Education

PRIMARY CARCINOMA OF THE LUNG' CHARLES F. GESCHICKTER, M.D.

Bal thore , M a .

ROBERT DENISON, M.D. Harrisburg, Penna.

Classijicatiorc: Although before the present century primary cancer of the lung was rarely diagnosed either clinically or at autopsy, it is now frequently seen. The rapid growth of the literature on pul- monary cancer has emphasized the increasing incidence of the disease, and its frequent occurrence in persons under forty o r even thirty years of age. The youngest patient, reported by Beardsley (l), was a child of sixteen months. More thorough studies have shown the protean nature of the clinical and radiological findings and the importance of the bronchoscope in early diagnosis. The course of disease is rapidly fatal, untreated patients rarely surviving diagnosis by more than six months. Metastases to other organs are widespread, and neither ir- radiation nor surgery offers much for the usual case. A study of the records available to us and a review of the literature permit the dis- tinction of two forms of the disease (Table I).

The most common form is bronchial or epidermoid carcinoma (Figs. 1,2 and 3). This type, referred to,also as hilar cancer, occurs in adults approaching or past the age of fifty years and appears in the roent- genogram as a solid shadow near the hilum. Histologically, the tu- mors are composed of epidermoid cells which resemble the lining cells of the large bronchi. The other form, sometimes referred to as lobular or pneumonic cancer, is a diffusely growing adenocarcinoma apparent in the roentgenogram as multiple nodules infiltrating one or both lungs, usually toward the base (Figs. 4, 5 and 6). Adults under forty-five years of age are often affected. Microscopically, the tumor has an adenomatous structure, resembling the terminal ramifications of the bronchioles, and it may contain a mucoid secretion. The so-called alveolar carcinoma referred to in the standard texts on pathology is not an established form, and its existence has never been conclusively demonst rated.

The division of carcinoma of the lung into the two types referred to affords a useful classification from the clinical, radiological, and pathological standpoints. It also has a firm histogenic basis. In the embryo the pulmonary buds begin as outpouchings of the entoderm of

I Aided by a grant from The Anna Fuller Fund. 2 Cases seen in private practice (R.D.) or on file in the Surgical Pathological Laboratory

of the Johns Hopkina Hospital. 854

FIQ. 1. ROENTQENOQRAM OF HILAR OR EPIDERMOID CARCINOMA IN A MAN OF FIFTY-SEVEN. PATH. No. 41979

The roentgeno- gram shows a circumscribed niass at the root of the right lower bronchus continuous with the mediastinal shadow.

Primary symptoms were referable to metastasis in the right humerus.

Autopsy revealed metastases in the kidneys and right humerus.

FIQ. 2. PHOTOMICROQRAPH SHOWINQ THE TRANSITION FROM BASAL TO SQUAMOUS CELLS TYPICAL OF THE MORE HIQHLY DIFFERENTIATED FORMS OF EPIDERMOID

CARCINOMA OF TIIE BRONCHUS, FROM THE CASE SHOWN IN FIQ. 1

855

856 UHARLEB F. QESCHIOKTER AND ROBERT DENISON

the foregut in the regions of the fifth and sixth branchial arches at the end of the first month. The primary or central foous of proliferation of the bronchial tree is at the root of the future lung and is carried down to the point of bifurcation of the future trachea. The sac-like ramifications of the terminal bronchioles, on the other hand, do not appear until the sixth month and proceed until as late as the eighth year after birth (Keith, 2). At this time the actively budding epi- thelial sprouts are at the periphery. The embryonic and post-em- bryonic growth centers are therefore at the root and tips of the

TABLE I: Comparative Dab on Two Major Tgpes of Primary CQWW of the Lung

Number of Cases *. . . . . . . . . . Females. . . . . . . . . . . . . . . . . . . Males. .................... Average age

Squamous-cell type. . . . . Basal-cell type . . . . . . . . .

Location. . . . . . . . . . . . . . . . . . . Type of growth. . . . . . . . . . . . . Major symptoms. . . . . . . . . . .

Typical roentgenogram. ,

Structures involved. . . . . . . . . Microscopic types. . . . . . . . . . .

Principal mettlstatic foci. . .

filar or Epidermoid Carcinoma

34 n L

32

50 yeim 43 years Hilum Solitary Cough- Wheezinaz reaDiration Blood-ti&ed sputum Dyspnea Effusion

Hilar circumscribed mass infiltrating in direction of major bronchus

Large bronchi Squamous-cell Bawl-cell Oat-cell Lymph nodes Pleura Lung, same aide Liver Bones

Lobular or Adenocarcinoma

18 3 15

40 years Periphery (toward bases) Multiple Cough Wheezing respiration Blood-tinged sputum D y spnea Effusion Cerebral or oweoua

symptoms produced by metastases

Multiple foci in one or both lungs maximal towardhses '

Terminal bronchioles Adenocolumnar Adenomucoid Adenocuboidal Lymph nodes Brain Lung, opposite aide Bones Adrenal Liver

* Eight additional cmes with mixed radioiogical or microampic features were not classified. B

bronchial tree respectively, and the occurrence of bronchial or hilar cancer at the hilum and of lobular or adenocarcinoma at the periphery of the adult lung corresponds in distribution with these two growth centers. Fried (3) is of the opinion that the air sacs in the adult lung aro lined only by mesothelium overlying the pulmonary capillaries, and that, therefore, alveolar carcinoma does not occur. From this stand- point bronchiogenic or hilar carcinoma arises from the epithelium of the large bronchi while the basal cells of the peripheral bronchioles, at the points of their terminal ramifications, give origin to lobular or ade- nocarcinoma.

PRIMARY CARCINOMA OF T H E L U N G 857

CLINICAL FEATURES Apparently primary tumors of the lung are on the increase. All

the larger series of cases have been compiled in the past few decades. Rosahn (4) in a review of the material at the Boston City Hospital stated that the incidence of the disease had risen from 4.39 per cent in 1910-19 to 6.98 per cent in 1920-29. Adler ( 5 ) in 1912 collected one of the earliest large series of cases (over 300), and in recent years numerous authors have reported series ranging from 20 to over 100 cases.s The tumors are more frequent in males than females and occur between the twentieth and seventieth years of life. The course is rapid, the patients rarely surviving more than a year. Radio-active substances, heavy oils and tar, and chronic inflammatory diseases of the lung are believed to be predisposing factors. The etiological sig- nificance of these agents, however, is not well established. Chimney sweeps, aniline and paraffin workers, and miners working with radio- active minerals have been known to develop the disease twenty or

FIG. 3. TYPICAL EPIDERMOID CARCINOMA AT THE ROOT OF A LAME BRONCHUS, IN A MAN AGED SIXTY. PATH. NO. 45444

thirty years after exposure. The most conclusive series of cases from an etiological point of view are those reported among the miners of Schneeberg and JBchymov after long contact with radio-active ores

The disease may exist for a considerable time without symptoms. When these occur they may be related to the lesion in the lung or to the metastases. There are cough, dyspnea, pain in'the chest, and oc- casionally fever and night sweats. Cough is usually an early symp- tom, and may be dry or mucopurulent. Material mixed with blood may be expectorated, or actual tumor tissue coughed up. I n one case of this series (Fig. 7) a mass of well preserved tissue weighing three grams was expectorated. Frank hemoptysis is a late sign. Pain may be referred to the pleura o r the upper extremities. Hoarseness may be a fairly early symptom, and there may be clubbing of the fingers and toes.

(9).

8 The largest serics of cases reported recently have been those of Edwards (6), 118 rases; Lemon, Vinsoii and co-worker8 at tho Mayo Clinic (7), 96 cases; Maxwell (8), 110 caaes.

858 OHARLES F. OESUHICKTER AND ROBERT DENISON

The physical signs due to the tumor in the chest are usually dull- ness to percussion, increased breath sounds, and diminished tactile fremitus. Because of necrosis and cyst formation cavernous breath- ing may be heard. Early hilar tumors may present no physical find- ingg. There are no general symptoms or signs which could not accom- pany either tuberculosis or abscess of the lung. Fungous disease of the lungs may also be simulated. Jackson (10) lays great stress on

%IO. 4. ROENTQENOQRAM OF A LOBULAR OR ADENOCABOINOMA OF THE LUNO IN A WHITE MALE AOED TWENTY-TWO YEARS. PATH. No. 51632

The tumor diffusely infiltrates both lungs after the manner of miliary tuberculosis. The shadows are more dense a t the bases and in the region of the right lower bronchus. The patient had had fever, night sweats, cough, and dyspnea of three weeks’ duration, and had lost eleven pounds. The Clinical impression was miliary tuberculosis.

the diagnostic value of cough of insidious onset and wheezing respira- tion. Dyspnea out of proportion to the physical findings is also an important clinical feature. Obstructive atelectasis and, obstructive emphysema are invariably present at some stage, dnd pleural effusion may be an early sign (Fig. 8).

The earliest signs and symptoms may be clue to metastases in the brain, bones, adrenals, or gastro-intestinal tract, which are frequent Rites for secondary deposits. A primary brain tumor was suspected in three of our cases (Figs. 9 and 10). Occipital headaches with hemi- plegia or paraplegia may suggest such a diagnosis. Disorientation, facial paralysis, and dysarthria, suggesting a diagnosis of encephalitis, occurred in the case illustrated in Fig. 17. The bones may be affected by painful deposits, appearing roentgenologically as areas of increased density and suggesting Paget’s disease (Fig. 11A, R, (7). Multiple punched-out areas in the skeleton may also occur, and when the pri- mary tumor is obscured by the mediastinal shadow a diagnosis of mul-

PRIMARY CARCINOMA OF THE L U N G 859

tiple myeloma has been made (Fig. 12A, B and C). Metastatic growths in the suprarenals may give the symptoms of Addison’s disease, the patients showing marked hypotension and pigmentation of the skin. More rarely metastases to the liver or spleen may suggest a lesion primary in the gastro-intestinal tract. This wide distribution of metastases has been attributed to the venous drainage of the lung, which enters the left heart and from thence supplies the major circulation.

FIQ. 5A. DISTRIBUTION OF TUMOR IN THE LUNQS, IN CASE SHOWN IN FIG. 4

PIQ. 5B. YETASTASES IN LIVER (LEFT) AND KIDNEYS (RIQHT) FROM PULMONARY ADENO- CARCINONA SHOWN I N FIQS. 4 AND 5

Extension to the pleural and neighboring pulmonary tissue is fa- cilitated by the channels of the bronchial tubes and the lymphatic drainage of the lung. Pressure on a main bronchus may collapse the entire lung (atelectasis) or pleural extension may result in massive effusion with a similar collapse. Aspiration of the pleural cavity may be carried out as a diagnostic procedure. The exudate is sometimes bloody (in one-third of our cases where effusion was present) and when centrifuged may show carcinoma cells. These cells may also be found in the sputum, or tumor tissue in one of the large bronchi may be ob- tained fo r biopsy by means of the bronchoscope.

FIO. 6. DIFFUSE AND IMPERFECT ACINAFZ ARRANOEMENT OF ADENOCUBOIDAL CARCINOMA OF THE LUNQS, FROM CASE SHOWN IN FIQS. 4 AND 5A AXD B

FIQ. 7. PHOTOMICROORAPH OF AN EPIDERMOID cARCINOMA OF THE BASAL-CELL TYPE, IN A

The section was made from a specimen weighiug three grams, expectorated by the patient. She had been under treatment for two years for infectious arthritis when a uon-productive cough developed, followed one mouth later by massive effusion. The roentgenogram showed nil indistiiict mass at the hilum of the left lung inflltratiug toward the upper left lobe.

WOMAN AOED FIFTY-THREE. PATH. No. 46602

860

PRIMARY CARCINOMA O F THE LUNG 861

RADIOLOGICAL AND PATHOLOGICAL FINDINGS The classificalion used in the present study is based upon an analy-

sis of the roentgenograms and pathological material obtained from a series of 60 cases. In all of these the diagnosis was microscopically verified and roentgenograms or autopsy findings were available to de- termine the distribution of the tumor in the lung. Autopsy was per- formed in 50 cases, and in the majority of these roentgenograms of the chest were available. In 20 additional cases biopsy material or tissue obtaiiied elsewhere was available, but only 10 of these, in which roent- genograms of the chest were studied, are included in this series. Eighteen cases could be classified as of the peripheral or adenocar-

FIG. 8. RoENToENOGRAM OF HILAR OR EPIDERLlOID CARCINOMA IN A MAN OF SIXTY YEARB. PATH. No. 51898

Histologically tlie tumor was of the squamous-cell type. The roentgenogram shows mas- sive effusion in the right chest with a collapse of tlie lung and pneuniothorax.

cirioma type with reasonable assurance. Thirty-four cases were hilar or epidermoid in type. The remaining cases could not be satisfactorily classified, either because the distribution of the tumor was obscured by pleural eff'usion in the roentgenogram or the microscopic findings showed a cancer in which epidermoid features and adenomatous ar- rangement were equally firominent (see Table I).

Lobular or Adenocarcilzd'ma of the Lung: The average age in eight- een cases of adenocarcinoma was forty years. Only four patients were over forty-five years of age, forty-nine, fifty, fifty-six and sixty-five re- spectively. The youngest patient was twenty-two, and the roentgeno- gram in this instance showed a diffuse spotting of both lungs, more pro- nounced a t the bases, resembling miliary tuberculosis. The history of this case is given in the legends of Figs. 4 to 6. A similar case has

FIG. 9A. ROENTQENOGRAM OF HILAE CARCINOMA OF THE LUNG EXPLORED FOR INTRACBANIAL LESION. PATH. No. 44471

FIG. 9B. PHOTOMICROGRAPH OF TUMOR SHOWN IN FIG. 9A Tho patient was a white man of thirty-two who two mouthsdpreviously had nausea, vomit-

ing, and headaches. Moisf rAles were heard in the left lower chest and the roentgenogram made before operation showed a circular shadow at the root of the left lung thought to be neoplasm. A tumor mass weighing 103 grams was shelled out of the right frontal lobe at a crrtniotomy. Although the provi6ional pathological report was ependymoblastomn, the operator deemed the mass metastatic because it did not connect with the ventri~~lc.

The left eye showed a choked disc.

862

FIQ. 10.4. ROENTGENOQRAM OF ADENOCARCINOMA OF THE LUNQ IN A MAN OF FORTY-SIX. PATH. No. 49481

FIG. 10B. PHOTOMICROQRAPH OF TISSUE REMOVED AT CRANIOTOMY IN CASE SHOWN IN FIQ. 10A The initial symptoms were paresis, tremor, aiid vertigo. Later the patient complained

of cough aiid blood-streaked sputum. The positive physiral findings were related to the right lower chest, although the roeritgeiiogram showed what was interpreted as tuberculosis in the left upper lung. A craiiiotomy was performed on October 1, 1930. Tissue was removed for b iopq but the ninjor tunior inass obliterating the right veiitricle was not entered. The provisional pathological report WRR mctastatic ndcnocarcinornn of a. papillomatous type.

863

864 CHARLES F. GESCHICKTER AND ROBERT DENISON

been described by Hamman (11). I n another patient, aged thirty, the entire left lung was infiltrated and finally obscured by effusion and collapsed (Fig. 13). This patient had cough and pleurisy, suggesting tuberculosis. At autopsy diffuse infiltration of the right lung made it impossible to determine the point of origin. In both these mses

FIG. 1 l A . ROENTGENOGRAM OF THE PELVIS 8HOWING METASTASES TO THE ILIUM AND SPINE OF THE OSTF&PLAZSTIC TYPE, IN A CASE OF BRONCHIAL CARCINOMA. PATH. No. 58722

The patient was a inan aged sixty-ow, a i d the pelvic lesion was thought to be Paget's osteitis deforriiaiis.

FIG, 11B. ROENTQENOGRAM OF THE &EST IN CASE BROWN IN FIQ. 11A Tile primary lesion above the heart shadow is obscured by pleural effusion.

there were numerous metastases involving the bones, brain, and vis- cera. In the majority of the other cases of the adenocarcinoma type the tumor was found in several lobes of one or both lungs. I n one caee, in a man aged forty-six, the tumor diffusely infiltrated the upper left chest, resembling tuberculosis (Fig. 10). In another case (Pig. 14) both lungs were the se& of multiple nodules, more densely crowded

PRIMARY CARCINOMA OF THE LUNG 865

toward the bases. The microscopic picture of the specimens removed from the lungs showed an adenomatous arrangement of cuboidal cells. The metastases in the bones, however, showed areas in which squamous cells were prominent. 111 another atypical case of adenocarcinoma a large solid tumor was found in the mid-portion of the left lung sug-

FlQ. 12A. ROENTGENOGRAM OF THE CHEST IN A CASE OF PRIMARY LUNQ CANCER. PATH. NO. 53418

The tumor is largely obscured b y the mediastinal shadow.

gesting the hilar type, while the right lung was diffusely infiltrated by tumor (Fig. 15).

The varying types of lung infiltration seen in adenocarcinoma, rang- ing from a miliary type to a form in which one or more large con- glomerate masses are seen, are explained by varying degrees of malig- nancy in the patholo@c subdivisions. Adenocarcinoma may be di- vided into adenocuboidal, adenocolumnar, and adenomucoid types ( MacCallum, 12) .4 The aclenocuboidal may approach the epidermoid type of bronchiogenic carcinoma in appearance, as in the case shown in Fig. 14. It is extremely malignant, often shows imperfect acinar arrangement with a tendency to grow in diffuse sheets (Fig. 16A), and may produce miliary involvement of both lungs. Metastases are early and widespread, and the clinical course is rapidly fatal. Both the adenocolumnar and adenomucoicl types are more differentiated but have a similar distribution at the lung periphery (Figs. 16B and C). The tumor masses, howcvc~’, may he more discrete and larger in these cases (Fig. 17).

4MaeCallum, i n a review of the autopsy nrntrrinl at the Johns Hopkiiis Hospital, con- cluded that an alvrwhr type of lung cancer may arise froin the walls of tho alveoli, but thie opiiiioii is not widely accepted. See Fried ( 3 ) .

FIQ. 12B. ROENTGENWEAM OF SKULL IN CASE SHOWN IN FIQ. 12A

FIG. 12C. ROENTGENOQEAM OF Pmvra IN CASE SHOWN IN FIQ. 12A The multiple areas of destruction here and in tho skull (Fig. 12B) were originally diag-

nosed a8 myeloma.

FIQ. 13A. ROENTQENOQRAM SHOWIXG MASSIVE EFFUSION IN TIIE RIQHT CHEST PRODUCED BY IXPILTRATION OF THE RIGHT LUNG BY ADENOCIRCINOMA. PATH. NO. 11118

FIU. 1313. GROSS SPECIMEN SHOWING MASSIVE CONSOLIDATION OF THE ENTIRE UPPER LEFT LOBE PRODUCED B Y DIFFUSE INFILTRATION OF ADENOCARCINOMA, SAME CASE AS IN FIQ. 13A

867

868 OHARLES F. OESCHICKTER AND ROBERT DENISON

Hilar or Epidermoid Carcimoma o f the Lung: The more common type of epidermoid or hilar carcinoma has a distinct primary focus near the hilum, with varying degrees of piieumonic infiltration in the direction of the bronchiis. The majority of the patients are fifty pears of age or over and the tumors are histologically of the squamouu-cell

FIG. 14A. ROENTQENOGRAM OF ADENOCUBOIDAL CANCER PRODUCINQ A PICTURE OF MILIARY

The secondary deposits i n the bone showed aquamous-cell cancer. TUBERCULOSIS IN THE CHEGT. PATH. NO. 12420

FIQ. 14B. GROSS SPECIMEN OF ADENOCUBOIDAL CANCER SHOWN ROENMENWBAPHICALLY IN FIQ. 14A

variety. In a smaller group the average age is slightly under forty- five and the tumor is histologically less differentiated and of the basal- cell type. In the roentgenogram the cases examined early show a soli- tary tumor mass, usually approaching the size of an adult fist, con- tinuous with the mediastiiial shadow. The shadow is never clearly

PRIMARY CARCINOMA OF THE LUNQ 869

demarcated, although it may have one or two sharply delineated bor- ders. Hazy infiltration proceeds outward in one or more directions, usually following the course of the afyected bronchus (Figs. 18 and 19). In the vast majority of instanccs the tumor shadow overlaps the shadow of the heart or the normal mediastinurn. If the roentgeno-

FIQ. 15. ATYPICAL ROENTQENOQRAM OF ADENOCUBOIDAL CARCINOM-4, SHOWINQ MASSIVE T'UMOR IN THE MID-PORTION OF THE LEFT LUNQ AND DIFFUSE METASTASIS

IN THE RIQHT CHEST. AUTOPSY No. 8609

grams are made later in the course of the disease, the area of infiltra- tion beyond the main tumor becomes more extensive and ultimately effusion or collapse obscures the findings. In the present series of epidermoid cancers the tumor mass was in the right chest more fre- quently than the loft. In six cases the root of the right upper bronchus, in four the right middle, and in six the right lower was affected. In the left lung the root of the uppcr bronchus was affected in seven cases: the mid-bronchus in four cases, and the lower in one. In three in- stances the tumor mass projected both to the right and left of the mediastinal shadow.

Pathologically the epidermoid group of hilar carcinoma can be di- vided into thc squamous-cell and basal-cell types. In patients over fifty years of age, squamous-cell cancer with epithelial pearls was the most common finding. In the younger group elongated basal cells and a less differentiated type of transitional epithelium was found. In a few instances the tumor was composed entirely of tightly packed elon- gated basal cells, the so-called oat-cell sarcoma of earlier authors (Figs. 20A and B).

In the epidermoid group of hilar carcinoma distant metastases are not as common as in the adenocarcinoma group. The more differenti- ated type of squamous-cell cancer in elderly patients pursues a chronic course. In one case a tumor of the chest was present for six years.

870 UHARLES F. OEBCHICKTER AND ROBERT DENIBON

A large local tumor with effusion is formed, and the growth extends into the pleura and to the oppositelung. Metastases to other organs occur relatively late. On the other hand, in the basal-cell and oat-cell types, occurring in younger individuals, death by local extension with- out metastasis to other organs is rare. These tumors are particularly prone to invade the mediastinum and to involve the regional lymph nodes.

FIQ. 16A. ADENOCUBOIDAL CARCINOMA OF TEEMINAL BROWHIOLES, BHOWINQ DIFFUSE PRO- LIFhXATION OF CUBOIDAL CELLS PATH. NO. 51632

From cam shown in Figs. 4, 5 aiid 6.

DIAGNOSIS AND TREATMENT I n differential diagnosis of carcinoma of the lungs the major con-

ditions to be borne in mind are tuberculous and mycotic infection, lung abscess, mediastinal lymphoma, and pleural tumors. In the roentgeno- gram tuberculosis rarely gives a solitary shadow in the region of the mediastinum except in young children and in healed cases. Diffuse infiltration in tuberculosis is most common in the apices, whereas in adenocarcinoma the lesions are toward the base. The tubercle bacillus can be recovered from the sputum in most cases of acid-fast infection and the newer diagnoetic cutaneous tests may be of importance. I n mycotic infection the diagnosis is often made by smear or culture of the sputum or pleural fluid. In lung abscess frank pus can often be ob-

FIG. 16B. ADENOCOLUMNAR CARCINOMA OF TERMINAL BRONCHIOLES. PATH. No. 47410 The patient, a woman of thirty-one, entered the hospital in a moribund condition, with

uultiple involvement of both lungs.

FIG. 16c. ADENOMUCOID CARCINOMA OF TEKMINAL BKONCHIOLES. PATH. NO. 45438 The patient was a woman of thirty-eight, whose first complaints were cerebral confusion

aud paresis of the left side.

871

872 CHARLES F. GESCHICKTER AND ROBERT DENISON

tained by postural drainage or by thoracentesis. The shadow in the x-ray plate is more clearly defined and away from the mediastinum. There is usually an antecedent history of operation or of the swallow- ing of a foreign body, and diagnosis can frequently be made by bron- choscopy. Pleural fluid associated with the abscess is not bloody and contains no tumor cells. This is also true of tuberculous effusion.

The mediastinal lymphomas may be distinguished by their reaction to irradiation. These growths shrink rapidly under radiotherapy, whereas lung cancer is radio-resistant. Tumors of the pleura and chest will usually have the base of their shadows lying against the

FIG. 1 7 . ROENTGENOQRAM OF THE CHEST IN THE CASE OF ADENOMUCOID CARCINOMA SHOWN IN FIQ. 16C

The clinical impression in this case was encephalitis.

pleura with the apex directed inwardly. &solitary large mass is the rule.

Neither surgery nor irradiation has met with much success in the treatment of lung cancer. In comparing irradiated and non-irradiated eases, approximately evenly divided, in a total series of 120 cases, Chandler and Potter (13) found the duration of life to be longer by five months in irradiated cases. The average duration after diagnosis was eleven months for the treated cases as compared with six months in the untreated cases, Maxwell and Nicholson (8) obtained similar results. Fried (14), however, in a recent review of the subject, has found little encouragement in the results obtained by the use of ir- radiation.

FIG. 18A. TYPICAL ROENTGENOQRAM OF HILAR OR EPIDERMOID CARCINOMA, BASAL-CELL TYPE. PATH. No. A8966

FIG. 18B. TYPICAL ROENTGENOGRAM OF HILAR OR EPIDERMOID CARCINOMA, SQUAXOUS-CELL TYPE

873

FIO. 196. ROENTGENOQRAM OF BASAL-CELL CARCINOMA OF THE HILAR TYPE IN A MALE OF THIRTY-EIQHT. PATH. No. 54146

The size of the tumor and its rapid growth are to be correlated with the undifferentiated histologic type and the age of the patient. Courtesy of Hines Hospital, Chicago, Ill.

FIG. 19B. ORO8S BPECIMEN OF TUMOR SHOWN ROENMENOORAPHICALLY IN FIQ. 19A 874

PRIMARY CARCINOMA OF THE L U N G 875

I n recent years excision of one or more lobes of thc lungs or re- moval of the entire lung has been attempted with operative success. Only a few of these lobectomies have been applied to carcinoma of the lung. Rienhoff and Broyles (15) have had favorable results in two cases recently reported. None of these cases has yet been followed for a period of five years.

CONCLUSIONS 1. An analysis of 60 cases of primary lung cancer indicates that

these tumors may be classified into two groups. The more common type, hilar or epidermoid carcinoma, occurs at the center of the lung and arises from the basal-cell layer beneath the lining cells of the large bronchi. The rarer form, lobular or adenocarcinoma, occurs at the

FIG. 20A. EPIDERMOID CARCINOMA OF THE IAJNQ, sQUAMOUS-CELL TYPE. PATH. NO. 41979

periphery of the lung, arising from the terminal ramifications of the bronchioles. A table contrasting the findings in the two groups is given.

2. The roentgenograms of typical cases of hilar carcinoma show a solitary mass, usually to the right of and overlapping the mediastinal shadow, In roentgenograms of typical lobular carcinoma multiple masses are seen in several lobes of one or both lungs. When both lungs are affected the major involvement is toward the bases.

3. Hilar o r epidermoid carcinoma may be graded into three forms. I n the least malignant histological grade, occurring in patients over fifty years, squamous cells predominate. The middle grade shows a proliferation of basal and transitional cells and occurs in patients under fifty years. The most malignant grade shows masses of com- pact or spindle cells, is referred to as oat-cell cancer, and is most com-

FIQ. 20B. EPIDERMOID CARCINOMA OF THE LUNG, BASAL-CELL TYPE. PATH. NO. 46800

Fro. 20C. EPIDE~MOID CARCINOMA OF THE LUNQ, OAT-CELL TYPE. PATH. NO. 46602

870

PRIMARY CARCINOMA OP THE LUNG 877

mon in young adults. Lobular adenocarcinoma is also divided his- tologically into three groups. The least malignant or most highly dif- ferentiated tumors are of two forms, adenocolumnar and adenomucoid. The average age of these patients is forty years. The most malignant histologic type of adenocarcinoma shows a diffuse proliferation of cuboidal cells (adenocuboidal cancer). The patielits affected are most often under forty years of age and sometimes under thirty.

BIBLIOGRAPHY 1. BEARDSLEY, J. M.: Primary carcinoma of the lung in a child of sixteen months,

2. KEITH, SIR ARTHUR: Human Embryology and Morphology, Wm. Wood &, Co., New

3. FRIED, B. M. : Primary carcinoma of the lung; bronchiogenic cnncer; clinical and

4. RQSAHN, P. D. : The incidence of primary carcinoma of the lung, Am. J. M. Sc. 179:

5. ADLER, J.: Primary Malignant Growths of the Lung, P. Hoeber, New York, 1912. 6. EDWARDS, A. T. : Malignant disease of the lung, Brit. M. J. 1 : 129, 1931. 7. LEMON, W. S., VINSON, P. P., MOERSCH, 13. J., AND KIRKLIN, B. R.: Primary carci-

8. MAXWELL, JAMES, A N D NICHOLSON, W. A.: Clinical study of bronchial carcinoma,

9. PIRCHAN, A., AND SIKL, H.: Cancer of the lung in the miners of JBchymov (Jo-

10. JACKSON, C. : Malignant growths of the lung; bronchoscopic diagnosis, Arch. Oto-

11. HAMMAN, L. : Diagnosis of carcinoma of the lung, Am. Rev. Tuberc. 28 : 711, 1933. 12. MACCALLUM, W. 0.: Carcinoma of the lung, Trans. Assoc. Am. Phys. 14: 77, 1930. 13. CHANDLER, F. G., AND POTTER, C. T.: An investigation into the result of x-ray treat-

14. FRIED, €3. M.: Bronchiogenic cancer: treatment with roentgen rays, Am. J. Cancer

15. RIENHOFP, W. F., AND BROYLES, E. N.: Surgical treatment of carcinoma of the bron-

Canadian M. A. J. 29: 257, 1933.

York, 1933, 5th ed., p. 386.

pathological study, Medicine 10 : 373, 1931.

803, 1930.

noma of the bronchus, Southwestern Med. 16: 485, 1932.

Quarterly J. M. 23: 29, 1930.

achimstal), Am. J. Cancer 1 6 : 681, 1932.

laryng. 12: ‘747, 1930.

ment of primary malignant iritrathoracic tumors, Lancet 2 : 596, 1927.

20: 791, 1934.

chi and lungs, J. A. M. A. 103: 1121,1934.