Surgically Treated Unsuspected Pulmonary Infarction

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1 Surgically Treated Unsuspected Pulmonary Infarction Joe I. Miller, M.D., Edgar G. Harrison, Jr., M.D., and Philip E. Bernatz, M.D. ABSTRACT At the Mayo Clinic during a thirty-year period, 31 patients (25 men and 6 women) underwent exploratory thoracotomy and pulmonary resection for unsuspected pulmonary infarction. Cough, hemoptysis, or pleuritic pain was present in approximately half the patients. Most patients underwent exploration for a suspected neoplastic process. Pathologically, there were 14 hemorrhagic infarcts, 4 fibrotic infarcts, and 13 infarcts that had characteristics of both. All patients underwent conservative surgical resection, either wedge resection or lobectomy. There were 3 operative deaths, and 25 of the 28 patients followed up had no further episodes of infarction. Subsequently, 6 died from other causes. G enerally, pulmonary infarction is not considered a surgically treatable lesion, and surgeons try to avoid operating on patients with this problem. However, we have had 31 patients in whom the nature of the abnormality on chest roentgenogram led to exploratory thoracotomy. Clinical Material At the Mayo Clinic during the thirty-year period from January 1, 1940, to July 1, 1970, 31 patients underwent pulmonary resection for previously undiagnosed lesions that proved to be pulmonary infarcts. Excluded from the study were patients who had infarcts associated with infectious diseases, necrotizing vasculitis, neoplasia, vascular anomaly, foreign body, or chronic organizing pneumonitis. Findings Age and Sex. The ages of the 31 patients (26 men and 5 women) ranged from 17 to 78 years, with most in the fifth to the seventh decade of life. Signs and Symptoms. Twenty-five of the 31 patients were symptomatic. The duration from the onset of symptoms to the time of surgical ex- From the Mayo Clinic and Mayo Foundation, Rochester, Minn. Presented at the Eight Annual Meeting of The Society of Thoracic Surgeons, San Francisco, Calif., Jan , Address reprint requests to Section of Publications, Mayo Clinic, Rochester, Minn VOL. 14, NO. 2, AUGUST,

2 MILLER, HARRISON, AND BERNATZ ploration was less than 4 months in 24 of the 25 patients; 1 patient had been symptomatic for one year. Sixteen patients had hemoptysis (Table 1). The duration of the hemoptysis ranged from 2 to 28 days, and the amount varied from blood-tinged sputum to several cupfuls of blood a day. Seven patients had a history of recent thrombophlebitis. Diagnoses. The preoperative clinical diagnoses varied (Table 2). In 23 of the 31 patients the preoperative suspicion was of a primary malignant process. Ancillary laboratory data were of little help in arriving at a correct clinical diagnosis. The electrocardiographic findings were normal in 27 of the 31 patients. An S1Q3 pattern and an interventricular conduction delay were each present in 2 patients. Diagnostic thoracocentesis was carried out in 5 patients. In all 5, the transudate was free of blood and negative for malignant cells. Bronchoscopic examinations were performed in 18 patients and revealed no abnormalities. Cytological examination of the sputum or bronchial secretions (or both) was carried out in most of the patients and was negative in all but 1 in whom the results were false-positive. Roentgenographic Features. A striking roentgenographic feature was the extreme variability. Pulmonary infarction was suggested in the differential diagnosis in only 4 of the 31 patients. The most frequent roentgenographic diagnosis (Table 3) was that of bronchogenic carcinoma (14 patients); in an additional 7 patients there was a pattern of obstructive pneumonitis suggestive of an underlying neoplasm. The variety of preoperative roentgenographic diagnoses indicates the diagnostic difficulties imposed by pulmonary infarction. Pathological Findings. Both gross specimens and microscopical slides of tissue sections from all patients were available for review. The right lung was involved in 20 patients, with the lesion being found in the right upper lobe in 6, the right middle lobe in 5, and the right lower lobe in 9. The left lung was involved in 11 patients, with the left upper lobe involved in 4, the lingula in 3, and the left lower lobe in 4. The size of the infarct varied from 1 to 10 cm., with an average of 2.8 cm. In 25 of the 31 patients a single TABLE 1. SIGNS AND SYMPTOMS IN 318 PATIENTS WITH UNSUSPECTED PULMONARY INFARCT Sign or Symptom No. of Patients Hemop tysis 16 Pleuritic pain 11 Cough 17 Thrombophlebitis 7 Pleural effusion 2 Gastrointestinal symptoms 3 Urological symptoms 1 %Six patients were asymptomatic. 182 THE ANNALS OF THORACIC SURGERY

3 Unsuspected Pulmonary Infarction TABLE 2. PREOPERATIVE CLINICAL DIAGNOSES IN 31 PATIENTS WITH UNSUSPECTED PULMONARY INFARCT.- Condition No. of Patients Bronchogenic carcinoma 16 Coin lesion 6 Malignant mesothelioma 1 Pleural effusion 2 Indeterminate inflammatory process 1 Pulmonary embolism with infarct 2 Tuberculosis 1 Bronchiectasis 1 Pulmonary abscess 1 Total 31 infarct was present, whereas in 6 patients multiple infarcts ranging from two to four in number were present. In 9 of the 31 patients an embolus or thrombus blocked a branch of the pulmonary artery. In the remaining 22 patients either no embolus was found or the embolus may not have been included in the resected specimen. Grossly, the fresh infarcts were peripheral, deep red, bloody parenchymal engorgements that were moderately firm but still friable, and they exuded dark blood when transected; whereas other infarcts were more firm and pale yellowish or brownish white. Microscopically, infarcts were classified as predominantly hemorrhagic, fibrotic (or white infarcts), or a combination of the two; all had some element of necrosis. In the present series, 14 patients were considered to have predominantly hemorrhagic infarcts, 4 had predominantly fibrotic or white infarcts, and 13 had infarcts that showed both hemorrhagic and fibrotic components. One hemorrhagic infarct was also considered to be a septic lesion because Aspergillus organisms were found to be invading it as well as the necrotic lung parenchyma. This organism had been previously isolated from the patient s bladder after treatment for bladder cancer. Of interest in 18 patients was the finding in adjacent small pulmonary arteries of nar- TABLE 3. ROENTGENOGRAPHIC DIAGNOSES IN 31 PATIENTS WITH UNSUSPECTED PULMONARY INFARCT Diagnosis No. of Patients Bronchogenic carcinoma 14 Pulmonary embolism with infarct 4 Mesothelioma 1 Obstructive pneumonitis 7 Undetermined inflammatory process 4 Undetermined mass lesion 1 Pleural effusion 2 Pulmonary edema 1 Pulmonary abscess 1 VOL. 14, NO. 2, AUGUST,

4 MILLER, HARRISON, AND BERNATZ TABLE 4. LOCATION OF LESION AND TYPE OF TREATMENT IN 31 PATIENTS WITH UNSUSPECTED PULMONARY INFARCT Infarct Treatment (No. of Patients) Total Location Wedge Resection Lobectomy Patients Right lung Upper lobe Middle lobe Lower lobe Left lung Upper lobe Lingula Lower lobe rowing of the lumen by intimal fibrosis. These changes in the smaller arteries may have been secondary to ischemic vascular damage, because they were usually found in zones adjacent to the infarct and had a patchy distribution. One patient also had some medial hyperplasia of medium-sized arteries. Pulmonary veins were not usual in appearance. Treatment. The types of surgical resection included wedge resection in 15 patients, lobectomy in 14 patients, lobectomy plus wedge resection in 1 patient, and biopsy only in 1 patient. In the 6 patients who had more than one infarct, two wedge resections were carried out in 1 patient and two lobes were removed from another patient. The location of the lung infarct and the type of surgical procedure carried out are shown in Table 4. Results of operation. There were 3 operative deaths: 2 patients died from pulmonary embolism 4 and 13 days, respectively, after operation, and the third died of massive gastrointestinal hemorrhage from a gastric stress ulcer 6 days after operation. Two of these 3 patients had hemorrhagic infarcts, and the third patient had a fibrotic infarct. All 3 patients were receiving anticoagulants at the time of their deaths. There was only 1 postoperative complication: 1 patient developed a bronchopleural fistula that required closure at a second operation. Follow-up was obtained on 25 of the surviving 28 patients. Six of this group subsequently have died from other causes: the times ranged from six months to eleven years after operation. The surviving 19 patients have been followed up from four months to twenty-two years, with a median of four years. Fifteen of the 19 patients were alive at the time of follow-up with no other thromboembolic episodes. The remaining 4 patients have developed other significant disease processes: 1 has chronic ulcerative colitis, 1 has multiple sclerosis, 1 has polymyositis, and 1 has carcinoma of the pancreas. Comment Pulmonary infarction may mimic various pulmonary disease processes and has stimulated case reports of patients treated surgically for infarcts ~8.4 THE ANNALS OF THORACIC SURGERY

5 Unsuspected Pulmonary Infarction simulating neoplasm [3, 7-10]. Cough, hemoptysis, and pleural pain are cardinal symptoms of infarct and were present in half of the patients in our series. Somehow the presence of these symptoms did not convince the clinician or the surgeon that an infarct had occurred. Review of the chest roentgenograms in our series makes it understandable why the clinicians were unwilling to accept the diagnosis of infarct in the presence of persistent, well-circumscribed shadows suggestive of neoplasm. If the diagnosis of infarct had been seriously considered, however, operation probably would have been avoided. Many excellent studies have described the roentgenographic characteristics of pulmonary infarction [4, Characteristic findings generally appear 12 to 24 hours after embolism has occurred. The often-described peripheral, triangular area of consolidation generally appearing in the lower lobes with the apex facing the hilus is seen in only 15 to 30% of patients [61. In another 15 to 30%, the roentgenograms may show areas of patchy pneumonitis or atelectasis in the lower lobes, with pleural effusion and elevation of the hemidiaphragm on the affected side appearing at a later time. In another 50% of patients the findings are either normal or nondiagnostic [6]. Pathologically, pulmonary infarction is best viewed as a series of events that is initiated by the complete and continued occlusion of an artery. In succession, the area supplied by the artery undergoes hyperemia, hemorrhage, degeneration, necrosis, and finally either encapsulation by connective tissue or conversion into a fibrous scar. In our series, only 9 specimens had pathological evidence of thromboembolism. Of the remainder, 18 specimens had varied degrees of intimal fibrosis in the periphery of the infarcts which could have contributed to the infarction, although proximal vascular thromboembolism that was not included in the specimens may have been present. No unusual primary vascular disease such as necrotizing arteritis or fibromuscular dysplasia was encountered. Pathologically, the differential diagnosis must include specific types of embolism, such as those which occur distal to bronchogenic carcinoma and are due to vascular involvement. Also, some pulmonary diseases simulate so-called white infarcts, including certain active caseous granulomas, Wegener s granuloma [l, 21 (especially the limited form), subpleural rheumatoid nodules, and rare human pulmonary dirofilariasis [5]. Differentiation requires careful morphological and microbiological examination of necrotic lung lesions. In our series, another problem was the false-positive sputum study for malignant cells reported in 1 of the patients. Review of the lung sections revealed that the abnormal-appearing cells were apparently exfoliated cells from alveolar hyperplasia and metaplasia in the organizing infarct. The treatment of choice for pulmonary lesions of undetermined cause is exploratory thoracotomy 171. Suspicious abnormalities on the chest roentgenogram should be checked for several weeks to determine whether they VOL. 14, NO. 2, AUGUST,

6 MILLER, HARRISON, AND BERNATZ resolve, as do most pulmonary hematomas, areas of pneumonitis, or incomplete infarcts [lo, 141. A conservative resection is generally performed for an unsuspected pulmonary infarct though lobectomy may be elected in an effort to reduce potential morbidity, especially if the necrotic infarct has been complicated by secondary infection. Although the 3 postoperative deaths in our series are disconcerting, most patients did well in long-term follow-up. Most did not have recurrent thromboembolic episodes even though anticoagulation therapy was continued for a maximum of six weeks. This review suggests that in spite of the increased sophistication of our diagnostic methods, pulmonary infarction will continue to plague the aggressive surgeon who is striving to make the diagnosis of cancer early rather than waiting for time to tell, which may be too late. References 1. Carrington, C. B., and Liebow, A. A. Limited forms of angiitis and granulomatosis of Wegener s type. Am. J. Med. 41:497, Cassan, S. M., Coles, D. T., and Harrison, E. G., Jr. The concept of limited forms of Wegener s granulomatosis. Am. J. Med. 49:366, Connolly, J. E., and Smith, J. W. Massive pulmonary infarction simulating carcinoma of the lung. Dis. Chest 39:429, Fleischner, F., Hampton, A. O., and Castleman, B. Linear shadows in the lung (interlobar pleuritis, atelectasis and healed infarction). Am. J. Roentgenol. Radium Ther. Nucl. Med. 46:610, Harrison, E. G., Jr., and Thompson, J. H., Jr. Dirofilariasis of human lung. Am. J. Clin. Pathol. 43:224, Hurst, J. W., and Logue, R. B. The Heart: Arteries and Veins (2d ed.). New York: McGraw-Hill, P Johnson, C. R., Clagett, 0. T., and Good, C. A. The importance of exploratory thoracotomy in the diagnosis of certain pulmonary lesions. Surgery 25218, Neville, W. E., and Munz, C. W. Pulmonary resection for infarction simulating bronchogenic carcinoma. Dis. Chest 27:447, Perkins, R. B., and Bradshaw, H. H. Pulmonary infarction mistaken for bronchogenic carcinoma. J.A.M.A. 151:545, Salyer, J. M., Blake, H. A., and Forsee, J. H. Pulmonary hematoma. J. Thorac. Surg. 25:336, Short, D. S. A radiological study of pulmonary infarction. Q. J. Med. 20:233, Smith, K. S. The radiology of pulmonary infarction. Q.J. Med. 7:85, Stein, I., and Weinstein, J. Localized pulmonary fluid collections in congestive failure simulating tumors: Phantom tumors of the lungs. Am. J. Cardiol. 5: 117, Williams, J. R. The vanishing lung tumor-pulmonary hematoma. Am. J. Roentgenol. Radium Ther. Nucl. Med. 81:296, Discussion DR. PAUL C. SAMSON (Oakland, Calif.): Thirty-two years ago, my first experience with infarction masquerading as carcinoma involved a patient who illustrated many of the points that the authors have made. The patient had 186 THE ANNALS OF THORACIC SURGERY

7 Unsuspected Pulmonary Infarction cough, pain, and hemoptysis. There was a mass lesion in the lingula. There was a false-positive Papanicolaou stain. Originally I was so chagrined that I never published the case, but review of the literature shows that others of our colleagues were not so reticent. I must remind you that in 1940 pneumonectomy carried somewhat less of a risk than left upper lobectomy, which was popularly believed in those days to be next to impossible as a surgical resection. In more recent years, Drs. Ivan May and Aaron Mittal and I have been very concerned with pulmonary embolus complicated by infected infarct, abscess, and empyema. This experience will be presented next month at the Pacific Coast Surgical meeting, but I think the discussion here is pertinent since we are dealing with infarction. We have seen 12 patients, and the majority of these were suspected of having pulmonary infarction. In this connection, unilateral biplane pulmonary angiography may be very helpful in the diagnosis, and I stress biplane because of the fact that obstruction of the pulmonary artery may not be visible in a single projection. As to the seriousness of disease in these patients, of the 12, 8 died-6 of uncontrolled infection, 3 of whom showed secondary nonfatal infarctions, and the 2 others of a second pulmonary infarct. Two points, therefore, are significant. First, these patients are difficult to manage and to cure. Second, early recognition of the pulmonary embolus as a cause of the presenting illness is essential because of the need for early, aggressive treatment of the infection-in the form of drainage, decortication, empyemectomy, or resection, as indicated-and for fairly prolonged preoperative and postoperative anticoagulation therapy. DR. JOHN CONNOLLY (Irvine, Calif.): I wish to emphasize this entity by briefly telling you about my first encounter with the surgical treatment of pulmonary infarction. The patient was seen by me in 1953 with a pulmonary mass, chills, and fever. Thoracocentesis produced serosanguineous fluid, and a diagnosis of carcinoma of the lung, probably inoperable, was made. At surgical exploration a large, firm pulmonary mass and thickened pleura appeared to confirm the diagnosis. Since frozen biopsies were not diagnostic, a decision was made to remove the lower lobe. Upon transecting the pulmonary artery, a completely occluding embolus was found. Microscopical examination of the excised lung tissue confirmed the diagnosis of pulmonary infarction. The patient was cured by the operation. Subsequently I encountered a similar patient. With the experience gained from the first patient, the possibility of pulmonary embolus and infarction was entertained and the diagnosis confirmed by pulmonary angiography. While such patients are not common, thoracic surgeons must be aware of this entity and consider it in their differential diagnosis. DR. C. THOMAS READ (Phoenix, Arid: The report that has just been presented is indeed unusual and interesting, particularly for the remarkable number of infarcts presenting as solitary nodules. Among the 200 patients with nodules whom I have operated upon, there was 1 infarct. Steele s series of 887 patients in 1963 included 1. Katz in 1961 reviewed thirty-four reports which included more than 2,500 nodules, and there is no specific mention of an infarct. Ford in 1956 reviewed fourteen papers comprising more than 700 nodules, none of which were reported as infarcts. A recent survey of some ten additional reports including 100 to 300 patients each showed only 1 other instance of pulmonary infarction presenting as a solitary nodule. It is interesting that Hood, Good, and Clagett in 1953 published a study on 156 nodules in patients operated upon at the Mayo Clinic; their report did not show any infarcts among the various benign lesions. When infarcts present as nodules, there are no differential radiological characteristics to separate them from neoplastic lesions. One would be justified in resecting such nodules, particularly if the patient is in the age group of 50 VOL. 14, NO. 2, AUGUST,

8 MILLER, HARRISON, AND BERNATZ years and older. A differential point in determining whether or not a nodule might be neoplastic is to apply the rule of tumor doubling time. In a report by Nathan, Collins, and Adams in 1962, among benign tumors showing definite socalled doubling times there was a pulmonary infarct. The doubling time reported was the same as that for a rapidly growing pulmonary neoplasm. It is not surprising, therefore, that many of us will be chagrined to discover the nodule we have resected is reported as a pulmonary infarct. DR. MILLER: Briefly, in response to Dr. Samson, our 1 false-positive sputum cytology occurred in 1947, which was just after sputum cytology was instituted on a large scale at the Mayo Clinic. In addition, bronchial brushing and needle biopsy have been available for the last several years, and in specimens from patients with pulmonary infarction these may be very difficult for the pathologist to interpret, particularly when he receives specimens from the infarct itself. In response to Dr. Connolly s remark, I might say again that 6 of our 31 patients were asymptomatic and presented a typical coin lesion in the lung without evidence of calcium in the nodule. As far as thrombophlebitis is concerned, 7 of our 31 patients had it. Four had latent thrombophlebitis within the month prior to their presentation at the hospital, and 3 had active lower extremity phlebitis on admission. However, as has also been pointed out, the clotting tendency in patients with cancer may also occur and complicate a thrombophlebitis. In addition to what Dr. Read has said, the point to stress from this study is the extreme variability in radiological appearance that a patient with pulmonary infarction may present. 188 THE ANNALS OF THORACIC SURGERY

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