Biology and Treatment of Metastatic Gastrointestinal Neuroendocrine Tumors

摘要

Neuroendocrine malignancies of the gastroenteropancreatic axis include carcinoid and pancreatic endocrine tumors. These heterogeneous neoplasms arise from the enterochromaffin cells of the gastrointestinal tract and the islet cells of the pancreas. Histologically, most well-differentiated endocrine tumors consist of small, round, monomorphic cells, arranged in islands or trabeculae, with a distinct “salt-and-pepper” pattern of nuclear chromatin. Chromogranin and synaptophysin are useful as immunohistochemical markers of neuroendocrine differentiation. Other common features include the capacity to secrete peptide hormones and biogenic amines. A relatively indolent growth rate is characteristic of most gastrointestinal neuroendocrine tumors, with the exception of poorly differentiated tumors which are usually aggressive. Treatment strategies are designed to limit tumor progression and palliate hormonal syndromes. This article reviews the diverse biologic characteristics of gastrointestinal neuroendocrine tumors and current treatment options for metastatic disease. Neuroendocrine malignancies of the gastroenteropancreatic axis include carcinoid and pancreatic endocrine tumors (PETs). Metastatic gastroenteropancreatic neuroendocrine tumors are typically indolent malignancies characterized by a propensity to secrete hormones and vasoactive substances, resulting in characteristic clinical syndromes. Their clinical behavior varies based on site of tumor origin and histologic differentiation, which appear to be the most important prognostic factors in the natural history of metastatic carcinoid tumors. Although most gastrointestinal neuroendocrine tumors (NETs) are characterized by a relatively slow growth rate, poorly differentiated (PD) neuroendocrine carcinomas are highly aggressive malignancies. Survival of patients with metastatic carcinoid and pancreatic endocrine tumors appears to have improved over the years. Treatment strategies largely aim to limit tumor progression and palliate hormonal syndromes. The distinct biologic characteristics of gastrointestinal neuroendocrine tumors and current treatment options for metastatic disease are reviewed herein.