- Email: [email protected]
“Scar” Carcinoma of The Lung
-I
SELECfED REPORTS
"Scar" Carcinoma of The Lung*
her 1, 1966 to August 31, 1968, 81 carcinomas of the lung were encountered. In 18 cases, the tumor was either too extensive or a lobectomy had been performed elsewhere so that the site of origin could not be determined. Twenty-three of the remaining were initially classified as being peripheral in origin; three of the latter were excluded from the study either because the tumor was so extensive that the site of origin could not be assessed with certainty ( two cases ) , or because the patient had received radiotherapy to the lung and the scarring might be considered secondary to this treatment (one case ) . Of the remaining 20 cases, 13 were associated with either isolated scars of the lung ( 11 cases), or pulmonary "honey-combing" (two cases.) In the other seven cases, the tumors, despite their peripheral location, did not appear to be related to focal or diffuse fibrosis. All the cases included in this report were reviewed thoroughly to exclude the presence of a primary tumor elsewhere metastasizing to the lung. The following stains were employed for evaluation of the tumor histology: hematoxylin and eosin, Aldan bluePAS, Masson's trichrome, EVG, and Wilder's reticulum. In order to characterize as "scar" the area where the tumor arose, the following criteria were used3.5,9: (a) the presence of a solid area of hyalinized fibrous tissue, ( b) dense collections of elastic fibers, and ( c) trapping of anthracotic material. For the classification of the tumors we used the nomenclature recommended by the World Health Organization.14
Catherine Limas, M.D., •• Hugo ]apaze, M.D. and Rafael Garcia-Bunuel, M.D.
In a review of 81 consecutive lung carcinomas encountered at autopsy at Baltimore City Hospitals in a two-
year period, 13 peripheral carcinomas were found, of which 13 arose in areas of scarring. There was histologic and c6nical evidence that the scars antedated the development of carcinoma and were directly related to theil' inception. Most of the tumors were adenocarcinomas (eight cases); six of these could be further classified as bronchiolo-alveolar carcinomas. The remaining cases were characterized as anaplastic, small cell, and squamous carcinomas.
F
riedrich, 1 was the first to draw attention to peripheral lung carcinoma arising on scars. Subsequently, several investigators noted the association of focal or diffuse pulmonary fibrosis with the development of carcinoma and suggested various pathogenetic mechanisms.2·9 Hyperplasia and occasional malignant changes of the bronchiolar and alveolar epithelium have been reported repeatedly in the margins of infarcts and in areas of organizing pneumonitis, 10· 12 as well as in lungs showing diffuse fibrosis, as in Hamman-Rich syndrome, scleroderma, rheumatoid lung etc.4,13 It is our purpose to review 13 cases of peripheral lung carcinoma arising on areas of scarring.
RESULTS
The classification of the lung carcinomas encountered according to site of origin and histologic type is given in Table 1. There were nine men and four women; the mean age at the time of death was 65.9 years with a range of 46 to 87 years (Table 2).
MATERIAL AND METHODS CLINICAL DATA
Among 1049 consecutive autopsies in adults performed at Baltimore City Hospital during the two-year period Septem-
Information concerning the smoking habits was available for 11 patients; there were five heavy (more than 30 cigarettes/ day), four moderate (less than 20 cigarettes/ day) smokers, and two nonsmokers. Symptoms referable to the respiratory system were often mentioned in the
0From the Department of Pathology, Baltimore City Hospitals and the Johns Hopkins University School of Medicine, Baltimore. ••Presently at Department of Pathology, Georgetown University Hospital, Washington, D.C.
Table 1--Cla..ification of 81 lung carcinoma according to hi11tologic type and 11ite of origin
Histologic Type Squamous Adenocarcinoma, well differentiated Adenocarcinoma, poorly differentiated Bronchiolo-alveolar Anaplastic Other Total
Bronchogenic 14 3 2 0 18* 3
40
No Scar
Site of Origin Peripheral Undetermined Scar
1 2 0
2* 2 1
2
6
2 0
2 0
1 0 0 1 0
7
13
3
Not Determined
Total
10 2
28 10
2 1 3 0
5 9 26
18
81
3
*In one patient two primary lung carcinomas were encountered (a bronchogenic small cell in the right lung and a squamous scar carcinoma in the left).
219
220
LIMAS, JAPAZE AND GARCIA-BUNUEL Table 2---Diatribution of c:aaea of ac:ar c:arcinoma
Case No.
2 3 4 5 6 7 8 9 10 ll
12 13
ac:c:ordin~r
to ae% 1 a~re, dinic:al dia~Jnoaia and c:auae of death
Sex
Age (years)
Clinical Diagnosis
M M F M F M M
65 67 65 53 46 65 72
M M
76 52 81 75
Carcinoma of lung Carcinoma of lung Metastatic carcinoma (origin unknown) Metastatic carcinoma (origin unknown) Metastatic carcinoma. (origin unknown) Bronchogenic carcinoma. • Hodgkin's disease and chronic obstructive pulmonary disease Pulmonary tuberculosis Diabetes mellitus-azotemia Arteriosclerotic cardiovascular disease Myocardial infarct Cerebrovascular accident Chronic renal failure
F
M F M
84
87
Cause of Death Carcinoma of lung Carcinoma of lung Carcinoma of lung Carcinoma. of lung Carcinoma of lung Carcinoma. of lung Hodgkin's disease Carcinoma. of lung Diabetic glomerulosclerosis Congestive heart failure Myocardial infarct Cerebral infarct Chronic renal failure
*Two primary lung carcinomas were found at autopsy; a small cell bronchogenic in the right lung and a peripheral squamous cell carcinoma in the diffusely fibrotic left lower lobe.
clinical history, but they were nonspecific and could be attributed to chronic lung disease or cardiac failure, both of which are common in this age group. A history of longstanding pulmonary disease (chronic obstructive and/ or restrictive lung disease, recurrent pneumonias) was obtained in five cases. In only two cases (1,2) was the diagnosis made antemortem. In three ( 3,4,5) a metastatic neoplasm of unknown origin was diagnosed on the basis of biopsy of extrapulmonary tumor sites. A lung lesion was recognized in two instances ( 7,8), but was not attributed to a neoplasm. Finally, in six instances, the tumor was an unexpected finding during autopsy. In the cases where information was available, a lung lesion had been seen on x-ray film a long time prior to death (five years in Case 13, three years in Case 12, two years in Case 3, and "many years" in Case 5). This had been initially interpreted as granulomatous disease; it corresponded to the site of the primary tumor found at autopsy.
retracted and puckered. Grossly, the main bulk of tumor appeared to be in the periphery of the scar. The center was firm and it usually had a mottled grayish and blackish appearance (Fig 1) . All but two tumors arose in the upper lobes-seven in the right and four in the left. There was a predilection for the apical segments. The size of the tumors ranged from 2 to 6 em in diameter. MICROSCOPIC APPEARANCE
In most cases ( 12 of 13), the neoplasm was subpleural in localization. The overlying pleura was thickened,
Microscopically, the lesion showed a central area of scarring and a peripheral zone of neoplastic cells fanning out towards the surrounding pulmonary parenchyma (Fig 2). The scarred central area consisted of hyalinized fibrous tissue with a striking amount of elastic fibers (Fig 3). Anthracotic pigment trapping was present in moderate to marked amounts (Fig 4) . Ossification was seen in two cases ( 8,13) and caseation in one ( 8). Stains for acid-fast bacilli and for fungi gave negative results. Occasional spaces were seen lined by respiratory epithelium which appeared normal or showed cuboidal or squamous metaplasia. Focal metaplasia of the bronchioloalveolar epithelium was evident elsewhere in the lungs
FIGURE I . Gross appearance of the lung tumor in case 2. Note subpleural localization, thickened pleura and growth of tumor in periphery of the scar.
FIGURE 2 ( Case 2). Small cell carcinoma arising in a lung scar. The bulk of the tumor is found in the periphery of the scarred area ( H and E, X 8).
CROSS APPEARANCE
CHEST, VOL. 59, NO. 2, FEBRUARY 1971
SCAR CARCINOMA OF THE LUNG
FIGURE 3 ( Case 4). Section through center of the pulmonary scar. Abundant elastic fibers and occluded blood vessels (EVG, X 80).
in three cases; in two, related to diffuse "honey-combing" ( 6, 7) and in one ( 12), related to multiple subpleural fibrotic areas. The histologic classification of these tumors is given in Table 3. Six (1,8,10-13) were classified as bronchioloalveolar carcinomas, three ( 4,9,3) as adenocarcinomas, two (6,7) as well differentiated squamous cell carcinomas, and two ( 5,2) as anaplastic carcinomas. METASTASES
The incidence of metastasis at the time of death as related to histologic type and size of the primary neoplasm is given in Table 3. All the tumors classified as anaplastic or adenocarcinomas and two of the bronchiolo-alveolar type had given metastases by the time of death. Five of them had metastasized beyond the regional lymph nodes. The three smaller (less than 3 em) bronchiolo-alveolar and the two squamous cell carcinomas had not metastasized. DISCUSSION
In this series peripheral lung carcinomas were quite often associated with focal or diffuse fibrosis of the pulmonary parenchyma. The fact that the tumor was
FIGURE 4 ( Case 2 ) . Small cell carcinoma arising in a lung scar. Note the heavy deposition of anthracotic pigment ( H and E, X 80).
CHEST, VOL. 59, NO. 2, FEBRUARY 1971
221
5 (Case 12). Bronchiolo-alveolar carcinoma; section through the periphery of the lung lesion ( H and E, X 80).
FIGURE
found mainly in the periphery of the scarred area might suggest the following possibilities: 1) the tumor may, by chance, merge with an adjacent scar unrelated to its genesis, 2) the tumor itself became scarred or caused the scarring, and 3) the scar might have preexisted and related to the inception of the neoplasm. The first assumption can be reasonably dismissed in view of the fact that these small tumors were found in solitary scars more often than would be expected by chance alone. In regard to the second hypothesis, it should be noted that the morphology of these scars is quite different from the common desmoplastic reaction of the tissues to tumor growth. It is difficult to rule out the possibility that the scar might be the end stage of atelectasis and vascular occlusion caused by the tumor proximal to it. In our material, however, we found evidence against this hypothesis. In patients who had multiple areas of scarring, we found scars without any associated change in the respiratory epithelium and others which showed small foci of epithelial hyperplasia, metaplasia, and atypia. The latter changes were also observed in the scar where the tumor had arisen. Ossification and caseation were occasionally seen in the scars associated with tumors. Moreover, in some cases, these lesions had been present on the chest x-ray fihns for a sufficiently long time to make it unlikely that they had been associated with the tumor from the very beginning. The bronchiolo-alveolar carcinomas were encountered in older patients and there was a positive correlation between the size of the tumor and the presence of metastases (Table 3). Among patients over 70 years of age, metastases were found in only one instance and were confined to the hilar and paratracheallymph-nodes. The tumors appeared histologically less differentiated and seemed to have a more aggressive clinical course in the patients under 70 years of age. Both cases of squamous cell carcinomas were found in men who were heavy smokers, but the number of cases is too small to permit any correlation between the histologic type and the smoking habits. These tumors seem to have a predilec-
222
PIESSENS ET AL Table 3-lncidence of meta.ta•e• in relation to hutolowic type and •ise of primary tumor
Histologic Type
Total
Anaplastic Adenocareinoma not further classified Bronchioalveolar Squamous Total
2 3 6 2 13
tion for men, but not as strikingly as bronchogenic carcinomas. On the basis of histologic and clinical evidence, the scar was thought to be tuberculous in four cases ( 3,5,8, 13) . In the remaining cases the data were not conclusive, but a healed infarct (cases 9,12,2,10), granulomatous disease ( 4,11), or nonspecific organized pneumonia ( 1 ) were considered to be the cause of the scarring. The role that the scar might have played in the pathogenesis of the neoplastic process is obscure. Some believe that the atypical epithelial proliferation and, in a further step, malignancy, are the results of an abortive effort of the damaged epithelium to regenerate. 8 Others have suggested the possibility of carcinogenic influence of foreign substances trapped in the scar, as anthracotic pigment or carcinogens (chemicals or viruses) adsorbed on the inhaled particles of carbon or dust. 12 Berkheiser15 has also discussed the role of tissue hypoxia in this context. Another possibility is that the "restless" epithelium in areas of tissue repair is more susceptible to neoplastic evolution or to carcinogenic agents. In conclusion, the scarring may play a dual role in the pathogenesis of these tumors, by causing· an increased concentration of potentially carcinogenic agents and by stimulating the epithelium to regenerate, thus rendering it more susceptible to the latter. ACKNOWLEDGMENT: The authors wish to thank Mr. Milton M. Tudahl, Sr. for the preparation of the photographic material. REFERENCES
2 3 4 5 6 7 8
Friedrich, G: Periphere Lungenkrebse auf dem Boden pleuranaher Narben. Virch Arch Path Anat 204:230, 1939 Bennett, DE, Sasser WF, Ferguson TB: Adenocarcinoma of the lung in men. A clinicopathologic study of 100 cases. Cancer,23:431,1969 Carroll R: The influence of lung scars on primary lung cancer. J Path Bact 83:293, 1962 Haddad R, Massaro D: Idiopathic diffuse interstitial pulmonary fibrosis, atypical epithelial proliferation and lung cancer. Amer J Med 45:211, 1968 Raeburn G, Spencer H: Lung scar cancer. Brit J Tuberc and Dis Chest 51:237, 1957 Ripstein CB, Spain DM, Bluth J: Scar cancer of the lung. J Thorac and Cardiovasc Surg 56:362, 1968 Rossie R: Die Narbenkrebse der Lungen. Schweiz Med Wschr 73: 1200, 1943 Theme! KG, Liiders CJ: Die Narbenkrebse der Lungen als Beitrag zur pathogenese des peripheren Lungencarcinomas. Virch Arch Path Anat 325:499, 1954
Metastases Present Size of primary (em) No. Cases 2 3 2 0 7
2-3 2-3 4.5-6
Metastases Absent Size of primary (em) No. Cases 0 0 4 2 6
2-2.5 3-3.5
9 Yokoo H: Peripheral lung cancers arising in scars, Cancer 14:1205, 1961 10 Balo J, Johasz E, Ternes J: Pulmonary infarcts and pulmonary carcinoma. Cancer 9:918, 1956 11 Beaver DL, Shapiro JL: A consideration of chronic parenchymal inflammation and alveolar cell carcinoma with regard to a possible etiologic relationship. Arner J Med 21:879, 1956 12 Meyer EC, Liebow A: Relationship of interstitial pneumonia, honeycombing and atypical epithelial proliferation. Cancer 18:322, 1965 13 Zatuchni }, Campbell WN, Zarafonetis CJD: Pulmonary fibrosis and terminal bronchiolar ( alveolar-cell ) carcinoma in scleroderma. Cancer 6:1147, 1953 14 World Health Organization: International histological classification of tumors. No. I, Histological typing of lung tumors, Geneva, 1967 15 Berkheiser SW: Bronchiolar proliferation and metaplasia associated with thromboembolism. A pathological and experimental study. Cancer 16:205, 1963
Anomalous Collateral Systemic Pulmonary Circulation to a Normal Lung* ]. Piessens, M.D., H. De Geest, M.D., H. Kesteloot, M.D., and ]. V. ]oossens, M.D.
A case of anomalous systemic pulmonary collateral circulation is reported. The left lung, which was somewhat smaller than normal but did not otherwise show any abnormalities, was perfused almost completely with arterial blood derived through precapillary anastomoses from a huge coUateral network. The latter was formed by the lateral thoracic, intercostal and internal mammary artery. No apparent reason for the development of this collateral circulation was found.
,t nomalous collateral systemic-pulmonary circulation fthas been well documented in chronic lung disease1-3 pleural adhesions, 4 congenital heart disease, 3·5 •6 isolated absence or malformation of one of the pulmonary arteries 7 · 11 and in veno-occlusive disease of the pulmonary veins. 12 Accessory pulmonary arteries derived from the systemic circulation to part of a lung, with otherwise normal bronchovascular connections, have repeatedly been described. 13-15 Massive systemic blood supply through collateral vessels to a lung with a normal bronchial tree and a nonobstructed pulmonary artery •From the Division of Cardiology, Deparbnent of Internal Medicine, St. Rafael Clinic, Leuven, Belgium.
CHEST, VOL 59, NO. 2, FEBRUARY 1971
SELECfED REPORTS
"Scar" Carcinoma of The Lung*
her 1, 1966 to August 31, 1968, 81 carcinomas of the lung were encountered. In 18 cases, the tumor was either too extensive or a lobectomy had been performed elsewhere so that the site of origin could not be determined. Twenty-three of the remaining were initially classified as being peripheral in origin; three of the latter were excluded from the study either because the tumor was so extensive that the site of origin could not be assessed with certainty ( two cases ) , or because the patient had received radiotherapy to the lung and the scarring might be considered secondary to this treatment (one case ) . Of the remaining 20 cases, 13 were associated with either isolated scars of the lung ( 11 cases), or pulmonary "honey-combing" (two cases.) In the other seven cases, the tumors, despite their peripheral location, did not appear to be related to focal or diffuse fibrosis. All the cases included in this report were reviewed thoroughly to exclude the presence of a primary tumor elsewhere metastasizing to the lung. The following stains were employed for evaluation of the tumor histology: hematoxylin and eosin, Aldan bluePAS, Masson's trichrome, EVG, and Wilder's reticulum. In order to characterize as "scar" the area where the tumor arose, the following criteria were used3.5,9: (a) the presence of a solid area of hyalinized fibrous tissue, ( b) dense collections of elastic fibers, and ( c) trapping of anthracotic material. For the classification of the tumors we used the nomenclature recommended by the World Health Organization.14
Catherine Limas, M.D., •• Hugo ]apaze, M.D. and Rafael Garcia-Bunuel, M.D.
In a review of 81 consecutive lung carcinomas encountered at autopsy at Baltimore City Hospitals in a two-
year period, 13 peripheral carcinomas were found, of which 13 arose in areas of scarring. There was histologic and c6nical evidence that the scars antedated the development of carcinoma and were directly related to theil' inception. Most of the tumors were adenocarcinomas (eight cases); six of these could be further classified as bronchiolo-alveolar carcinomas. The remaining cases were characterized as anaplastic, small cell, and squamous carcinomas.
F
riedrich, 1 was the first to draw attention to peripheral lung carcinoma arising on scars. Subsequently, several investigators noted the association of focal or diffuse pulmonary fibrosis with the development of carcinoma and suggested various pathogenetic mechanisms.2·9 Hyperplasia and occasional malignant changes of the bronchiolar and alveolar epithelium have been reported repeatedly in the margins of infarcts and in areas of organizing pneumonitis, 10· 12 as well as in lungs showing diffuse fibrosis, as in Hamman-Rich syndrome, scleroderma, rheumatoid lung etc.4,13 It is our purpose to review 13 cases of peripheral lung carcinoma arising on areas of scarring.
RESULTS
The classification of the lung carcinomas encountered according to site of origin and histologic type is given in Table 1. There were nine men and four women; the mean age at the time of death was 65.9 years with a range of 46 to 87 years (Table 2).
MATERIAL AND METHODS CLINICAL DATA
Among 1049 consecutive autopsies in adults performed at Baltimore City Hospital during the two-year period Septem-
Information concerning the smoking habits was available for 11 patients; there were five heavy (more than 30 cigarettes/ day), four moderate (less than 20 cigarettes/ day) smokers, and two nonsmokers. Symptoms referable to the respiratory system were often mentioned in the
0From the Department of Pathology, Baltimore City Hospitals and the Johns Hopkins University School of Medicine, Baltimore. ••Presently at Department of Pathology, Georgetown University Hospital, Washington, D.C.
Table 1--Cla..ification of 81 lung carcinoma according to hi11tologic type and 11ite of origin
Histologic Type Squamous Adenocarcinoma, well differentiated Adenocarcinoma, poorly differentiated Bronchiolo-alveolar Anaplastic Other Total
Bronchogenic 14 3 2 0 18* 3
40
No Scar
Site of Origin Peripheral Undetermined Scar
1 2 0
2* 2 1
2
6
2 0
2 0
1 0 0 1 0
7
13
3
Not Determined
Total
10 2
28 10
2 1 3 0
5 9 26
18
81
3
*In one patient two primary lung carcinomas were encountered (a bronchogenic small cell in the right lung and a squamous scar carcinoma in the left).
219
220
LIMAS, JAPAZE AND GARCIA-BUNUEL Table 2---Diatribution of c:aaea of ac:ar c:arcinoma
Case No.
2 3 4 5 6 7 8 9 10 ll
12 13
ac:c:ordin~r
to ae% 1 a~re, dinic:al dia~Jnoaia and c:auae of death
Sex
Age (years)
Clinical Diagnosis
M M F M F M M
65 67 65 53 46 65 72
M M
76 52 81 75
Carcinoma of lung Carcinoma of lung Metastatic carcinoma (origin unknown) Metastatic carcinoma (origin unknown) Metastatic carcinoma. (origin unknown) Bronchogenic carcinoma. • Hodgkin's disease and chronic obstructive pulmonary disease Pulmonary tuberculosis Diabetes mellitus-azotemia Arteriosclerotic cardiovascular disease Myocardial infarct Cerebrovascular accident Chronic renal failure
F
M F M
84
87
Cause of Death Carcinoma of lung Carcinoma of lung Carcinoma of lung Carcinoma. of lung Carcinoma of lung Carcinoma. of lung Hodgkin's disease Carcinoma. of lung Diabetic glomerulosclerosis Congestive heart failure Myocardial infarct Cerebral infarct Chronic renal failure
*Two primary lung carcinomas were found at autopsy; a small cell bronchogenic in the right lung and a peripheral squamous cell carcinoma in the diffusely fibrotic left lower lobe.
clinical history, but they were nonspecific and could be attributed to chronic lung disease or cardiac failure, both of which are common in this age group. A history of longstanding pulmonary disease (chronic obstructive and/ or restrictive lung disease, recurrent pneumonias) was obtained in five cases. In only two cases (1,2) was the diagnosis made antemortem. In three ( 3,4,5) a metastatic neoplasm of unknown origin was diagnosed on the basis of biopsy of extrapulmonary tumor sites. A lung lesion was recognized in two instances ( 7,8), but was not attributed to a neoplasm. Finally, in six instances, the tumor was an unexpected finding during autopsy. In the cases where information was available, a lung lesion had been seen on x-ray film a long time prior to death (five years in Case 13, three years in Case 12, two years in Case 3, and "many years" in Case 5). This had been initially interpreted as granulomatous disease; it corresponded to the site of the primary tumor found at autopsy.
retracted and puckered. Grossly, the main bulk of tumor appeared to be in the periphery of the scar. The center was firm and it usually had a mottled grayish and blackish appearance (Fig 1) . All but two tumors arose in the upper lobes-seven in the right and four in the left. There was a predilection for the apical segments. The size of the tumors ranged from 2 to 6 em in diameter. MICROSCOPIC APPEARANCE
In most cases ( 12 of 13), the neoplasm was subpleural in localization. The overlying pleura was thickened,
Microscopically, the lesion showed a central area of scarring and a peripheral zone of neoplastic cells fanning out towards the surrounding pulmonary parenchyma (Fig 2). The scarred central area consisted of hyalinized fibrous tissue with a striking amount of elastic fibers (Fig 3). Anthracotic pigment trapping was present in moderate to marked amounts (Fig 4) . Ossification was seen in two cases ( 8,13) and caseation in one ( 8). Stains for acid-fast bacilli and for fungi gave negative results. Occasional spaces were seen lined by respiratory epithelium which appeared normal or showed cuboidal or squamous metaplasia. Focal metaplasia of the bronchioloalveolar epithelium was evident elsewhere in the lungs
FIGURE I . Gross appearance of the lung tumor in case 2. Note subpleural localization, thickened pleura and growth of tumor in periphery of the scar.
FIGURE 2 ( Case 2). Small cell carcinoma arising in a lung scar. The bulk of the tumor is found in the periphery of the scarred area ( H and E, X 8).
CROSS APPEARANCE
CHEST, VOL. 59, NO. 2, FEBRUARY 1971
SCAR CARCINOMA OF THE LUNG
FIGURE 3 ( Case 4). Section through center of the pulmonary scar. Abundant elastic fibers and occluded blood vessels (EVG, X 80).
in three cases; in two, related to diffuse "honey-combing" ( 6, 7) and in one ( 12), related to multiple subpleural fibrotic areas. The histologic classification of these tumors is given in Table 3. Six (1,8,10-13) were classified as bronchioloalveolar carcinomas, three ( 4,9,3) as adenocarcinomas, two (6,7) as well differentiated squamous cell carcinomas, and two ( 5,2) as anaplastic carcinomas. METASTASES
The incidence of metastasis at the time of death as related to histologic type and size of the primary neoplasm is given in Table 3. All the tumors classified as anaplastic or adenocarcinomas and two of the bronchiolo-alveolar type had given metastases by the time of death. Five of them had metastasized beyond the regional lymph nodes. The three smaller (less than 3 em) bronchiolo-alveolar and the two squamous cell carcinomas had not metastasized. DISCUSSION
In this series peripheral lung carcinomas were quite often associated with focal or diffuse fibrosis of the pulmonary parenchyma. The fact that the tumor was
FIGURE 4 ( Case 2 ) . Small cell carcinoma arising in a lung scar. Note the heavy deposition of anthracotic pigment ( H and E, X 80).
CHEST, VOL. 59, NO. 2, FEBRUARY 1971
221
5 (Case 12). Bronchiolo-alveolar carcinoma; section through the periphery of the lung lesion ( H and E, X 80).
FIGURE
found mainly in the periphery of the scarred area might suggest the following possibilities: 1) the tumor may, by chance, merge with an adjacent scar unrelated to its genesis, 2) the tumor itself became scarred or caused the scarring, and 3) the scar might have preexisted and related to the inception of the neoplasm. The first assumption can be reasonably dismissed in view of the fact that these small tumors were found in solitary scars more often than would be expected by chance alone. In regard to the second hypothesis, it should be noted that the morphology of these scars is quite different from the common desmoplastic reaction of the tissues to tumor growth. It is difficult to rule out the possibility that the scar might be the end stage of atelectasis and vascular occlusion caused by the tumor proximal to it. In our material, however, we found evidence against this hypothesis. In patients who had multiple areas of scarring, we found scars without any associated change in the respiratory epithelium and others which showed small foci of epithelial hyperplasia, metaplasia, and atypia. The latter changes were also observed in the scar where the tumor had arisen. Ossification and caseation were occasionally seen in the scars associated with tumors. Moreover, in some cases, these lesions had been present on the chest x-ray fihns for a sufficiently long time to make it unlikely that they had been associated with the tumor from the very beginning. The bronchiolo-alveolar carcinomas were encountered in older patients and there was a positive correlation between the size of the tumor and the presence of metastases (Table 3). Among patients over 70 years of age, metastases were found in only one instance and were confined to the hilar and paratracheallymph-nodes. The tumors appeared histologically less differentiated and seemed to have a more aggressive clinical course in the patients under 70 years of age. Both cases of squamous cell carcinomas were found in men who were heavy smokers, but the number of cases is too small to permit any correlation between the histologic type and the smoking habits. These tumors seem to have a predilec-
222
PIESSENS ET AL Table 3-lncidence of meta.ta•e• in relation to hutolowic type and •ise of primary tumor
Histologic Type
Total
Anaplastic Adenocareinoma not further classified Bronchioalveolar Squamous Total
2 3 6 2 13
tion for men, but not as strikingly as bronchogenic carcinomas. On the basis of histologic and clinical evidence, the scar was thought to be tuberculous in four cases ( 3,5,8, 13) . In the remaining cases the data were not conclusive, but a healed infarct (cases 9,12,2,10), granulomatous disease ( 4,11), or nonspecific organized pneumonia ( 1 ) were considered to be the cause of the scarring. The role that the scar might have played in the pathogenesis of the neoplastic process is obscure. Some believe that the atypical epithelial proliferation and, in a further step, malignancy, are the results of an abortive effort of the damaged epithelium to regenerate. 8 Others have suggested the possibility of carcinogenic influence of foreign substances trapped in the scar, as anthracotic pigment or carcinogens (chemicals or viruses) adsorbed on the inhaled particles of carbon or dust. 12 Berkheiser15 has also discussed the role of tissue hypoxia in this context. Another possibility is that the "restless" epithelium in areas of tissue repair is more susceptible to neoplastic evolution or to carcinogenic agents. In conclusion, the scarring may play a dual role in the pathogenesis of these tumors, by causing· an increased concentration of potentially carcinogenic agents and by stimulating the epithelium to regenerate, thus rendering it more susceptible to the latter. ACKNOWLEDGMENT: The authors wish to thank Mr. Milton M. Tudahl, Sr. for the preparation of the photographic material. REFERENCES
2 3 4 5 6 7 8
Friedrich, G: Periphere Lungenkrebse auf dem Boden pleuranaher Narben. Virch Arch Path Anat 204:230, 1939 Bennett, DE, Sasser WF, Ferguson TB: Adenocarcinoma of the lung in men. A clinicopathologic study of 100 cases. Cancer,23:431,1969 Carroll R: The influence of lung scars on primary lung cancer. J Path Bact 83:293, 1962 Haddad R, Massaro D: Idiopathic diffuse interstitial pulmonary fibrosis, atypical epithelial proliferation and lung cancer. Amer J Med 45:211, 1968 Raeburn G, Spencer H: Lung scar cancer. Brit J Tuberc and Dis Chest 51:237, 1957 Ripstein CB, Spain DM, Bluth J: Scar cancer of the lung. J Thorac and Cardiovasc Surg 56:362, 1968 Rossie R: Die Narbenkrebse der Lungen. Schweiz Med Wschr 73: 1200, 1943 Theme! KG, Liiders CJ: Die Narbenkrebse der Lungen als Beitrag zur pathogenese des peripheren Lungencarcinomas. Virch Arch Path Anat 325:499, 1954
Metastases Present Size of primary (em) No. Cases 2 3 2 0 7
2-3 2-3 4.5-6
Metastases Absent Size of primary (em) No. Cases 0 0 4 2 6
2-2.5 3-3.5
9 Yokoo H: Peripheral lung cancers arising in scars, Cancer 14:1205, 1961 10 Balo J, Johasz E, Ternes J: Pulmonary infarcts and pulmonary carcinoma. Cancer 9:918, 1956 11 Beaver DL, Shapiro JL: A consideration of chronic parenchymal inflammation and alveolar cell carcinoma with regard to a possible etiologic relationship. Arner J Med 21:879, 1956 12 Meyer EC, Liebow A: Relationship of interstitial pneumonia, honeycombing and atypical epithelial proliferation. Cancer 18:322, 1965 13 Zatuchni }, Campbell WN, Zarafonetis CJD: Pulmonary fibrosis and terminal bronchiolar ( alveolar-cell ) carcinoma in scleroderma. Cancer 6:1147, 1953 14 World Health Organization: International histological classification of tumors. No. I, Histological typing of lung tumors, Geneva, 1967 15 Berkheiser SW: Bronchiolar proliferation and metaplasia associated with thromboembolism. A pathological and experimental study. Cancer 16:205, 1963
Anomalous Collateral Systemic Pulmonary Circulation to a Normal Lung* ]. Piessens, M.D., H. De Geest, M.D., H. Kesteloot, M.D., and ]. V. ]oossens, M.D.
A case of anomalous systemic pulmonary collateral circulation is reported. The left lung, which was somewhat smaller than normal but did not otherwise show any abnormalities, was perfused almost completely with arterial blood derived through precapillary anastomoses from a huge coUateral network. The latter was formed by the lateral thoracic, intercostal and internal mammary artery. No apparent reason for the development of this collateral circulation was found.
,t nomalous collateral systemic-pulmonary circulation fthas been well documented in chronic lung disease1-3 pleural adhesions, 4 congenital heart disease, 3·5 •6 isolated absence or malformation of one of the pulmonary arteries 7 · 11 and in veno-occlusive disease of the pulmonary veins. 12 Accessory pulmonary arteries derived from the systemic circulation to part of a lung, with otherwise normal bronchovascular connections, have repeatedly been described. 13-15 Massive systemic blood supply through collateral vessels to a lung with a normal bronchial tree and a nonobstructed pulmonary artery •From the Division of Cardiology, Deparbnent of Internal Medicine, St. Rafael Clinic, Leuven, Belgium.
CHEST, VOL 59, NO. 2, FEBRUARY 1971