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J Thorac Cardiovasc Surg 1994;107:611-0614
© 1994 Mosby, Inc.
General Thoracic Surgery |
Lille, France
Received for publication April 9, 1993. Accepted for publication July 7, 1993. Address for reprints: M. Ribet, MD, Hôpital Calmette, CentreHospitalier Universitaire, F. 59037 Lille Cedex, France.
Abstract
Sixty-five patients, aged 15 to 65 years, including 48 men (73.8%), were operated on for pulmonary (60) or endobronchial (5) hamartoma: there were 36 enucleations, 17 lobectomies (1 sleeve resection), 7 wedge resections, 4 segmentectomies, and 1 pneumonectomy. The average tumor diameter was between 2 and 4 cm; 15 were calcified. All were benign. Two were parts of an incomplete Carney's triad. Eight were associated with carcinomas, and three of these were bronchial carcinomas. Concerning these latter three tumors, a study of the incidence tables for northern France and of the standardized mortality ratio showed that the risk of bronchial cancer developing in patients with hamartoma, after a sufficient follow-up (61 patients), was multiplied by 6.66, and the 
2 test showed a significant difference of incidence compared with that in the general population (p < 0.001). It is concluded that patients with hamartoma should be submitted to a complete evaluation and to a regular follow-up. (J THORAC CARDIOVASC SURG 1994;107:611-4)
The origin, nature, and significance of pulmonary hamartoma have been debated. Considered as benign and also called mesenchymoma, hamartoma has, however, been observed in association with malignancy, particularly with bronchial carcinoma. The purpose of this study was to try to determine whether or not this association between pulmonary hamartoma and lung cancer is fortuitous.
MATERIALS AND METHODS
The review concerned 65 patients, 48 men (73.8%) and 17 women (26.2%) who were operated on between 1967 and 1991. The medical records were retrospectively reviewed, as were the chest radiographs, operative findings, and pathologic reports. The mean age was 46 years (range 15 to 74 years). Thirty-four (52.3%) were cigarette smokers and 20 (30.7%) had bronchopulmonary chronic obstruction, the latter all being smokers. Seven had asthma. Six had a history of tuberculosis. In 33 patients (50.8%) the hamartomas were discovered during the evaluation of respiratory symptoms, whereas in the other 32 patients they were an incidental finding on a chest radiograph. No previous chest radiograph was available in 37 patients, but 19 had previous radiographs that showed a slow increase in size of the nodules (with a doubling time varying between 2 and 26 years): six patients had former radiographs that showed no nodule 1, 2, 6, 8, 10, and 26 years before, respectively; three had radiographs that showed exactly the same nodules 2, 2, and 3 years before, respectively.
The hamartomas were pulmonary in 60 patients and endobronchial in 5 patients. The pulmonary locations were peripheral in 48 cases and central in 12 cases. There were 29 hamartomas in the right lung and 33 in the left lung (one patient had 1 hamartoma in the left upper lobe and 2 in the left lower lobe). The bronchial locations were 3 in the right upper lobe bronchus, 1 in the middle lobe bronchus, and 1 in the left lower lobe bronchus. Bronchoscopy showed them as regularly shaped, hard, and difficult to biopsy. One sputum cytologic sample was positive for malignancy with no other finding (a bronchial carcinoma was diagnosed 2 years later).
Thirty-six hamartomas were enucleated (55.4%) and 17 were resected by a lobectomy, including 1 sleeve resection (26.15%); 7 by a wedge resection (10.8%); 4 by a segmentectomy (6.15%); and 1 by a pneumonectomy (1.5%). The size of the hamartomas varied from 0.5 to 30 cm in diameter and was between 2 and 4 cm in 35 patients (53.8%). Eighteen hamartomas were calcified and one contained no cartilage. The intrabronchial hamartomas were accompanied by various degrees of peripheral bronchiectasis and chronic pneumonitis. There was no other anomaly in the lung tissue of 29 resection specimens. When anthracosis pigments were abundant in the surrounding tissue, they were not present in the hamartomas. Nine lymphadenectomies, done because of suspected carcinoma, showed inflammatory reactions.
The patients were followed up during a mean 9-year period (range 1 to 22 years). We did not consider for statistics the most recent four patients operated on for hamartomas, for whom the follow-up period was less than 1 year.
We used the standardized incidence ratio (SIR) to compare the incidence of bronchial carcinoma in these 61 patients with that in the general population. Age/sex specific French standard rates for 1978 through 1982 were obtained from INSERM (the National Institute for Health and Medical Research).
1 This period of time was adequate because it included the year 1979, which was the median of the period under study (1967 to 1991) and because the progression of the incidence of lung cancer was linear (Fig. 1). In northern France, the mortality rate for lung cancer is estimated to be 21% higher than in the rest of the country. 2 Thus we calculated age/sex specific rates by multiplying the French standard rates by 1.21. The SIR compared the observed number of bronchial carcinomas in our patients by applying the standard rates to the cohort age/sex/person-years structure. SIR = O/E, where O expressed the observed number of bronchial carcinomas and E the expected number. The significance of SIR was calculated by the 2 test
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RESULTS
Among 61 patients, 10 had associated malignancies, either synchronous or metachronous. Two were part of an incomplete Carney's triad 3: one 19-year-old woman had a pulmonary hamartoma that was resected by a segmentectomy; 7 years later she had a stage III gastric leiomyosarcoma that was treated by a total gastrectomy associated with a splenectomy and caudal pancreatectomy and 2 years later she had two more pulmonary hamartomas that were enucleated. One 15-year-old girl had, within a year, a right upper lobectomy for a pulmonary hamartoma and a total gastrectomy for a stage I leiomyoblastoma.
Eight patients had a carcinoma: one skin cancer had been resected 4 years before a lobectomy with lymph-node dissection was done for a pulmonary hamartoma considered as a metastasis in a 66-year-old woman. Three hamartomas, also considered as secondary tumors, were treated by wedge resection during an esophagectomy in a 63-year-old man, during a gastrectomy in a 52-year-old man, and during a thyroidectomy in a 63-year-old woman. Four male patients, aged 45, 52, 49, and 52 years, were first operated on for a lung hamartoma and later had, respectively, one cancer of the tongue with positive neck node biopsy samples and brain metastasis (after 9 years) and three bronchial squamous carcinomas (after 2 years, 3 years, and 15 years, respectively), which were not resectable because of mediastinal invasion (one case) or metastasis (two cases). The successive locations of the hamartomas and bronchial carcinomas were left lower lobe and lingula, right upper lobe and left upper lobe, and left upper lobe and left main bronchus.
The three patients with bronchial carcinomas were cigarette smokers who smoked 20, 15, and 40 cigarettes, respectively, a day. The patients with carcinomas of the esophagus and of the tongue were also smokers (20 cigarettes a day). The patients with skin, stomach, and thyroid carcinomas did not smoke.
We excluded from this statistical study the two cases of incomplete Carney's triad, which does not include carcinomas. As for the eight carcinomas, they were too disparate to be considered as a whole. We limited our survey to the three squamous bronchial carcinomas in a group of 61 hamartomas.
The estimated incidence of lung carcinoma for 100,000 people in northern France during the considered period of time is expressed in Table I. The number of expected bronchial carcinomas in a population, according to age intervals and sex, is equal to the number of person-years in each interval as shown in Table II multiplied by the estimated incidence in this interval. The number of observed bronchial carcinomas in the 61 patients with hamartoma (compared with the sum of expected cases in each interval), was
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DISCUSSION
There has been a lasting controversy concerning the origin of pulmonary hamartoma: is it dysembryoplasia or inflammation? For Bateson, 4 the tumor is caused by metaplasia. The doubling time of the tumor in adults has been estimated at 36.4 ± 27.7 months. 5 We could confirm a slow and continuous increase in size in 12 patients in our series. Hamartomas can be multiple and can recur. Their malignant degeneration has been discussed. 6, 7 For Gebauer, 8 external factors help their development. It is possible that inflammatory respiratory disease and tobacco smoking might stimulate the growth of a latent lesion, which would explain the maximum of observed pulmonary hamartomas in patients aged 40 to 70 years and the greater prevalence of male patients. In children, pulmonary hamartoma is seldom observed; our youngest patient was 15 years old. 9 This study confirms the association of hamartomas with Carney's triad, which can be metachronous.
Various extrapulmonary associated malignancies have also been observed: breast carcinoma, 5 pancreatic cancer, 10 testis teratoma, 11 and sarcoma. 12 In 24 cases of hamartoma, Gabrail and Zara 13 noted two carcinomas of the colon, two bronchial carcinomas, and one esophageal carcinoma. They did not consider hamartoma as a solitary lesion and, apart from Carney's triad, tried to define a "pulmonary hamartoma syndrome." Van Den Bosch and associates 14 found no evident reason for these associations and thought that the existence of a cancer could lead to the discovery of an asymptomatic hamartoma that would have remained unknown otherwise. However, the number of malignancies observed in our series is important, considering the age distribution of the patients. The associations are synchronous or metachronous, which is a result of the very slow evolution of hamartoma: three were synchronous and five were metachronous in our series.
There appears to be a higher than expected incidence of lung cancers in patients who have or have had hamartomas, but this must be considered with caution. There was no correlation between the increasing curve of mortality from lung cancer in France between 1960 and 1985 and the number of hamartomas resected in our institution (Fig. 1). However, this disparity allows no conclusion, inasmuch as a minority in our series of resected cancers were T1 N0 (8%), and a majority of solitary pulmonary nodules are treated elsewhere. Many factors indeed influence the incidence of bronchogenic carcinoma, but a multivariate analysis of environmental factors is impossible to conduct properly on such a long period of observation in which changes in environment were many. Considering the age of the patients, the maximum incidence of hamartoma starts 10 years earlier than the maximum incidence of bronchial carcinoma. Considering their habits, the 61 patients included 31 tobacco smokers (50.8%), and smokers made up 52.7% of the general population during that period.
Karasik and associates 10 were the first to consider that the association of pulmonary hamartoma and bronchial carcinoma was not fortuitous and that the risk was 6.3 times more important than in a general population. This study was based on 52 patients operated on between 1960 and 1975, with four associated carcinomas (two synchronous, two metachronous). They statistically proved this was not pure chance. We have noted the frequency of associated bronchial carcinomas in several series of resected hamartomas (Table III); it is high and our results come close to those of Karasik and associates, 10 whose population was evenly distributed between 33 and 72 years. Various histologic types were described. 21, 22
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Footnotes
From the Service de chirurgie thoracique, Hôpital Calmette,a and the Departement d'information medicale,b Centre Hospitalier Universitaire, Lille, France. 
References
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