Neuroendocrine tumors and second primary malignancy--a relationship with clinical impact?

BACKGROUND Neuroendocrine tumors (NET) are frequently associated with synchronous or metachronous secondary primary malignancies (SPM). The aim of this study was to report on 14 patients with NET and SPM from a series of 96 patients with NET. PATIENTS AND METHODS Fourteen patients with NET and synchronous or metachronous SPM were reviewed for primary site and characteristics of NET and associated SPMs as well as the outcome of these combined malignancies. RESULTS From 1987 to 2002, 14 (14.6%) out of 96 patients with NET were identified with SPM. The median age of the patients at diagnosis of NET was 69 years (range: 56-86 yrs). There were nine female and five male patients. The localization of NET was: four in appendix, three ileum, two duodenum, one stomach, one jejunum, one pancreatic tail, one rectum and one lung. Five patients had synchronous SPM (two colon cancers with one double colon cancer, one gastric cancer, one bladder cancer, one ovarian cancer) and nine metachronous SPM (two basal cell carcinomas, one colon cancer, two breast cancer, one gastric MALT-lymphoma, one ductal pancreatic adenocarcinoma, one bladder cancer, one hepatocellular carcinoma), three months to five years after diagnosis of NET. Five patients died of metastatic tumor (three SPM: 1, 7, 10 yrs; two NET: 1, 9 yrs), two patients died of other causes (1, 7 yrs), three patients are alive with metastatic tumor (two NET: 5, 6 yrs; one SPM: 10 yrs) while four patients are tumor-free (6 ms, 2, 9, 10 yrs). CONCLUSION NET is associated to a high degree with gastrointestinal and genitourinary SPM. In 5/14 (36%) patients SPM was diagnosed synchronously, while in 8/14 (57%) patients SPM was diagnosed metachronously. In 8/14 patients (57%) primary symptoms were caused by SPM. As a consequence, every NET should be regarded as an index tumor and risk-adapted follow-up with thorough investigation, mainly of the GI and genitourinary tracts, is to be recommended.