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September - December 2003: 
Volume 16, Issue 3

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Bronchoscopic diagnosis of typical pulmonary carcinoid tumors. Review of the years 1990-2001
Abstract
ABSTRACT. Typical pulmonary carcinoid tumors are well-differentiated neuroendocrine tumors. The objective of the present study is to review cases of typical pulmonary carcinoid tumors diagnosed in the Bronchoscopy Department of the General Regional Hospital “G. Papanikolaou” over the period from 1990 through 2001. Reviewing the medical records of this period, 25 patients [16 male, 9 female, aged (mean±SD) 56,96±15 years] with typical pulmonary carcinoid tumors were identified, which account for 0.32% of all lung tumors diagnosed during the same period. All cases of pulmonary carcinoid tumor were diagnosed by endobronchial biopsy, whereas additional cytology studies on specimens obtained by brushing, lavage, or transbronchial needle aspiration (TBNA) were performed in the majority of the patients. Locations of typical carcinoid tumors, presenting symptoms, as well as sensitivities of the available diagnostic methods are also presented. In conclusion, bronchoscopy is very effective in the diagnosis of typical carcinoid tumors due to their frequent occurrence in major airways. Endobronchial biopsy and, to a lesser extent, TBNA are considered bronchoscopical diagnostic methods of choice, whereas the risk of bronchoscopy associated bleeding is insignificant. Pneumon 2003, 16(3):327-331.
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Introduction

Pulmonary carcinoid tumors are malignant neoplasms with neuroendocrine activity1. When first described in the beginning of the 20th century they were thought to be benign tumors. In 1944 a distinction between typical carcinoid tumors and the more aggressive atypical forms of these tumors was established; histologic criteria for classifying a carcinoid tumor in either form were laid out by Arrigoni et al in 1972. Large cell neuroen docrine carcinoma had not been recognized as a distinct entity until the 80s'4. According to the most recent classification for neuroendocrine lung tumors proposed by the World Health Organization (WHO)5, these tumors are divided into four major categories: low grade typical carcinoid, intermediate grade atypical carcinoid and high grade large cell neuroendocrine carcinoma and small cell carcinoma.

Pulmonary carcinoid tumors comprise 1‑2% of all lung neoplasms6 and 25% of all human carcinoid tumors7. In general, patients with a typical pulmonary carcinoid tumor have a good prognosis, rarely present with metastases and their 5-year survival rates range from 87 to 100%. In contrast, patients with atypical carcinoid tumors show a greater tendency to have metastases and a 5-year survival rate between 25 and 69%.8 The present paper is a review of the pulmonary typical carcinoid tumor cases diagnosed in the Bronchoscopy Department of the General Regional Hospital "G. Papanikolaou" over the period from 1990 through 2001. Specifically, incidence rates, locations, bronchoscopic findings and presenting symptoms of pulmonary typical carcinoid tumors, as well as the sensitivities of various methods of bronchoscopic diagnosis are discussed.

Material and Methods

Histologic or cytologic findings of lung cancer were found in 7,812 patients from a series of 19,535 subjects who underwent bronchoscopy in the Bronchoscopy Department of the General Regional Hospital "G. Papanikolaou" during the period between 1990 and 2001. A flexible Pendax 19T20 bronchoscope was used and patients were put under anesthesia. Endobronchial biopsy specimens were obtained from all patients with abnormal bronchoscopic findings; in addition, specimens for cytologic examination were acquired from the majority of the patients using brushing, lavage or transbronchial needle aspiration (TBNA). All histologic preparations were re-examined by the same pathologist (A.A.) for the definite diagnosis of a carcinoid tumor in the context of the present study. Bronchoscopy, pathology and cytology data were entered in Excel 97 software spreadsheets. SPSS 10.0 (Statistical Package for Social Sciences) was used for statistical analyses, which were assessed with chi square test.

Results

Among the 19,535 subjects who underwent bronchoscopy over the period from 1990 through 2001, the presence of a primary lung cancer was demonstrated by histology or cytology in 7,812 patients (39.9%). Of these, 25 patients (0.32%) aged 59,96±15 years (mean age±SD) (16 male, aged 57.43±15.65 years, and 9 female, aged 58.88±13.10 years) were shown to have a carcinoid tumor.

Presenting symptoms included cough in 6 patients, fever in 6 patients, hemoptysis in 4 patients and hoarseness in 1 patient. Eight patients were asymptomatic and the carcinoid tumor was a contingent finding in a chest radiograph. As regards the chronological order of pulmonary carcinoid tumor diagnoses, 1 patient was diagnosed in 1991, 3 in 1993, 3 in 1995, 6 in 1996, 2 in 1998, 6 in 1999, 3 in 2000 and 1 in 2001. Cases of pulmonary carcinoid tumor were not diagnosed in the years 1990, 1992, 1994 and 1997.

Diagnosis was based on histologic examination of tumor biopsy samples. In addition, transbronchial needle aspiration was performed in 16 patients; cytologic examination of the respective specimens indicated a carcinoid tumor in 10 of these patients (sensitivity rate 62.5%). In the rest of the cases, TBNA specimens showed cytologic features suggestive of lung cancer in two cases, suspicious of malignancy in three and negative for malignancy in one case. Brushing samples for cytology testing were also obtained from 7 patients and all were negative for malignancy. The same applied for lavage samples obtained from 11 patients. Those with positive cytology results for a carcinoid tumor had also a positive biopsy.

In 10 of the 25 patients with histologically confirmed carcinoid tumors there was bronchoscopic evidence suggestive of a carcinoid tumor (40%). Twenty-two patients presented a prominently vascularized mass, two patients had a polypoid mass and one a multilobular mass. As regards the location of carcinoid tumors, the left lower lobar bronchus represented the most common location (7 cases). Table 1 lists the locations of all pulmonary carcinoid tumors we diagnosed.

Bleeding occurred immediately after acquiring an endobronchial biopsy sample in 11 patients, and was treated bronchoscopically by continuous suction and infusion of 2-3 adrenaline ampoules. As soon as the bronchoscopy had been completed, three of these patients further received 1 adrenaline ampoule and 3 ml of a 2% lidocaine solution via nebulizer. None of the patients required hospitalization for the management of bronchoscopy-associated bleeding.

 

Table 1. Distribution of typical carcinoid tumors in various locations based on bronchoscopic findings.

Site                                   No. of cases                    Site                                    No. of cases

Left mainstem bronchus            4                            Right mainstem bronchus           0

Left upper lobar bronchus         2                            Right upper lobar bronchus        2

Lingula                                       2                            Right middle lobar bronchus       3          

Left lower lobar bronchus          7                            Right lower lobar bronchus         5

Left lung                                  15                            Right lung                                 10

Discussion

Pulmonary neuroendocrine tumors originate from Kulchitsky cells and they all are malignant9. For many years they had been separated in only two distinct categories of neuroendocrine tumors: carcinoid tumors and small cell carcinomas of the lungs. The classification of these tumors has been extensively and internationally debated. The most recent revision of the working classification system by the World Health Organization (WHO) and the International Association for the Study of Lung Cancer (IASLC)5 classifies them into four histopathological entities with increasing grade of malignancy: low grade typical carcinoid tumors, intermediate grade atypical carcinoid tumors and high grade large cell neuroendocrine carcinomas and small cell carcinomas. Nevertheless, some authors indicate that the terms "typical" and "atypical" carcinoid tumor are misleading and, therefore, suggest a system for classifying pulmonary neuroendocrine tumors into five types: well-differentiated neuroendocrine carcinoma (typical carcinoid), moderately differentiated neuroendocrine carcinoma (low grade atypical carcinoid), poorly differentiated neuroendocrine carcinoma (high grade atypical carcinoid), and undifferentiated large cell neuroendocrine carcinoma and undifferentiated small cell neuroendocrine carcinoma10.

Typical carcinoid tumors comprised 0.32% of all primary pulmonary neoplasms diagnosed by bronchoscopical investigation in the Bronchoscopy Department of the General Regional Hospital "G. Papanikolaou". This occurrence rate is consistent with respective rates reported in the international literature11,12, although in some series higher rates, coming up to 2%, have been observed6,13,14. In our series the male to female ratio indicated a higher prevalence of carcinoid tumors in men; that is in contrast to other series in which either females prevailed13 or tumors were equally distributed between sexes12. Skuladottir et al pointed out that the percentage of all neuroendocrine tumors but small cell carcinoma in the total of primary lung cancer cases is higher in females compared to males12. Specifically, typical carcinoid tumors accounted for 0.21% and 0.31% of the total lung cancer cases in males and females, respectively; the respective rates for atypical carcinoid tumors were 0.22% and 0.35%. In the same study, the mean age of patients with typical or atypical carcinoid tumor was 60 and 64 years, respectively; another study, however, conducted in Israel, indicated that the mean age of patients with carcinoid tumor is 52 years. The mean age in our series of patients was somewhat higher (56.96 years).

The most common presenting symptoms in patients with pulmonary carcinoid tumor include cough, hemoptysis and frequent respiratory infections11,13, which is in agreement with the symptoms recorded in our series. Eight of the 25 patients with histologically confirmed carcinoid tumor were symptom-free (32%); the respective rates in the literature range between 30 and 36%11,13. Carcinoid syndrome has been rarely reported to be associated with a pulmonary carcinoid tumor13,15 and was not observed in any of our patients.

Pulmonary carcinoid tumor incidence rates ranged from 0 in the years 1990, 1992, 1994 and 1997 to 6 in the years 1996 and 1999. The observed differences in inci dence rates are attributed to chance. In contrast to other reports12, no trend for an increase in the incidence of carcinoid tumors was observed during the time frame of the study. Fink et al reviewed a series of 142 patients and reported an incidence rate for pulmonary carcinoid tumors of 7 cases per year in a population of 2.5-3 million people13, whereas our incidence rate data on a comparable population base varied from 0 to 6 cases per year.

Bronchoscopy is a highly efficient method for the diagnosis of carcinoid tumors. In the above-mentioned study by Fink et al, diagnosis was made by bronchoscopy in 51%, by transthoracic fine needle aspiration in 14% and by open thoracotomy in 35% of the patients13. Conley et al reported that biopsy samples obtained during bronchoscopy were diagnostic for carcinoid tumor in all of the patients whom they originated from. Among the 25 patients comprising our series, the presence of a pulmonary carcinoid tumor was macroscopically suspected during bronchoscopy in a remarkable percentage (40%). A definite diagnosis was then made by histological examination of biopsy samples obtained from the total of the patients. Cytologic testing of samples obtained via transbronchial needle aspiration (TBNA) was positive in 62.5% of the patients subjected to this procedure, as opposed to cytology testing of lavage or brushing samples, which was negative in all of the cases in whom it was applied. Consequently, these two methods do not conduct at all to the diagnosis of pulmonary carcinoid tumors.

In our series, carcinoid tumors were located in the left lung in 60% and in the right lung in 40% of the patients, which is exactly the inverse of what Fink et al reported, i.e. that 60% of the cases had carcinoid tumors in the right lung and 40% in the left lung13. In the series of Fink et al as well as in others16, the most common site of origin was the middle lobe, whereas in our series it was the left lower lobe (7 patients, 28%). This finding is consistent with a report from Okike et al who also observed a higher occurrence of carcinoid tumors in the lower lobes in their series17.

As regards bleeding during bronchoscopy, there have been cases of serious bleeding in some series; some of them even required emergency pneumonectomy18. In our series, however, as well as in others13,15 significant bleeding requiring hospital admission was not observed.

In conclusion, typical carcinoid tumors are uncommon primary malignant neoplasms of the lungs usually presenting with cough, hemoptysis and recurrent respiratory infections, whereas carcinoid syndrome rarely occurs. Bronchoscopy is highly effective in the diagnosis of carcinoid tumors, as most of these tumors arise in the major bronchi. Endobronchial biopsy and, to a lesser extent, TBNA are considered as the bronchoscopic diagnostic methods of choice, whereas the risk of bronchoscopy associated bleeding is insignificant.


REFERENCES

1. Sheppard MN. Neuroendocrine differentiation in lung tumors. Thorax 1991; 46:843-850.

2. Engelbreth-Holm J. Benign bronchial adenomas. Acta Chir Scand 1944; 7:21-47.

3. Arrigoni MG, Woolner LB, Bernatz PE. Atypical carcinoid tumors of the lung. Thorac Cardiovasc Surg 1972; 64:413-421.

4. Travis WD, Linnoila RI, Tsokos MG, Hitchcock Cl, Cutler GB Jr, Nieman L, Chrousos G, Pass H, Doppman J. Neuoendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma; an ultrastructural, immumohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 1991; 15:529-553.

5. Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilia E. Histological typing of lung and pleural tumors, 3rd ed. Geneva: World Health Organisation, 1999.

6. Carter D, Eggleston JC. Tumors of the lower respiratory tract. In: Atlas of tumor pathology. Washington: AFIF, 1983 p. 162.

7. Ullman R, Petzmann S, Klemen H, Fraire AE, Hasleton P, Popper HH. The position of pulmonary carcinoids witnin the spectrum of neuroendocrine tumors of the lung and other tissues. Genes Chromosomes Cancer 2002; 34:78-85.

8. Τhomas CF, Tazelaar HD, Jett JR. Typical and atypical pulmonary carcinoids. Chest 2001; 119:1143-1150.

9. Paladugu RR, Benfield JR, Pak HY, Ross RK, Teplitz RL. Bronchopulmonary Kulchitzky cell carcinomas: a new classification for typical and atypical carcinoids. Cancer 1985; 55:1303-1311.

10. Huang Q, Muzitansky A, Mark EJ. Pulmonary neuroendocrine carcinomas. Arch Pathol Lab Med 2002; 126:545-553.

11. Conley YD, Cafocelli AR, Khan JH, Khan MZ, Aburama AF, Boland JP. Bronchial carcinoid tumor: experience over 20 years. Am Surg 1992; 58:670-672.

12. Skuladottir H, Hirsch FR, Hansen HH, Olsen JH. Pulmonary neuroendocrine tumors: Incidence and prognosis of histological subtypes. A population-based study in Denmark. Lung Cancer 2002; 37:127-135.

13. Fink G, Krelbaum T, Yellin A, Bendayan D, Saute M, Glazer M, Kramer MR. Pulmonary carcnoid: presentation, diagnosis and outcome in 142 cases in Israel and review of 640 cases from the literature. Chest 2001; 119:1647-1651.

14. Harpole DH, Feldman JM, Bucchanan S, . Bronchial carcinoid tumors: a retrospective anlysis of 126 patients. Ann Thorac Surg 1992; 54:50-54.

15. Hurt R, Bates M. Carcinoid tumors of the bronchus: a 33 year experience. Thorax 1984; 39:617-623.

16. Ranchod M, Levine GD. Spindle-cell carcinoid tumors of the lung. Am J Surg Pathol 1980;4:315-330.

17. Okike n, Bernatz PE, Wollner LB. Carcinoid tumors of the lung. Ann Thorac Surg 1976; 22:275-275.

18. Todd Tr, Copper JD, Weissberg D, Delarue NC, Pearson FG. Bronchial carcinoid tumors. Twenty years' experience. J Thorac Cardiovasc Surg 1980; 79:532-536.

References