarse 
 meshed hyaline fibrin. In most places the fibrin lies directly 
 upon degenerated collagenous material, but there are some 
 large areas of granulation tissue. 
 
420 WOLBACH. 
 
 The smooth muscle in all sections examined shows very 
 marked changes in the walls of vessels and in the arrector 
 pili muscles. In the latter the cells are of increased thick- 
 ness, and the myoglia fibrils are of unusual size, though this 
 may be due to the fusion of fibrils. Many of the cells are 
 vacuolated, others are filled with a hyaline brownish stained 
 material. In arteries and veins of the subcutaneous tissues 
 the muscle cells show the same changes as in the arrector 
 pili muscles, though there are many atrophic muscle cells 
 which are surrounded by dense collagenous material of 
 which there is a great increase in the media. In some ves- 
 sels most of the muscle fibers in a given section are swollen, 
 widely separated by connective tissue and all are filled with 
 masses of h\-aline brownish stained material. 
 
 Besides the thickening of the media above noted, a few 
 arteries and veins show marked thickening of the intima due 
 to an increase of connective tissue and to swelling and 
 vacuolization of the endothelium. Many arteries and veins 
 are normal in appearance. In the arteries showing the 
 above changes the elastic lamina has disappeared and its 
 place is occupied by a thick dense band of hyaline fibrillary 
 material stained brownish and probably collagenous in nature. 
 
 Hair bulbs and sebaceous glands are absent in all parts of 
 this specimen. Certain linear areas filled with inflammatory 
 cells and young connective tissue cells undoubtedly represent 
 the sites once occupied by these structures. 
 
 Remains of coil glands are found in all sections. The 
 changes are those of simple atrophy — degeneration with 
 infiltration. 
 
 Case II. (Case III., Dr. Porter). — E. R. ; female; 30 
 years. Was treated with the Rdntgen rays for ulcerations on 
 outer side of knee and elbow for about one month during 
 March and April of 1908. Healing of the ulcers followed, 
 then rapid breaking down, ulceration, and severe acute 
 dermatitis. From Aug. 18 until Nov. 7, 1908, there was 
 severe pain from the dermatitis and ulcerations. Examina- 
 tion Dec. 4, 1908, showed characteristic X-ray changes 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 42 1 
 
 over the inner aspect of the right elbow. The skin was 
 thickened, there were telangiectases and a small ulcera- 
 tion covered with a yellow fibrinous layer. There was 
 marked dermatitis of the left leg from the middle of the 
 thigh to the top of the boot. On the outer side of the knee 
 there was an area six by five inches showing reddened pig- 
 mented scars which have healed peripherally, leaving in 
 the center an ulceration three by one inches in extent. 
 Jan. 21, 1901, the ulcer was removed with a surrounding 
 zone of skin one-half inch in diameter. 
 
 This tissue was received after hardening in Zenker's fixa- 
 tive. It consisted of an ulcer of the skin three and a half by 
 one and two-tenths centimeters in extent surrounded by a 
 zone of epidermis one to one and a half centimeters in 
 width. The disc of tissue was about one centimeter thick 
 and included the subcutaneous fat. 
 
 Description under the microscope. There are the same 
 changes in this specimen that were found in Case I. There 
 are differences of degree, however, that deserve description. 
 
 The deeper layers of the corium contain dense collagenous 
 material similar to that in Case L There are, however, 
 more numerous and larger connective tissue cells throughout. 
 Towards the zone of rarefied corium there is a very cellular 
 layer of connective tissue, the cells of which occur singly or 
 in groups and are separated by wide bands of refractive 
 hyaline collagenous material. The connective tissue cells 
 are large with prominent nuclei and abundant protoplasm 
 having many processes and conspicuous fibroglia fibrils. 
 Elastic fibers are present in extraordinary numbers, in 
 places they run in directions parallel to the connective tissue 
 cells and many are in contact with connective tissue cells. 
 
 The connective tissue between the lobules of the subcu- 
 taneous fat is dense and similar to that of the corium. 
 
 The vessels show much more marked changes than in Case 
 I. There are numerous completely obliterated arteries and all 
 of the vessels in the sections show thickening of the walls 
 with reduction of the caliber of the lumen. The obliteration 
 
422 WOLBACH. 
 
 and thickening of the walls is due to proliferation of con- 
 nective tissue in the intima and media and to increased thick- 
 ness of the smooth muscle fibers. In vessels showing lesser 
 changes, the muscle fibers of the media are large, and widely 
 separated by coarse collagenous fibrils and vacuoles. The 
 location of the vacuoles is difficult to determine. Some of 
 them are within young connective tissue cells, which are 
 increased in number particularly in the adventitia. The 
 smooth muscle fibers are swollen, many contain two to four 
 nuclei. The rnyoglia fibrils are either normal in appearance 
 or more conspicuous than the normal. Where the process 
 is more advanced, the smooth muscle fibers are surrounded 
 by dense fibrous tissue, the 'myoglia fibrils cannot be dem- 
 onstrated and the protoplasm has become homogeneous and 
 hyaline in appearance and takes a brownish blue stain. 
 
 The thickening of the intima is due to the presence of a 
 dense yet cellular fibrous tissue. In the arteries the elastic 
 lamina is usually totally absent, its place being indicated by 
 a dense band of collagenous material. Occasionally remains 
 of the elastic lamina are found and in these the elastic tissue 
 is broken up into delicate filaments which stain a deep 
 brownish. 
 
 The endothelium is often redundant, the cells are large, 
 cuboidal or elongated in shape and often contain large 
 vacuoles. The above changes are most marked in the arter- 
 ies. In the veins the media shows less marked changes and 
 the thickening of the walls and diminution of caliber of the 
 lumen is due chiefly to a thick concentric layer of large con- 
 nective tissue cells, with much or little collagenous inter- 
 cellular substance in the intima. 
 
 The corium just below the epidermis shows more marked 
 rarefication and contains more and larger telangiectases than 
 that in Case I. Many very large blood spaces lie directly in 
 contact with the epidermis, separated only by a narrow border 
 of hyaline-changed collagenous material. Others are sur- 
 rounded by necrotic tissue and are filled with fibrin. 
 
 The many capillaries just beneath the epidermis are lined 
 with large endothelial cells, a few are filled with loose 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 423 
 
 endothelial cells. In occasional areas capillaries thus occluded 
 are found, about which all of the connective tissue has under- 
 gone hyaline change. 
 
 The epidermis is uniformly markedly thickened. In gen- 
 eral the relations of the different cell strata are the same as 
 in Case I. But there are many places in the tissue where 
 the lowermost layers of cells present differentiated groups 
 and strata of large deeply-stained cells. In places where the 
 basement membrane is not demonstrable there are irregularities 
 of the bottom layer of cells and individual cells are some- 
 times found in spaces of the corium, though always connected 
 above with the epidermis. Irregular downgrowths between 
 adjacent telangiectases are common, though there is nowhere 
 any evidence of actual invasion or of independent growth, 
 except the doubtful evidence of increased size of the cells and 
 a marked affinity for basic stains. IMitoses are very rare. 
 
 Hair bulbs and sebaceous glands are entirely absent. 
 Areas of intense infiltration and active connective tissue mul- 
 tiplication probably represent the former site of these struc- 
 tures. A few atrophic remains of coil glands are found 
 surrounded always by lymphoid and plasma cells. 
 
 The ulcerated surface of the tissue is covered for the most 
 part with granulation tissue. In many places dense hyaline 
 fibrous tissue, infiltrated with polymorphonuclear leucocytes, 
 is directly exposed. There is in places slight downgrowth of 
 the epidermis at the edges of the ulcer comparable to that 
 found in cases of chronic ulcer. 
 
 Case III. (Case IV., Dr. Porter). — F. H. S. ; male; 40 
 years. Received Rontgen ray treatment for eczema five 
 years ago. There was marked improvement of the eczema 
 and during that year occasional treatments were given which 
 finally resulted in a severe dermatitis with exfoliation of the 
 skin of both thighs and legs. Four years ago a small ulcer 
 developed on the inner side of the calf and has never healed. 
 Another small ulcer which formed on the thigh healed after 
 a few months. There has been no pain. In August, 1908, 
 the ulceration of the left leg began to spread rapidly, in spite 
 
424 WOLBACH. 
 
 of various forms of treatment including two applications of 
 radium. Examination on Nov. lo, 1908, showed an irregu- 
 larly-shaped ulcer three by two and a fourth inches. In the 
 center there were occasional islands of growing epidermis, 
 the rest was covered with fibrinous exudate. The skin was 
 undermined and showed no evidence of repair. The whole was 
 excised on Nov. 19, 1908. The tissue received for examina- 
 tion had been hardened in Zenker's fixative. It included the 
 ulcer and subcutaneous fat with a surrounding margin of 
 skin one centimeter in width. 
 
 Examination under the microscope. — The deeper layers of 
 the corium are composed of the same dense tissue found in 
 Cases I. and 11. In places there are very many young con- 
 nective tissue cells with conspicuous fibroglia fibrils in the 
 meshes of hyaline-changed collagenous fibers. Some of 
 these connective tissue cells are surrounded by narrow zones 
 of paler staining normal collagenous fibrils. The picture 
 suggests the proliferation of connective tissue and the deposit 
 of fresh collagenous material in the meshes of degenerated 
 fibrous tissue. 
 
 The corium immediately beneath the epidermis shows the 
 changes previously described, i.e., the more delicate structure, 
 presence of young connective tissue cells, dilated blood 
 spaces, absence of papillae and occasional thrombosed tel- 
 angiectases in contact with the epidermis. 
 
 The ulcerated surfaces show active granulation tissue enclos- 
 ing masses of hyaline changed collagenous material. The 
 granulation tissue arises from a base of very cellular connec- 
 tive tissue in which the connective tissue cells are imbedded 
 in degenerated collagenous material. The epidermis is 
 markedly thickened. The horny layer is almost lacking. 
 The granular layer is narrow, so that the width of the epider- 
 mis is composed chiefly of prickle cells. At the edges of 
 the ulcer are downgrowths of the epidermis into the granu- 
 lation tissue. 
 
 The blood vessels show very marked changes. Many 
 large arteries of the corium and subcutaneous tissue are 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 425 
 
 completely obliterated. In these sections it can be shown 
 that the characteristic irregularity of the muscle fibers is 
 largely due to the ingrowth from the adventitia of large 
 fibroblasts, the prominent fibrils of which make it difficult to 
 distinguish these cells from smooth muscle cells. The first 
 suspicion that some of the cells of the media, while appar- 
 ently smooth muscle, were connective cells was awakened by 
 the finding of branched cells with coarse fibrils. Some of 
 these cells are surrounded by considerable collagenous 
 material and these facts together with the presence of occa- 
 sional mitoses prove the connective tissue origin of these cells. 
 The vacuoles in the media are probably within degenerated 
 smooth muscle cells. Some small veins and arteries have 
 the media completely replaced by dense collagenous material 
 in which atrophic remains of smooth muscle cells can be 
 found. In all partially or completely obliterated arteries the 
 elastic lamina is replaced by a thick convoluted band of 
 dense collagenous material. In a few large vessels the 
 endothelium of the intima is strikingly swollen and redundant 
 and many of the cells contain large clear vacuoles. 
 
 The appendages of the skin are absent. Remains of the 
 arrector pili muscles are found consisting of tracts of young 
 connective tissue enclosing degenerated smooth muscle cells. 
 
 Case IV. (Case VIII., Dr. Porter). — Female; 40 years; 
 S. After an abdominal hysterectomy for a tumor of the 
 uterus was treated with the Rontgen rays for a slowly grow- 
 ing tumor of the abdominal wall which appeared one year 
 after operation. She received one hundred and thirty-six 
 treatments between Jan. 28, 1902, and May 20, 1904. 
 She was well for four years, when characteristic Rontgen 
 ray ulcerations developed, involving the whole lower abdo- 
 men. There was necrosis and ulceration of the skin with 
 nodules suggesting small carcinomata. On March 7, 1908, 
 the whole area of skin containing ulcers was excised down to 
 the aponeurosis of the abdominal muscles, where a mass of 
 dense tissue was encountered, supposedly the remains of the 
 tumor for which treatment was given. 
 
426 WOLBACH. 
 
 Description of gross appearances of excised tissue (by Dr. Thomas 
 Ordway). "The specimen consists of a large irregularly triangular 
 piece of skin and subcutaneous tissue. Its base is 9 centimeters and the 
 sides are 10 centimeters and 11. 5 centimeters respectively. It is from 
 2 to 2.5 centimeters thick except in the central part, where it is .5 centi- 
 meter to .7 centimeter thick. The skin surface shows a large irregularly 
 triangular ulcer (5.2 centimeters x 7.5 centimeters x 8 centimeters) con- 
 forming in general to the shape of the specimen. The base of the ulcer 
 is depressed from .2 centimeter to .6 centimeter below the rough, irreg- 
 ular, ragged, overhanging and undermined, non-indurated edges. The 
 edges are necrotic, reddish-gray in color, and bathed in bright yellow puru- 
 lent exudation. The base of the ulcer is bright red to grayish red in color ; 
 it is rough and ragged and is irregularly covered with purulent exudate. 
 
 " The lower surface of the specimen consists of bright yellow fat tissue 
 through which is a delicate tracery of grayish white fibrous tissue. In the 
 central part of this surface of the specimen (the thinner area referred to 
 above) there is an area (3.5 centimeters x 4 centimeters) of firm, dense, 
 grayish white, glistening, elastic fibrous tissue which is found to be, in 
 many places, in continuity with the base of the ulcer, in other places it is 
 connected by fine and coarse fibrous strands. 
 
 "The margin of the skin surrounding the ulcer is from i to 3 centi- 
 meters in width. It is thicker and firmer than normal skin ; it is diffusely 
 reddened with a deep punctate erythema except for numerous slightly 
 elevated, rounded, whitened areas (.3 centimeter to .6 centimeter in size) 
 which have a distinct nodular, almost ' shotty,' feel. On section these 
 nodules are .4 centimeter to .6 centimeter in thickness. The surrounding 
 skin is .2 centimeter to .3 centimeter thick. The bright punctate appear- 
 ance in the diflfuse erythema of the skin surrounding the ulcer is appar- 
 ently due to marked injection of very small blood vessels." 
 
 Microscopic examination : I. Disc of fibrous tissue below 
 floor of ulcer. The tissue consists chiefly of dense fibrous 
 tissue, the bundles of which run in all directions. There are 
 groups of bundles where the collagenous fibrils are fused into 
 hyaline masses and regions where the connective tissue is very 
 cellular and edematous in appearance. The latter areas 
 surround thin walled vessels which often are immediately 
 surrounded by fibrin. Many arteries and capillaries are sur- 
 rounded by masses of lymphoid and plasma cells with occa- 
 sional eosinophiles. The amount of elastic tissue is small, 
 and that present is in small masses composed of swollen tor- 
 tuous poorly-staining clumps. 
 
 II. Sections of skin surroundini^ the ulcer. The corium 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 427 
 
 is composed of dense fibrous tissue rich in elastic fibers and is 
 in general similar to the tissues already described. There is, 
 however, no hyaline change of the collagenous material, and 
 there are no areas containing many young connective tissue 
 cells. The corium immediately beneath the epidermis shows 
 remains of the papillary structure, but shows the same rarefi- 
 cation and other characteristics noted in the other cases. 
 There are numerous large connective tissue cells in this part 
 of the corium with abundant spongy protoplasm and numerous 
 coarse fibrils (Foam cells of Unna). Particularly striking is 
 the occurrence of a layer of homogeneous hyaline changed 
 collagenous material separating the epidermis from the cellu- 
 lar loose connective tissue below. In places this hyaline 
 layer contains migrating polymorphonuclear leucocytes, and 
 occasionally there are groups of a few small, widely separated 
 epidermal cells occupying spaces in this layer, surrounded 
 and infiltrated with leucocytes. 
 
 The epidermis is much increased in thickness, chiefly due 
 to the great depth of the prickle cells. Mitotic figures are 
 common in the basement row of cells. Some of the large 
 subcutaneous arteries show eccentric thickenings of the walls. 
 
 None of the sections show any trace of hair follicles or 
 glands. An occasional remains of the arrector pili muscles . 
 is found in wnich the muscle fibers are small, vacuolated and 
 hyaline degenerated. The fibrils are usually demonstrable. 
 
 III. Sections of the elevated areas of skin or nodules 
 found in the skin surrounding the ulcer. The elevation of 
 these areas is due to a great increase in dense fibrous tissue 
 in the corium, which extends down as a continuous layer to 
 the subcutaneous fat. Laterally it gradually merges into the 
 corium of the surrounding skin; there is no line of demarca- 
 tion. The bundles of collagenous fibers in the nodules and 
 surrounding skin are very dense and hyaline in appearance. 
 The number of elastic fibers is enormously increased. There 
 are no papillae so that the epidermis lies evenly upon dense 
 hyaline collagenous material or in places upon rarefied con- 
 nective tissue; in the latter case there is a line of hyaline 
 collagenous material without nuclei immediately beneath the 
 
42 8 wo LB AC H. 
 
 epidermis. There are numerous telangiectases beneath the 
 epidermis and in the dense corium are large blood spaces 
 lined only with endothelium. The skin surrounding the 
 nodules shows marked rarefication of the upper layer of the 
 corium which contains many large telangiectases, some of 
 them filled with fibrin ; most of them are surrounded by zones 
 of hyaline collagenous material continuous with the layer 
 beneath the epidermis. 
 
 The epidermis in places is greatly thickened and there are 
 processes extending down between the dilated blood spaces 
 or telangiectases. Some of these processes are thick and 
 branched and contain typical epithelial pearls (Figs. 13 and 
 14). They are always surrounded by zones of lymphoid 
 and plasma cells and an occasional eosinophilic cell. There 
 are numerous mitoses present in these processes and in the 
 adjacent epidermis. 
 
 IV. The ulcer and adjacent skin. The floor of the 
 ulcer consists of granulation tissue covered with fibrin and 
 purulent exudate. In numerous places the ulceration extends 
 nearly to the subcutaneous fat. The granulation tissue 
 includes islands of degenerated collagenous material. In 
 places there is no granulation tissue and degenerated colla- 
 genous material, infiltrated with leucocytes, forms the floor 
 of the ulcer. 
 
 The corium adjacent to the ulcer shows the changes de- 
 scribed in the sections from the other parts of this tissue ; 
 hyaline change of the collagenous fibrils, and a diff"use 
 appearance of new connective cells between the collagenous 
 bundles without the formation of granulation tissue. Beneath 
 the epidermis there are the same changes observed in the 
 other sections. Near the edge of the ulcers, however, there 
 are many large telangiectases some of which are filled with 
 fibrin (Figs. 4 and 5). In places the fibrin extends through 
 the walls of the vessel into the surrounding tissue. In a few 
 places where a dilated thrombosed vessel is surrounded by 
 epidermis there are masses of epidermal cells extending into 
 the fibrin (Figs. 8 and 9). These cells form tortuous cords 
 and irregular masses of cells sometimes nearly completely 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 429 
 
 filling the vessel. In other places compact groups of cells 
 from the epidermis extend for considerable distances into the 
 corium, and the relations of these epidermal processes is such 
 as to make it certain that extension has taken place into 
 and along the course of one of the dilated vessels. These 
 cell processes show epithelial pearls and many mitoses. 
 Occasionally, in such a process a group of epithelial cells is 
 found which stains more deeply than the surrounding cells, 
 and the individual cells show great irregularity in shape with 
 distorted fibrils, many of which are intracellular (Fig. 14). 
 Here and there in the basal layer are groups of epidermal 
 cells which contain large irregular nuclei often with budding 
 processes containing chromatin material. There are also 
 cells containing two or more nuclei. The cells of these 
 groups are closely packed and are, roughly, concentrically 
 arranged, individually the cells are approximately spindle 
 shaped. Numerous mitoses are also found in these small 
 groups of cells and the whole picture suggests that these 
 groupsrepresent isolated, independently-growing portions of 
 the epidermis. 
 
 Many large arteries and veins of the subcutaneous tissue and 
 corium are completely obliterated chiefly through the multi- 
 plication of connective tissue cells of the intima (Figs. 18, 
 21, and 22). In some instances the muscle cells of the media 
 are largely replaced by leucocytes and fibroblasts (Fig. 22). 
 In general the obliterated vessels show the same characteris- 
 tics as those described in preceding cases. 
 
 Case V. (Case XV., Dr. Porter). — Male; 40 years; a 
 maker of Rontgen ray tubes since 1897. ^^^ had several 
 acute attacks of " eczema." The first ulceration commenced 
 in 1905 on the left hand between the knuckles of the first and 
 second fingers. This has healed and broken down several 
 times. At the time of operation, in April, 1908, there were 
 several keratoses and small ulcerations on the hands. On the 
 whole there has been very little pain associated with any of 
 the lesions. The tissues excised were an ulcer from the back 
 of the left hand, measuring about two by one centimeters ; 
 
430 WOLBACH. 
 
 a horny keratosis from between the knuckles of the index 
 and middle fingers of the left hand, a soft wart-like growth 
 from the nose one-half centimeter in diameter capped with a 
 layer of horny epithelium and a piece of tissue from the 
 chest which came from the center of a thickened pigmented 
 area of the skin showing prominent telangiectases (the chest 
 has been frequently exposed to the rays in making fluoro- 
 scopic examinations). This piece of tissue from the chest had 
 a scaly surface with minute elevated scar-like areas. The 
 excision included all the tissues of the skin and subcutaneous 
 fat. 
 
 Microscopic examination : I. Keratosis from the back 
 of the hand (Fig. i6). The greatly thickened epidermis has 
 long processes extending into the corium. Between the 
 processes of epidermis are papillae of the corium, usually 
 long and slender, but occasionally short and thick and con- 
 taining dilated blood spaces filled with fibrin and leucocytes. 
 The collagenous material of the papillae, as elsewhere in the 
 corium immediately beneath the epidermis, shows the hya- 
 line change and rarefication noted in the other cases. The 
 vessels in the papillae are of large caliber and many are sur- 
 rounded by areas of faintly stained collagenous material in 
 which are strands of fibrin and young connective tissue cells. 
 Collections of plasma cells are common in the neighborhood 
 of capillaries and at the tips of the epithelial processes. The 
 cell masses also contain numerous mononuclear eosinophiles 
 and lymphoid cells and occasionally polymorphonuclear 
 leucocytes. The deeper part of the corium is of the dense 
 hyaline type, with great numbers of elastic fibers, already 
 described. 
 
 None of the sections include the large vessels of the deep 
 corium and subcutaneous tissues. 
 
 The epithelial processes of the epidermis consist of prickle 
 cells with an abrupt change towards the surface into cells of 
 the type of the stratum lucidum (Fig. 19). Cells of the 
 granular layer type are almost entirely absent. The horny 
 layer is very thick and consists of fused elements in which 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 43 1 
 
 cell and nuclear outlines can often be distinguished (acantho- 
 sis). In places there are spaces in the horny layer contain- 
 ing refractive hyaline transformed cells in which are nuclear 
 remains. The basement layer of cells of the epithelial pro- 
 cess is for the greater part regularly arranged and composed 
 of columnar cells. In places the arrangement is irregular, 
 the cells are irregular in shape and widely separated. Such 
 groups are invaded by plasma cells and polymorphonuclear 
 eosinophiles. The epithelial cells show numerous mitoses 
 and in general are small in size and show very prominent 
 prickle fibrils. In places there is growth of epidermis into 
 dilated vessels filled with fibrin which lie in the papillae or at 
 the base of the keratosis. The epidermis on each side of 
 the keratosis is uniformly thickened and for the most part 
 lies upon a rarefied corium without papillae. In places there 
 are processes of epidermis extending into the corium, usually 
 around or between telangiectases. The cells of such pro- 
 cesses consistof irregularly shaped many processed pricklecells 
 with no definite arrangement. Mitoses are common. These 
 groups of cells are invaded with plasma cells and eosinophile 
 cells and in general present an at\'pical arrangement and 
 relationship to the surrounding densely infiltrated corium. In 
 addition to such processes there are long stretches of epider- 
 mis where the deeper layers consistof similar cells with simi- 
 lar atypical arrangement. 
 
 Keratosis from tip of nose (Fig 17). The gross structure 
 is similar to the lesion from the hand. The changes in the 
 corium are also similar. The epidermis is strikingly differ- 
 ent because the entire depth of the epithelial processes are 
 composed of a uniform type of cell ; large cells with great 
 numbers of mitoses. There are three or four mitoses 
 to every oil immersion field even immediately beneath the 
 layer of horny cells, in some fields there are eight to ten 
 mitoses (Fig. 23). Prickle fibrils can occasionally be dem- 
 onstrated ; usually they are absent. There is a thin la}'er of 
 horny epithelium which is in many places detached from the 
 active cells below. 
 
432 WOLBACH. 
 
 At the base of the epithelial processes there are irregular 
 offshoots extending into the corium, always surrounded by 
 densely packed zones of lymphoid and plasma cells and 
 eosinophiles. The epithelial cells composing these offshoots 
 are irregularly arranged, and show absence of or atypical 
 arrangement of prickle fibrils. 
 
 In this lesion the picture indicates that differentiation of 
 the epidermal cells into keratohyaline and keratin has 
 ceased and that the whole depth of cells is in active growth 
 with beginning invasion at the base. 
 
 Large ulcer from hand. The ulcerated surface is the 
 exposed surface of a vascular new growth of epidermis, 
 atypical in arrangement and containing many mitoses and 
 whorls of keratinized cells. This tissue is microscopically 
 a typical epidermoid carcinoma, and there is invasion of the 
 corium by slender processes of cells on all sides. 
 
 The skin on each side of the carcinoma shows the same 
 changes that have been described in the preceding cases, i.e., 
 rarefication of the corium beneath the epidermis, atypical 
 downgrowths of epidermis, vascular changes and hyaline 
 change of the collagenous fibrils in the deep layers of the 
 corium. 
 
 Tissue from the chest. This consists of a semi-circular 
 piece of tissue the convex border of which is covered by 
 epidermis, and measures fourteen millimeters long. On 
 each side of the center of the epidermis is an area of new 
 growth very similar to that from the ulcer of the hand. 
 These areas are three to four millimeters long and consist of 
 a vascular new growth of epithelium with whorls of kerati- 
 nized cells and many mitoses. There is no definite covering 
 of epidermis and the surface is covered with a few small 
 patches of horny epithelium and fibrin. The corium sur- 
 rounding these two areas is infiltrated in every direction. 
 The whole picture is typical of epidermoid carcinoma. The 
 epidermis between these two areas and outside of them is 
 thick with large processes. The corium and vessels show 
 the same changes that have been described above. In 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 433 
 
 addition to the two areas of carcinoma there is one small 
 area of marked downgrowth of the epidermis, the processes 
 of which are surrounded by masses of lymphoid and plasma 
 cells (Fig. 15). From one of these processes there is a 
 large mass of cells, containing many mitoses, extending into 
 the corium (Fig. 20). Smaller masses project from two 
 adjacent epidermal processes. All are surrounded by 
 densely packed zones of lymphoid and plasma cells. It is 
 evident that the process here is the beginning of a growth 
 similar to the larger ones in the same piece of tissue. A 
 series of twenty-seven sections through this region excluded 
 the possibility of this appearance being due to a tangential 
 section of a larger growth. 
 
 Case VI. (W. W. G., Case III., Dr. Porter). — Male ; 41 
 years. Began work with the X-rays in 1897. I" 1900 he 
 suffered from X-ray dermatitis on the dorsum of the right 
 hand, which after healing left the skin dry and reddened. 
 In 1901 the nail of the index finger was removed because of 
 severe pain. In 1903 the characteristic telangiectases and 
 keratoses developed. Persistent painful ulceration neces- 
 sitated the amputation of several fingers and numerous areas 
 of skin between the years 1903 and 1908. In August, 1908, 
 the small lesion was excised from which the following 
 description is taken. 
 
 The material consisted of a circular piece of skin eight 
 millimeters in diameter. The center is covered with a thick 
 layer of horny epidermis, forming an elevated area five 
 millimeters in diameter. 
 
 Microscopic examination. The corium shows marked 
 hyaline change of the collagenous fibrils and a great increase 
 in elastic fibers. There are few connective tissue cells to be 
 found except immediately beneath the epidermis where the 
 corium is less dense in structure and where there are minute 
 foci of necrosis and infiltration. Small arteries show thick- 
 ening of the intima due to a layer of dense collagenous 
 material between the media and endothelium. There are 
 
434 WOLBACH. 
 
 a few normal coil glands but many showing atrophy. The 
 very few hair bulbs and shafts which are in the sections are 
 normal. 
 
 The corium immediately beneath the epidermis shows 
 traces only of the papillae in the form of very slight slender 
 elevations extending into the epidermis. These papillae 
 contain each a single large capillary with prominent endo- 
 thelium. The epidermis is thick and forms an even layer 
 except where interrupted by the small papillae. In many 
 places, however, there are large capillaries running high up 
 into the epidermis, surrounded by a thin zone of refractive 
 hyaline collagenous material. The thickness of the epider- 
 mis is chiefly due to increase in the prickle cell layer. The 
 stratum lucidum is of increased thickness. The granular 
 layer is not demonstrable. The horny layer is very thick 
 and consists of a fused mass of incompletely keratinized 
 cells in which the nuclei are large and easily visible (acan- 
 thosis). In places where the corium contains areas of frag- 
 mented collagenous material and masses of lymphoid and 
 plasma cells, there are shallow downgrowths of the epidermis. 
 The cells of these downgrowths extend laterally between 
 bundles of hyaline collagenous material. 
 
 In addition to the above cases, sections prepared at the 
 Massachusetts General Hospital of a case reported by Dr. 
 C. A. Porter (Annals of Surgery, November, 1907) have 
 been studied (Case XIX., Dr. Porter's paper, this issue). 
 The sections were described for the above report by Dr. C. J. 
 White, who paid particular attention to changes in the 
 epidermis. 
 
 The series of sections include thirty lesions removed in 
 eight or nine different operations. 
 
 All of the changes described in detail from the tissues of 
 the six cases reported above have been found in the tissues 
 from this one individual. This man, according to Dr. Porter 
 and corroborated by the sections, had ten different epider- 
 moid carcinomata removed in five years. 
 
 This case, therefore, furnishes strong evidence that the 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 435 
 
 changes described in the epidermis are progressive and 
 develop into carcinomata. 
 
 SUMMARY OF THE HISTOLOGICAL CHANGES. 
 
 The changes that have been found in the cases described 
 can be summarized best under separate headings as follows : 
 connective tissue, smooth muscle, blood vessels, and epider- 
 mis with its appendages 
 
 I. Changes in the connective tissue of tJie corium and sub- 
 cntajieons tissue. — The most conspicuous of the constant 
 changes in the corium are the rarefication immediately 
 beneath the epidermis and the great density of the connec- 
 tive tissue deeper down (Figs, i to 6). The loose textured 
 connective tissue immediately below the epidermis is best 
 interpreted as imperfect repair of degenerated connective 
 tissue due at first to the direct action of the X-rays. The 
 imperfect repair and subsequent degenerations are due most 
 probably to the vascular lesions. The presence of degener- 
 ated hyaline collagenous material throughout the depth of 
 the corium must be a direct effect of the rays. That this 
 modified collagenous material represents inert or dead tissue, 
 if such a term may be used in speaking of intercellular sub- 
 stance, is proved not only by the physical appearance and 
 staining reactions, but also by the presence of young con- 
 nective tissue cells surrounded by normal appearing collage- 
 nous fibrils between the masses of this dense collagenous 
 material (Figs. 10 and ii). Further proof is furnished by 
 the finding of isolated masses of similar material, identical in 
 appearance and staining, in the granulation tissue below the 
 ulcerations. This diffuse aseptic necrosis of connective tissue 
 and resulting dift'use proliferation of connective tissue cells is 
 probably directly responsible for the obliteration of blood 
 and lymph vessels. Repeated exposures to the X-rays is in 
 this way accountable for the production of successive depos- 
 its of collagenous material, and this is the only satisfactory 
 explanation of the great density of the deep corium. Areas 
 of fibrin in tissues many months after the last exposure to 
 the rays prove that the lesions are slowly progressive. The 
 
436 WOLBACH. 
 
 marked increase of elastic tissue almost constantly found is 
 difficult to account for. That a new formation occurs, may be 
 proved by the association of delicate elastic fibers with new 
 connective tissue cells. Coarse fibrils present may represent 
 remains from successive crops of connective tissue which 
 have undergone degeneration. The presence of many 
 degenerated fibers suggests this explanation. The question 
 needs more elaborate study for its solution than the scope of 
 this paper will permit. 
 
 Many of the connective tissue cells in the rarefied corium 
 are of extraordinary size with large processed nuclei (Fig. 
 7). Many have numerous small nuclei each containing a 
 particle of chromatin. These cells may be distinguished 
 from endothelial cells by the presence of fibroglia fibrils. 
 Apparently they do not form collagenous material. With 
 the methylene blue and eosin stain the protoplasm stains a 
 deep blue. A few are vacuolated. Similar large cells are 
 found in the fat lobules of the subcutaneous tissue, where 
 the fat is undergoing resorption. The interpretation is that 
 these cells are the result of proliferation under conditions of 
 poor nutrition. As they are found only where there is mul- 
 tiplication of connective tissue cells, they must represent 
 imperfect growth and differentiation. 
 
 2. Changes in the smooth ninscle. — The large size of the 
 arrector pili muscle and the thickness of the nuclei of arteries 
 has led some authors (Unna and Wyss) to speak of the con- 
 dition as one of smooth muscle hypertrophy. In the present 
 study degenerative changes were always present and the 
 large size of the smooth muscle cells is due to vacuolization 
 (noted by numerous authors) and distension of the cell with 
 hyaline material, the latter easily demonstrable by the phos- 
 photungstic acid hematein stain. In cases of long duration 
 only atrophic remains of the arrector pili muscles were found, 
 showing that the changes noted are unquestionably degenera- 
 tive. This degeneration of smooth muscle will be considered 
 again in connection with vessel changes. 
 
 3. Changes in the vessels. — The study of lymphatics 
 in skin, which is the seat of chronic changes, presents 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 437 
 
 extraordinary difficulties when attempted by the methods em- 
 ployed in this study. The unquestionable obliteration of 
 blood capillaries and the extreme difficulty of demonstrating 
 lymphatics in the tissues studied makes the assumption war- 
 rantable that there also has been obliteration of lymphatics. 
 
 The changes in blood vessels on the other hand are easily 
 demonstrable. The telangiectases apparently develop from 
 preexisting capillaries, those of the papillae of the corium 
 (Figs. 2, 3, 4, and 5). Various stages of dilatation of these 
 capillaries can be seen in connection with other changes, in 
 lesions of varying intensities from different cases. The 
 mechanism of their formation cannot be discovered through 
 histological examination, though obliterative changes in the 
 larger vessels and in the deeper anastomosing capillaries 
 must play a part. Another factor to be taken into considera- 
 tion is possible traction upon the capillary walls exerted by 
 contracting connective tissue. New collagenous material is 
 frequently laid down between the meshes of older degenerated 
 fibrous tissue and undoubtedly must undergo some contrac- 
 tion before the dense stage is reached. Thrombosis of these 
 telangiectases is common and is usually associated with 
 necrosis of the tissue immediately surrounding as well as of 
 the lining endothelium. Obliteration of capillaries by prolif- 
 eration of endothelium is a fairly constant finding in most of 
 the cases studied. 
 
 The obliterative changes in the veins and arteries are 
 manifested chiefly in a great increase of connective tissue 
 beneath the endothelium and in marked thickening of the 
 media. In the arteries there is disappearance of the elastic 
 lamina and a substitution of a thick, irregular band of hyaline 
 collagenous material. The thickened intima is composed of 
 connective tissue with much collagenous intercellular sub- 
 stance. The endothelium is often composed of swollen and 
 vacuolated cells which occasionally form tufts of ceils project- 
 ing into the lumen. 
 
 The thickening of the media is due to an increase of con- 
 nective tissue. By means of the stains employed it is possi- 
 ble to demonstrate large fibroblasts and abundant collagenous 
 
438 WOLBACH. 
 
 material between the smooth muscle cells. The latter show 
 varying degrees of atrophy and degeneration — hyaline 
 change and vacuolization (Figs. 17, 21, and 22). 
 
 The finding of mitotic connective tissue cells in one case 
 (No. III.) four years after the last exposure illustrates the 
 extreme slowness of this process, as well as its progressive 
 character. In advanced cases of obliterative endarteritis the 
 media is wholly replaced by connective tissue with many 
 large branching fibroblasts. In all of the cases studied oblit- 
 erative changes have been found in some of the vessels, though 
 normal vessels are usually also present. 
 
 4. Changes in the epidermis. — Except over foci of acute 
 degeneration of the corium, hypertrophy of the epidermis is 
 a constant finding. The hypertrophy in most cases is in the 
 form of a fairly uniform thickening of the epidermis. In 
 other cases there are local more marked hypertrophies taking 
 the form of keratoses and downgrowths (Figs, 13, 14, 15, 16, 
 and 17). In nearly every case there are numerous areas 
 where the proliferation of epidermis seems unquestionably to 
 be due to disappearance of connective tissue in the corium 
 which has not the power to repair itself (Figs. 12, 4, and 5). 
 The downgrowth of epidermis is analogous to the growth of 
 the corneal epithelium following an incised wound of the 
 cornea, or even gaping wounds of the cornea such as may be 
 made by plowing beneath the corneal epithelium with a 
 sharp triangular-shaped needle (Glover's needle). 
 
 Extensive downgrowths of epidermis are found, in several 
 cases, having all of the characteristics of carcinoma with and 
 without evidence of invasion. The cases showing metastatic 
 growths have, not been included in this report. Growth of 
 epidermis into thrombosed telangiectases is unusual and must 
 be interpreted as indicative of increased powers of growth 
 (Figs. 8 and 9). Generally the epithelial downgrowths are 
 surrounded by zones of dense infiltration with lymphoid and 
 plasma cells, cosinophiles and polymorphonuclear leucocytes. 
 The epidermis where there is evidence of greatest prolifera- 
 tion of the basal layers has a thin horny layer, as if the 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 439 
 
 whole capacity of the epitheHum was taxed to preserve its 
 continuity (Fig, 2). 
 
 In general the increased thickness of the epidermis and the 
 production of wart-like growths or keratoses and down- 
 growths is best explained as the result of constant active 
 proliferation called for by the constant production of small 
 defects in the underlying corium. In Case V. the ulcer from 
 the hand shows undoubted signs of malignancy. 
 
 Complete absence of hair follicles, sebaceous and coil 
 glands is the rule in cases of long duration. In less marked 
 cases atrophic glandular structures were found. In no case 
 was there evidence of proliferation of any of the skin append- 
 ages. Coil glands were often found in regions where there 
 was total absence of hair follicles and sebaceous glands. 
 
 In the description of cases minute cell changes have been 
 omitted. The finding in the epidermis of cells with extraor- 
 dinarily large nuclei with evidences of direct division into 
 several smaller nuclei was of frequent occurrence. Such 
 cells are most often in small downgrovvths or in compact 
 masses of cells inserted in the basal layers. This change and 
 others such as irregularity in size, greater affinity for basic 
 stains and confused arrangement of prickle fibrils have been 
 regarded as concomitant with proliferative and degenerative 
 changes. Possibly the finding of such changes in down- 
 growths and isolated masses of cells has a slight value as 
 evidence of altered function and increased proliferative 
 power. 
 
 Discussion. — All of the cases of this series present only 
 late effects of single or repeated X-ray exposures ; and it is 
 therefore beyond the scope of this paper to give a complete 
 account of the effects of X-rays upon human skin. The 
 chronic changes described were necessarily preceded by 
 acute changes, which were the immediate result of the 
 X-ray exposures. No complete investigation of the acute 
 changes has as yet been made. As many of the changes 
 described in this paper have been previously described, 
 a short review of the most important papers is included. 
 
440 WOLBACH. 
 
 Gassmann (Archiv. f. Dermat. u. Syphilis, 1904, Heft I.) 
 described the vessel changes produced in rabbits. He 
 exposed rabbits until ulcers of one month's duration had 
 been produced and found the following changes in the 
 arteries : The muscularis showed a sieve-like meshwork due 
 to vacuolization. The intima was thickened and broken up, 
 the elastica was fragmented and the endothelium was 
 thickened and in places heaped up two or three cells deep. 
 He claims to have demonstrated obliteration of lymphatics 
 through excessive proliferation of endothelium. 
 
 Linser (Fortschritte auf dem Gebiete der Rontgenstrahlen 
 No. 8, 1904—5) excised human skin at varying intervals 
 while the patient was receiving treatment for lupus. At the 
 end of four days there were vessels occluded by thrombi. 
 The endothelium was absent in places and in other places 
 swollen and projecting into the lumen. The media was 
 " broken up " and " fissured." There was slight perivascular 
 infiltration Avith " round cells." At eight days thrombosed 
 vessels were most numerous and the perivascular infiltration 
 was most marked. At sixteen days there was beginning 
 thickening of the intima. The breaking up of the media and 
 invasion by leucocytes was at its maximum. At twenty days 
 there was marked thickening of the intima due to pure con- 
 nective tissue without elastic fibers. Many vessels were 
 completely obliterated. At the end of thirty days the 
 " inflammatory changes " were absent. The arteries showed 
 typical thickening of the intima with newl}' formed elastic 
 fibers, giving to the vessels a shrunken, irregular form with 
 polyp-like projections into the lumen. Linser concludes 
 that the epithelium is not primarily affected even after severe 
 exposure. The only changes that he found was an increase 
 of pigment in the Malpighian layer. The hairs and glands 
 remained normal. 
 
 Unna (Fortschritte auf dem Gebiete der Rontgenstrahlen 
 No. 8, 1904—5) reported a study of four cases of chronic 
 X-ray dermatitis. He emphasized the latent period, which 
 varied from a few months to two or three years, and in view 
 of the experimental work already done upon animals stated 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 44 1 
 
 that the etiology of the lesions was unquestionable. The 
 origin of the telangiectasis is discussed at length. Unna 
 says that a deep obliterating endophlebitis would explain the 
 production of the telangiectasis, but that this has not been 
 proved. The arterial obliteration does not explain it. Unna 
 agrees with Baer and Linser (Miinch. Med. Wochenschr. 
 No. 23, 1904) in believing that the blood transforms the 
 X-rays into a form of energy that is injurious to the vessel 
 walls. This he says is supported by the fact that tissues 
 rich in blood as granulation tissue, either exposed or covered 
 by epithelium, is more affected by the X-rays than is normal 
 tissue. 
 
 The microscopic appearance of the tissues is given in great 
 detail. Great stress is laid upon the density of the connective 
 tissue of the cutis, which is attributed to degenerative changes 
 following edema. In one case he describes atypical growth 
 of epithelium at the edge of an ulcer, which he believed to be 
 a beginning carcinoma. He did not find changes in the 
 larger vessels of the deep cutis and hypoderm. As a possi- 
 ble cause of the telangiectasis he suggests tension of the 
 smooth muscle bundles called into play by the general 
 atrophy of connective tissue and by the disappearance of 
 intercellular substance between the muscle cells. The kera- 
 toses are manifestations of the atrophy of the epidermis, 
 analogous to those occurring in senile changes, sailor's car- 
 cinoma, and xeroderma pigmentosum. In retrospectfon he 
 says that the effects of the X-rays are not limited to the 
 vessels, but affect all parts of the skin, and that there is no 
 indication of an especial susceptibility of the epidermis. The 
 epidermis becomes markedly cornified, in part hypertrophic 
 and predisposed to cancer, in part atrophic. The appendages 
 atrophy, first of all the hair follicles and sebaceous glands. 
 In the cutis there is a marked chronic interstitial edema 
 which loosens and rarefies the collagen and leads to atrophy 
 of the elastic fibers. The smooth muscle alone becomes 
 thickened. Unna emphasizes the difificulty of obtaining good 
 sections because of the great density of the cutis. 
 
 Schumann's (Archiv. f. Klin. Chirurg. Berlin, 1907, 
 
442 WOLBACH. 
 
 LXXXIV., Heft 3) description of cases differs from that of 
 Unna's only in the statement that there was proliferation of 
 the sweat glands producing tortuous solid chains of cells. 
 He states that the chronic X-ray dermatitis predisposes to 
 carcinoma and points out similarities between it and other 
 conditions followed by carcinoma such as xeroderma pig- 
 mentosum, senile changes, and Unna's carcinoma of sailors. 
 
 VVyss (Beitrage z. klin. Chir. Tiibingen, 1906, XLIV. ) 
 argues for the connection between vessel changes and the 
 origin of carcinoma and says that he is the first to insist 
 upon this point. Following Ribbert's ideas that connective 
 tissue changes precede carcinoma of the skin, and bring 
 about isolation of epithelial cells, he comes to the following 
 conclusions : That the carcinoma cell is one isolated from 
 the rest of the body through the gradual withdrawal of nutri- 
 tion owing to successive obliteration of vessels ; that the 
 cells thus gradually acquire greater capacity for securing 
 nutrition and finally become capable of living at the expense 
 of other cells. He claims that similar vascular changes pre- 
 cede many kinds of carcinomata associated with peculiar 
 practises or occupations. 
 
 In a subsequent paper upon the origin of carcinoma 
 (Deutsch, Archiv. f. Chirurgie, Leipzig, XCIH., Heft 6), 
 Wyss offers the evidence furnished by the X-ray carcinomata 
 and the results of a study of fifty early carcinomata in 
 support of Ribbert's theories. In all cases he insists that 
 vascular changes are primary. 
 
 Lindenhorn (Beitrage zur klin. Chir. Tiibingen, LIX., 
 Heft 2) has collected twenty-nine cases of X-ray tumors, 
 most of them carcinoma and very malignant. The two 
 cases which he adds were in lupus patients treated with the 
 X-rays. The vessel changes described by him were limited 
 to the media. In general he corroborates the work of VVyss 
 and others, but states that the condition is essentially that 
 of premature senescence. 
 
 Porter and White (Annals of Surgery, November, 1907) 
 contribute the only important paper on the subject from this 
 country. The histological changes are described without 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 443 
 
 attempt at a summary. Particular attention is paid to the 
 fine changes in the epidermis. Obliterative changes of large 
 veins and arteries are noted as well as obliteration of capil- 
 laries by proliferation of the endothelium. Very excellent 
 objective descriptions are given of the keratoses and epithe- 
 lial hypertrophies and of the telangiectases. Several typical 
 epidermoid carcinomata are described as such, in the case 
 presented by Porter. 
 
 GENERAL SUMMARY. 
 
 The value of this study of cases here reported is largely 
 dependent upon the wide range of time represented after 
 receipt of the injuries and in the varying amounts of expos- 
 ure to the X-rays received in the different cases. A sequence 
 of changes can be seen which previous studies have not 
 brought out. The immediate effects of the X-rays, of course, 
 are not included, but the early changes can be inferred from 
 the nature of the chronic changes and the possibilities agree 
 with the results obtained by Linser upon human skin and 
 by others upon animals. 
 
 The most important fact brought out in the present study 
 is that after sufficient injury has been done complete repair 
 does not take place. There are in every case active pro- 
 cesses going on, and when we consider that some of the 
 cases had received the last exposure two to four years before 
 excision, this fact becomes of great importance. Not only 
 are degenerative and r-eparative changes constantly taking 
 place in the corium, but the occurrence of progressive vascu- 
 lar lesions is proved by the findings in the media of arte- 
 ries of young fibroblasts and, in one instance, mitosis of 
 connective tissue cells. 
 
 All the changes primarily produced by the X-rays are 
 probably degenerative in character. Normal repair is im- 
 possible after a certain amount of injury has been done 
 because of the vascular changes. Thus there is constant 
 degeneration of the tissue in foci and constant efforts at 
 repair. The non-vascular rarefied corium beneath the 
 
444 WOLBACH. 
 
 epidermis is an example of imperfect repair. The finding of 
 necrotic foci here and deeper in the corium, many months 
 and even years after the last X-ray exposure, is conclusive 
 proof of the vascular origin of the degenerations. If the 
 focus of degeneration is small, ulceration does not occur. 
 The continuity of the epidermis is preserved through down- 
 ward proliferation, and thus a deeper stratum of connective 
 tissue is reached better able to maintain nutrition. That 
 proliferative changes in the epidermis are constantly going 
 on in these cases is proved by the character of the cells of 
 the basal layers and the presence of many mitoses. In 
 many instances the growth into such foci of degeneration 
 has been observed, and even into thrombosed telangiectases. 
 Other evidences of impaired nutrition of the skin are the 
 atrophy of the glands and the absorption of fat tissue and 
 replacement by connective tissue. 
 
 The large size of the arrector pili muscles is not due to 
 hypertrophy, but to swelling of the cell and fusion of the 
 myoglia fibrils. In cases of greatest duration these muscles 
 are entirely replaced by connective tissue. The same degen- 
 erative changes in the smooth muscle of the media of vessels 
 account for the vacuolization and later the replacement of 
 muscle tissue by connective tissue. 
 
 The obliteration of small vessels and capillaries probably 
 taT<es place slowly and continuously owing to the swelling 
 of collagenous material and proliferation of connective tissue. 
 Endothelial proliferation is possibly a primary cause of 
 capillary obliteration. It would also occur in capillaries 
 occluded from other causes. Excessive infiltration of the 
 corium by lymphoid and plasma cells undoubtedly, as Wyss 
 suggests, helps to interfere with nutrition of epithelium by 
 pressure upon capillaries. 
 
 Epithelial proliferation is a constant finding over foci of 
 degeneration in the corium. Ulceration occurs only if the 
 degenerated area is too large to be bridged over by the epi- 
 dermis. It is probable that long continued proliferative 
 processes are responsible for the hypertrophy of the epi- 
 dermis. Downgrowth of epidermis takes place to fill small 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 445 
 
 gaps in the corium. This property of downgrowth to fill 
 gaps in the epidermis as well as the growth of epidermis 
 into thrombosed telangiectases must be taken as evidence of 
 increased vitality of the epidermis. Some downgrowths, of 
 a size discoverable only with the microscope, show all of the 
 characteristics of epidermoid carcinoma including the pres- 
 ence of whorls of cornified cells and evidence of invasion 
 between bundles of connective tissue. There are larger epi- 
 thelial downgrowths which are apparently limited in their 
 growth. The depth seems to be determined by the reach- 
 ing of viable connective tissue. In the same case all degrees 
 of epithelial hypertrophies, downgrowths, and keratoses may 
 occur, and also growths which are histologically carcinoma 
 and which grow slowly and invade normal tissues. Although 
 this series does not include cases in which metastases have 
 occurred, such cases are too well known to admit of any 
 doubt as to the malignancy of the slowly growing invasive 
 tumors such as are described in Case V. 
 
 The evolution of X-ray carcinoma from the smaller lesions, 
 scaly patches, and keratoses has been constantly observed in 
 the clinical study of reported cases so that there can be no doubt 
 that the smaller epithelial growths described in this paper are 
 the starting points of the malignant growths and especially 
 is this true in those cases where similar lesions had already 
 developed into ulcerations which microscopically were unques- 
 tionable carcinomata. This evidence is of course wholly 
 clinical, but the observers of these cases have been for the 
 greater part prominent physicians who often were caring for 
 their colleagues. Because the subjects of these experi- 
 mental carcinomata have been men instead of animals and 
 the observers not laboratory workers does not invalidate the 
 evidence. And this evidence is overwhelming that the car- 
 cinomata are produced by changes following severe X-ray 
 exposures. As Wyss has already insisted, the X-ray carci- 
 noma is the first experimental carcinoma. 
 
 What then gives rise to the carcinoma? Is it the direct 
 action of the X-rays upon the epithelium or is it the result 
 
446 WOLBACH. 
 
 of changes produced in the deeper tissues? All the evidence 
 advanced by Unna and by Wyss and that found in the pres- 
 ent study of cases proves that the epidermis is the least 
 susceptible of the tissues of the skin to direct injury by the 
 X-rays. Even if this were not the case the long " latent" 
 period elapsing between the last exposure to the rays and 
 the appearance of proliferative changes in the skin could not 
 be accounted for except by assuming that the repeated 
 action of the rays excites proliferative powers which remain 
 dormant for months to years. But we do know that during 
 this " latent " period the epidermis is subject to changed 
 conditions involving marked alterations in the character of 
 the connective tissue supporting it and presumable marked 
 changes in the nutrition of the cells. And also that constant 
 proliferative changes are necessitated on the part of the epi- 
 dermis in order to preserve its integrity. We must then 
 conclude that the factors responsible for the acquisition of 
 great powers to proliferate and eventually the properties of 
 malignancy, are those furnished by the changes in blood 
 supply and in the connective tissue. This theory is sup- 
 ported very completely by the microscopic appearances, 
 especially in those instances where we find evidence of active 
 proliferation of epidermis but incomplete or no differentia- 
 tion into horny epithelium. The finding of growth of epi- 
 dermis into fibrin thrombi and into areas of dense bloodless 
 collagenous material seems to be evidence of increased pow- 
 ers of proliferation. Such reasoning as the above, based as 
 it is upon microscopical findings and upon observed gross 
 changes in the living, leads to the conclusion that a slow 
 augmentation of the growth power is achieved (attended with 
 a loss of differentiation) that finally results in the ability of 
 the epithelial cells to derive their sustenance at the expense 
 of other living tissues. The fact that the " virulence " or 
 growth power of mouse tumors may be increased by suc- 
 cessive transplantations helps to make the idea acceptable 
 that a similar change may occur in normal human epithe- 
 lium. There must be conditions however which call for, as 
 does the chronic X-ray dermatitis, a continuous series of 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS, 447 
 
 proliferative processes, which in a sense are auto-inocula- 
 tions extending over years. 
 
 That connective tissue changes precede and lead to the 
 development of malignant epithelial growths is essentially the 
 theory of Ribbert as propounded in his second Beitrage zur 
 Enstehung der Geschwultse. It is essentially the conclusion 
 reached by Goebel (Zeitschr. f. Krebsforschung, Bd. Ill,, 
 Heft 3) in his study of bladder tumors associated with 
 Bitharzia disease. It is the conclusion reached by Wyss in 
 his study of X-ray carcinoma and of early carcinoma in gen- 
 eral. But none of these observers has described the mechan- 
 ism leading to the repeated proliferation of the epidermis. 
 Neither have they furnished microscopic evidence of the vari- 
 ous histological changes assumed to take place, and the idea 
 conveyed is that the acquisition of malignant power takes 
 place suddenly. 
 
 The acquisition of malignant powers is completed during 
 years of active proliferation accompanied by progressive 
 impairment of nutrition. This much we have microscopic 
 evidence for, and the hypothesis that the former is a direct 
 sequence of the latter seems justifiable. 
 
 Finally it is not far removed from von Hansenmann's 
 hypothesis of tumor origin, -that of anaplasia wherein the 
 power of growth is attributed to reversion to the stage of 
 proliferative function at the expense of that of differentiation. 
 The only difi^erence between this and the theory suggested 
 above is, that in the latter this power is assumed to be 
 acquired through changed environment. 
 
 The apparent demonstration of the origin of the multiple 
 carcinomata of chronic X-ray dermatitis in primary connec- 
 tive tissue changes and the attending disturbances of physi- 
 cal and nutritive conditions does not speak for the acceptance 
 of the old ideas of trauma and irritation as causes for the 
 origin of carcinoma. In the case of X-ray carcinoma we are 
 dealing with injuries incapable of complete repair and there- 
 fore progressive in character. 
 
 Other peculiar forms of injury associated with carcinoma, 
 such as those occurring- in aniline workers and workers in the 
 
448 wo LB AC H. 
 
 various products of combustion and distillation of coal, those 
 associated with certain diseases, as syphilis (leukoplakia) and 
 lupus, the Kangri carcinoma of the natives of Kashimir and 
 " horn core" cancer of cattle in India, deserve the most care- 
 ful study to see if the antecedent processes are similar to 
 those in X-ray cases. There is an apparent analogy in the 
 instances of cancer associated with lupus and syphilis in 
 that in these diseases there are continuous connective tissue 
 changes taking place for years. 
 
 Considering the present great activity in cancer research it 
 seems strange that more attention has not been given to this 
 field of work and it is the earnest hope of the writer that this 
 paper may stimulate investigation and experimental work 
 along these lines. 
 
 FThe writer is greatly indebted to Professor Councilman for the privilege 
 of using the photomicrographic apparatus of the Pathological Department 
 of the Harvard Medical School, where these photographs were made.] 
 
 DESCRIPTION OF PLATES. 
 Plate XXXIX. 
 
 Fig. I. — Case V. Second operation. Skin from chest showing a 
 recent focus of degeneration in the cqrium beneath the epidermis. Epider- 
 mis remains intact. 
 
 Fig. 2. — From Case IV. shows rarefication of the corium immediately 
 beneath the epidermis. The lower strata of cells in the epidermis are 
 large and are stained deeply with the basic stain. The horny layer is 
 imperfect. Rapid multiplication of the epidermis is evidenced by the find- 
 ing of many mitoses. The large capillaries are probably the precursors 
 of telangiectases. 
 
 Fig. 3. — Higher power of Fig. 2 showing the character of the basal 
 lavers of epidermal cells and the structure of the corium. 
 
 Figs 4 and 5. — From Case IV. These photographs show many large 
 telangiectases and extreme rarefication of the corium beneath the epider- 
 mis. Fibrinous thrombi are forming in several of the telangiectasis. 
 The downgrowth of epidermis in the rarefied corium is well shown. 
 This condition is always accompanied by endarteritis and endophlebitis. 
 
 Plate XL. 
 
 Fig. 6. — From Case IV. High power showing structure of rarefied 
 corium and a connective tissue cell in mitosis. 
 
 Fig. 7. — From Case IV. Connective tissue cell from, rarefied corium. 
 Atypical cells of this type and cells in mitoses are abundant in the corium 
 
HISTOLOGY OF CHRONIC X-RAY DERMATITIS. 449 
 
 beneath the epidermis and furnish evidence of the continuous change 
 which is reparative in nature and secondary to obliteration of vessels. 
 
 Fig. S. — Case IV. Low power photograph of epidermis growing into 
 thrombosed telangiectases. 
 
 Fig. 9. — High power detail of Fig. 8. 
 
 Fig. id. — Case I. shows hyaline change of collagenous material with 
 absence of connective tissue cells. 
 
 Fig. II. — Case I. Hyaline degenerated collagenous material in the 
 neighborhood of vessels showing invasion by connective tissue cells and 
 deposit of new collagenous material between the masses of the old. 
 
 Plate XLI. 
 
 Fig. 12. — From Case IV. High power photograph of epidermis grow- 
 ing into rarefied corium. At this point the corium is represented by a 
 delicate homogeneous material without cells. The epidermis dips down at 
 this point. The large size and deep staining of the cells is shown. 
 There is a single mitosis. 
 
 Fig. 13. — Case IV. High power view of epidermal processes extend- 
 ing into rarefied corium. The process on the left shows a whorl of kera- 
 tinized cells. At the tip of the process there is marked lymphoid and 
 plasma cell infiltration and the epithelial cells are large and irregular with 
 many mitoses. 
 
 Fig. 14. — Case IV. Epidermal process extending into rarefied corium. 
 Evidence of independent growth shown by the arrangement of cells and 
 production of epithelial whorls. In the bar connecting the two larger 
 masses is a nest Of cells with atypical arrangement suggesting indepen- 
 dent growth. 
 
 Fig. 15. — Case V. From chest. Epidermal process extending into 
 corium and having the characteristics of the larger growths which were 
 frankly malignant in character. 
 
 Fig. 16. — Case V. Keratosis from back of hand showing activity of 
 cells at the base, but also the presence of the different layers of the epider- 
 mis with dense horny layer. 
 
 Fig. 17. — Case V. Keratosis from tip of nose showing absence of 
 differentiation. The whole thickness of the epidermal process is composed 
 of large cells of a uniform type. There are many mitoses. 
 
 Plate XLII. 
 
 Fig. 18. — Case III. Obliterated artery from the deep corium showing 
 separation of muscle cells by connective tissue. The lumen is filled by 
 connective tissue. 
 
 Fig. 19. — High power view of Fig. 16. 
 
 Fig. 20. — High power detail from Fig. 15 showing invasion of epider- 
 mis into the corium. 
 
 Fig. 21. — Low power photograph of an obliterated artery from Case 
 III. 
 
 Fig. 22. — Obliterated artery from Case V. At this stage the muscle 
 fibers have disappeared and there is marked infiltration. 
 
 Fig. 23. — High power detail of Fig. 17 showing large number of mitoses. 
 
 The Journal of Medical Research, Vol. XXI., No. 3, October, 1909. 
 
JOURNAL OF Medical Research. 
 
 Vol XXI. Plate XXXIX. 
 
 ^ae*"- 
 
 .^^:^^ 
 
 *' 
 
 
 0^' 
 
 ^'■Z .^' ^ 
 
 l\> 
 
 ^ us^ 
 
 ft 
 
 
 "^ML.^ 
 
 ^ 
 
 I Wolbach. 
 
 Chronic X ray dermatitis. 
 
Journal of Medical Research. 
 
 ^.<«* 
 
 Vol. XXI. Plate XL. 
 
 ^ 
 
 7 V 
 
 4 
 
 J*^ 
 
 
 '^ 
 
 ;-■***>• 
 
 'x' 
 
 M 
 
 § 
 
 10 
 
 Wolbach. 
 
 
 t 
 
 4 
 
 y 4 J -g 
 
 
 4j . »» V. 
 
 
 77 
 
 <K 
 
 Chronic X ray dermatitis. 
 
Journal of Medical Research. 
 
 Vol. XXI. Plate XLI. 
 
 12 
 
 l.:i 
 
 '\^-''' 
 
 *^ >* • '• 
 
 14 ' 
 
 
 7,) ^^ii'5i.-''"s'-*.. 
 
 Wolbach. 
 
 Chronic X ray dermatitis. 
 
Journal of Medical Rf'^farch, 
 
 
 
 '*^";ifeil'' 
 
 
 IS 
 
 
 VoL. XXI. Plate XLII. 
 
 1!) 
 
 
 *^ 
 
 ■-r» 
 
 
 
 -<M«?'' 
 
 
 2S 
 
COLUMBIA UNIVERSITY LIBRARIES 
 
 This book is due on the date indicated below, or at the 
 expiration of a definite period after the date of borrowing, as 1 
 provided by the rules of the Library or by special arrange- 1 
 ment with the Librarian in charge. i 
 
 DATE BORROWED 
 
 DATE DUE 
 
 DATE BORROWED 
 
 DATE DUE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 "^ 
 
 
 
 
 
 
 
 
 
 ^ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 c2e(n4i)Mioo 
 
 
 
 
RD135 
 Porter 
 
 /^Dj3S 
 
 P83 
 
 The surQical treatment of X-ray carcinom 
 
 2002128748