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Trauma and malignant tumors
TRAUMA
AND MALIGNANT LEILA CHARLTON NEW
T
KNOX,
TUMORS
M.D.
YORK CITY
HE question of how far a single mechanica trauma may be assumed to be the soIe etiologica1 agent in the production of a mahgnant tumor is receiving more and more attention of Iate with the extension of Iabor compensation Iaws and the increased number of accidents folIowing the widespread use of motor vehicIes. Speaking generaIIy, the opinion of almost a11 pathoIogists and experimenta students of cancer is that a singIe trauma cannot cause a maIignant neopIasm. On the other hand a good many cIinicians give court testimony or publish articIes supporting the thesis that in rare instances a singIe trauma does cause the appearance of a maIignant neopIasm. This correIation is assumed chiefly in connection with the sarcomata of bone or soft tissues; it is rareIy heId for the carcinomata. The courts on the whoIe take a neutra1 position and juries frequentIy find for the pIaintiff if the evidence is contradictory. The feeIing in compensation cases is often that since the doctors disagree, the plaintiff shouId have a smaI1 award inasmuch as the disease is fatal, even if an absoIuteIy clear-cut reIationship between the injury and the appearance of the tumor cannot be estabIished. The reasons for the differences in opinion between the Iaboratory workers and the cIinicians are mainIy as foIIows: Extensive experimenta work on animaIs has been done by infficting various types of physica tissue injuries without any recorded instance of the production of a maIignant tumor. Yet cancer is easiIy produced in these same animaIs by the action of chemicaIs, chronic inflammation due to irritants, physical agents such as radium’ or x-ray and parasites, a11 of which produce cancer in man with equa1 faciIity, though of course in the case of
the parasites the types effective in the human being differ from those which are found to be carcinogenic in animaIs. The pathoIogist cannot understand why if it is so easy to produce cancer in animaIs by the same agents that act effectiveIy in human beings, is it impossibIe to produce cancer by a trauma in these animaIs if trauma is a factor in human neopIasms. He is aIso daiIy confronted with the discovery of undiagnosed cancer in persons coming to autopsy and, therefore is, aIways thinking of a tumor unsuspected by the patient and undiagnosed by the physician which may be revealed by a trauma. When from IO to 20 per cent of undiagnosed cancer cases come to the autopsy tabIe there is aIways in his mind the possibiIity of a coincidenta occurrence of a neopIasm at the time of the injury. Further he is famiIiar with the statistica reports which show that there has been no obvious increase in cancer foIIowing injuries during the great war and that certain countries with extremeIy accurate death certification, despite the increase in industria1 and motor accidents, show no increase in neopIastic disease in their offIcia1 records. The cIinician on the other hand sees. the dramatic aspect of the situation. A patient states very definiteIy that though in perfect heaIth a tumor has appeared after an injury at the site of a bIow so the gravity of the situation makes a strong impression upon the physician. It is too frequentIy assumed that almost anyone without much experience can diagnose a tumor from a microscopic section or that microscopic examination may be unimportant as compared to cIinica1 judgment. UnfortunateIy this is not true, as any pathoIogist with a Iarge consuIting practice knows, for it is some66
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times only with the greatest difficulty that a differential diagnosis can be made between certain types of traumatic bone and a malignant neoplasm. The repair experienced pathologist is also aware of the fact that while clinical experience is in many cases very capabIe of affording an accurate diagnosis of a mahgnant growth, it not infrequently faiIs, especially with the sarcomata. It is of the greatest importance therefore that al1 these alleged cases of traumatic production of cancer be studied thoroughly, and some real progress in this branch of pathology may be expected if large institutions which are equipped to make and keep carefu1 records, clinica1, radioIogica1 and pathoIogica1, study such material and make it available for the guidance of the experts who are called upon to give testimony in court. In this way cases may be reviewed from time to time in the light of the changing knowledge of neoplasms and form homogeneous groups of tumors of special types in which at least some of the circumstances surrounding the early stages of a tumor and the position which the trauma may have held in that history are clearIy defined. For instance, it is recorded in Troell’s excelIent paper, referred to later, that a carefuI gross and microscopic study was made of a number of bone sarcomata considered as traumatic in origin from the history but that no evidence of injury was found at the site of the tumor; hence the cases had to be excluded from the trauma group. If each hospitaI preserved an adequate museum to which such tumors might be admitted with their fuI1 histories, and a critical study of the traumatic factor in each one was carefully appended, it might be that some usefu1 information could be collected. This has frequentIy been done, especialIy in the case of the more superficia1 tumors where the presence of scars from injury or burns has offered indisputabIe evidence of the importance of trauma as a sensitizing agent for the ultimate appearance of cancer, though
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usualIy, as is discussed later, a period of years intervenes between the development of the neopIasm and the injury to the longer period from scar, and a much the time of the original injury and the secondary one; but a Iarge number of other tumors, especially in the sarcoma group, may offer no physical indication as to their past history, and therefore our knowledge of such a relationship remains largely speculative. An admirable iIlustration of the possibilities of confusion which may way!ay the unwary is contained in the followmg recent report by Barret 9 A man of forty-five feII and fractured the left femur. X-ray pictures taken at that time were interpreted as showing nothing but a fracture. HeaIing was rather sIow but after about three months the patient got about. Eight months later he had a pathologica fracture at the site of the previous injury. The x-ray showed a vohrminous tumor diagnosed clinicahy as an osteosarcoma and the leg was amputated. Microscopic examination, however, showed that instead of a sarcoma the tumor was an aIveoIar growth which OberIing regarded as probabIy originating from the thyroid gland ahhough no evidence of a neopIasm couId be found on cIinica1 examination of that organ. In the discussion refers to two other Balthazard :3
of this examples
paper Barret published by
The first was that of a robust man of fiftyfour who sIipped whiIe carrying a heavy Ioad and was found to have a subtrochanteric fracture of the femur. At the time it was reported that the radiographic examination reveaIed nothing abnorma1 except the fracture, but two months Iater the physician representing the insurance company noted that a tumor appeared at the site of the fracture and three and one-half months after the accident the patient died. The cIinica1 diagnosis was obviousIy a traumatic osteosarcoma, but on carefu1 resurvey of the origina radiograph evidences of bone destruction were found and the Iater radiograph showed extensive invoIvement of the shaft of the femur, so that it was evident that either a primary myeIoma or a metastatic
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deposit from a carcinoma whose existence had not been recognized was present before the injury. UnfortunateIy a full record of the materia1 is not avaiIabIe as no autopsy was done. In the second case cited a Iaborer of twentythree years was shot in the Ieft knee. The wound heaIed rapidIy and the patient Ieft the hospita1 in a short time. Later he complained of pain in the caIf of the Ieg and the interna condyIe was found to be rarefied; there was a shadow in the upper portion of the popIitea1 space. This shadow was thought to be an abscess but no evidence of infection was found. Before the microscopic examination of this materia1 was completed there was such a rapid increase in the popIitea1 tumor that the Ieg was amputated. When the report on the biopsy was obtained it recorded onIy inffammatory tissue and detaiIed examination of the suspected area from the amputated limb, whiIe it showed considerabIe bone production with giant cells, was in the opinion of Professor Roussy onIy an inflammatory lesion. These three interesting medicolega1 cases iIIustrate onIy too cIearIy the necessity for fuI1 information before an opinion is rendered. The lega decisions which have been rendered in these and simiIar cases can of course add nothing to the facts. They merely indicate the trend of social and economic thought with regard to compensation for persons who deveIop tumors while empIoyed in industry, or who have suffered accidents of various sorts. Since a legal decision is made by lay persons, it may have IittIe to do with the facts and Iegal opinions, whiIe of medicine, they estabIish precedent, do not contribute to medica knowIedge. There is apparent in the Iiterature of cIinica1 medicine a strong desire to explain the phenomena which bring about disaster, and even when no Iogical expIanation is obvious, the habit of medical philosophy appears to enter in and permit the assumption of some mysterious outside factors. This is perhaps derived from the German Iiterature, which has formed so large a part of the scientific background of medi-
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cine, but one cannot overIook the eIement of the supernatura1 which causes the German clinician, having eIiminated a11 reasonabIe possibiIity, to assume that trauma is the aushende IMoment, or the immediately exciting cause which has to be invoked if the transition from a norma to a maIignant tissue is to be adequately expIained. This explanation is to be found in so many of the otherwise cIear and IogicaI discussions that its presence aIone excites scepticism. The confidence in predisposition occupies the same place in much of the contemporary Iiterature. Yet any vaIid evidence for such a vague idea as predisposition is not at present avaiIabIe. The mere occurrence of high cancer rates in one famiIy or one strain of animaIs and low rates in another does not prove immunity or resistance. (See on this point Curtis, Dunning and Bullock.4) A sharp distinction must be drawn between the effect of a singIe mechanical injury and the Iong-continued irritations which may resuIt from an injury which has been the origin of some scar, uIcer, or specia1 inflammatory lesion upon which a tumor Iater deveIops. In the Iatter group, there are unquestionabIy many genuine cases, and even hitherto unare being discovered suspected agents which wiI1 stand the scrutiny aIike of the statistician and the physician. Skin carcinoma, whiIe ordinariIy easily recognized microscopicaIIy, may not always be correctly diagnosed by those unfamiliar with heaIing of injuries or chronic inflammatory various dermatoses and benign Iesions, lesions. Scars, rarely, even in childhood, may be the site of epithelioma, as in the case reported by DuBoisj in which a child of ten years sustained a lacerated wound of the forehead and live months Iater a basaI-cell epithelioma appeared which was microscopically diagnosed. Most of the cases, however, are in aduIts in whom irritation has been present for a considerabIe length of time, as in the case reported by Maiditsch6 of a man sixtyfive years of age who had at the age of
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fifteen received a lacerated wound of the leg which ulcerated fifty-one years later and formed the basis for an extensive epithelioma. The average elapsed period for the appearance of the malignant lesion is about thirty-two years. (See for examples Arndt,7 also Treves and Pack.8) This group of tumors has also varied in position, being found on the face and extremities in about equal numbers. Burns with asphalt,g tar, fat, acids, hot metals, various fluids, and excessive exposure to sunlight, and many types of lacerated wounds have been described as the basis of scars which have ulcerated, either spontaneously or following a secondary trauma, and then a neoplasm has developed in the site of injury. Maude Slye’O has recorded a number of neoplasms arising in mice at the site of healing injuries or the resultant scars. Special types of irritants, such as ulceration with a pessary, of which 3 new cases, in addition to 19 or more in the German literature, have been reported by von W01ff’~ which when examined eleven and thirty years after their insertion were found to have caused epithelioma. In von Wolff’s opinion irritation, infection, and predisposition were all necessary for the production of such a tumor. But in none of these examples can a single trauma be incriminated. A tumor of the tongue is reported by Ullmann12 in a man aged forty whose tongue was traumatized for only “a short time” by a filled tooth. But the whole value of the report is vitiated by the fact that the patient’s story of feeling a slight pain in the tongue a few days before is accepted as fixing the date of origin of the neoplasm. The pain was undoubtedly due to the epithelioma already present. If the accuracy of such reports is accepted as absolute, it is obvious that the interva1 necessary for the appearance of the tumor cannot with certainty be predicted either from the age of the patient, the duration of the irritant, or from the type of original injury. On the other hand,
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when the most accurate records are studied, the length of time which must elapse between the beginning of the irritation process and the appearance of the neoplasm is always a matter of years. The best examples are the tar, oil and x-ray cancers in which the period of exposure is accurately known. Even with the highly carcinogenic substances recently discovered, of which methylcholanthrene is the most active, at least two and one-half months must elapse before a carcinoma appears in a mouse, or a tenth of the animal’s life. It is noteworthy that cancer of the breast has recently received scant attention from the advocates of trauma as an etioIogica1 factor in cancer. However, there is one report of a tumor in a man forty-eight years of age who had received a war wound of the right nipple fourteen years before. l3 A claim is also made’4 that a trauma to the breast caused a rapid spread of a breast carcinoma which was undoubtedly present before the accident. Such traumatic spread is generally accepted as possibIe. Fischer-Wasels, who has vigorously opposed the theory that brain tumors are to any considerable extent caused by trauma, admits the possibility that growth of a carcinoma of the lung might be somewhat accelerated by a trauma to the chest.15 The brain tumors have during recent years perhaps aroused more interest and discussion than almost any other group, the extreme position being taken by R. Beneke, l6 who believes that at Ieast 40 per cent of brain tumors are caused by trauma, and includes under this term not only falls and blows on the head causing violent injuries and unconsciousness down to those not even causing headache, but also fright or shock without physical injury; also accidents causing injury to other parts of the body; or anything else capabIe of setting up direct or reflex ischemia of the brain and resulting necrosis of glial tissue, might be
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the cause of a glioma. This position is definiteIy opposed by Fischer-WaseIs, who does not beheve that a transitory vasospasm can be the excitant for tumors, necrosis, or other pathoIogica1 changes, and who insists upon a scientific study of the data rather than the attachment of too much importance to the possibIe connection in any one patient between an intracrania1 tumor and trauma to the head. NevertheIess, in Fischer-Wasels’ case a buIIet wound of the brain occurring nine years before is assumed by him to be the cause of a gIioma which apparentIy arose in the scar tissue. Parker and Kernohan17 made a very compIete study of a Iarge number of cerebral cases in an effort to eIiminate the factor of coincidence, and report upon carefu1 histories taken to evamate trauma in 43~ cases of ghoma. Injury was stated to have been present in 58 cases, or 13.4 per cent. In the contro1 cases without tumors injury was claimed in 44, or 10.4 per cent, whiIe in a group of 200 norma persons 7 I, or 35.5 per cent, reported cerebra1 injuries. The authors therefore fee1 that the argument for trauma must be abandoned in this group of tumors. Tumors of the eye form a specia1 group which, because of their infrequency, shouId be studied thoroughIy and carefu1 reports on the part of eye surgeons may add greatIy to our knowIedge of the importance of trauma. This fact has been pointed out by Stieren,18 who has coIIected from the Iiterature a group of cases in which trauma was mentioned by the patients. The interva1 between the injury and the discovery of a tumor in these cases was eight months, three months, sixteen years, one week, three years, three years, and in Stieren’s case, nine years. The injuries consisted in bIows and lacerations of some portion of the eyebaI1, probabIe in 2 cases. The discussion which foIIowed was somewhat critica as to any correIation for it was feIt by some of those present that the injury may have onIy set up a chronic irritation which gave
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opportunity for the Iater development of a neoplasm. Recently Bonnet and Paufiquelg have reported a case of meIanosarcoma deveIoping in an eye which had sustained a severe bIow sufficient to cause separation of the retina two years before. Carcinoma of the interna organs, especiaIIy the stomach and pancreas, with trauma as the etiological agent, has again been mentioned in the Iiterature onIy infrequentIy. A traumatic gastric cancer is reported by Luckow?’ In a man wounded by shrapne1 in 1917, examined because of epigastric pain in 1928, the x-ray showed splinters of meta in the liver, gal1 bIadder and the greater curvature of the stomach. Laparotomy showed an extensive gastric cancer which had deveIoped not around the meta fragments on the greater curvature, but where such tumors most frequently develop, in the pyIoric region. This wouId seem to indicate that the metal fragments had nothing to do with the carcinoma. If the spIinters caused the gastric cancer, why shouId they not have caused cancer of the Iiver and gaII bIadder? The question of the possibIe production of tumors of the Iymphogranuloma group has been raised. For exampIe, S. Hirsch21 in a detaiIed Iegal opinion stated that in a case of Hodgkin’s disease the process was initiated or if not, definiteIy hastened by an injury. However, IymphogranuIomatosis is somewhat foreign to the discussion as onIy a few pathologists regard it as a tumor. The study of the reIationship between trauma and Ieucemia wiI1 probabIy attract more attention in the future than in the past as the newspaper pubIicity recentIy has stimuIated Iay given the disease interest. Acute Ieucemia, though probabIy infectious in origin, wiII now presumabIy be associated in its inception with some accident; especiaIIy since chiIdren sustain an enormous number of both major and minor injuries this factor can aIways be invoked as a cause. Norikoff22 has reported a patient receiving a fracture of a rib in
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the region of the spleen which was followed later by chronic Iymphatic one year Ieucemia. P. KeIIer23 has aIso described a case of myeloid Ieucemia with a history of injury. AI1 this seems rather vague as the spIeen is not the site of origin of the disease. Not very convincing aIso is the case reIated by OIshausen24 where a man deveIoped a myeIosis two years after a fracture of a Iumbar vertebra. The exampIe of pIasma-ceI1 myeIoma occurring in the upper jaw of the patient of Rocquefer and Ruck25 and cited as traumatic was on the cheek opposite to the traumatized area, and therefore can scarceIy be incIuded among the cases in which such an etioIogy is even remoteIy possibIe. VerdeIetZ6 has aIso reported a Iymphosarcoma of the axiIIa occurring in a man twenty-two years of age, six months after trauma to the chest and shouIder, but without any concrete evidence that the two were reIated. The case of so-caIIed traumatic Iymdescribed by Jarmai”’ phatic Ieucemia injury is occurring in a dog folIowing inadmissibIe on the basis of the bIood counts as reported, since the Ieucocytes did not exceed 21,600 with 62 per cent polynucIears, 30 per cent Iymphocytes, and 7 per cent monocytes. These counts continued for eight weeks at approximateIy the same IeveI and the Iiver, spIeen, intestinal foIIicIes and nodes were enIarged. In man the diagnosis of Ieucemia wouId be improbabIe from these data. In fact the author states that the trauma couId not have been the fina cause of the Ieucemia but that if ceIIuIar proliferation was aIready under way the injury might stimuIate the ceI1 growth and thus make the Ieucemic process evident. ArdoinXs in an interesting report of a chordoma with numerous metastases has assumed without any definite evidence that since his patient was traumatized this was the exciting cause of the growth of the tumor. He cites four simiIar exampIes from the Iiterature. Stanton2g aIso reports two exampIes of chordoma with a
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history of injury two and four years previously but does not greatIy stress the Chordomata are so fact etioIogicaIIy. rare that a few observations can have no statistica value even in suggesting that the trauma stimuIated a pre-existent tissue. No one wouId object to the possibiIity of trauma causing metastasis at a distance after the experimenta work of Tyzzer30 and Knox,31 and the disastrous resuIts observed after the attempts by charIatans to dissipate tumors by vioIent manipuIation methods. In connection with the meIanomas there aIways arises the question as to whether a singIe injury appIied to a preexisting benign tumor, such as a nevus, bears a definite reIationship to a Iater development of maIignancy. Fenwick and WeIIs32 described the case of a gir1 having a smaI1 non-pigmented nevus in the temporofrontal region injured by a bIow some six weeks before seeking advice. Nine months Iater she died with generalized metastases despite radica1 surgica1 remova and heavy radiation. The authors assume that the mechanism of the deveIopment of this maIignancy is by way of injury to the trophic nerve suppIy. The weak point in the argument is that the nevus was evidently maIignant before the injury and the Iatter onIy stimulated the growth and probabIy distributed the neopIastic ceIIs inciting a maIignant change in a quiescent growth. Fabre and Gadrat described a simiIar case of a man twentyeight years oId who sustained an injury to a nevus on the chest and severa months Iater a Iarge fibrosarcoma had deveIoped. It is in the group of osteogenic sarcomas and giant-ceI1 tumors that the question of trauma assumes perhaps its greatest importance, since the etiology of this group occurring in the extremities, and therefore subject to injury, provides a constant chahenge to our knowIedge of tumors. The excellent paper by TroeII”? incIudes a careful anaIysis of 78 cases which have been described as sarcoma
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of bone. TroeII is not at al1 deceived by the post hoc, propter hoc argument but has tried to anaIyze the cases in a IogicaI manner. He concIudes that onIy 59 of these cases are truIy sarcoma, and in 24 of them there is a history of injury to the bone in the region of the growth, but even these 24 contained so many doubtfu1 statements that onIy 9 wouId bear uItimate anaIysis. It must be remembered, as is expIained by TroeII, that many cases at first diagnosed sarcoma even from histoIogica1 and radiological evidence do not prove to be maIignant tumors, but very frequentIy are essentiaIIy benign Iesions, reparative processes or other diseases. This greatIy confuses the issue in records that have been made by enthusiastic observers even before the patient has been observed Iong enough for the actual progress of the disease to be understood. A case of bone sarcoma is reported b Y Cahen:3” A man of seventy-nine sustained a severe bIow on the right tibia1 tuberosity, very rapid growth taking pIace so that in three weeks the tumor was ten times the circumference of the norma bone. EventuaIIy amputation was necessary, the tumor obviously becoming a malignant one. HaIer36 has reported a synovia1 sarcoma of the knee: A woman of forty-one “jumped off a chair” and felt severe pain in the knee. The joint was expIored seven months after the injury and found to be norma except for the media1 meniscus which was ruptured. This was excised and the joint closed. Four months Iater the Ieg was amputated. The joint was found to be fiIled with a waxy homogeneous growth which invaded the pateHa. Microscopic diaghosis was round- and spindle-ceI1 sarcoma, probabIy synovia1 in origin. In this case the exploration might IogicaIIy be bIamed rather than the first injury; in other words, neither was responsibIe for the tumor. The second case was that of a man of thirtyseven who struck his Ieg. The swelling never went down and two months Iater a biopsy revealed a spindle-ceI1 sarcoma. The author is careful to say that the growths were associated with trauma, not caused by it.
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The cases reported by Byron H. Jackson37 were undoubtedly carefuIIy studied and the author suggests that they may have some relation to trauma. One was a miner who sustained a contusion on both femurs by falling across a rail. Two months afterwards pain was stiI1 present in the left femur and the radiograph showed a periostea1 osteogenic sarcoma, which however had no microscopic confirmation as the patient refused operation. The second case was a chiid of thirteen who three weeks before examination struck his knee against a hydrant. A tibia1 osteogenic sarcoma, microscopically verihed, was found. These and a number of other cases Iess we11 observed stiI1 remain baffling but important observations, and onIy by the collection of a Iarge amount of such material can the importance of trauma be positively ascertained. StatisticaIIy there is no reason to beheve that trauma of this type is more than an incident, since the number of traumatic Iesions sustained by any individua1, even those causing necrosis, hemorrhage, thrombosis and regeneration, is too numerous even for compiIation. A patient’s statement that he beIieves a tumor .to be due to trauma, whiIe to be recorded with cannot be considered a conrespect, tribution to the subject. Anyone accustomed to history-taking is we11 aware of the fact that a patient nearIy always has an explanation for every symptom and disease, and an affect is often present regarding these causes which the doctor does we11 to Ieave undisturbed. There can be no question that trauma in the form of sudden shock or over-exertion is an extremely important agent in the production of a decompensated heart, the localization of certain types of abscesses and tubercuIous foci, but the explanation of the patient regarding these matters, whiIe intended to be honest, is often wrong. No doctor assumes that a patient knows that he has vegetations on his heart vaIve, and the embolic result of these vegetations is entirety outside the patient’s ability to predict or understand. No
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matter how good his intentions, his observations and explanations are at fauIt. A patient cannot be expected to know whether the pain which he feeIs in his upper abdomen has originated from above or beIow the diaphragm, but the doctor regards it as his obligation to ascertain this fact, regardIess of the patient’s opinion. Therefore it seems remarkabIe that many physicians attach such great importance to the patient’s interpretation of the cause and time of origin-of his tumor. CONCLUSION
In concIusion, it may be said that the genera1 trend of medica thought has influenced in the Iast probabIy been five years, perhaps unconsciousIy, by the Iegal and compensation verdicts which have been returned. On the other hand, medicine has contributed a considerable number of usefu1 observations, but has offered no definitive answer to the question of the reIationship of trauma and tumor. ProbabIy the most vaIuabIe work which can be done in this field is to educate the medica profession toward
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more compIete factua1 case histories in which persona1 opinions of an inexpert type either as regards the interpretation of cIinica1 observations, radiographs, or pathoIogica1 sIides shouId take second pIace, and in each of these fieIds consuItations from a number of experienced persons shouId be appIied to an understanding of the individua1 probIem. From this aspect the practice of some of the German writers who record in great detai1 the very compIete physica examination made of the injured person together with the names and opinions of the experts who have made the pathoIogica1 diagnosis on the microscopic sIides of the tumor under discussion is a good example too infrequentIy folIowed. FinaIIy, the writer beIieves that no valid evidence has been offered since 1929 to change the opinion expressed in a more extensive survey of this subject pubIished at that time that as yet no causa1 reIationship has been established between a singIe trauma to heaIthy tissues and the appearance of a maIignant neopIasm.
REFERENCES
Bibliographic references have been given only to the papers cited. The oIder literature wiIl be found in the paper by the author in the Archives ofPathology (7: 274, Igzg) referred to above. That which has appeared since Igzg is fairIy voIuminous and inostIy of doubtfu1 value. The titles to these papers will be found in the Quarterly index of the American Medical Association, and abstracts in the Cancer Review, Tbe American Journal of Cancer, and Index Analyticus Cancerologiae. I. MARTLAND, H. S. Am. J. Cancer, 15: 2435, ‘931. SABIN, DOAN and FORKNER.J. Exper. Med., 56: A-289, 1932. 2. BARRET.Ann. de m&d. l&ale. 14: 518-528, IQZ& 3. BALTHAZARD.Ann. de r&d.- l&aie, 1;: 101,_- 1932. 4. CURTIS, DUNNING and BULLOCK.Am. J. Cancer, 5. 6. 7. 8. g. IO. I I. 12. Is. 14.
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DuBors. Rev. mkd. de la Suisse Rom., $I: 65, 1931. MAIDITSCH.Deutscbe Ztschr. f. Chir., 238: 5%8,;933. ARNDT. Beitr. z. klin. Cbir., 157: 305-332, 1933. TREVESand PACK. Surg. Gynec. Obst., 5 I : 749, 1930. GUNSETT. Bull. de I’Assoc. franc. p. l’ttude du cancer, Ig: 459-462, rg3o. SLYE, M. Ann. Surg., 93: 40-49, 1931. VON WOLFF. Zentralbl. f. Gyniik., 55: 942, 1931. ULLMANN. Wien. klin. Wcbnschr., 46: 250, 1933. PLAZY, GOURIOU and GERMAIN. Presse mid., 39: _. 89% 1931. GOUGEROT,CARTEAUD,GUILHALand WEILL. Bull. Sot. franc. dermat. et sypb., No. 7; I 123, 1930.
15. FISCHER-WASELS.Monatscbr. 335-346s
f.
Unfallheilk.,
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16. BENEKE. R. Monatschr. f. Unfallbeilk.. 19: 49. 1932. Ergebn. d. allg. Patb. u. patb. Anat., 26: 8g3-roz7, rg3z (very compIete bibhography). 17. PARKER~~~ KERNOHAN.J. A. M. A., 97: 535,193r. 18. STIEREN.J. A. M. A., 103: 311-313, 1934. 19. BONNETand PAUFIQUE.Bull. Sot. d’opbtbal., p. 679 I
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(Dec.) 1933. 20. LUCKOW.Ztscbr. f. iirztl. Fortbild., 30: 288, 1933. 21. HIRSCH. Klin. Wcbnschr., g: 1872, 1930. 22. NORIKOFF. Vracb delo, 5: 277. 1933; Abst. in Am. J. Cancer, 19: 993, 193j. 21. KELLER. P. Med. Klinik. 28: 1811-1812, 1912. 24. - OLSHAUSEN.Med. Klinik, 28: 1358, 193.2.c25. ROCQUEFER and RUCK. L’Odontol., 6g: 76, 1930. 26. VERDELET.J. mtd. Bordeaux, 104: 559, 1927. 27. J.&RMAI.Beitr. z. oath. Anat. u. a&. Patb., 92: I 19-126, 1933, b;bIiography. 28. ARDOIN. Thtse de Paris, 1927. 29. STANTON.Canad. M. A. J., 27: 20-22, 1932. 30. TYZZER. J. Med. Research, n.s., 23: 3Ow332, 1913. 31. KNOX. Ann. Surg. 75: 129-142, 1922. 32. FENWICKand WELLS. Lancet, I : 1085-1086, rgzg. 33. FABREand GADRAT.Presse m&d., 39: 1222, 1931. 34. TROELL. Arch. f. path. Anat., 283: 550, 1932. 35. CAHEN. Scalpel, 84: 865, 193 I. 36. HALER. Brit. M. J., 2: 748, Ig3I. 37. JACKSON,B. H. Radiology, 16: 766-769, 1931.
AND MALIGNANT LEILA CHARLTON NEW
T
KNOX,
TUMORS
M.D.
YORK CITY
HE question of how far a single mechanica trauma may be assumed to be the soIe etiologica1 agent in the production of a mahgnant tumor is receiving more and more attention of Iate with the extension of Iabor compensation Iaws and the increased number of accidents folIowing the widespread use of motor vehicIes. Speaking generaIIy, the opinion of almost a11 pathoIogists and experimenta students of cancer is that a singIe trauma cannot cause a maIignant neopIasm. On the other hand a good many cIinicians give court testimony or publish articIes supporting the thesis that in rare instances a singIe trauma does cause the appearance of a maIignant neopIasm. This correIation is assumed chiefly in connection with the sarcomata of bone or soft tissues; it is rareIy heId for the carcinomata. The courts on the whoIe take a neutra1 position and juries frequentIy find for the pIaintiff if the evidence is contradictory. The feeIing in compensation cases is often that since the doctors disagree, the plaintiff shouId have a smaI1 award inasmuch as the disease is fatal, even if an absoIuteIy clear-cut reIationship between the injury and the appearance of the tumor cannot be estabIished. The reasons for the differences in opinion between the Iaboratory workers and the cIinicians are mainIy as foIIows: Extensive experimenta work on animaIs has been done by infficting various types of physica tissue injuries without any recorded instance of the production of a maIignant tumor. Yet cancer is easiIy produced in these same animaIs by the action of chemicaIs, chronic inflammation due to irritants, physical agents such as radium’ or x-ray and parasites, a11 of which produce cancer in man with equa1 faciIity, though of course in the case of
the parasites the types effective in the human being differ from those which are found to be carcinogenic in animaIs. The pathoIogist cannot understand why if it is so easy to produce cancer in animaIs by the same agents that act effectiveIy in human beings, is it impossibIe to produce cancer by a trauma in these animaIs if trauma is a factor in human neopIasms. He is aIso daiIy confronted with the discovery of undiagnosed cancer in persons coming to autopsy and, therefore is, aIways thinking of a tumor unsuspected by the patient and undiagnosed by the physician which may be revealed by a trauma. When from IO to 20 per cent of undiagnosed cancer cases come to the autopsy tabIe there is aIways in his mind the possibiIity of a coincidenta occurrence of a neopIasm at the time of the injury. Further he is famiIiar with the statistica reports which show that there has been no obvious increase in cancer foIIowing injuries during the great war and that certain countries with extremeIy accurate death certification, despite the increase in industria1 and motor accidents, show no increase in neopIastic disease in their offIcia1 records. The cIinician on the other hand sees. the dramatic aspect of the situation. A patient states very definiteIy that though in perfect heaIth a tumor has appeared after an injury at the site of a bIow so the gravity of the situation makes a strong impression upon the physician. It is too frequentIy assumed that almost anyone without much experience can diagnose a tumor from a microscopic section or that microscopic examination may be unimportant as compared to cIinica1 judgment. UnfortunateIy this is not true, as any pathoIogist with a Iarge consuIting practice knows, for it is some66
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times only with the greatest difficulty that a differential diagnosis can be made between certain types of traumatic bone and a malignant neoplasm. The repair experienced pathologist is also aware of the fact that while clinical experience is in many cases very capabIe of affording an accurate diagnosis of a mahgnant growth, it not infrequently faiIs, especially with the sarcomata. It is of the greatest importance therefore that al1 these alleged cases of traumatic production of cancer be studied thoroughly, and some real progress in this branch of pathology may be expected if large institutions which are equipped to make and keep carefu1 records, clinica1, radioIogica1 and pathoIogica1, study such material and make it available for the guidance of the experts who are called upon to give testimony in court. In this way cases may be reviewed from time to time in the light of the changing knowledge of neoplasms and form homogeneous groups of tumors of special types in which at least some of the circumstances surrounding the early stages of a tumor and the position which the trauma may have held in that history are clearIy defined. For instance, it is recorded in Troell’s excelIent paper, referred to later, that a carefuI gross and microscopic study was made of a number of bone sarcomata considered as traumatic in origin from the history but that no evidence of injury was found at the site of the tumor; hence the cases had to be excluded from the trauma group. If each hospitaI preserved an adequate museum to which such tumors might be admitted with their fuI1 histories, and a critical study of the traumatic factor in each one was carefully appended, it might be that some usefu1 information could be collected. This has frequentIy been done, especialIy in the case of the more superficia1 tumors where the presence of scars from injury or burns has offered indisputabIe evidence of the importance of trauma as a sensitizing agent for the ultimate appearance of cancer, though
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usualIy, as is discussed later, a period of years intervenes between the development of the neopIasm and the injury to the longer period from scar, and a much the time of the original injury and the secondary one; but a Iarge number of other tumors, especially in the sarcoma group, may offer no physical indication as to their past history, and therefore our knowledge of such a relationship remains largely speculative. An admirable iIlustration of the possibilities of confusion which may way!ay the unwary is contained in the followmg recent report by Barret 9 A man of forty-five feII and fractured the left femur. X-ray pictures taken at that time were interpreted as showing nothing but a fracture. HeaIing was rather sIow but after about three months the patient got about. Eight months later he had a pathologica fracture at the site of the previous injury. The x-ray showed a vohrminous tumor diagnosed clinicahy as an osteosarcoma and the leg was amputated. Microscopic examination, however, showed that instead of a sarcoma the tumor was an aIveoIar growth which OberIing regarded as probabIy originating from the thyroid gland ahhough no evidence of a neopIasm couId be found on cIinica1 examination of that organ. In the discussion refers to two other Balthazard :3
of this examples
paper Barret published by
The first was that of a robust man of fiftyfour who sIipped whiIe carrying a heavy Ioad and was found to have a subtrochanteric fracture of the femur. At the time it was reported that the radiographic examination reveaIed nothing abnorma1 except the fracture, but two months Iater the physician representing the insurance company noted that a tumor appeared at the site of the fracture and three and one-half months after the accident the patient died. The cIinica1 diagnosis was obviousIy a traumatic osteosarcoma, but on carefu1 resurvey of the origina radiograph evidences of bone destruction were found and the Iater radiograph showed extensive invoIvement of the shaft of the femur, so that it was evident that either a primary myeIoma or a metastatic
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deposit from a carcinoma whose existence had not been recognized was present before the injury. UnfortunateIy a full record of the materia1 is not avaiIabIe as no autopsy was done. In the second case cited a Iaborer of twentythree years was shot in the Ieft knee. The wound heaIed rapidIy and the patient Ieft the hospita1 in a short time. Later he complained of pain in the caIf of the Ieg and the interna condyIe was found to be rarefied; there was a shadow in the upper portion of the popIitea1 space. This shadow was thought to be an abscess but no evidence of infection was found. Before the microscopic examination of this materia1 was completed there was such a rapid increase in the popIitea1 tumor that the Ieg was amputated. When the report on the biopsy was obtained it recorded onIy inffammatory tissue and detaiIed examination of the suspected area from the amputated limb, whiIe it showed considerabIe bone production with giant cells, was in the opinion of Professor Roussy onIy an inflammatory lesion. These three interesting medicolega1 cases iIIustrate onIy too cIearIy the necessity for fuI1 information before an opinion is rendered. The lega decisions which have been rendered in these and simiIar cases can of course add nothing to the facts. They merely indicate the trend of social and economic thought with regard to compensation for persons who deveIop tumors while empIoyed in industry, or who have suffered accidents of various sorts. Since a legal decision is made by lay persons, it may have IittIe to do with the facts and Iegal opinions, whiIe of medicine, they estabIish precedent, do not contribute to medica knowIedge. There is apparent in the Iiterature of cIinica1 medicine a strong desire to explain the phenomena which bring about disaster, and even when no Iogical expIanation is obvious, the habit of medical philosophy appears to enter in and permit the assumption of some mysterious outside factors. This is perhaps derived from the German Iiterature, which has formed so large a part of the scientific background of medi-
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cine, but one cannot overIook the eIement of the supernatura1 which causes the German clinician, having eIiminated a11 reasonabIe possibiIity, to assume that trauma is the aushende IMoment, or the immediately exciting cause which has to be invoked if the transition from a norma to a maIignant tissue is to be adequately expIained. This explanation is to be found in so many of the otherwise cIear and IogicaI discussions that its presence aIone excites scepticism. The confidence in predisposition occupies the same place in much of the contemporary Iiterature. Yet any vaIid evidence for such a vague idea as predisposition is not at present avaiIabIe. The mere occurrence of high cancer rates in one famiIy or one strain of animaIs and low rates in another does not prove immunity or resistance. (See on this point Curtis, Dunning and Bullock.4) A sharp distinction must be drawn between the effect of a singIe mechanical injury and the Iong-continued irritations which may resuIt from an injury which has been the origin of some scar, uIcer, or specia1 inflammatory lesion upon which a tumor Iater deveIops. In the Iatter group, there are unquestionabIy many genuine cases, and even hitherto unare being discovered suspected agents which wiI1 stand the scrutiny aIike of the statistician and the physician. Skin carcinoma, whiIe ordinariIy easily recognized microscopicaIIy, may not always be correctly diagnosed by those unfamiliar with heaIing of injuries or chronic inflammatory various dermatoses and benign Iesions, lesions. Scars, rarely, even in childhood, may be the site of epithelioma, as in the case reported by DuBoisj in which a child of ten years sustained a lacerated wound of the forehead and live months Iater a basaI-cell epithelioma appeared which was microscopically diagnosed. Most of the cases, however, are in aduIts in whom irritation has been present for a considerabIe length of time, as in the case reported by Maiditsch6 of a man sixtyfive years of age who had at the age of
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fifteen received a lacerated wound of the leg which ulcerated fifty-one years later and formed the basis for an extensive epithelioma. The average elapsed period for the appearance of the malignant lesion is about thirty-two years. (See for examples Arndt,7 also Treves and Pack.8) This group of tumors has also varied in position, being found on the face and extremities in about equal numbers. Burns with asphalt,g tar, fat, acids, hot metals, various fluids, and excessive exposure to sunlight, and many types of lacerated wounds have been described as the basis of scars which have ulcerated, either spontaneously or following a secondary trauma, and then a neoplasm has developed in the site of injury. Maude Slye’O has recorded a number of neoplasms arising in mice at the site of healing injuries or the resultant scars. Special types of irritants, such as ulceration with a pessary, of which 3 new cases, in addition to 19 or more in the German literature, have been reported by von W01ff’~ which when examined eleven and thirty years after their insertion were found to have caused epithelioma. In von Wolff’s opinion irritation, infection, and predisposition were all necessary for the production of such a tumor. But in none of these examples can a single trauma be incriminated. A tumor of the tongue is reported by Ullmann12 in a man aged forty whose tongue was traumatized for only “a short time” by a filled tooth. But the whole value of the report is vitiated by the fact that the patient’s story of feeling a slight pain in the tongue a few days before is accepted as fixing the date of origin of the neoplasm. The pain was undoubtedly due to the epithelioma already present. If the accuracy of such reports is accepted as absolute, it is obvious that the interva1 necessary for the appearance of the tumor cannot with certainty be predicted either from the age of the patient, the duration of the irritant, or from the type of original injury. On the other hand,
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when the most accurate records are studied, the length of time which must elapse between the beginning of the irritation process and the appearance of the neoplasm is always a matter of years. The best examples are the tar, oil and x-ray cancers in which the period of exposure is accurately known. Even with the highly carcinogenic substances recently discovered, of which methylcholanthrene is the most active, at least two and one-half months must elapse before a carcinoma appears in a mouse, or a tenth of the animal’s life. It is noteworthy that cancer of the breast has recently received scant attention from the advocates of trauma as an etioIogica1 factor in cancer. However, there is one report of a tumor in a man forty-eight years of age who had received a war wound of the right nipple fourteen years before. l3 A claim is also made’4 that a trauma to the breast caused a rapid spread of a breast carcinoma which was undoubtedly present before the accident. Such traumatic spread is generally accepted as possibIe. Fischer-Wasels, who has vigorously opposed the theory that brain tumors are to any considerable extent caused by trauma, admits the possibility that growth of a carcinoma of the lung might be somewhat accelerated by a trauma to the chest.15 The brain tumors have during recent years perhaps aroused more interest and discussion than almost any other group, the extreme position being taken by R. Beneke, l6 who believes that at Ieast 40 per cent of brain tumors are caused by trauma, and includes under this term not only falls and blows on the head causing violent injuries and unconsciousness down to those not even causing headache, but also fright or shock without physical injury; also accidents causing injury to other parts of the body; or anything else capabIe of setting up direct or reflex ischemia of the brain and resulting necrosis of glial tissue, might be
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the cause of a glioma. This position is definiteIy opposed by Fischer-WaseIs, who does not beheve that a transitory vasospasm can be the excitant for tumors, necrosis, or other pathoIogica1 changes, and who insists upon a scientific study of the data rather than the attachment of too much importance to the possibIe connection in any one patient between an intracrania1 tumor and trauma to the head. NevertheIess, in Fischer-Wasels’ case a buIIet wound of the brain occurring nine years before is assumed by him to be the cause of a gIioma which apparentIy arose in the scar tissue. Parker and Kernohan17 made a very compIete study of a Iarge number of cerebral cases in an effort to eIiminate the factor of coincidence, and report upon carefu1 histories taken to evamate trauma in 43~ cases of ghoma. Injury was stated to have been present in 58 cases, or 13.4 per cent. In the contro1 cases without tumors injury was claimed in 44, or 10.4 per cent, whiIe in a group of 200 norma persons 7 I, or 35.5 per cent, reported cerebra1 injuries. The authors therefore fee1 that the argument for trauma must be abandoned in this group of tumors. Tumors of the eye form a specia1 group which, because of their infrequency, shouId be studied thoroughIy and carefu1 reports on the part of eye surgeons may add greatIy to our knowIedge of the importance of trauma. This fact has been pointed out by Stieren,18 who has coIIected from the Iiterature a group of cases in which trauma was mentioned by the patients. The interva1 between the injury and the discovery of a tumor in these cases was eight months, three months, sixteen years, one week, three years, three years, and in Stieren’s case, nine years. The injuries consisted in bIows and lacerations of some portion of the eyebaI1, probabIe in 2 cases. The discussion which foIIowed was somewhat critica as to any correIation for it was feIt by some of those present that the injury may have onIy set up a chronic irritation which gave
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opportunity for the Iater development of a neoplasm. Recently Bonnet and Paufiquelg have reported a case of meIanosarcoma deveIoping in an eye which had sustained a severe bIow sufficient to cause separation of the retina two years before. Carcinoma of the interna organs, especiaIIy the stomach and pancreas, with trauma as the etiological agent, has again been mentioned in the Iiterature onIy infrequentIy. A traumatic gastric cancer is reported by Luckow?’ In a man wounded by shrapne1 in 1917, examined because of epigastric pain in 1928, the x-ray showed splinters of meta in the liver, gal1 bIadder and the greater curvature of the stomach. Laparotomy showed an extensive gastric cancer which had deveIoped not around the meta fragments on the greater curvature, but where such tumors most frequently develop, in the pyIoric region. This wouId seem to indicate that the metal fragments had nothing to do with the carcinoma. If the spIinters caused the gastric cancer, why shouId they not have caused cancer of the Iiver and gaII bIadder? The question of the possibIe production of tumors of the Iymphogranuloma group has been raised. For exampIe, S. Hirsch21 in a detaiIed Iegal opinion stated that in a case of Hodgkin’s disease the process was initiated or if not, definiteIy hastened by an injury. However, IymphogranuIomatosis is somewhat foreign to the discussion as onIy a few pathologists regard it as a tumor. The study of the reIationship between trauma and Ieucemia wiI1 probabIy attract more attention in the future than in the past as the newspaper pubIicity recentIy has stimuIated Iay given the disease interest. Acute Ieucemia, though probabIy infectious in origin, wiII now presumabIy be associated in its inception with some accident; especiaIIy since chiIdren sustain an enormous number of both major and minor injuries this factor can aIways be invoked as a cause. Norikoff22 has reported a patient receiving a fracture of a rib in
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the region of the spleen which was followed later by chronic Iymphatic one year Ieucemia. P. KeIIer23 has aIso described a case of myeloid Ieucemia with a history of injury. AI1 this seems rather vague as the spIeen is not the site of origin of the disease. Not very convincing aIso is the case reIated by OIshausen24 where a man deveIoped a myeIosis two years after a fracture of a Iumbar vertebra. The exampIe of pIasma-ceI1 myeIoma occurring in the upper jaw of the patient of Rocquefer and Ruck25 and cited as traumatic was on the cheek opposite to the traumatized area, and therefore can scarceIy be incIuded among the cases in which such an etioIogy is even remoteIy possibIe. VerdeIetZ6 has aIso reported a Iymphosarcoma of the axiIIa occurring in a man twenty-two years of age, six months after trauma to the chest and shouIder, but without any concrete evidence that the two were reIated. The case of so-caIIed traumatic Iymdescribed by Jarmai”’ phatic Ieucemia injury is occurring in a dog folIowing inadmissibIe on the basis of the bIood counts as reported, since the Ieucocytes did not exceed 21,600 with 62 per cent polynucIears, 30 per cent Iymphocytes, and 7 per cent monocytes. These counts continued for eight weeks at approximateIy the same IeveI and the Iiver, spIeen, intestinal foIIicIes and nodes were enIarged. In man the diagnosis of Ieucemia wouId be improbabIe from these data. In fact the author states that the trauma couId not have been the fina cause of the Ieucemia but that if ceIIuIar proliferation was aIready under way the injury might stimuIate the ceI1 growth and thus make the Ieucemic process evident. ArdoinXs in an interesting report of a chordoma with numerous metastases has assumed without any definite evidence that since his patient was traumatized this was the exciting cause of the growth of the tumor. He cites four simiIar exampIes from the Iiterature. Stanton2g aIso reports two exampIes of chordoma with a
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history of injury two and four years previously but does not greatIy stress the Chordomata are so fact etioIogicaIIy. rare that a few observations can have no statistica value even in suggesting that the trauma stimuIated a pre-existent tissue. No one wouId object to the possibiIity of trauma causing metastasis at a distance after the experimenta work of Tyzzer30 and Knox,31 and the disastrous resuIts observed after the attempts by charIatans to dissipate tumors by vioIent manipuIation methods. In connection with the meIanomas there aIways arises the question as to whether a singIe injury appIied to a preexisting benign tumor, such as a nevus, bears a definite reIationship to a Iater development of maIignancy. Fenwick and WeIIs32 described the case of a gir1 having a smaI1 non-pigmented nevus in the temporofrontal region injured by a bIow some six weeks before seeking advice. Nine months Iater she died with generalized metastases despite radica1 surgica1 remova and heavy radiation. The authors assume that the mechanism of the deveIopment of this maIignancy is by way of injury to the trophic nerve suppIy. The weak point in the argument is that the nevus was evidently maIignant before the injury and the Iatter onIy stimulated the growth and probabIy distributed the neopIastic ceIIs inciting a maIignant change in a quiescent growth. Fabre and Gadrat described a simiIar case of a man twentyeight years oId who sustained an injury to a nevus on the chest and severa months Iater a Iarge fibrosarcoma had deveIoped. It is in the group of osteogenic sarcomas and giant-ceI1 tumors that the question of trauma assumes perhaps its greatest importance, since the etiology of this group occurring in the extremities, and therefore subject to injury, provides a constant chahenge to our knowIedge of tumors. The excellent paper by TroeII”? incIudes a careful anaIysis of 78 cases which have been described as sarcoma
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of bone. TroeII is not at al1 deceived by the post hoc, propter hoc argument but has tried to anaIyze the cases in a IogicaI manner. He concIudes that onIy 59 of these cases are truIy sarcoma, and in 24 of them there is a history of injury to the bone in the region of the growth, but even these 24 contained so many doubtfu1 statements that onIy 9 wouId bear uItimate anaIysis. It must be remembered, as is expIained by TroeII, that many cases at first diagnosed sarcoma even from histoIogica1 and radiological evidence do not prove to be maIignant tumors, but very frequentIy are essentiaIIy benign Iesions, reparative processes or other diseases. This greatIy confuses the issue in records that have been made by enthusiastic observers even before the patient has been observed Iong enough for the actual progress of the disease to be understood. A case of bone sarcoma is reported b Y Cahen:3” A man of seventy-nine sustained a severe bIow on the right tibia1 tuberosity, very rapid growth taking pIace so that in three weeks the tumor was ten times the circumference of the norma bone. EventuaIIy amputation was necessary, the tumor obviously becoming a malignant one. HaIer36 has reported a synovia1 sarcoma of the knee: A woman of forty-one “jumped off a chair” and felt severe pain in the knee. The joint was expIored seven months after the injury and found to be norma except for the media1 meniscus which was ruptured. This was excised and the joint closed. Four months Iater the Ieg was amputated. The joint was found to be fiIled with a waxy homogeneous growth which invaded the pateHa. Microscopic diaghosis was round- and spindle-ceI1 sarcoma, probabIy synovia1 in origin. In this case the exploration might IogicaIIy be bIamed rather than the first injury; in other words, neither was responsibIe for the tumor. The second case was that of a man of thirtyseven who struck his Ieg. The swelling never went down and two months Iater a biopsy revealed a spindle-ceI1 sarcoma. The author is careful to say that the growths were associated with trauma, not caused by it.
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The cases reported by Byron H. Jackson37 were undoubtedly carefuIIy studied and the author suggests that they may have some relation to trauma. One was a miner who sustained a contusion on both femurs by falling across a rail. Two months afterwards pain was stiI1 present in the left femur and the radiograph showed a periostea1 osteogenic sarcoma, which however had no microscopic confirmation as the patient refused operation. The second case was a chiid of thirteen who three weeks before examination struck his knee against a hydrant. A tibia1 osteogenic sarcoma, microscopically verihed, was found. These and a number of other cases Iess we11 observed stiI1 remain baffling but important observations, and onIy by the collection of a Iarge amount of such material can the importance of trauma be positively ascertained. StatisticaIIy there is no reason to beheve that trauma of this type is more than an incident, since the number of traumatic Iesions sustained by any individua1, even those causing necrosis, hemorrhage, thrombosis and regeneration, is too numerous even for compiIation. A patient’s statement that he beIieves a tumor .to be due to trauma, whiIe to be recorded with cannot be considered a conrespect, tribution to the subject. Anyone accustomed to history-taking is we11 aware of the fact that a patient nearIy always has an explanation for every symptom and disease, and an affect is often present regarding these causes which the doctor does we11 to Ieave undisturbed. There can be no question that trauma in the form of sudden shock or over-exertion is an extremely important agent in the production of a decompensated heart, the localization of certain types of abscesses and tubercuIous foci, but the explanation of the patient regarding these matters, whiIe intended to be honest, is often wrong. No doctor assumes that a patient knows that he has vegetations on his heart vaIve, and the embolic result of these vegetations is entirety outside the patient’s ability to predict or understand. No
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matter how good his intentions, his observations and explanations are at fauIt. A patient cannot be expected to know whether the pain which he feeIs in his upper abdomen has originated from above or beIow the diaphragm, but the doctor regards it as his obligation to ascertain this fact, regardIess of the patient’s opinion. Therefore it seems remarkabIe that many physicians attach such great importance to the patient’s interpretation of the cause and time of origin-of his tumor. CONCLUSION
In concIusion, it may be said that the genera1 trend of medica thought has influenced in the Iast probabIy been five years, perhaps unconsciousIy, by the Iegal and compensation verdicts which have been returned. On the other hand, medicine has contributed a considerable number of usefu1 observations, but has offered no definitive answer to the question of the reIationship of trauma and tumor. ProbabIy the most vaIuabIe work which can be done in this field is to educate the medica profession toward
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more compIete factua1 case histories in which persona1 opinions of an inexpert type either as regards the interpretation of cIinica1 observations, radiographs, or pathoIogica1 sIides shouId take second pIace, and in each of these fieIds consuItations from a number of experienced persons shouId be appIied to an understanding of the individua1 probIem. From this aspect the practice of some of the German writers who record in great detai1 the very compIete physica examination made of the injured person together with the names and opinions of the experts who have made the pathoIogica1 diagnosis on the microscopic sIides of the tumor under discussion is a good example too infrequentIy folIowed. FinaIIy, the writer beIieves that no valid evidence has been offered since 1929 to change the opinion expressed in a more extensive survey of this subject pubIished at that time that as yet no causa1 reIationship has been established between a singIe trauma to heaIthy tissues and the appearance of a maIignant neopIasm.
REFERENCES
Bibliographic references have been given only to the papers cited. The oIder literature wiIl be found in the paper by the author in the Archives ofPathology (7: 274, Igzg) referred to above. That which has appeared since Igzg is fairIy voIuminous and inostIy of doubtfu1 value. The titles to these papers will be found in the Quarterly index of the American Medical Association, and abstracts in the Cancer Review, Tbe American Journal of Cancer, and Index Analyticus Cancerologiae. I. MARTLAND, H. S. Am. J. Cancer, 15: 2435, ‘931. SABIN, DOAN and FORKNER.J. Exper. Med., 56: A-289, 1932. 2. BARRET.Ann. de m&d. l&ale. 14: 518-528, IQZ& 3. BALTHAZARD.Ann. de r&d.- l&aie, 1;: 101,_- 1932. 4. CURTIS, DUNNING and BULLOCK.Am. J. Cancer, 5. 6. 7. 8. g. IO. I I. 12. Is. 14.
17:8ww3.
1933;
zI:869&554-57o,
1934.
DuBors. Rev. mkd. de la Suisse Rom., $I: 65, 1931. MAIDITSCH.Deutscbe Ztschr. f. Chir., 238: 5%8,;933. ARNDT. Beitr. z. klin. Cbir., 157: 305-332, 1933. TREVESand PACK. Surg. Gynec. Obst., 5 I : 749, 1930. GUNSETT. Bull. de I’Assoc. franc. p. l’ttude du cancer, Ig: 459-462, rg3o. SLYE, M. Ann. Surg., 93: 40-49, 1931. VON WOLFF. Zentralbl. f. Gyniik., 55: 942, 1931. ULLMANN. Wien. klin. Wcbnschr., 46: 250, 1933. PLAZY, GOURIOU and GERMAIN. Presse mid., 39: _. 89% 1931. GOUGEROT,CARTEAUD,GUILHALand WEILL. Bull. Sot. franc. dermat. et sypb., No. 7; I 123, 1930.
15. FISCHER-WASELS.Monatscbr. 335-346s
f.
Unfallheilk.,
40:
1933.
16. BENEKE. R. Monatschr. f. Unfallbeilk.. 19: 49. 1932. Ergebn. d. allg. Patb. u. patb. Anat., 26: 8g3-roz7, rg3z (very compIete bibhography). 17. PARKER~~~ KERNOHAN.J. A. M. A., 97: 535,193r. 18. STIEREN.J. A. M. A., 103: 311-313, 1934. 19. BONNETand PAUFIQUE.Bull. Sot. d’opbtbal., p. 679 I
I
-_
__.
(Dec.) 1933. 20. LUCKOW.Ztscbr. f. iirztl. Fortbild., 30: 288, 1933. 21. HIRSCH. Klin. Wcbnschr., g: 1872, 1930. 22. NORIKOFF. Vracb delo, 5: 277. 1933; Abst. in Am. J. Cancer, 19: 993, 193j. 21. KELLER. P. Med. Klinik. 28: 1811-1812, 1912. 24. - OLSHAUSEN.Med. Klinik, 28: 1358, 193.2.c25. ROCQUEFER and RUCK. L’Odontol., 6g: 76, 1930. 26. VERDELET.J. mtd. Bordeaux, 104: 559, 1927. 27. J.&RMAI.Beitr. z. oath. Anat. u. a&. Patb., 92: I 19-126, 1933, b;bIiography. 28. ARDOIN. Thtse de Paris, 1927. 29. STANTON.Canad. M. A. J., 27: 20-22, 1932. 30. TYZZER. J. Med. Research, n.s., 23: 3Ow332, 1913. 31. KNOX. Ann. Surg. 75: 129-142, 1922. 32. FENWICKand WELLS. Lancet, I : 1085-1086, rgzg. 33. FABREand GADRAT.Presse m&d., 39: 1222, 1931. 34. TROELL. Arch. f. path. Anat., 283: 550, 1932. 35. CAHEN. Scalpel, 84: 865, 193 I. 36. HALER. Brit. M. J., 2: 748, Ig3I. 37. JACKSON,B. H. Radiology, 16: 766-769, 1931.