THE AMERICANJOURNAL OF CANCER

A Continuation of The Journal of Cancer Research

VOLUME XVI JULY, 1932 NUMBER 4

CANCER OF THE LUNG IN THE MINERS OFJ ACHYMOV (JOACHIMSTAL)

REPORT OF CASES OBSERVED IN 1929-1930

DR. AUG. PIRCHAN

Head Physician, State Radium Institute, Jdchumo»

AND

DR. H. SIKLProfessor Exlraordinaru of Pathology at the Czech University, Prague

INTRODUCTIONA miner's life has always been fraught with danger. Besides

various traumatic accidents, to which the miner is exposed, hishealth and life are endangered by the poisonous atmosphere of hisenvironment.

In the mines of the Erz Mountains, on both the Bohemian andSaxon sides, it has been known for some centuries that the minersdie in the prime of life with symptoms of damaged lungs and rapidlyprogressing cachexia. These conditions, especially well known atthe Schneeberg mines in Saxony, have been mentioned or describedby many writers, viz. Agricola in 1500, Matthesius in 1559, Pansa in1814, Scheffler (1) in 1770, and others. The real nature of theaffection was not discovered, however, until 1879, when Hartingand Hesse (2), by clinical and anatomical research, proved it to be amalignant tumor of the lungs. Latterly, the matter has beenstudied by Cohnheim, 1882 (3) ; Ancke, 1884 (4) ; Arnstein, 1913 (5) ;M. Uhlig, 1920 (6); and Risel, 1921 (7). Finally, in 1926, by thethorough research of Rostoski, Saupe, and Schmorl (8), thecarcinomatous nature of the tumors was definitely established.

681

682 AUG. PIRCHAN AND H. SIKL

On the Bohemian side of the Erz Mountains, in Czechoslovakia,about 30 kilometers southeast of Schneeberg, lies Jachymov(Joachimstal), a small mining town of about 8,000 inhabitants.It has been world famous as a source of radium from the beginningof the present century, but the history of its mines is much older.

Jaohymov was first heard of in 1516, when rich veins of silverwere found in the deep valley cutting into the southern slopes of theErz Mountains. A lively exploitation was then begun, but owingto the wasteful methods of that time, the veins were almostexhausted by the end of the sixteenth century. Later, cobalt,nickel, bismuth, and arsenic were worked, but the original pros­perity was never regained, and the working, in general, remainedunprofitable. In the second half of the IDth century, the ex­ploitation of uranium ore-found here chiefly in the form ofpitchblende-was taken up,. and a government factory for theproduction of uranium dyes was established. At the beginning ofthe present century, after Mme. Curie's discovery of radium in thepitchblende of Jachymov, measures were immediately taken toproduce radium on .industrial lines. At the present time theannual production of radium chloride in the government factoryamounts to 2 gm. The further discovery that the waters of themines were strongly radio-active has led to the establishment ofbaths, and today Jachymov is well known as a spa.

In Jaehymov, as in Schneeberg, there has been for a long time aconsiderable mortality among miners from pulmonary disease.The miners themselves called the disease Bergkrankheit or Bergsucht,terms which were in common use at Schneeberg. It seems strangethat the true nature of the condition should have remained so longunknown to the physicians of Jachymov, since it would appeareasy to realize that it was the same as that affecting the miners ofSchneeberg. Harting and Hesse, in 1879, had addressed an inquiryto J achymov concerning the occurrence of cancer of the lungs andwere answered in the negative. In 1921, M. Uhlig made a similarinquiry, with the same result.

Professor Hlava, late pathologist at the Czech University,Prague, pointed out on several occasions the possibility of cancer ofthe lungs occurring among J achymov miners; but he did notsucceed in bringing the matter to the attention of either theadministration of the Jachymov mines or the health authorities,and without their permission or collaboration no investigationcould be made.

CANCER OF LUNG IN MINERS OF JACHYMOV 683

Five years ago, when Dr. Aug. Pirchan, joint author of thepresent report, took over the post of Chief Physician at theJriohymov Radium Institute, he immediately turned his attentionto this question. The first case of cancer of the lung in a radiumfactory worker (J. P.) was observed by Dr. Pirchan in 1926. Thediagnosis was made _by roentgen studies, and the patient wassubsequently admitted to the medical clinic of the GermanUniversity at Prague, where he died. A post-mortem examinationwas carried out at the German Pathological Institute.

No further cases of cancer of the lung were seen un til 1928,when three suspicious cases came under observation. It should benoted that, at that time, there was no possibility of performingautopsies on deceased miners.

In 1929 Lowy's paper (9) appeared with reports on two cases ofcancer of the lung among the Jachymov miners. One of thesecases was the one mentioned above (J. P.). The diagnosis of thesecond (J. Sch.) was made at the Nonnenbruch Clinic. The manlater returned to his home, where he died on March 2, 1929 (seeCase 3, below).

As a result of Lowy's communication, public attention wasaroused, especially after the daily press and political authoritieshad intervened. The Ministry of Public Works-to which theJachyrnov mines are subordinate-in collaboration with theMinistry of Public Health, formed a commission for the study of thequestion. The Health Organization of the League of Nations wasalso interested, and arrangements were made for a continuousenquiry into cancer morbidity among the Jachymov miners withthe financial assistance of the League.

PREVALENCE OF LUNG CANCER IN JACHYMOV MINERS

First, a thorough systematic physical and x-ray examination ofall the mine workers (323 persons) was carried out by Drs. Markland Pirchan; no suspicious case was found. Afterwards, pensioned­off miners, here referred to as Provisionisten, were examined, atotal of 83 persons. Among these were found 3 in whom aprobable diagnosis of cancer 'of the lungs could be made.' Itshould be noted, however, that the whole number of Provisionis tencould not be examined, as some of the men living in outlyingvillages were not able to appear for examination, since they werealready seriously ill. Otherwise the results of the examination

I The diagnosis was confirmed anatomically in two of these cases. See Cases 8 and9. below,

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CANCER m' LUNG IN MINERS OF JACHYMOV 685

were negative, except for a slight degree of anthracosis, which in nocase had reached stage II (according to Staub and Oetiker).

The chief attention was directed to the post-mortem exami­nation of deceased miners, which was obviously the best means ofestablishing the prevalence of the disease. The first post-mortemswere carried out by Drs. Markl and Pirchan; later ProfessorSikl as pathological expert was charged with this task.

During the period under review (1929-1930) 19 miners died.Of these, 10 belonged to the active staff, while the others wereProvisionisten. Post-mortem examinations were made in 13 casesonly, in 9 of which cancer of the lungs was found; 4 cases proved tobe non-cancerous. In one of the latter group death was due to anaccident, and autopsy was performed by Dr. Mahler. In one case

TABLE II

Other Deaths among Miners during the Period lDtlJ-lDaO

Name AgePeriod of

DieuCause of Death Accoruing Post-mortem

Employment to Clinical Finding. Diagnosis---J. R... 44 1902-1929 Feb. 6, 1929 Cancer of the lung (?) Chronic pneumonia

with cirrhosis of thelungs

V. Z... 43 1905--1920 Feb. 12, 1929 Influenza; pleuritis ex- No post-mortemudativa; pneumonia

A.K .. 33 1913-1929 June 12,1929 Tuberculosis of the No post-mortemlung

It. Zoo. 47 1908-1929 June 14, 1929 Acute miliary tubereu- Acute miliary tuber-losis culosis

A.O... 40 1906-1929 Aug. 19, 1929 Suicide No post-mortemJ. Roo. 72 1873-1893 Oct. 19, 1929 Bronchitis; myodegene- No post-mortem

ratio cordisFr. P .. 59 1920--1929 Nov. 28,1929 Pulmonary tuberculo- No post-mortem

sis; aortic aneurysmR.P... 36 1911-1930 Aug. 3, 19:30 Cancer of the larynx No post-mortemJ. x. 28 1927-1930 Dec. 3, 19:30 Accident Forensic autopsy

chronic pneumonia terminating in cirrhosis of the lungs wasdiagnosed anatomically; no signs of a neoplasm could be found, noteven microscopically. In the remaining cases death was due, inthe first, to generalized miliary tuberculosis; in the second, tochronic tuberculosis of the lungs.

We have suggested that in every case of death among theminers post-mortem examination should be made, in order toobtain a reliable estimate of the frequency of the disease, takinginto account any cases of incipient cancer not manifest on clinicalexamination. Practically, we were obliged to refrain from per-

686 AUG. PIRCHAN AND H. 8IKL

forming autopsies in 6 cases, for reasons not under our control. Innone of these cases, however, was there any clinical suspicion ofcancer of the lungs. We are, nevertheless, of the opinion that theexistence of cancer of the lungs-as the cause of death or, at least,as an accessory disease-cannot be absolutely denied in most ofthese cases. The supposed causes of death are given in Table II.

To confine ourselves, however, to proved cases, we have seenthat in 9 cases out of 17 (not considering 2 cases of violent death)­i.e. 53 per cent-cancer of the lungs was the cause of death. Sucha high percentage admits of little doubt as to the existence here ofan occupational disease.

REPORTS OF FATAl, CASES 2

CASE 1: V. M., aged thirty-nine, had been a carpenter in the minesince 1909. In 1923 he complained of a stabbing pain in the region of theheart and was declared unfit for work. His state of health subsequentlyvaried; he worked at home occasionally, but at times was quite inca­pacitated by increased pain. He did not cough. The loss of weight hadbeen marked during the last year. Clinical and x-ray examination,Nov. 16, 1928, and Dec. 5, 1928, showed infiltration of the left lung,starting from the hilus. Cancer of the lung was suspected. Deathoccurred Feb. 5, 1929.

The post-mortem examination was carried out by Dr. Markl and Dr.Pirchan under very unfavorable conditions in the home of the deceased;no autopsy record was made.

Post-mortem Diagnosis: Scirrhous carcinoma of the left upper lobe(lingula), progressing into the pleura and pericardium; a few cancer nodes(implanted metastases) in the epicardium; marked anthracosis of theperibronchial lymph nodes; small calcified focus in one peribronchialnode in the hilus of the left lung; nodular colloid and cystic struma.

Description of Specimen: The description of the specimen (Fig. 1) sentto the Pathological Institute, Prague, is as follows: The lingula of the leftlung is markedly shrunken and adherent to the surrounding tissues bymeans of the thickened pleura, forming a hard skin, about 1 em. in thick­ness. The parenchyma is spotted with irregular foci of whitish canceroustissue of rather firm consistency, between which the lung tissue is apneu­matic, indurated, and blackish. Towards the hilus the tumor in­filtration is rather vaguely limited, not reaching the hilus itself. Thethickened pleura is closely adherent to the adjacent portions of diaphragm

I A preliminary communication of the first three cases reported here was presentedto the Health Organization of the League of Nations on May 3, 1929, and appeared inCompies rendus de la Com1lli~.,ion internationale IJermanenle pour l'etude de« maladiesp7'Ofessionelles, IV"'· reunion, Lyon 1929, Vol. II, 338. A short report on the wholequestion was given by Dr. 8ikl at the Krebskonferenz in Dresden on June 11, 19:~0 (secZtschr.J. Krebsforsclutnq 32: 600,1930. Abst , in Am. J. Cancer 15: 948,1931).

CANCER OF LUNG IN MINERS OF JACHYMOV 687

and pericardium. On the inner surface of the pericardium is It flat,prominent tumor mass. In the epicardium arc several flat cancer nodes.

Microscopic Examination (Hist. No. 4595): On large topographicalsections from the infiltrated ventral portion of the left upper lobe (Fig. 2)a compact mass of tumor tissue the size of a bean was found. It showed arather typical epidermoid structure (Fig. 3), its center consisting of

Fro. 1. CASE 1: SECTION THROUGH THE LEFT LUNG, PERICARDIUM, AND HEART

(Mus. SPEC. No. 2564)

keratin, Adjacent to it, towards the hilus, was a bronchus totallydestroyed by cancer tissue, so that it was detectable only by the remainsof cartilages. The impression gained from the topography was that thegrowth arose from the epithelium of a small bronchiectasis. In thevicinity the cancerous epithelium was sometimes less typical, showingtransitions to cuboid, polymorphous, and even cylindric forms, but theepidermoid structure was largely predominant. Towards the peripheryof the lung the cancerous tissue was less dense, forming small foci in theindurated parenchyma only. There were numerous areas of necrosis,

FIG. 2. CASE 1: TOPOGRAPHY OF TUMOR.

GIESON.

\VEIGERT'S FUCHSIN-HEMATOXYLIN-VAN

X7

FIG. 3. CASE 1: MICROSCOPIC STRUCTlTRE OF TUMOR. HEMATOXYLIN-EoSIN. X 140

688

CANCER OF LUNG IN MINERS OF JACHYMOV 689

but no signs of a tuberculous process could be distinguished. Theperipheral bronchi were partly widened and filled with detritus containinga large quantity of anthracotic pigment, partly obliterated by cancerousor granulation tissue. Many vessels, arteries, and veins were occluded byorganized thrombi sometimes containing cancerous foci. The thickenedpleura was densely infiltrated with epidermoid carcinoma.

FlO. 4. CASE 2: LEFT LUNG CUT OPEN (Mus. SPEC. No. 2597)

Epurisis: Epidermoid cancer starting probably from a small bronchi­ectasis in the left upper lobe and spreading towards the lingula. No meta­stases, either lymphatic or by the blood stream. Duration of the malady sixyears at least.

The prominent features of this case are the long duration and thecomplete absence of generalization of the growth.

CASE 2: H., aged forty-two, had been at the mine since 1908 as acarpenter. He gave a history of violent gastric symptoms in 1920,pointing to gastric ulcer, and of pleurisy of the left lung a year later. Inthe summer of 1928 he was pensioned off on account of gastric symptoms.Since the end of October 1928 he had experienced stabbing pain in theback, radiating forwards, dyspnea, cough with purulent bloody sputum,loss of appetite, and loss of weight. Examination on Nov. 14, 1928,

690 AUG. PIRCHAN AND H. SIKL

showed infiltration of the left lung starting from the hilus. The leftsupraclavicular glands were enlarged. A diagnosis of cancer of the lungwas made.

Signs of a transverse lesion of the spinal cord subsequently appeared,and death ensued Feb. 28, 1929.

Post-mortem Diagnosis (March 2): Cancer of the left lung (rnediastino­pulmonary form), penetrating into the pericardium; metastases inmediastinal, supraclavicular, and periportal lymph nodes, sternum, fourthleft rib, sixth and eleventh thoracic vertebrae, pancreas, and liver;compression myelitis in the dorsal and lumbar segments, caused by the

FlO. 5. C.~SE 2: MICROSCOPIC STRUCTURE OF TUMOR. HEMATOXYLIN-EOSIN.

X 140

penetration of vertebral metastatic growths into the spinal canal; pseudo­membranous cystitis; bedsores in the sacral region and on the legs;advanced emaciation; recent bronchopneumonia of the right lung; fiatscar on the lesser gastric curvature, evidently from a peptic ulcer.

Extract from Autopsy Record: The left lung (Fig. 4) was slightlyshrunken, and closely fixed to the mediastinum and pericardium. Thcpleura on the mediastinal surface was rather thickened; elsewhere it wasroughened in places. In a section cut through the lung and the medi­astinum a whitish, soft, partially necrotic cancerous mass was found,infiltrating confiuently the hilus of the lung and the mediastinum. Thehilar lymph nodes were enlarged and infiltrated by tumor tissue, fusedalmost completely with the tumor mass, and recognizable only by theremains of anthracotic pigment. The bronchial branches of first and

CANCER OF LUNG IN MINERS OF JACHYMOV 691

second degree, imbedded in the tumor, were infiltrated and occluded withcancer tissue. The growth penetrated the lung parenchyma in the formof irregular ramifications, some of which, in places, almost reached theexternal pleura. The rest of the parenchyma was mostly apneumatic andinfiltrated with gelatinous or purulent exudate. The widened peripheralbronchi were filled with pus. Following along the pulmonary veins, thetumor penetrated into the pericardium and formed several flat pro­jections.

Microscopic Excminaiioii (Hist. No. 4598): The tumor tissue consistedof small round cells (Fig. 5) with a very faint protoplasm, so that thefirst impression was that of lymphosarcoma, but the alveolar arrangementwas pronounced and the oat-like shape of the cells was rather marked inplaces. Cylindric cells, limiting small lumina, though rare, were to befound. There can bp no doubt that the tumor was a small-cell carcinoma.

Epicrisis: Small-cell carcinoma of the left lung, starting fr 1m the hilw~

(probably from the bronchi), spreading into both the upper and lower lobe,penetrating into mediastinum and pericardium; widespread lymphatic andhematogenous metastases, affecting chiefly the bones; compressive myelitisdue to metastases into spinal column.

The malady could be traced back definitely for only four months.Nine years earlier, however, the patient suffered from gastric trouble,believed to be due to a gastric ulcer, which was confirmed at autopsy bythe presence of a characteristic scar in the stomach. On the other hand,it is possible that the pleurisy from which the patient suffered one yearlater had some connection with the tumor. Yet in the years following nosigns of cancer of t he lungs appeared.

The most striking features of this case are the uncommonly rapidprogress of the malady and the widespread generalization, with involve­ment of the spinal cord.

CASE 3: .J. Sch., aged fifty-one, had worked in the Jachymov minessince 1905 as a hewer. In 1922 he was pensioned off because of "rheu­matoid" pains. During the latter part of his employment, he hadsuffered from shortness of breath and cough, symptoms which hadincreased progressively, especially during the last two years. He wasadmitted to the Nonnenbruch medical clinic at Prague, where thediagnosis of cancer of the lower lobe of the right lung was established.!Later he returned home, where he died on March 2, 1929.

Post-mortem Diagnosis (March 2): Carcinoma of the right lower lobe,starting from the hilus (mediastino-pulmonary or lobar form), penetratinginto the lung veins; cancerous infiltration of the mediastinal and rightcervical glands; small bronchial carcinoma, apparently of differentstructure, in the left upper lobe (second primary growth); metastaticnodule in the right adrenal; a few indurated spots in the left upper lobe,but otherwise only moderate anthracosis; chronic myocarditis with oldfibrous and recent foci of softening in the wall of the left ventricle;circumscribed adhesions of the pericardium above the same; both

3 As mentioned above, this case was described from the clinical standpoint byLowy (7), in whose paper the full morbid history may be found.

692 AUG. PIRCHAN AND H. SIKL

ventricles dilated on the right; moderate hypertrophy of the auricle andventricle; parietal thrombus in the right auricle; moderate passivecongestion of the abdominal organs; several recent infarcts in the spleen;atheromatosis of the aorta and coronary arteries; slight arterioscleroticcontraction of kidneys; moderate ascites; slight edema of legs.

Extract from Autopsy Record: The right lung (Fig. 6) was enlarged andvery heavy. Both the parietal and the visceral layers of the pleura werethickened, especially over the lower lobe. The pleural cavity was

FIG. 6. CASE 3: RIGHT LUNG CUT OPEN (Mus. SPEC. No. 2599)

obliterated by extensive, very close adhesions. Only over the upper lobesome flat cavities, filled with fluid, remained. The thickening was duein part to whitish, soft cancerous tissue, especially on the diaphragmaticand pericardial surface. On section, the whole lower lobe was found to beinfiltrated with a soft, whitish cancerous mass extending from the hilusto the pleura. In the hilus portion it was very dense. In the peripheralportions, on the contrary, it consisted of numerous small, rather coalescentfoci. The upper limit of the tumor, formed by the interlobular incisure,was very sharp. The interlobular pleura was also infiltrated. Thegrowth invaded the mediastinum, which was infiltrated with a confluenttumor mass. It was rather difficult to discern some of the enlargedlymph nodes. There was direct penetration into the pulmonary veins,through which the tumor clots almost reached the atrium. The peri-

CANCER OF LUNG IN MINERS OF JACHYMOV 693

cardial cavity contained about 150 c.c. of bloody fluid. On the ventralsurface on the left ventricle was a circumscribed concretion consisting ofloose fibrous tissue, in which a cancerous nodule the size of a pea wasfound. The cervical lymph nodes on the left side were swollen and fusedinto a bulky growth the size of a goose egg.

In the upper lobe of the left lung (Fig. 7) a small tumor was found.It was situated in the bronchial mucosa at the ramification of the upperbronchial branch, about :3 em. distant from the hilus, and partially

FIG. 7. CASE 3: LEFT LUNG CUT OPEN (Mus. SPEC. No. 26(0)

blocked t he bronchial lumen. Its consistency was rather firm. Theadjacent lymph nodes were hyperplastic up to the size of a pea, ratheranthracotic, with prominent follicles, but no cancerous infiltration couldbe distinguished. In the right adrenal a tumor nodule the size of ahazelnut was found. Its consistence was similar to that of the smallgrowth in the left upper lobe.

Microscopic Examination (Htst. No. 4599): The cancerous massesin the right lower lobe (Fig. 8) showed the structure of a small-cellcarcinoma. An oat-like aspect of the tumor cells was rather prevalent.

66

G94 AUG. pmCHAN AND H. SIKL

The same structure was found in the infiltrated pleura and lymph nodes.The small cancer node in the left upper lobe, on the contrary, was foundto be a squamous-cell epidermoid cancer (Fig. 10). Topographicalsections (Fig. 9) showed the cancerous mass infiltrating the mucosa andprojecting into the lumen. The adjacent lymph nodes showed simplehyperplasia but no cancerous infiltration. There was a moderate anthra­cosis, with no induration or scarring. The metastasis found in the rightadrenal (Fig. 11) had exactly the same structure as the small growth inthe left upper lobe.

FlU. 8. CASE 3: MICROSCOPIC STRUCTURE OF TUMOR OF RIGHT LUNG. HEMATOXYI.IN­

EOSIN. X 140

Epicrisis: Large oat-cell carcinoma of the right lower lobe with extensionto the pleura and mediastinum, and lymphatic metastases in cervical glands.Second 1Jrimary carcinoma in a bronchus of the left upper lobe, with singlehematogenous metastasis in the right adrenal. General atherosclerosis 'Withnujocardiiis and slight contraction of kidneys.

Sure signs of carcinoma of the lungs had been evident for at leastseven years.

The most remarkable feature of this case is the presence of twoobviously primary carcinomas of different histologic structure, both ofwhich produced metastases. This is 11 striking case of multiple primarycarcinoma, satisfying entirely the most rigorous criteria fixed by BillrothAmong the cancers of the lung in Schnee berg miners, Schroorl foundseveral eases of multiple primary tumors, including one very like our own.

FIG. 9. CASE 3: TOPOGRAPHY OF TUMOR OF LEFT UI'PER LOBE. HEMATOXYLIN­

EOSIN. X 5

FlO. 10. CASE 3: MICROSCOPIC STRUCTURE OF TUMOR OF LEFT UPPER LOBE. HEMA­

TOXYLIN-EoSIN. X 132

695

696 AUG. PIRCHAN AND H. SIKL

The small primary carcinoma offered a most favorable opportunity forstudying the histogenesis. The adjacent lymph nodes, which were freefrom tumor tissue, showed no signs of cicatrization, not even markedanthracosis, a fact which may be emphasized, since Schmorl (10), inagreement with Wolf (11), states that bronchial carcinomata generallyoriginate in cicatrices resulting from the breaking through of softenedanthracotic lymph nodes into the bronchi.

FlO. 11. CASE 3: MICROSCOPIC STRUCTURE OF METASTMllS IN THE HI<lHT ADR.;NAI..

HEMATOXYLIN-VAN GIESON. X 25.

CASE 4: Ed. T., aged sixty-three, had worked in the Most coal minesince 1898. He became a foreman in the Werner pit at Jiichymov in1907, and was pensioned off in 1920.

According to the statement of the doctor in charge of this case (Dr.Kretschmer), the patient visited him about Christmas 1920, complainingof severe pains in the left side of the chest, unaccompanied by coughing.In the spring of 1920, a pleural exudate on the left side was found. Itrecurred continually, so that thoracentesis had to be done every fortnight.The patient did not appear when the systematic examination of theminers was made in 1929. Only at a subsequent examination was theexudate found, and a pulmonary tumor suspected. Dcath occurredOct. 28, 1929.

Post-mortem Diagnosis (Oct. 29, 1929): Diffuse cancerous infiltration ofthe left pleura; slight cancerous infiltration of the hilus and periaorticlymph nodes and of those in the thoracic and upper abdominal cavity;metastatic cancer nodule in the subdermal tissue over the sixth rib, leftside (implanted metastasis after puncture); confluent bronchopneumonia

CANCER OF LUNG IN MINERS OF J ACHYMOV 697

in the right lower lobe; atherosclerosis of the aorta and the coronaryvessels; pronounced general atrophy.

Extract from Autopsy Record: The entire left pleura was thickened to atough, whitish-gray mass (Fig. 12), which had penetrated deep into theinterlobular scissurae almost down to the hilus. The pleural cavity hadbeen practically obliterated owing to the adhesion of the pleural layers.At the base of the lung only a pocket-shaped cavity as large as the palm

FIG. 12. CASE 4: LEFT LUNG CUT OPEN (Mus. SPEC. No. 2671)

of the hand, containing a bloody serous fluid, remained. In additionthere were some smaller sacs behind the upper lobe filled with purulentserous exudate. The thickened pleura adhered firmly to the diaphragmand the pericardium, and both were partly permeated with canceroustissue. On the inner surface of the pericardium, flat cancer nodules werefound. The lung tissue was pale, anemic, and moderately pigmented.With the exception of a narrow subpleural layer, to which the cancerousproliferation had spread direct from the pleura, no cancerous tissue was tobe found in any part of the parenchyma of the lung.

In the left hilus of the lung and at the bifurcation of the tracheawas a group of enlarged lymph glands which coalesced in places, but werestill easily distinguishable. Their cut surfaces showed blackish pig­mentation. They were somewhat soft in places, and here and thereshowed whitish cancerous foci. Several lymph glands along the lowerbronchial aorta and on the upper section of the abdominal aorta wereenlarged to approximately the size of a bean and were permeated withwhitish cancer tissue.

FIG. 13. CASE 4: MICROSCOPIC STRUCTURE OF TUMon: CYSTO-PAPILLARY AUEA WITH

CUBOIDAL EPITHELIUM. HEMATOXYLIN-EoSIN. X 140

FIG. 14. CASE 4: MICROSCOPIc 8TRUCTURE or TUMon: CYSTO-PAPILLARY AREA WITH

CYLINDRIC EPITHELIUM, HEMATOXYLIN-EoSIN. X 140

698

CANCER OF LUNG IN MINERS OF JACHYMOV 699

Microscopic Examination (Hist. No. 4681): The structure of thecancerous tissue was highly polymorphous. The relatively undevelopedstroma was for the most part fairly rich in cells and vessels. The tumorparenchyma consisted mostly of solid nests, varying considerably both inshape and size, containing polygonal epithelial cells. In the larger focithe cells persisted only on the periphery; in the center there were necrosisand decay. In some places, on the other hand, the cancer foci showed adistinct cystopapillary arrangement, generally with a single layer ofcuboidal epithelium (Fig. 13). More remarkable still were similarformations lined with definitely cylindric epithelium (Fig. 14). In otherplaces, there was a tendency to infiltrative proliferation, the cancer cellsbecoming more atypical and polymorphous. Some of the cells showed

FIG. 15. CASE 4: PENETRATION O~· THE TUMOR FROM THE PLEURA INTO THE LUNG

PARENCHYMA. WEIGERT'S FUCHSIN-HEMATOXYLIN-EOSIN. X 1:32

large, curiously shaped nuclei. This form of growth was to be foundprincipally in the places where the cancerous epithelium had brokenthrough the elastic layer of the pleura and penetrated a short way into thelung tissue (Fig. 15). In general, however, the cancer did not spreadbeyond the lower elastic layer of the pleura towards the parenchyma ofthe lung. Deeper infiltration into the lung was found only in theinterlobular septa-apparently through the lymphatic vessels-and eventhen it. had not spread to any considerable extent.

Enicrisi»: Both the macroscopic aspect and the microscopic structureof the growth seem to give evidence that here we have to deal with a easeof primary cancer of the pleura. The polymorphous arrangement of thetumor tissue is not inconsistent with this supposition, since it tallies withthe description given, especially by Ribbert (12), in relation to certain

700 AUG. PIRCHAN AND H. SIKL

pleural cancers. On the other hand, we can but agree with the criticalstand taken by Ribbert (13) and, recently, by Huguenin (14) on theorigin of these tumors, whether from the lining epithelium of the pleura orfrom the lung parenchyma.

In our case the tumor was of a rather medullary character in com­parison with the structure generally found in pleural cancers, whichusually have a definite scirrhous aspect due to the predominance of a firmfibrous stroma. In.spite of .this histologic difference, the clinical courseof the malady, which shows that the tumor had persisted for a very longtime, as well as the almost complete absence of metastases, corresponds to

FlO. 16. CASE 5: LEFT LUNG CUT OPEN (Mus. SPEC. No. 2674)

the features of pleural cancers in general. The duration of the maladycan be estimated at nine years at least.

CASE 5: Jos. S., aged forty, had worked from 1914 as a hewer in the"Saxon Nobility" pit at Jachymov. He was examined on Feb. 22, 1929,when he complained of an oppression in the region of the heart andbelching. The general examination was negative.

X-ray examination showed a slight sinistro-convex scoliosis in theupper thoracic region and moderate goiter with deviation of the tracheato the left. The lung area was for the most part clear; the shadowthrown by the hilus was moderately accentuated on both sides. Thus, onthe whole no indication of cancer of the lung was found.

CANCER OF LUNG IN MINERS OF JACHYMOV 701

The doctor in charge of the case (Dr. Kretschmer) stated that thesick man had visited him on several occasions, complaining of pains inthe chest. His sputum contained blood. In November 1929, he wasplaced on the sick-list 'Owing to weakness in the legs. A diagnosis ofparaparesis and pronounced enlargement of the liver was made. Theparesis gradually increased, until complete paraplegia set in, and duringthe last fortnight of the patient's life there was paralysis of the rectum andbladder. The enlargement of the liver progressed noticeably during theperiod of observation. Death occurred Dec. 29, 1929.

Diagnosis: Cancer of the lung with metastases in liver and spine.

FIG. 17. CASE 5: MICROSCOPIC STRUCTURE OF TUMOR. HEMATOXYLIN-EoSIN. X 140

Post-mortem Diagnosis (Jan. 1, 1930): Carcinoma in the lower lobe ofthe left lung (circumscribed form); isolated secondary cancer nodulesin the left lower and middle lobes; metastases in the visceral pleura onboth sides, the hilus and peritracheal and periaortic glands, the liver, andthe lumbar vertebrae; compression of the spinal cord; moderate generaldropsy; pleural adhesions on the left lower lobe; chronic bronchitis;general emaciation.

Extract from A utopsy Record: In the left lower lobe there was acompact tumor about the size of a goose egg. The main bronchialbranch for the lower lobe entered the tumor immediately after leaving themain bronchial tube; its lumen was from the beginning considerablyconstricted by whitish, fairly tough cancerous tissue. In the region ofthe main tumor there were, in the lower and middle lobes, several smallnodules of the same kind, from the size of a pea to that of a hazelnut. The

702 AUG. pmCHAN AND H. HIKL

hilus glands formed a compact mass which on the cut. surface showed areal'of blackish pigmentation alternating with grayish-white patches (Fig. 16).

Microscopic Examination (Hist, No. 4737): The tumor tissue wascomposed of small, generally oat-shaped cells (Fig. 17). In places the'cells had a pronounced cylindrical shape, but nowhere did they formglandular structures. The stroma was very poorly developed. Withordinary stain, it appeared to consist of the original alveolar septa, but.special stain showed that the elastic fibers disappeared immediately afterthe invasion of the lung parenchyma by the growth. Topographicalsections through the tumor showed that the large bronchi were infiltratedand obliterated by tumor tissue, 1'0 that it seemed probable that thegrowth had arisen from the bronchial mucosa. Proof of this supposition,however, can not be given.

In the other portions of the lung parenchyma numerous foci ofcancerous tissue, visible only microscopically, were found. There werealso large numbers of tumor emboli. In the dilated perivascular lym­phatics there was a quantity of loose anthracotic pigment, but induratedspots were rare.

Epicrisis: Small circumscribed cancer in the left lower lobe near the hilus,microscopically oat-cell carcinoma; bronchial origin probable. Widespreadmetastases both lymphatic and hematogenous; compressive myelitis due tometastases into vertebral column.

Subjective symptoms of the malady were present for about elevenmonths only. The x-ray examination made eleven months before deathgave no decisive indication of cancer of the lung.

The most prominent feature of this case is the rapid progress of thedisease, due to the widespread generalization, while the primary growthremained relatively small.

CASE 6: J. H., aged fifty-three, had been working in the radiumfactory at Jachymov since 1900, and as a carpenter in the Werner pitsince 1908. He was pensioned off in 1923.

On examination, May 1.5, 1929, it was found that both parents haddied of cancer. The chief complaints were shortness of breath andgiddiness. General examination showed goiter. Lungs and heart werenormal. X-ray examination also showed a normal lung picture. Thethorax was short and broad.

A second examination was made on Jan. 14, 1930. For the past eightweeks the patient had suffered severe pains in the sacral region, radiatingto the left sciatic region. There were shortness of breath and coughing,but no expectoration; marked cachexia and pallor; hemorrhage in the leftsclera. On the isthmus of the thyroid gland was a nodule the size of ahen's egg, and over the left sternoclavicular joint was a swelling sensitiveto pressure. Lascgue's sign was present on the left side. Albumin wasfound in the urine. The x-ray photograph showed no indication ofcancer of the lung. There was a suspicion of malignant struma withmetastases in the' bones. The cachexia increased, and severe pains in thelegs developed. Death occurred Jan, 28, 19ao.

Post-mortem Diaqnosis (Jun. 29, 1930): Circumscribed medullarycarcinoma in the right lower lobe; multiple periosteal mctastnsos in

CANCER OF LUNG IN MINERS OF JACHYMOV 703

the skull, vertebral column, ribs, sternum, and pelvis, the last causingcompression of the sacral nerve roots; numerous metastatic nodules inthe liver; mild icterus; several small adenomatous nodules in the thyroidgland, and a large cicatrized and calcified nodule on the isthmus; nomarked emaciation.

Extract from A utopsy Record: In the posterior lower portion of theright lower lobe, there was a tumor about the size of a pigeon's egg, oflong, irregular shape, a large bronchial branch forming its axis. By atongue-shaped process running along the bronchial tube towards the

FIG. l~. CASE 6: RIGHT LUNG, LOWER LOBE CUT OPEN (Mus. SPEC. 2(70)

hilus, the tumor was connected with a large tumor mass filling the wholehilus of the lung. This muss consisted mainly of infiltrated peribronchialglands, and penetrated and constricted the bronchial tube leading to thelower lobe. At the bifurcation of the trachea was a compact nodule thesize of a plum, consisting of soft, pulpous, moderately pigmented glands,partly interspersed with whitish cancerous tissue. The other glands werefree from cancer (Fig. 18.)

Microscopic Examination (Hist. No. 4735): The structure of thetumor (Fig. 19) was very similar to that in the preceding case. The

704 AUG. PIRCHAN AND H. SIKL

cancerous tissue was composed of small cells with scanty protoplasm, andround, or, more often, oat-shaped nuclei. In the peripheral portions ofthe tumor the stroma was formed by thickened alveolar septa, in whichthe elastic fibers were sometimes still preserved. In topographicalsections it was noticed that the growth followed several bronchialbranches, the walls of which were widely infiltrated with cancer tissue.Thus the bronchial origin of the carcinoma seems highly probable.

Epicrisis: Circumscribed, probably bronchial, small-cell carciuoma Lnthe right lower lobe, with widespread generalization, both lymphatic and byway of the blood stream, especially inio the periosteum of numerou.~ bones,

FIG. 19. CASE 6: MICROSCOPIc STRUCTURE OF TUMOR. HEMATOXYLIN-EoSIN. X 140

The subjective symptoms can be traced back for seven months. Amost interesting fact is that fourteen days before death the tumor couldnot be detected by means of x-rays,

On the whole, this case has a very strong resemblance to Case 5, withthe exception that here the spinal cord was not affected, the nerve-rootsof the left sciatic only being involved. Though it is impossible toestablish the real duration of the malady, the rapid final progress, dueespecially to the generalization of the growth, is very remarkable.

CASE 7: Johann J., aged forty-six, had worked in the Werner pit atJachymov since 1913, as a carpenter. He was a resident of Abertham,about 10 km. from Jachymov. He was examined Feb. 2, 1929. Hisfamily history was irrelevant, and he himself had formerly always beenhealthy. He complained of stabbing pains in the chest. Exuminution ofthe heart and lungs showed nothing of significance. In roentgenograms

CANCER OF LUNG IN MINERS OF JACHYMOV 705

the shading of the lungs was clear, the hilus shadows rather accentuated onboth sides. No lymph glands were visible. The heart was normal, butthe aorta elongated. A goiter was present.

History of Case (according to Dr. Baum, of Abertham, who attendedthe patient): In August 1929 the patient was suffering from generalizedpains in the chest and general debility. There was no dyspnea. X-rayexamination (by Dr. Nitzl, head physician of the local" Sick Club" atFalknov) showed the outlines of the apices of both lungs slightly blurred,and a dark shadow, the breadth of the palm of the hand, stretching fromthe right hilus downwards. The right diaphragm was immobile. Adiagnosis of pleuritis was made.

FIG. 20. CASE 7: HIGHT LUNG CUT OPEN (Mus. SPEC. No. 2673)

On Jan. 25, the patient was declared by the panel doctor at Falknovto be well and able to resume work. On Feb. 1, he was despatched to thehospital at Karlovy Vary, but was again sent home without the results ofhis examination being indicated.

In January his physician found dulness over the base of the rightlung. At the beginning of February, clonic convulsions set in, whichwere more severe on the right side. Paralysis gradually developed,affecting mainly the right half of the body. Cachexia and paralysisincreased, and death occurred March 7, 1930.

Post-mortem Diagnosis (March 9, 1930): Circumscribed carcinomatending to lobar progression in the right lower lobe; multiple metastases,mainly hematogenous; three large cancer nodules in the brain (Fig. 21),

706 AUG. PIRCHAN AND H. SIKL

(1) in the left frontal lobe over the corpus callosum, partially extendingto the right hemisphere, (2) in the left occipital lobe, and (3) in the righthemisphere of the cerebellum; several large nodules in the pancreas;numerous nodules in the liver, some of them confluent; a flat nodule in themucous membrane of the duodenum; some small foci in both kidneys;edema and incipient aspiration pneumonia in the left lower lobe; severegeneral atrophy; moderate anthracosis of the lungs; healed fracture of theright clavicle, with resultant deformity.

Extract from A utopsy Record: The posterior portion of the right lowerlobe was occupied by a compact tumor the size of a fist (Fig. 20). Its

FIG. 21. CASE 7: METASTATIC TUMORS IN THE BRAIN (Mus. BI'EC. No. 2li72)

extent was somewhat ill-defined. The principal bronchial tube leading tothe lower lobe entered the tumor about 3 em. from the hilus and wasshortly afterwards entirely obstructed by cancerous growth. On theside of the tumor facing the hilus were some cancer-infiltrated lymphnodes of about the size of a cherry, in places already confluent with themain mass of the tumor, their area being defined by their pigmentation.The remaining lymph nodes were free.

Microscopic Examination (Hist. No. 4761): Microscopic examinationshowed small-cell carcinoma (Fig. 22) consisting chiefly of oat-shaped

CANCER OF LUNG IN MINERS OF JACHYMOV 707

cells. The stroma, on the whole, was very scanty. In the peripheralportions of the growth the original gross structure of the lung parenchymawas rather well preserved, the alveoli being filled with tumor cells, thealveolar septa forming the stroma. No topographical sections weremade, so that the true source of the growth cannot be established, but abronchial origin seems probable.

Epicrisis: Rather circumscribed small-cell carcinoma of the right lowerlube, with widespread, mainly hematdgenous generalization. Three largemetastases in the brain, causina clonic convulsions and paralysis.

Objective signs of the malady were first established seven months

FIG. 22. CASE 7: MICROSCOPIC STRUCTURE OF A PERIPHERAL PORTION OF THE TUMOR

OF THE LUNG. HEMATOXYLIN-EoSIN. X 140

before death, while subjective symptoms could be traced back at leastthirteen months. Toward the end, the disease progressed very rapidly, afact which must be attributed to the generalization of the growth,especially to the exist.ence of brain metastases. The most interestingfeature in this case is the occurrence of numerous blood-borne metastases,while lymphatic metastases were almost entirely lacking.

CASE 8: Ernest Z., aged fifty-two, had been working since 1907 in theJachymov mines as a carpenter. He had been pensioned off in 1923.When examined, May 30, 1929, he complained of severe tremor of theright half of the body. Over the right stemoclavieular joint was apainless swelling barely the size of the palm of the hand. Heart and lungswere normal. Roentgenograms revealed in the left upper segment of thelung, a ball-shaped shadow about as large as the palm of the hand,

708 AUG. PIRCHAN AND H. BIKL

adjacent to the aorta, showing weak pulsation. Otherwise, nothingremarkable was observed. Cancer of the lung was suspected.

According to the statement of the doctor in charge of the case (Dr.Kretschmer) the patient suffered from severe pains in the left part of thechest in the summer of 1929 and his sputum contained blood. Therewere no abnormal physical signs. Later, paralysis of the legs set in, and,finally, paralysis of the rectum and bladder, with symptoms of cystitis.Death occurred April 2, 1930. The diagnosis was cancer of the lungswith metastases in the spinal cord.

Post-mortem Diaqnosis (April 4, 1930): Circumscribed subpleuralcarcinoma of the left upper lobe; multiple metastases in the bones (sixthrib, head of left humerus, tenth thoracic and first and second lumbar

FIG. 23. CASE 8: MICROSCOPIC STRUCTURE OF TUMOR OF THE LEFT LUNG. HEMA­

TOXYLIN-EOSIN. X 132

vertebrae); pathological fracture of the neck of the humerus; thrombosisof the left axillary and jugular veins; compression of the spinal cord bycancerous growth in the tenth dorsal vertebra; edema and musculuratrophy of both lower extremities; decubitus in the sacral region; ulcerouscystitis; inflammatory swelling of the spleen; severe emaciation.

Extract from Autopsy Record: The medial area of the left upper lobewas firmly adherent to the mediastinum. Here was a tumor the size of afist, which occupied the middle portion of the upper lobe between thehilus and the apex of the lung. The hilus and apex were free. Thetumor consisted of a tough, grayish-white mass of tissue which formed alayer on the pleura about 2 em. thick in the middle, thinning off towardsthe edges, infiltrating the lung parenchyma beneath to a depth of :3 to 4

CANCER OF LUNG IN MINERS OF JACHYMOV 709

em. The consistency was fairly tough, but there were several softenedfoci, which, on pressure, exuded atheromatous, yellowish, cancerousmatter resembling the caseation of tuberculosis.

The lymph nodes were not enlarged. The left humerus head wasentirely replaced by yellowish cancerous tissue, around which the cartilageformed an elastic, easily compressible shell.

Microscopic Examination (Hist, No. 4776): On microscopic examina­tion the tumor proved to be a rather atypical epidermoid carcinoma(Fig. 23). The larger cancerous foci were almost all necrotic in thecenter. Between the tumor masses beneath the pleura, which was alsoinfiltrated with cancer, were several hyaline-fibrous, heavily pigmentedareas, but no signs of a recent tuberculous process were noticeable. Therest of the lung parenchyma was only slightly pigmented and was freefrom indurated areas.

Epicrisis: Circumscribed epidermoid carcinoma in the left upper lobe,with exclusively hematogenous generalization, especially in the bones.Compressive myelitis due to metastases to vertebral column.

The cancer was demonstrated by x-rays ten months before death.There were then objective signs of a metastatic lesion of the spinal cordand a metastatic tumor in the sternoclavicular joint, while subjectivesymptoms of pulmonary cancer were absent.

An interesting feature of this case is the uncommon localization of thetumor, which was situated beneath the pleura on the medial surface of theleft upper lobe. This fact, together with the special structure of theneoplasm (epidermoid carcinoma) and the presence of pigmented scars inthe tumor, leads one to think that the growth developed on the basis of atuberculous process. Evidence of this, however, cannot be shown. Thealmost exclusively hematogenous generalization is also rather remarkable.

CASE 9: J. 0., aged sixty-seven, had worked in the Jachymov minesfrom 1887, first as pumper, then as carpenter, up to 1903, when he waspensioned off owing to rheumatic pains in the whole body and deafness.He appeared at the systematic examination of miners on May 29, 1929.Physical examination of the lungs gave a negative result. X-rayexami­nation showed accentuated marking of the hila with several small foci ofdensification. In the right lower field, above the dome of the diaphragm,was an elliptical shadow with a rather sharp contour, about the size of agoose egg. A probable diagnosis of carcinoma was made.

Only very incomplete reports of the further development of this caseare available. Dr. Kretschmer states that in May 1930 he was called tothe patient, who was suffering from pains in the back and paralysis of theupper extremities. There was no cough or expectoration. Deathoccurred Oct. 21, 1930.

Post-mortem Diagnosis (Oct. 23, 1930): Circumscribed carcinoma inthe right lower lobe; spotted cancerous infiltration in the bronchial andhilus glands; one small metastatic node in the left apex, and several nodesin the liver; small (metastatic?) growth in the spleen; pronouncedemaciation; slight trabecular hypertrophy of the bladder; small nodularcolloid struma.

67

710 AUG. PIRCHAN AND H. SIKL

Extract from Autopsy Record: In the lower lobe of the right lung(Fig. 24) was a tumor the size of a goose egg. This occupied the centralportion of the lobe, and in the scapular line reached only a limited areaof the pleura, which showed thickening at that point. The main bronchialbranch of the lower lobe was intact. The bronchi of second degreeentered the tumor at a distance of about 3 em. from the hilus. Here theywere soon penetrated and obstructed by cancerous tissue. The contourof the tumor was indistinct at some points and sharp at others. Thecancerous tissue was whitish, rather firm, somewhat crumbly. No largenecrotic or softened areas were visible, however. In the apex of the leftlung a small tumor nodule of similar appearance was found.

FIG. 24. CASE 9: RIGHT LUNG CUT OPEN (Mus. SPEC. No. 3035)

The rest of the parenchyma of both lungs was pneumatic. Thedorsal portions were somewhat edematous. There was rather abundantanthracotic pigment in the form of minute indurated foci, which werealmost regularly distributed. Only in the apices were somewhat largersubpleural slaty scars found.

In the midst of the splenic pulp was a whitish nodule the size of a pea.The liver contained several nodes up to the size of a hazelnut.

Microscopic Examination (Hist. No. 4888): The tumor tissue had arather irregular alveolar structure (Fig. 25). The alveoli were separatedby slender fibrous strands. These were in part thickened alveolar septa

CANCER OF LUNG IN MINERS OF JACHYMOV 711

containing the remains of elastic fibers, in part newly formed fibroustissue. The parenchyma was composed of small cells, for the most partdistinctly oat-shaped, with a slight amount of cytoplasm. The cellswere, on the average, a little larger than those seen in the cases describedabove. Sporadic hyperchromatic giant nuclei also appeared. Where thecells were adjacent to the septa they preserved in general a pronouncedcylindrical form and strongly resembled the epithelium of bronchioli.Glandular formations were nowhere to be found. Throughout the tumorwere small necrotic foci, which, in general, concerned only the centralportions of the alveoli, but in part extended also to the septa.

The growth in the left apex had exactly the same structure, There

FlO. 25. CASE 9: MICROSCOPIC STRUCTURE OF TUMon OF RIOHT LUNG. HEMA­

'l'OXYLIN-EoSIN. X 140

was no reason to regard this as asecond primarytumor. The structure ofthe nodes in the liver resembled on the whole that of the tumor of thelungs. The small nodule in the spleen was composed of rather spindle­like cells, which were partly arranged in bundles, without however, anytrace of intercellular substance. At first glance the structure remindedone of a purely cellular spindle-cell sarcoma, yet it is possible that we havehere a modification of structure caused by local conditions.

Epicrisis: Circumscribed small-cell carcinoma in the right lower lobe,with slight lymphatic generalization and several blood-borne metastases.

The duration of the malady can not be estimated, even approximately.Objectively, the existence of the tumor was demonstrated by x-raysseventeen months before death, on the occasion of the systematic examina-

712 AUG. PIRCHAN AND H. SIKL

tion of the miners. The patient had had no definite subjective signs ofthe disease. The shadow of the tumor on the x-ray film was nearly aslarge as the tumor found at autopsy, so that the rate of growth must havebeen very slow. Although the generalization was rather slight, and therewas no ulceration or hemorrhage in the tumor, marked cachexia developed,and was apparently the immediate cause of death.

The most remarkable feature of this case is the fact that the man hadceased work fully twenty-seven years before the cancer became manifest.Such a long period of latency of an occupational tumor has not yet beenobserved, even in anilin workers. It cannot be decided whether we aredealing here with a question of true incubation; it seems probable that thetumor had persisted for a very long period in a latent form. If the casewere not a link in a series of similar observations, there might be doubt asto the causal connection between the profession and the cancer.

DISCUSSION OF ANATOMICAL FINDINGS

In 8 cases reported more or less circumscribed primary cancersof the lung parenchyma were found. In one case (Case 3) twoprimary cancers of distinctive structure were observed, both ofwhich had produced .independent metastases. Case 4 is a specialcase, inasmuch as it is a primary pleural carcinoma. It might,indeed, be asked whether, as such, it ought to be included here.We think so, for it is a matter of common knowledge that thepleura plays an active part in carrying and depositing inhaledforeign substances and there seems to be no reason why it shouldnot be attacked by the noxious cancerogenic agent. In view of theextreme rarity of primary pleural cancer, the probability of itsbeing found fortuitiously among such a small number of cases isextremely slight.

As regards the localization of the carcinoma, it was found thatthe left side was affected in 5 cases, the right side in 3 cases; in onecase each lung contained a primary tumor. The right lower lobewas the seat of the cancer 4 times, the left upper lobe 3 times, theleft lower lobe once. In one case the tumor started from the hilusof the left lung t111rl ~preatl QVQr.b~ lobes equally.

An attempt was made to classify the tumors as to theirmacroscopic aspeet, on ihe ~aSls III H~nin's scheme (14).Thus we were able fo labe! Cases 1,5,6,8,9, and the small primarycancer of the left lung. iu. 08,6e is as "circumscribed forms." The"lobar form" was represented by Case 3 (right lung), whereas Case7 comes somewhere between the circumscribed and the lobar form.Case 2 could just as well be regarded as belonging to the "massive"as to the" mediastino-pulmonary " form. Case 4 corresponds tothe "pleural" farm.

CANCER OF LUNG IN MINERS OF J ..\CHYMOV 713

HISTOLOGY

Aside from the case of pleural cancer, 6 of the tumors wereunripe small-cell carcinomata, and 3 (including the small primarytumor in case 3) were squamous epidermoid carcinomata. As thislast form of cancer represents a heteroplastic tumor in the lung,implying metaplasia of the epithelium, it must he assumed that inthese cases formation of the cancer was preceded by metaplasticprecancerous processes.

In Case 1, we formed the impression from the topographicalsections that the cancer arose from a small bronchiectatic cavity inthe lingula, although this cannot be proved. In Case 8, we found,between the largely necrotic cancerous masses under the pleura,several cicatricial, hyaline-fibrous pigmented areas, which mayperhaps be regarded as cicatrized tuberculous foci. No lesionsof undoubtedly tuberculous origin could be found, however, andthe apices of the lungs were free, so that here, also, no definiteconclusion can be arrived at. On the other hand, the squamous­cell cancer of the left upper lobe in Case 3, which had evidentlyarisen from the bronchial mucosa, was found in a part of the lungwhich was normal, save for slight anthracosis, and the lymphglands lying directly under the tumor, which were still entirely freefrom cancer, showed microscopically no trace of tuberculosis orcicatrization or even any considerable pigmentation.

In the cases of small-cell carcinomata, the point of origin couldno longer be determined with any certainty. In Cases 5, 6, 7, and9, bronchial origin seems probable; for the rest, we are entirely inaccord with Huguenin's critical view with regard to the histo­genetic derivation of the various forms of carcinoma of lungs.

One might be inclined to examine the finer structure of thebronchial and alveolar epithelium in the areas of the lung paren­chyma adjacent to the tumors, where, perhaps, some precancerouschanges, indicative of the histogenesis of the tumors, might befound. For practical reasons, however, it was impossible toperform the post-mortem examinations as early after death ·aswould be necessary to avoid cadaverous alterations, which, in allour cases, were too advanced to allow of such studies.

Most significant in our opinion is the exclusive appearance ofthe two histologic forms of carcinoma referred to (with the ex­ception of the pleural cancer) in the series examined. In view ofthe small number of cases, it is, of course, possible that the absenceof other forms of cancer, such as the cylindrocellular, glandular, or

714 AUG. PIRCHAN AND H. SIKL

alveolar, is a coincidence, but it is noteworthy that Schmorl hadthe same experience with the far larger number of cases of cancerfrom Schneeberg. We cannot, therefore, say for the present towhat degree this is a peculiarity of cancer in miners.

METASTASES

With regard to the mode of generalization, the pleural cancerfollowed the course usually taken by this kind of carcinoma; that isto say, the lymph glands were only very slightly affected, in spiteof the fact that the primary tumor had existed for a long time. InCase 1, there seem to have been contact metastases in the epi­cardium exclusively, but the data in this case are very incomplete.In five cases (Cases 2, 3, 5, 6, 9) there were lymphogenous meta­stases as well as generalization by way of the blood stream. Intwo other cases (Cases 7 and 8) hematogenous metastases werefound almost exclusively. In four cases (Cases 2, 5, 6, 8) therewere multiple foci in the bones. Cerebral metastases were foundonly in Case 7, while in three cases (Cases 2, 5, 8) myelitis due tocompression occurred as a consequence of metastases in thevertebral column. Metastasis by way of the blood stream is notunusual in carcinoma of the lung. It is significant, however, thatin some cases extensive hematogenous metastases developed beforethe lymph nodes were affected-at least to any considerableextent. This can be explained only by the fact that the primarytumor had broken into the veins of the lungs at a very early stage.That this actually happens is proved by the small primary epi­dermoid cancer of the left lung in Case 3, which, in spite of its smallsize and obviously early stage of development, had alreadyproduced metastasis in the right suprarenal body.

DEVELOPMENT OF TUMORS

With regard to the rate of growth, nothing definite can, ofcourse, be said. The duration of the disease-that is to say of themanifest symptoms-ranged from ten weeks to six years. Thecase of pleural cancer, which lasted nine years, forms an exceptionin this respect, corresponding to the characteristics of this type ofgrowth in general.

It is true that any estimate of the period of development of thetumors in the light of the clinical symptoms can be only approxi­mate, since the first symptoms-whether subjective or ohjective­do not always coincide with the real beginning of the cancer. Case G

CANCER OF LUNG IN MINERS OF JACHYMOV 715

is particularly illuminating in this respect, as in this case theclinical symptoms became apparent only ten weeks before death,when they were due to periosteal metastases in the sacrum. Inmost of our cases, however, the usual symptoms of cancer of thelung, viz. stabbing pains in the region of the chest, respiratorydifficulties, cough, and bloody expectoration, were present at thebeginning of the disease, though it is doubtful even here whetherthis may be said to correspond to the true onset, as in many casesthe history points to the existence of cancer for a longer period.In Case 2, for instance, the apparent duration of the disease wasonly four months; but the patient had, about seven years before,suffered from pleurisy in the side where the tumor later appeared.The question may be asked, therefore, whether the pleurisy was notthe first symptom of cancer.

It is further significant that 6 of the men who died of cancer ofthe lung had been pensioned off several years previously (six totwenty-seven years) owing to various complaints, for the most partindefinite. In Cases 1, 3 and 4, it may be concluded almost withoutdoubt from the history and the subsequent development of thedisease that those complaints were the first symptoms of pulmonarycancer. In Cases 6 and 8, in which the cancer manifested itselfonly about six years later and then developed rapidly, we can saynothing definite.

It is extremely difficult to decide whether the interval (often ofmany years) observed in several cases of occupational cancer, bothat Schneeberg and at Jachyrnov, between the beginning of disabilityand the appearance of the tumor, is to be regarded as an incubationperiod in the true sense of that term, or as a latent stage of thedisease. In this respect the greatest interest is attached to Case 9,which ended fatally twenty-seven years after the man had beenpensioned off. There were no definite symptoms of cancer of thelungs up to the time of death, although the tumor had been visibleby x-rays seventeen months before.

The cases which were included in the systematic examinationsof the miners in the Spring of 1929 (Cases 5 to 9) are of specialinterest. In Case 8, the patient, who was examined about tenmonths before death, suffered from acute tremor of the right partof the body, the first symptom, as was discovered later, of com­pression of the spinal cord through metastasis in the vertebralcolumn. There were no lung symptoms. On x-ray examination,however, a shadow was found along the aorta in the left upper

716 AUG. PIRCHAN AND H. 8IKL

area of the lung, and cancer of the lung was suspected. Thissuspicion was subsequently confirmed by post-mortem exami­nation. Case 9 has been mentioned above. In the three othercases, nothing abnormal in the lung was revealed either by clinicalor x-ray examinations made eleven, thirteen, and eight months,respectively, before death. In Cases 5 and 7 there were pains inthe chest and in Case 6 shortness of breath and giddiness, and it isobvious that, in spite of the negative result of the examination,these may have been the first symptoms of cancer of the lung.The last patient had a goiter with deviation of the trachea, towhich his troubles were attributed.

We think we are safe, therefore, in saying that in all these casescancer of the lung had been present long before any outwardsymptoms appeared; this, indeed, is in accordance with the generalexperience regarding the difficulty, if not impossibility of recog­nizing cancer of the lung in its initial stages (15). In this respect,the most striking fact is the negative result of the x-ray examinationfourteen days before death in Case 6.

In spite of this, we may state that, on an average, the cases ofcancer observed at Jachymov took a considerably more rapidcourse, and were more malignant, than those at Schneeberg, in sofar as the summary description given by Rostoski, Saupe, andSchmorl allows of a comparison. According to these writers, in theSchneeberg cases the stage of manifest symptoms lasted anywherefrom a few months to three and a half or four years. The firststage, with slight or moderate dyspnea, could be traced back forseveral years-as long as seven, twelve, or twenty years (16)­and the possibility must be admitted of these early symptoms beingdue to the presence not of cancer of the lung, but of the usualpneumoconiosis (17). As regards our cases, only 3 (Cases 1,3,4)were of protracted duration (six, six, and nine years respectively).In Case 9 the disease probably also ran a very chronic course, butthis cannot be demonstrated. Of the other 5 cases, the longestlasted less than a year; in some of them (2 and 6) the rapid de­velopment was a particularly striking feature. Moreover, inseveral of these cases extensive metastases were very much in theforeground of the clinical picture, if not its principal feature. Thisis especially true of compression of the spinal cord through affectionof the vertebral column (Cases 2, 5, 8). In the Schneeberg cases,metastases, so far as can be gathered from the work referred to, donot appear to have played a very important part.

CANCER OF LUNG IN MINERS OF JACHYMOV 717

We will not discuss further the clinical course of the disease,since we were dependent for the most part on the somewhatincomplete information which the doctors in charge of the caseswere able to give. We would only say that it has not been possibleto establish any clearer relation between the histologic structureand the clinical course. In our cases of cancer the age rangedbetween forty and sixty-seven, the average age being aboutfifty years. Only 2 men belonged to the active staff; 7 had beenout of work for periods of from one to twenty-seven years. Thetime during which they were employed in the mines (or in theradium factory) varied from thirteen to twenty-three years andaveraged seventeen years. The period of time between thecommencement of work in the mines and death from cancer wasfrom fifteen to forty-three years, and averaged twenty-five years.

ETIOLOGY

The problem of the true nature of the noxious agent whichcauses the cancer is a very delicate one, and has not yet beensolved satisfactorily either in Schneeberg or in Jachymov. InSchneeberg miners, Rostoski, Saupe and Schmorl found severeanthracosis of the lungs, to which they are prone to attribute thecausation of the cancers. In our cases, on the contrary, there wereonly very moderate degrees of anthracosis. Some small induratedspots were found, of course, in an occasional case, but on thewhole, these changes did not surpass the average for the 'age of thepatients. This may seem surprising in view of the fact that withthe boring work there is always a great deal of dust, but it can per­haps be explained by the regular use of respirators by the miners:Further, it may be pointed out that among our cases only twooccurred in hewers, that is to say in the men who are most exposedto dust, the other six having been chiefly in carpenters. It is,however, rather difficult with Jachymov miners to be exact as tothe special type of occupation, since this is subject to frequentchange, the men no longer fit for hewers' work being employed ascarpenters or even in the radium factory. For this reason we havebeen able to indicate the predominant occupation only.

We are not inclined to attach any particular importance to thedegree of pneumoconiosis as a cause of cancer. The question maybe somewhat different with regard to the quality of the foreignsubstances deposited in the lung. In order to make this matterclear, in Case 7 we subjected to chemical examination large

718 AUG. PIRCHAN AND H. SIKL

portions of the left lung, which was not affected by cancer. Thisexamination, which Prof. Tomieek, Director of the Institute forAnalytical Chemistry at the Czech University of Prague, was goodenough to undertake, gave the following result:

"The tissue, which weighed 140 gm. in all, was completelymineralized with permanganate of potash and hydrochloric acid.After filtration, the filtrate and the residue were tested for radio­activity with entirely negative results. Chemical analysis ac­cording to the usual methods revealed only calcium, magnesium,aluminum, silicic acid, chlorides, and phosphates. On the otherhand, no trace even of arsenic, bismuth, cobalt, nickel, or uraniumwas found."

The result of the chemical examination was, therefore, rutherdiscouraging. It should be noted that the result of the chemicalanalysis carried out by Beyreuther (18) in one Schneeberg case wasalso negative. We propose, nevertheless, to pursue these investi­gations further when opportunity offers.

It cannot be proved, however, that the noxious agent inquestion is not stored in the body, but is rapidly eliminated ordestroyed. The suspicion which is always arising that radiumemanation may be responsible for the occurrence of cancer atSchneeberg is largely supported by the fact of similar tumorsbeing found at Jachymov. As to the contents of radium emanationin the air of the pits, the conditions in Jrichymov are very similar tothose in Schneeberg.

In the Schneeberg mines, Ludewig and Lorenser (19) found anamount up to 50 mac he units. In Jachymov, three pits only arebeing worked to-day; "Harmony" (depth 500 meters), "Werner"(476 meters), and "Saxon Nobility" (120 meters). The quantitiesof radium emanation found in the air discharged from these pits are4 mache units, 1.5 mache units, and 10 mache units respectively,The radio-activity varies, however, at different spots of the samepit, reaching especially high degrees in the vicinity of the radio­active sources. On floor XII of "Harmony," 4 for example, theoutput is 52 mache units. It is interesting, also, that the degree ofactivity of the discharged air parallels closely the richness of theuranium ore (pitchblende) worked. The miners themselves statethat discovery of a rich uranium vein is always followed some yearslater by a strongly increased mortality among them.

4 New accurate measurements just made hy Dr. Sandholzer, memher of the StateRadiologic Institute, showed somewhut lower rutes of radium omunntion ut variouspoints in the pits. It is probable that the contents of emanation from time to lime varyto a great extent; systematic meusurements should he made.

CANCER OF LUNG IN MINERS OF JACHYMOV 719

It would seem from the foregoing, that the average radio­activity is not especially high and might be tolerated for some timewithout injury. When, however, we remember that the minersspend about seven hours daily, day after day, in this atmosphere, itis not surprising that the enormous quantities of the emanationinhaled in the course of a number of years may end by injuring theorganism through their cumulative action." This is, of course, atthe present stage no more than a hypothesis.

The most weighty argument against the assumption of theexclusive etiological significance of the emanation is the fact thatboth at Schneeberg and at Jachymov the air of the pits containsanother notoriously cancerogenic substance, namely arsenic. Asarsenic combinations are fairly rapidly absorbed in the body andfinally eliminated, the negative result of the chemical analysis ofthe lung is not a conclusive argument against its importance in theetiology of cancer. It might be well to make investigations inmines, the air of which contains arsenic but not radium emanation,with reference to the occurrence of cancer of the lung.

It seems doubtful whether experiments with animals couldfinally clear up the etiological aspect of the problem, first becausesuch prolonged exposure to the noxious agent as is necessary for theformation of cancer in miners can hardly be achieved artificially inexperiments with animals, and, secondly, because we do not knowwhether the noxious agent in question has the same cancerogeniceffect in animals as it has in man. In order to clear up this lastquestion Dr. Markl and the present writers have set up cagescontaining white mice in the pits themselves, as far as possible inthe vicinity of the drilling operations. We cannot, however,expect this experiment to yield any positive results for some time.

PREVENTION

If our supposition is correct, that radium emanation is responsi­ble for the development of tumors in the miners at Jachymov,some form of artificial ventilation to reduce as far as possible theconcentration of the noxious matter in the air of the pits would

& If we take the average contents of 10 mache units in 1 liter of air we may calculatethat It miner inhales

in 1 minute. . . . .. . . . . . . . . ... . . 80 M.u.in 1 hour. . . . . . . . . . . . . . . . . . . . . 4800 M.u.in 1 day. . . . . . . . . . . . . . . . . . . . . . 33,600 M.u.in 1 year. . . . . . . . . . . . . . . . . . . .. 10,080,000 M.u.in 15 years 151,200,000 M.u.

this last number being equivalent to 55 mg. radium chloride.

720 AUG. PIRCHAN AND H. SIKL

seem essential. (Up to the present, change of air in the pits hasbeen accomplished chiefly by natural currents, due to differences oftemperature, ventilators having been used to a very restrictedextent.) The best means of ventilation would be to force freshair into the pits. The alternative-i.e. suction-seems lessefficacious, since it might facilitate the escape of radium emanationfrom its natural sources. Furthermore, we have suggested pro­tection of the miners by means of respirators containing animalcharcoal, which almost completely absorbs radium emanation.

It cannot, however, be expected that these precautions willshow their efficacy for a number of years, since a great part of thepresent staff probably already has cancer in a latent stage.

SUMMARY

1. By systematic clinical examination and by necropsies inparticular it has been established that lung cancer is highly pre­valent in Jaehymov miners. On 13 of 19 miners dying in 1929­1930 necropsy was performed; in 9 of these pulmonary cancer wasfound (including 1 case of pleural cancer). Four were non­cancerous.

2. The anatomical form of the tumors showed no specialfeatures; most often a circumscribed form was found.

3. With regard to metastases, the tumors showed variouscourses. In 5 cases there was generalization by way of thelymphatics as well as the blood stream. In 2 cases metastases bythe blood stream were almost exclusively present. The bones wereinvolved in 4 cases. In 3 there was compressive myelitis due tometastases in the vertebrae. Metastases to the brain occurred illone case.

4. Aside from the case of primary pleural carcinoma, micro­scopic examination showed oat-cell carcinoma 5 times and epi­dermoid carcinoma twice. In one case two primary lung tumors ofdifferent structure were found, the one, fully developed, being oat­cell carcinoma, the other, quite small, epidermoid carcinoma.Both had caused separate metastases.

5. The time spent in the mines amounted to thirteen totwenty-three years in the cancerous cases. Only two of the menbelonged to the active staff, the others having been out of work for aperiod of one to twenty-seven years.

6. The course of the disease was varied. In 3 cases there was along history of specific symptoms (six to nine years). In the

CANCER OF LUNG IN MINERS OF JACHYMOV 721

remaining cases the course was much shorter, the shortest durationof manifest symptoms being ten weeks. It is highly probablethat the tumors had developed for a considerable time before thefirst appearance of the symptoms, which, at times, were due togeneralization. For this reason it was impossible to draw definiteconclusions regarding the incubation of the tumors after the menhad ceased work. This period in one case amounted apparently to27 years. This long interval was probably one of latency due tothe slow development of the tumor rather than a true incubationperiod.

7. Unlike the Schneeberg cases, no notable degree of anthracosisor silicosis was found in the lungs of miners submitted to autopsy(with the exception of one, who was non-cancerous), so that noimportance can be attached to this factor in the genesis of thetumors. Chemical analysis of lung tissue in one case gave anegative result as to arsenic, bismuth, cobalt, nickel, and uranium;neither could radio-activity be proved.

8. As the most probable cause of the tumors, radium emanation,which is contained in the air of Jachymov pits up to 50 macheunits, might be considered. A cumulative effect of small quantitiesof emanation inhaled for a period of many years may be assumed.This question, however, requires further investigation.

REFERENCES

1. SCHEFFLER: Die Gesundheit der Bergleute, 1770, Chemnitz.2. HARTING AND HESSE: Der Lungenkrebs, die Bergkrankheit in den

Schneeberger Gruben, Vierteljahrsch. fur gerichtl. Med. u. offentl,Sanitatswesen 30: 296, 1879; 31: 102, 1879.

3. COHNHEIM: Vorlesungen tiber allgem. Pathologie, 1882.4. ANCKE: Der Lungenkrebs in den Schneeberger Gruben, Inaug. Diss.

M tmchen, 1884.5. ARNSTEIN, A.: fiber den sogenannten II Schneeberger Lungenkrebs,"

Verhandl. d. deutsch. path. Gesellsch. 16: 332, 1913.6. UHLIG, MARGARETE: fiber den Schneeberger Lungenkrebs, Virchow's

Arch. f. path. Anat. 230: 76, 1921.7. RISEL: Quoted by Rostoski, Saupe, and Schmorl.8. ROSTOSKI, SAUPE, AND SCHMORL: Die Bergkrankheit der Erzbergleute

in Schneeberg in Sachsen (" Schneeberger Lungenkrebs "), Ztschr.f. Krebsforsch. 23: 360, 1926.

9. Lowv, JULIUS: Uber die Joachimstaler Bergkrankheit, Med. Klin.25: 141, 1929.

10. SCHMORL, G.: Ueber die Beziehungen anthrakochalikotischer bron­chialer Lymphknoten zu Bronchialerkrankungen und tiber Bron­chitis deformans, Munchen, med. Wchnschr. 72: 757, 1925.

722 AUG. PlRCHAN AND H. SIKL

11. WOLF: Der primare Lungenkrebs, Fortschr. d. Med. 13: 725, 1895.12. RIBBERT: Geschwulstlehre, Bonn, F. Cohen, Ed. 2, 1914.13. RIBBERT: Das Karzinom des Menschen, Bonn, 1911.14. HUGUENIN, RENE: Le cancer primitif du poumon, 1928, Masson,

Paris.15. JUNGHANNS, HERBERT: Klinische Fehldiagnosen bei Lungenkarzi-

nomen, M unchen. med. Wchnschr. 77: 925, 1930.16. ROSTOSKI, SAUPE, AND SCHMORL: lac. cit. p. 364.17. ROSTOSKJ, SAUPE, AND SCHMORL: lac. cit. p. 367.18. BEYREUTHER, HANS: Multiplicitiit von Carcinomen bei einern Fall

von sag. "Schneeberger" Lungenkrebs mit Tuberkulose, Virchow'sArch. f. path. Anat. 250: 230, 1924.

19. LUDEWIG AND LORENSER: Quoted by Rostoski, Saupe, and Schmorl.

NOTE: The present paper was completed in April 1931. Since the be­ginning of that year, it has been impossible, for reasons we need not statehere, to perform any necropsies of deceased miners. Up to the presenttime (May 1932) 12 miners have died, in 9 of whom 1\ clinical diagnosis oflung cancer was made.

Though the prevalence of lung cancer has been definitely proved byour findings and, in the majority of cases, the diagnosis can be madeclinically, we do not regard further anatomical inquiry as superfluous.There are still many questions to be answered concerning the pathogenesisof the tumors, especially as to the existence of precancerous changes ofthe lung tissue in non-cancerous miners. Further chemical and radiologi­cal analyses of the organs of cancerous and non-cancerous miners are alsodesirable, in view of the possibility of the existence of radio-active depositsin the body according to the findings of Martland (see Am..J. Cancer15: 2435, 1931) and others.

We hope to be successful in our efforts to resume our anatomicalstudies on the subject.

TilE AUTIIORS