Neuroendocrine tumors

Neuroendocrine tumors (NETs) originate from single or clustered neuroendocrine cells, distributed in the gastrointestinal tract, urogenital tract, endocrine, and bronchopulmonary system. NETs account for approximately 2.2% of all malignancies. These slow growing tumors are difficult to localize and often metastatic at diagnosis. Surgery can be curative in only 20% of cases. A syndrome of flushing, diarrhea, sweating, and bronchospasm due to secretion of multiple hormones (carcinoid syndrome) occurs in 20% of patients. Most NETs are sporadic, but occasionally, they may be part of inherited syndromes, known as multiple endocrine neoplasia type 1 and 2 (MEN1 and MEN2). The European Neuroendocrine Tumor Society diagnostic and prognostic stratification criteria are based on histological typing, differentiation, grading, and TNM staging. Immunostaining for the neuroendocrine markers synaptophysin and chromogranin and for the proliferation marker Ki67/MIB1 is mandatory, while immunostaining for hormones, receptors, and other markers is optional. The grading proposal stratifies tumors in G1 (1 mitotic count/10 HPF, Ki67 ≤ 2%), G2 (2–20 mitotic counts/10 HPF, Ki67: 3–20%), and G3 (mitotic count >20/10 HPF, Ki67 > 20%). The tumor grading, together with histopathology type and staging, reflects the potential metastatic spread and, therefore, has an impact on the therapy options (surgery, biotherapy, and chemotherapy). CT, MRI, and radionuclide imaging of somatostatin receptor expression or catecholamine uptake is helpful to localize the lesions. Somatostatin receptor imaging utilizes111In-pentetreotide (OctreoScan®), or68Ga-octreotide, while catecholamine uptake is usually imaged with123 I-metaiodobenzylguanidine (131I-MIBG). [18F]FDG PET/CT is less useful than somatostatin/catecholamine receptor imaging. Main indications for radionuclide imaging of NETs are for localization (also as a guide to surgery), for staging, for assessing response to therapy, and for selecting patients for possible therapy with radiolabeled somatostatin analogues or with131I-MIBG. Peptide receptor radionuclide therapy (PRRT) uses high doses of radiolabeled peptides to treat unresectable or metastasized NETs.