Pulmonary neuroendocrine tumors: Incidence and prognosis of histological subtypes. A population-based study in Denmark
Introduction
For many years, only two main categories of pulmonary neuroendocrine tumors, which originate from neuroendocrine cells, were recognized: carcinoid tumors and small-cell lung cancer. The classification of these tumors has been the subject of much discussion in the literature. The most recent World Health Organization (WHO)–International Association for the Study of Lung Cancer (IASLC) classification gives four pathological entities of increasing malignancy: low-grade typical carcinoid, intermediate-grade atypical carcinoind and high-grade large-cell neuroendocrine carcinoma and small-cell carcinoma [1].
Several epidemiological studies have been reported on pulmonary neuroendocrine tumors, which were based on clinical and pathological series. Patients in such series are inevitably selected to a certain degree, and the results do not necessarily reflect the epidemiology of these tumors in general or allow an evaluation of trends in incidence over time. Population-based cancer registries continuously collect information on the incidence and survival rates of malignant diseases over time on all individuals in a defined population, regardless of their prognosis. Not all cancer registries include benign tumors, and some underreporting can be expected in registries that include selected subgroups of benign tumors.
Few reports from population-based cancer registries are available that include specific information on pulmonary neuroendocrine tumors [2], [3], [4], [5]. The largest study was that of Modler and Sandor, who reported on 2084 cases of bronchial carcinoid identified in the Surveillance, Epidemiology, and End Results program in various parts of the USA during three periods between 1950 and 1991 [5]. They found a marked increase in the annual age-adjusted incidence rate over time, which increased in white men from 0.22 to 0.38 per 100 000 inhabitants, in white women from 0.24 to 0.49 per 100 000, in African–American men from 0.15 to 0.32 per 100 000 and in African–American women from 0.06 to 0.38 per 100 000. The authors attributed this increase in incidence to widespread use of fiberoptic bronchoscopy and biopsy during the second half of the study period. A study in England and Scotland that excluded benign carcinoids covered 203 cases of bronchial carcinoid notified to regional cancer registries between 1979 and 1987 [2]. The actual incidence of bronchial carcinoid was not stated, but the authors found increasing numbers with increasing age. In a study in Switzerland of 79 cases of benign and malignant bronchial carcinoid diagnosed between 1974 and 1997, the age-standardized incidence was 0.46 and 0.40 per 100 000 male and female inhabitants, respectively [3].
The objective of the study reported here was to describe the demographics of pulmonary neuroendocrine tumor diagnosed in Denmark in 1978–1997 and to identify differences in the incidence and prognosis of the four histological subtypes of neuroendocrine tumor in a population-based study. Small-cell carcinoma was considered to be a separate category as it is the most clinically distinctive of the main histological subtypes of lung cancer and is far more frequent than the other neuroendocrine tumors. Small-cell carcinoma is diagnosed in one-fifth of all lung cancer patients in Denmark and typical carcinoids, atypical carcinoids and large-cell neuroendocrine carcinomas in less than 1% [6].
Section snippets
Material and methods
Since 1943, the Danish Cancer Registry has issued annual publications of the incidence of cancer and of some benign tumors, including carcinoids, in Denmark. Physicians provided notifications to the Registry voluntarily until 1987, when notification of malignant and related diseases became compulsory. This change of practice did not influence the registered incidence of malignancies in Denmark. Cancer registration is virtually complete owing to the multiple sources used for certification,
Results
During the period 1978–1997, 347 patients received a diagnosis of typical carcinoid (60), atypical carcinoid (192) or large-cell neuroendocrine carcinoma (50), collectively comprising 0.5% of all lung cancer cases in Denmark (Table 1). In the same period, small-cell carcinoma was diagnosed in 11 998 patients, comprising 18% of all lung cancers in the country.
Table 1 shows selected characteristics of patients with pulmonary neuroendocrine tumors by increasing grade of malignancy, from the
Discussion
This study of the demographics, incidence and survival of 12 345 patients with pulmonary neuroendocrine tumors diagnosed in the well-defined population of Denmark in 1978–1997 illustrates the spectrum of these malignancies.
Carcinoid tumors were first described in the early twentieth century and considered to be benign. In 1972, it was recognized that carcinoid tumors consisted of two pathological entities, the indolent typical carcinoid and the more aggressive atypical carcinoid. Finally, in
Conclusions
Our findings support the pathological classification of neuroendocrine tumors into a spectrum ranging from low-grade typical carcinoids, intermediate-grade atypical carcinoids to the two highly malignant pathological entities, large-cell neuroendocrine and small-cell carcinoma. More research is needed to establish the etiological factors in the development of bronchial carcinoids.
Acknowledgements
We thank Ms. A. Meersohn of the Danish Cancer Society for computer assistance.
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