Scar Carcinoma of the Lung

Transcription

1 THE ANNALS OF THORACIC SURGERY Journal of The Society of Thoracic Surgeons and the Southern Thoracic Surgical Association VOLUME 17 NUMBER 6 JUNE 1974 Scar Carcinoma of the Lung Fact or Fantasy? Lawrence J. Freant, M.D., William L. Joseph, M.D., and Paul C. Adkins, M.D. ABSTRACT Previous reports on lung surgery have considered scar carcinoma of the lung as a separate clinical entity associated.with a fairly favorable prognosis. The clinical and morphological characteristics of peripheral adenocarcinoma or adenosquamous cell carcinoma in 75 patients and of scar carcinoma in 19 individuals were compared. Location of the lesions, sex distribution, patient age, and tumor size were similar for both groups. Although the extent of vascular invasion was also similar, lymph node involvement was greater in the group with scar carcinoma. Five-year survival was far less in the scar carcinoma group (5%) than in the adenocarcinoma (22%) or adenosquamous cell carcinoma (28%) groups. The characteristics of scar carcinoma of the lung appear to be no different than those of similar cell types without scarring. T he importance of chronic damage to tissues as a predisposing factor in the etiology of carcinoma is well recognized. Bowen s disease of the skin, intraepithelial cancer of the cervix and esophagus, and Paget s disease of the breast are but a few such examples. The relationship of primary malignant tumors of the lung with preexistent pulmonary scars secondary to either chronic inflammation, old infarcts, or other parenchymal diseases has also been noted [3, 11, 141. Previous reports have considered scar carcinoma of the lung as a separate clinical entity that is (1) peripheral in location, (2) usually less than 3 cm. in diameter, (3) predominantly in the From the Department of Surgery, George Washington University Medical Center, Washington, D.C. Presented at the Twentieth Annual Meeting of the Southern Thoracic Surgical Association, Louisville, Ky., Nov. 1-3, Address reprint requests to Dr. Joseph, Department of Surgery, George Washington University Medical Center, 2150 Pennsylvania Ave., N.W., Washington, D.C

2 FREANT, JOSEPH, AND ADKINS upper lobes, (4) more frequent in men, (5) usually adenocarcinoma, and (6) associated with a more favorable prognosis than other types of lung cancer [2, 5, 141. In order to examine this interesting potential association, the present study was undertaken. Clinical Material and Results During the period between 1961 and 1972, a total of 119 patients with circumscribed, peripherally located pulmonary adenocarcinoma or adenosquamous cell carcinoma were seen (Fig. 1). Resection for cure was performed in 94 of the 119 patients (79%). Fifty-eight individuals had pure adenocarcinoma in their resected specimens, while 17 were found to have adenosquamous carcinoma: in this group there were 41 men with a mean age of 58 years and 34 women whose mean age was 55 years. In addition, 19 patients with scar carcinoma were found, 12 with adenocarcinoma and 7 with adenosquamous cell carcinoma; there were 10 men and 9 women with a mean age of 57 years. Histologically, adenocarcinoma was diagnosed when the tumor showed definite papillae or gland formation, regardless of whether it contained mucin when stained with mucicarmine. Poorly differentiated tumors without papillae or glands were diagnosed as adenocarcinoma only when mucinpositive. The term adenosquamous was applied when the tumor combined areas of mucin-producing epithelium, with or without papilla formation, and areas of sheetlike squamoid cellular proliferation with hyalinization and pearl formation. The presence of a lung scar was diagnosed both grossly and microscopically (Fig. 2). In all such cases the lesion was peripheral in location, often subpleural in placement, and had a definite fibrous consistency on gross examination. On microscopical examination the tumor mass was located within or immediately adjacent to an area of dense hyalinized connective tissue with an abundance of elastic and anthracotic pigment scattered throughout the lesion. At the periphery of a few scars a Resected For Cure (94) Not Resected-For Cure (25) Pure Adeno- Adenosauamous Scar Carcinoma FIG. 1. The treatment of I19 patients with peripheral adenocarcinoma, adenosquamous cell carcinoma, or scar carcinoma. 532 THE ANNALS OF THORACIC SURGERY

3 Scar Carcinoma of the Lung FIG. 2. Photomicrograph of scar Carcinoma shows malignant cells trapped in a scarred area. Note dense hyalinization and fibrosis. (H&E; ~ 40.) gradual transition from epithelial hyperplasia or metaplasia to frank carcinoma could be seen. In the majority of cases, however, the fibrosing process was nonspecific, and relatively few scars could be identified as chronic granulomas or old infarcts. Pulmonary resection was the primary treatment in all 94 patients whose lesions were judged to be potentially curable. This 79y0 resectability rate was unquestionably due to the peripheral location of the tumors. The Table summarizes the average size of the individual lesions as well as the number of patients with lymph node and vascular invasion. Lesion size was not appreciably different for any one group. In the group with adenocarcinoma 64y0 had lymph node or vascular involvement, while more than 85y0 of the patients with adenosquamous or scar carcinoma had lymph node involvement or vascular invasion, or both, at the time of resection. Figure 3 illustrates the distribution of the lesions by lobe. As in other series, upper lobe sites predominated in each group, with 65% of all peripheral lesions found in these locations. In the group with scar carcinoma, however, 320/, of the lesions were found in the lower lobes. Ten patients with peripheral adenocarcinoma in whom the tumors crossed fissure lines are not included in Figure 3. For the 83 patients followed at least five years or until death, the mean survival rate for each group after resection is shown in the Table. The fiveyear survival rate in the group with adenocarcinoma was 22%, while that in the group with adenosquamous carcinoma was 28yo. One patient is alive and well seven years after removal of a peripheral adenosquamous cell carcinoma with vascular and lymph node invasion. Only 1 patient who had scar car- VOL. 17, NO. 6, JUNE,

4 FREANT, JOSEPH, AND ADKINS MORPHOLOGICAL CHARACTERISTICS, PATIENT SURVIVAL, AND RECURRENCE RATES WITH VARIOUS TYPES OF LUNG CANCER Adeno- Adenosquamous Scar Characteristics carcinoma Carcinoma Carcinoma Average size Associated lymph node invasion only Associated vascular involvement with or without lymph node invasion No associated vascular or lymph node invasion Recurrence Lymph node involvement only Vascular invasion with or without lymph node involvement Five-year survival 2.92 cm cm cm. 10 pts. 3 pts. 6 pts. 27 pts. 12 pts. 11 pts. 21 pts. 2 pts. 2 pts mo. 42 mo. 18 mo mo mo. 9.4 mo. 11 /50 pts. (22%) 4/ 14 pts. (28%) 1 / 19 pts. (5%) cinoma has survived five years. With lymph node and vascular invasion, recurrence rates were essentially the same in all groups, the mean recurrence interval being 11.5 months. With lymph node involvement only, intervals between resection and recurrence increased to an average of months. With scar carcinoma, recurrence intervals were shorter in both categories. Comment Scar carcinoma of the lung was brought into prominence about 1940 by Friedrich [4] and Rossle [12], both of whom described a group of primary 534 =HE ANNALS OF THORACIC SURGERY

5 Scar Carcinoma of the Lung pulmonary malignancies that were closely associated with old areas of scarring in the lungs. These peripheral cicatricial cancers were further evaluated by Raeburn and Spencer [lo] and Luders and Theme1 [7], who sectioned whole lungs at postmortem examination. From these studies they were able to relate many peripheral lung cancers to previous scarring and to show that all stages-from simple reparative hyperplasia of bronchiolar epithelium to fully developed carcinoma-could be found in association with lung scars. Since that time a considerable body of evidence has accumulated showing that cancers of the lung can arise in relation to dense and often pigmented scars [3, 11, 13, 141. The majority of these tumors are located subpleurally in the upper lobes, usually in men. A variety of histological types of lung cancer have been found in association with lung scars, but a preponderance (63 to 78%) of mucus-secreting adenocarcinoma less than 3 cm. in diameter has been reported [3, 11, 131. Although lung scars seem to play a large part in the genesis of certain primary carcinomas of the lung, the etiology of the scar-whether inflammatory, traumatic, or secondary to an infarct-does not appear to be important. Montgomery [9] studied the process of repair in animal lungs after making small incisions into the lungs and allowing them to heal. On subsequent microscopical examination of the terminal bronchiolar epithelium he found fibroelastic tissue formation and regeneration of lung tissue with proliferation of bronchial channels lined by cuboid or squamous epithelium. Most commonly, this reparative hyperplastic epithelium regressed with accompanying fibrous tissue reaction. In some animals, however, for unknown reasons, a typical, frankly malignant transformation occurred. This same spectrum of tissue reaction to injury, with areas of hyperplasia, squamous metaplasia, carcinoma in situ, and invasive carcinoma, has been noted in relation to the walls of old fibrocaseous tuberculous foci and foreign metallic bodies in the lung such as bullets, as well as adjacent to old infarcts and to lungs with a chronic antecedent pulmonary infection [I, 8, 131. It should not be surprising that the majority of these scar carcinomas are adenocarcinoma or adenosquamous cell carcinoma. Embryologically, all respiratory epithelium originates from the squamous cell-lined foregut [6]. During embryological growth, continuous differentiation of the epithelium ultimately results in a pseudostratified columnar epithelial lining for the larger bronchi, while cuboid epithelium eventually lines the smaller bronchi. In an attempt to recover from injury, the bronchiolar epithelium reverts to a more primitive epithelial tissue [ll]. This precursor of the cuboid epithelial lining in the peripheral terminal bronchioles is the high columnar epithelium that lines the smaller bronchi in early embryonic life. As malignant transformation occurs, the primitive columnar cells proliferate into the alveolar spaces, replacing the cuboid epithelium and producing the characteristic glandular pattern of pulmonary adenocarcinoma. Our series of 119 patients tends to corroborate the cell type and periph-

6 FREANT, JOSEPH, AND ADKINS era1 location of scar carcinoma that have been noted by others. Scar carcinoma, rather than appearing as a distinct clinical entity, had clinical and morphological characteristics similar to those of all the peripheral carcinomas studied during the same period. Although 32y0 of the lung scars occurred outside the upper lobes, 35y0 of the adenocarcinomas and adenosquamous carcinomas were located in the middle or lower lobes. The age distribution was also similar, while the male-to-female ratio in the patients with scar carcinoma was equal. Although most of the tumors were small (< 3.5 cm.), small size did not necessarily denote a biologically early lesion for any cell type (see the Table). Peribronchial or hilar lymph nodes contained tumor more frequently in the patients with scar carcinoma (32y0) than in those with either adenocarcinoma or adenosquamous cancer ( 17y0). On the other hand, the incidence of vascular involvement with or without nodal invasion was 57y0 for those with scar carcinoma and 52y0 for the others. Previous reports have considered scar carcinoma of the lung to be associated with a relatively favorable prognosis. Five of 6 patients reported by Bennett and associates [2] were alive and well five years after lobectomy for scar carcinoma. These authors could offer no explanation for the increased survival in this group of patients; they noted that tumor size was similar for the scar-associated cancers and the entire series. Hukill and Stern [5] also found that patients with scar cancers seemed to have a favorable prognosis, with 3 of 7 patients surviving five years. In our series only 1 patient with scar carcinoma survived five years (see the Table); although the incidence of vascular invasion was similar in both groups, lymph node involvement was greater in the patients with scar carcinoma (32y0) than in the remainder of the series (17%). These findings would tend to support both Bennett s and Hukill s views that microscopical vascular invasion seems to be of little prognostic value in adenocarcinoma and that lymph node metastasis is the most important prognostic feature. Indeed, based on nodal invasion, the lesions recurred earlier in the scar carcinoma group (18 months) than in either the adenocarcinoma or adenosquamous carcinoma group (39.6 and 42 months, respectively). Why the scar carcinomas have such a poor prognosis, at least in this series, is unknown. However, a possible explanation is suggested by Carroll [3]: the earlier blockage of lymphatic drainage by the scarring process and the accumulated pooling of carcinogens within the scar for much longer periods results in more extensive vascular and lymphatic seeding than is seen in either adenocarcinoma or adenosquamous cell carcinoma. The data reported here suggest that although previous lung scars appear to be important in the genesis of primary lung carcinoma, the diagnosis of scar carcinoma is purely histological. We question whether scar carcinoma is a separate clinical entity and suggest that its clinical characteristics are no different than those of similar cell types without associated lung scarring. 536 THE ANNALS OF THORACIC SURGERY

7 References Scar Carcinoma of the Lung 1. Balo, J., Juhasz, E., and Temes, J. Pulmonary infarcts and pulmonary carcinoma. Cancer 9:918, Bennett, D. E., Sasser, W. F., and Ferguson, T. B. Adenocarcinoma of the lung in men. Cancer 23:431, Carroll, R. Influence of lung scars on primary lung cancer. J. Pathol. Bacteriol. 83:293, Friedrich, G. Periphere Lungenkrebse auf dem pleuranaher Narben. Virchows Arch. [Pathol. Anat.] 54:230, Hukill, P. B., and Stern, H. Adenocarcinoma of the lung-histological factors affecting prognosis. Cancer 15:504, Lisa, J. R., Trinidad, S., and Rosenblatt, M. B. Site of origin, histogenesis, and cytostructure of bronchogenic carcinoma. Am. J. Clin. Pathol. 44:375, Luders, C. J., and Themel, K. G. Die Narbenkrebse der Lungen als Beitra zur Pathogenese des peripheren Lungencarcinoms. Virchows Arch. [Pathof Anat.] 325:499, Meyer, E. C., and Liebow, A. A. Relationship of interstitial pneumonia honeycombing and atypical epithelial proliferation to cancer of the lung. Cancer 18:322, Changes in lung architecture following trauma. Br. J. 9. Montgomery, G. L. Surg. 31:292, Raeburn, C., and Spencer, H. A study of the origin and development of lung cancer. Thorax 8:1, Raeburn, C., and Spencer, H. Lung scar cancers. Br. J. Tuberc. 51:237, Rossle, R. Die Narbenkrebse der Lungen. Schweiz. Med. Wochenschr. 73: 1200, Walter, J. B., and Pryce, D. M. The site of origin of lung cancer and its relation to histological type. Thorax 10: 117, Yokoo, H., and Suckow, E. F. Peripheral lung cancers arising in scars. Cancer 14: 1205, NOTICE FROM THE AMERICAN BOARD OF THORACIC SURGERY The 1975 annual certifying examination (written and oral) of the American Board of Thoracic Surgery will be held in Dallas, Tex., in March, Final date for filing application is August 1, Please address all communications to the American Board of Thoracic Surgery, Inc., E. Seven Mile Rd., Detroit, Mich