SMALL INTESTINAL NEUROENDOCRINAL TUMORS

Abstract

The rising incidence of SI-NET might be explained by a combination of improved diagnostic techniques, improved reporting to different registries, and possibly also a true rise in SI-NET incidence. Another imaginable explanation for the increase in clinical incidence might be a greater tendency for metastatic spread during the latter decades in previously dormant SI-NET. Neuroendocrine tumors of the GI tract arise from the neuroendocrine cells of the GIT mucosa, which arise from the fetal nervous system. While most of the epithelial neuroendocrine cells reside in endocrine organs, such as the thyroid and adrenal glands, a large number of them are present in, and have essential roles in the function of, the mucosa by the production and secretion of a variety of peptide hormones. Expression of all of these markers is dependent on the cell and site of origin but also on the degree of differentiation of the tumor. For example, high-grade tumors may have decreased or absent staining. They also should demonstrate epithelial differentiation by the expression of keratins, particularly low-molecular-weight keratins. Identification of the exact site of origin is difficult, but production of specific peptide hormones can give clues. CDX-2 for intestinal origin versus TTF-1 (thyroid transcription factor 1) for lung/thyroid origin can be of use in metastatic lesions. Chromosomal gains, or losses, or both have been described in small intestinal NETs using LOH analysis, CGH, and array CGH analyses. Several studies have not been able to correlate development of carcinoid tumors with theMEN-1 gene mutation. Genetic events leading to development of ileal carcinoid tumors are grossly unknown. Previous studies have shown that deletions on 18q21-qter occur in sporadic tumors. SI-NETs originate from the EC-cells in the small intestinal mucosa. The primary tumor is often small but SI-NETs are irrespective of primary tumor size, nonetheless in a majority of cases spread to mesenteric lymph nodes at time of diagnosis and many patients also display liver metastases. To diagnose the patient, to assess disease dissemination (staging), to evaluate treatment effect and to investigate complications due to treatment or from the disease itself. Several different imaging techniques can be used and the following is a survey of the most common imaging modalities with focus on evaluation of disease dissemination and treatment effect (mainly RFA). Most studies regarding liver metastases are of mixed NET populations. Imaging of loco regional tumor, extra-hepatic metastases, liver metastases and finally imaging after RFA will be discussed. All patients with small intestinal NETs should be treated peri-operatively with octreotide in order to prevent carcinoid crises