Carcinoids and their variant endocrinomas. An analysis of 11842 reported cases.

Endocrinocarcinomas consisting of carcinoids and their variant carcinomas with endocrine features are neoplasms of relatively rare occurrence but have often been reported in many countries and regions of the world. The largest series of 13715 cases from the United States was published in 2003. A total number of 11842 reported cases of endocrinocarcinomas from the Niigata Registry were divided into two groups: the carcinoid group (n = 10804) with the typical (n = 9430) and the atypical (n = 1374) series and the variant group (n = 1038). These cases came from 64 countries and reports were written in 17 different languages. They were statistically evaluated for comparison between the two groups or series in various aspects, including gender and age, tumor-size, rate of metastases, immunohistochemistry, and survival after curative resection. In the carcinoid group, more frequent cases were found in the digestive system (64.2%) than in the extradigestive system (35.8%). Organ distribution of carcinoid cases exhibited the most frequent site to be the respiratory system (19.8%), followed by the rectum (15.0%), jejunoileum (12.0%), stomach (11.4%), appendix (9.6%) and duodenum (8.3%). An extremely small number of cases (less than 0.7%) were found in the middle ear, testicle, kidney, and several others. The highest rate of metastases was noted in the ileocecum (75.3%), followed by the jejunoileum (65.2%), pancreas (64.2%), and larynx (61.4%). Small carcinoids with invasion confined to the mucosa and submucosa, indicated an unexpectedly high metastasis rate of 13.8% for lesions 20 mm or less, and 10.0% for those 10 mm or less, and 6.1% for those 5 mm or less. The carcinoid syndrome was found to occur at the rate of 7.7% of overall 11057 cases reported between 1953 and 2002, with the highest incidence of 28.8% in the 5-year period between 1963 and 1967, gradually decreasing down to 3.7% in the last 5 years. The 5-year survival rate after curative resection of lesions showed a significant difference between the carcinoid group and the variant group (82.0% vs 41.8%: P < 0.0001). In the former group, the 5-year survival rate showed a significant difference between cases with or without metastases (61.4% vs 95.7%: P < 0.0001). In the latter group, the 5-year survival rate was 74.5% for cases without metastases and 24.1% for those with metastases (P < 0.0001). The highest 5-year survival rate in the carcinoid group was noted in the ovary (93.6%), followed by the liver (92.6%), the respiratory system (89.7%), the appendix (89.5%), and the rectum (85.4%), while poor 5-year survival rates were recorded in the pancreas (43.2%), the esophagus (43.5%) and the larynx (47.6%). It should be emphasized that there is a significant statistical difference in many aspects between the carcinoid group and the variant group. The present study confirms that the malignant nature of these endocrine tumors is well reflected in their metastasis rates, even in small lesions with submucosal invasion, resulting in the 5-year survival rates of a significant difference among the groups or series.