A STUDY OF 57 CASES OF BRONCHOGENIC CARCINOMA

RAYMOND S. ROSEDALE, M.D., AND DONALD R. McKAY, M.D.

(Front the Departments of Patlzology and Medicine, Buf falo City Hospital aird the University of Bziflalo Medical School)

I t is our purpose to report the essential data of 57 cases of bronchogenic carcinoma which were recorded in the Buffalo City Hospital from 1924 to 1934. Thirty-seven of these were autopsied; the diagnosis in the remainder was established by a critical evaluation of what was considered definite clinical evidence, plus positive biopsy, bronchoscopic and radiographic findings, or a combination of all these. The term ( ( bronchogenic ” carcinoma is used because we have no evidence that the tumor originated from the pulmonary alveoli in any of the cases.

The literature concerning bronchogenic carcinoma has been reviewed and requoted so often within recent years that further reference to it here is unnecessary. Those who wish to acquaint themselves further with this phase of the subject are referred to the papers of Fried ( 3 ) , Geschickter (4), David- son (2), and others.

INCIDENCE

There were slightly more than 100,000 patients admitted to the Buffalo City Hospital in the ten year period, 1925-1934, This hospital receives and treats individuals with all types of disease. There were 10,121 deaths and 4,670 autopsies. Among the latter, 466 malignant neoplasms of all types, including brain tumors, were found. Bronchogenic carcinoma constituted 7.5 per cent of this number. The figures for the twelve most frequently autopsied malignancies were as follows:

Stomach . . . . . . . . 71 Uterus . . . . . . . . . . . . . . . . . . . . . . . . . 33 Lung . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Rectum . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Prostate . . . . . . . . . . . . . . . . . . . . . . . . . 24 Brain tumors . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Colon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Breast . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Bladder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 7 Pancreas . . . . . . . . . . . . . . . . . . . . . . . 16

. . . . . . . . . .

Esophagus . . . . . . . . . . . . . . . . . . . . . . . . . 30

Tongue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

From these figures it will be seen that bronchogenic carcinoma was at least the third in order of carcinomas autopsied in this period. There are, however, so many factors determining this figure, that it cannot be said un- equivocally that bronchogenic carcinoma is the second or third most common malignancy, but it is obviously relatively frequent.

493

494 RAYMOND S . ROSEDALE A N D DONALD R. MCKAY

Fifty-two cases, or 91 per cent of our group, occurred in males (Fig. 1). The ratio of colored individuals to white was 6 to 51, which is approximately the division of these two races in the City of Buffalo. The age of the youngest

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FIG. 1. Am, RA(.L, AND SLX INCIDENCE OP BRONCJLOGENIC CARCINOMA

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FIG. 2. OCCUPATIONS or 5 7 IKnIVlDUAl S WITH BRONCHOGENIC CARCINOMA

individual in the group was thirty-three, of the eldest seventy-three, the average being 50.4 years. The majority of individuals were between the ages of forty-four and fifty-eight.

From a knowledge of local The occupational incidence is shown in Fig. 2 .

A STUDY OF 57 CASES OF BRONCHOGENIC CARCINOMA 495

conditions it was estimated that 43 patients, or 75.4 per cent of the total number, were employed in occupations requiring exposure to dust or other irritating atmospheric factors. We feel that this may possibly be an etiologic

INFILTRATION vl [UNRECORDED) )LLfTl 16 - CASfS 20 - CA3ES I - CASE

*LOCATION OF TUMOR IN RELATION TO BRONCHI. -97 AUTOMILD CIWLS. F M

FIG. 3. LOCATION OF TUMOR IN RELATION TO THE TRACIIEOBRONCHIAL TREE

factor in producing chronic irritation of the bronchial epithelium, resulting in protoplasia and metaplasia.

MORBID ANATOMY

The following observations were made from the study of the 37 autopsied cases. The tumor was present in the right lung in 20 cases and, in the left in 16. In one case the location was unrecorded.

The majority of the tumors were located in the first order or larger bronchi, near the hilus (Fig. 3 ) . In 2 2 cases the tumor was concentrated about a first order bronchus, in 3 cases about a second order bronchus, and, in 1 case about a third order bronchus. In each of 3 cases the tumor was in relation to the carina, and in 2 of these in relation, also, to a first order bronchus and to the trachea respectively. In 4 cases concentration of tumor about a bronchus was not demonstrated, but the growth diffusely pervaded the lung parenchyma.

From observations in the autopsy room one might state for the guidance of clinicians and roentgenologists, that bronchogenic carcinoma is usually a

Flo. 4. MASSIVE HIT,AR GROSS T Y P E OF BRONCIIOGFNIC CARCINOMA The right chief bronchus has been opened and a portion of the lung turned to the left

FIG. 5 . ANOTHER GROSS TYPE OF BROS(:IIO(:RR.IC CARCISOMA, A SlscLc MASS IN T13E PERIPIIERY OF A LUNG

496

A STUDY OF 57 CASES OF B R O N C H O G E N I C CARCINOMA 497

single unilateral massive lesion situated near the lung hilus, in contradistinc- tion to metastatic tumors, which generally are distributed bilaterally, are multiple, and located near the periphery of the lungs. An outstanding excep- tion is the single " cannon ball " pulmonary metastasis of hypernephroma.

The gross form of bronchogenic carcinoma may be resolved into three principal types: (1) the massive hilar nodule (Fig. 4) , the majority of our cases being of this type; ( 2 ) carcinoma originating from a small bronchus in the periphery of the lung (Fig. 5 ) ; ( 3 ) what may be described as a diffuse type. This last type in a few instances resembles the stage of gray hepatiza- tion of lobar pneumonia (Fig. 6 ) . Within the last year we have had two examples of the diffuse type. Both occurred in individuals with an extensive

FIG. 6 . DIFFUSE TYPE OF BRONCHOGENIC CARCINOMA

pneumonoconiosis and pulmonary fibrosis and were overlooked in the autopsy dissection, to be recognized in the routine histological examination.

Many of the cancers in our series were characterized grossly by centripetal growth. This, plus tumor permeation of the peribronchial lymphatics and the coincident productive inflammation, leads to bronchostenosis (Fig. 7 ) . Diminution in size of the bronchus lumen and fixation of its walls predisposes to infection or may aggravate a pre-existing bronchitis. Infection, weakening of the walls, and the strain of repeated coughing are followed in some instances by bronchiectasis. Complete occlusion of the bronchus by tumor (Fig. 8) leads to atelectasis of the lung parenchyma distal to the point of obstruction. If abscesses have not been present prior to this, they may now develop, and, if they are peripheral or subpleural, may be responsible for empyema. Such associated pulmonary pathology is often confusing to the clinician and roent- genologist.

In several of our cases a carcinoma which was concentrated in the wall of Its occurrence in our cases is shown in Fig. 9.

F I G . 7 ALMOST COMPLATE OCCLUSlOK OF THE RIGHT CHIEF BRONCHUS The right lowcr lobe is atelectatic. I n it there are four abscesses. There was an associated

c.rnpyema.

Fro. 8. EXAMPLE OF A BRONCHUS COMPLETELY OCCLUDED BY TUMOR

498

A STUDY OF 57 CASES OF BRONCHOGENIC CARCINOMA 499

the bronchus infiltrated centrifugally into the adjacent lung parenchyma (Fig. lo ) , In such cases ulceration of the bronchial mucosa is not so apt to develop and the individual, therefore, is likely not to have blood-streaked sputum. In such cases, also, bronchostenosis is not likely to be a prominent feature, and the common sequence of bronchitis, bronchiectasis, atelectasis, abscess, and empyema is not encountered.

ASSOClATeD LUNG PATHOLOGY IN 37 CAS€S OF PRIMARY LUNG CARCINOMA

l~CISCJ,BRONCHlLCTA51~ PNCUMOKONlOJlJ S C A S E ~ c MPY E M A/

FIG. 9. ASSOCIATED LUNG P.ITIIOI.OC:Y F o c s ~ AT AUTOPSY OF 3 7 CASES OF RHOXITOGENIC CARCINOMA

The association of pneumonoconiosis or of tuberculosis with bronchogenic carcinoma has been reported principally in isolated cases. I t is to be noted that these were associated in 14 and 7 respectively of our autopsied cases (Fig. 9).

HISTOLOGY

The histologic types in our autopsied material were classified as round-cell ( 4 cases), spindle-cell ( 5 cases), squamous-cell ( 13 cases), so-called basal-cell ( 3 cases), adenocolumnar mucus-secreting ( 3 cases), adenocolumnar non- mucus-secreting ( 3 cases), undifferentiated ( 6 cases). I t was not unusual to find representatives of most of the cell types in examining sections from a number of blocks of the same case. Kegardless of the predominant cell type,

500 RAYMOND S. ROSEDALE AND DONALD R. MCKAY

round or spindle cells could be found in all cases. These can be said to be the primal or parent cells of all bronchial epithelium. We are unable to divide our histologic material into two characteristic groups as Geschickter (4) has done.

METASTASES

The distribution of metastases in the autopsied groups is shown in Fig. 1 2 , and the clinically demonstrated metastases in the unautopsied group in Fig. 11. The low number of brain metastases is probably explained by the fact that the brain is not examined frequently in our autopsy service because of restricted consent. This organ is believed by some to be one of the most conlmon sites of distal metastases of bronchogenic carcinoma. I t is similarly

F I G . 10. LARGE B~o~ciror:c.yic C \RCIXOMA WITH PRACTICALLY NO BRONCIIOSTENOSIS In this gross type the sequence of bronchitis, bronchiectasis, atelectasis, abscesscs and empyema

is not SO likely to develop.

probable that bone metastases were commoner than is indicated in Fig. 11, for only those bones to which attention had been directed clinically were dissected.

I t is noteworthy that there were metastases to the pulmonary lymph nodes in all the patients. The cervical lymph nodes were involved in 7 instances and the supraclavicular nodes in 2. Dr. William Boyd ( l ) , in a personal com- munication, has recently commented on the frequency of cervical lymph node metastases in the large number of cases he has studied. Extension of tumor into the superior vena cava was found 3 times. Since our data were compiled we have studied 3 other cases with vena cava invasion. The superior vena cava was involved in two, and the inferior vena cava in one. The growth in a caval vein might give rise to bilateral peripheral pulmonary metastases, but this was not observed in our material.

FIG. 11. CLINICALLY DEMOKSTRATED METASTASES IN UNAUTOPSIED CASES OF BRONCIIOGENIC CARCINOMA

M€TA.STAS I3 D€MONSTRATED AT AUTOPSY --_

0 -NUMBER OF CASE

URVICAL NODE@

LAVICULAR NODC58

FIG. 12. DISTRIBUTION OF METASTASES IN 37 AUTOPSIED CASES OF BRONCHOGENIC CARCINOMA

501

502 RAYMOND S. ROSEDALE A N D DONALD R. MCKAY

I t was repeatedly observed that massive distal metastases arose from a relatively small and innocuous appearing primary tumor. In a number of such cases focal symptoms or signs due to metastases clinically eclipsed those later attributed to the primary growth. A relatively small carcinoma of the left chief bronchus is shown in Fig. 13 with its hepatic metastases. The liver weighed 13.5 lbs., at least three times the normal weight. The clinical im- pression was primary carcinoma of the liver, or hepatic metastasis from gastric carcinoma. This case was seen in another hospital, where the radio- graphic shadow of pleural fluid and that of a unilateral hilar area of increased density were not integrated with the clinical findings.

FIG. 13. RELATIVELY SMALL BRoNcrrocesrc CA\H(’INOMA WITH MASSIVI. METASTASES The liver (right) wcighed 13.5 Ibs.

CLINICAL AND ROENTGEN FINDINGS

The clinical diagnosis of primary lung cancer was made in 10 of the autopsied cases, suspected in 5 others, and not made in 2 2 . In a more recent twelve-month period, bronchogenic carcinoma was successfully diagnosed in 6 of 11 autopsied cases. In 5 of the autopsied cases reported in the present series there was advanced secondary pulmonary or pleural pathology which obscured the clinical features of tumor. In one, complicated by empyema, the patient underwent thoracotomy. In 8 others the metastases were responsi- ble for misleading focal clinical symptoms or signs. In 3 cases, dissociated diseases engaged the exclusive attention of the clinician. One other patient was moribund on admission, and one died within twenty-four hours, of lobar pneumonia.

The duration of the symptoms (Fig. 14) varied widely, the average being ten months, which is shorter than in most reported groups of cases. This variation is in a general way due to three factors: (1) the rate of tumor growth, ( 2 j the incidence of secondary pulmonary pathology, (3 j extent of the metastases.

This at first was Cough was the most constant early symptom (Fig. 15).

A STUDY OF 5’7 CASES OF BRONCHOGENIC CARCINOMA 503

-

non-productive and hacking; later in the disease it was accompanied by the expectoration of mucoid, mucopurulent, or even purulent sputum. I t was often particularly troublesome at night.

The amount of sputum in most cases was less than that produced by the common pulmonary diseases. Histologic examination of the sputum may in a few instances reveal tumor cells. At autopsy of one individual a plug of tumor was found lying free in a bronchus. Post-mortem perusal of the record revealed that this patient had expectorated fleshy fragments, which, however, were not submitted to the laboratory. Not uncommonly associated with pro- ductive cough was blood streaking at irregular intervals. Frank and severe

- n

DU RAT I ON.0 F 5Y MPTOM 3. PRIMARY. LUNG . CARClN OM A.

0 AUTOPSILD C A S t 5 - 31 0 UNAUTOPSICD CASES - 2 0

FIG. 14. DURATION OF SYMPTOMS IN 57 CASLS OP BRONCIIOGEKIC CARCIKOMA

hemoptysis was not common except as a terminal event. Eight cases not recorded in Fig. 15 had slight interval streaking.

Dyspnea was a fairly common feature and was often accompanied by asthmatic symptoms. These were more marked in the group of patients who had pneumonoconiosis or other types of pulmonary fibrosis. We have been led to believe that dyspnea and wheezing in a patient of the cancer age, who has been previously relatively well, with no history of foreign body aspiration or cardiovascular disease, should be regarded with grave suspicion.

I t commonly was substernal, dull, aching or boring, and continuous. In some tumors in the periphery of the lung, there was pain over the region of the tumor. The pain in these cases apparently was aggravated more by cough than in some cases of hilar tumors.

Dysphagia, which was a feature at some time in about one-fourth of the patients, did not occur early. This symptom may be due to extension of the tumor into the esophagus or to compression of that organ by the tumor or its lymph node metastases.

Symptoms of cachexia, such as loss of weight, appetite or strength, are shown in Fig. 15. Epigastric pain, dysphagia, nausea and vomiting were suf- ficiently common in this series to suggest that bronchogenic carcinoma should always be considered in the differential diagnosis of what appears to be an obscure intra-abdominal lesion.

Pain in the chest often occurred early.

5 04 RAYMOND S . ROSEDALE AND DONALD R. MCKAY

Pain in muscles and joints was complained of occasionally. Severe back pain denoted spine metastases.

The physical signs noted in our series of cases are illustrated in Fig. 16. Abnormal pulmonary findings were few early in the disease. There appeared to be no characteristic feature. It was found that widening of the area of sternal dullness was to be regarded with suspicion. Suggestive, too, were wheezing rgles or rhonchi in a person who previously had been well.

As the disease advanced, many chest signs, due to the secondary pulmonary pathology, were noted. Dullness, diminished breath sounds, and ipsolateral deviation of the trachea were commonly present with well developed broncho- stenosis. Moist rkles, a late sign, apparently were an acconipaniment of bronchitis, bronchiectasis, or abscess. The chest was notably dry until one of these conditions supervened. Pulmonary osteo-arthropathy was present

Loss of weight occurred early.

ANALYSIS OF PRINCIPAL SYMPTOMS 57 CA3€.3 O r PRIMARY CARCINOMA LUNG

49 CASW .._ COUGH-

COPIOUS SPUTUM 4 8 ”

PAIN IN CHCST - 34 DYSPNOCA - - 2 6 . H€MOPTYSIS -- I 0

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FIG. IS. ANALYSIS OF TIIE PmivcIPhi. SYMPTOMS IN 5 7 CASES or BRONCHOGENIC CAR(:IROMA

with about the same frequency as in chronic pulmonary diseases. Contra- lateral deviation of the trachea in some of the individuals was due to two factors, viz., the large and increasing size of the tumor or its hilar lymph node metastases, and extensive pleural exudates.

Enlarged firm supraclavicular or cervical lymph nodes in bronchogenic carcinoma sig- nify metastasis and call for biopsy.

The superficial veins of the thorax, neck, and arms were distended in three individuals with partial obstruction of the superior vena cava.

Pleural fluids late in the disease are apt to be purulent. Early, the fluid is serous and bloody. Histologic examination of the fluid should always be undertaken.

Roentgenograms of uncomplicated hilar bronchogenic carcinoma generally presented a widened mediastinal shadow, with a unilateral, round or ovoid extension, not sharply circumscribed, into the lung hilus. Lateral views

Signs of metastases appeared early in some of our patients.

A STUDY OF 57 CASES OF BRONCHOGENIC CARCINOMA 505

showed (' filling in " of the retrocardiac or upper mediastinal space. In some cases there was a partial or complete collapse of a lobe or portion of a lobe.

Roentgenograms were made in 30 of the autopsied cases. A positive impression of bronchogenic carcinoma was obtained in 14 cases; tumor was suspected in 1 case and missed in 15 cases. In 12 cases where the tumor was not suspected there was secondary pulmonary or pleural pathology which obscured the tumor. In 3 other cases where tumor was not reported, attention was focussed on shadows of unrelated pathology, in one that of aortic aneu- rysm, in one tuberculosis, and in one pneumonoconiosis.

Bronchoscopy, a most valuable diagnostic procedure, was performed in 6 of our autopsied cases. A diagnosis was definitely established by biopsy in 4 cases, and suspected in one. In the unautopsied group bronchoscopy estab- lished a diagnosis of carcinoma in 3 cases and revealed pressure on a bronchus in 2 cases.

ANALYSIS O r CnlU PHYSICAL FINDINGS 57 CASES OF PRIMARY CARCINOMA LUNG

FIG. 16. PRIVTIPAI. PIIYSIC~L F~NDIXGS IN 57 CASES OF Bmsrtroct ~ i c CARCINOMA

S u M MARY

In the past ten years 466 cases of malignant disease were autopsied at the Buffalo City Hospital. Bronchogenic carcinoma constituted 7.5 per cent of these.

In this district this tumor appears to predominate in people employed in irritating atmospheric conditions.

Bronchogenic carcinomas are situated most frequently at or near the lung hilus, commonly taking origin in a first order bronchus. They occur usually as a single massive lesion at one hilus in contrast to the multiple bilateral peripheral nodules of metastatic tumors.

Histologically the tumors in our series consisted of various predominant cell types.

Bronchogenic carcinoma may metastasize widely. The regional lymph nodes were involved in all our cases.

Clinically the symptoms produced by these tumors closely simulate other diseases of the lungs, such as tuberculosis, pneumonoconiosis, and bronchiec- tasis.

Round or spindle cells were found in all cases.

5 06 RAYMOND S. ROSEDALE AND DONALD R. MCICAY

Roentgenographic study may be of aid in differentiating between the several diseases simulating tumor ; but in the presence of secondary pulmonary or pleural pathology the diagnosis may not be suspected.

Because of this and other reasons bronchoscopy with removal of tissue for microscopic examination is a most valuable procedure.

We feel, from the study of our material, that bronchogenic carcinoma occurs frequently enough for it to enter the differential diagnosis of all obscure chest diseases in individuals over thirty years of age.

NOTE: We wish to acknowledge our appreciation of the kindly interest manifested in this study by Dr. Wm. I:. Jacobs and our other associates in the Buffalo City Hospital.

BIBLIOGRAPHY

1. BOYD, WM, : Personal coinmunication to the authors. 2. DAVIDSON, M.: Cancer of the Lung and other Intrathoracic Tumors, Wm. Wood and Co.,

3 . FRIED, B. M.: Medicine 10: 373, 1931. 4. GESCIIICKTER, C. F., A N D DENISON, R.: Am. J. Cancer 2 2 : 853, 1934.

New York, 1933.