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Revised 27 November 2018
General Aspects - Introduction
From a clinical standpoint, NETs can be divided into two groups: functioning and nonfunctioning. Functioning NETs hypersecrete hormones that cause specific syndromes (e.g. carcinoid syndrome) and they are named according to the hypersecreted hormone (insulinoma, gastrinoma, etc). The symptoms caused by the hypersecretion of these hormones often lead to their discovery. Nonfunctioning tumours, which account for about one-third to one-half of NETs, are not associated with a hypersecreted-related clinical syndrome. They come to attention because of their “mass effect” due to tumour bulk. Metastatic disease is often present at diagnosis. Because they are usually slow growing, NETs are frequently diagnosed late in their course. Those arising in the gut can cause intermittent abdominal discomfort for months or years, often interpreted to be a functional disorder. Later, bowel obstruction occurs secondary to desmoplastic reaction of the mesentery or, less commonly, from the tumour.
A correct histological diagnosis is critical and this requires an adequate biopsy. A distinction should be made between a well-differentiated and a poorly differentiated neoplasm as well as between well differentiated benign endocrine neoplasms, neoplasms of uncertain behavior and malignant neoplasms. This distinction can be aided by several features of the tumour: size, invasion of adjacent tissue or wall, invasion beyond the submucosa, angioinvasion, perineural invasion, a solid organoid structure, presence of necrosis, mitoses per high power field, Ki67 index, loss of chromogranin A immunoreactivity or hormone expression.
Radiologic studies and nuclear imaging play an important role in the diagnosis and management of patients with NETs.
Definitive management includes tumour resection for cure. When this is not achievable, the goals of treatment include symptom control, biochemical control (i.e. controlling excess bioactive peptides), objective tumour control and improving patient quality of life. In recent years, the management has become complex with the introduction of a number of new strategies; hence, a multidisciplinary approach is recommended.
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