Markers Symptoms from secreted hormones may prompt measurement of the corresponding hormones in the blood or their associated urinary products, for initial diagnosis or to assess the interval change in the tumor. Secretory activity of the tumor cells is sometimes dissimilar to the tissue immunoreactivity to particular hormones. Synaptophysin immunohistochemistry of<unk> , staining positively. Given the diverse secretory activity of<unk> s there are many other potential markers, but a limited panel is usually sufficient for clinical purposes. Aside from the hormones of secretory tumors, the most important markers are: * chromogranin A (CgA), present in 99% of metastatic carcinoid tumors * urine 5-hydroxyindoleacetic acid (5-HIAA) * neuron-specific enolase (NSE, gamma-gamma dimer) * synaptophysin (P38) Newer markers include N-terminally truncated variant of Hsp70 is present in<unk> s but absent in normal pancreatic islets. High levels of CDX2, a homeobox gene product essential for intestinal development and differentiation, are seen in intestinal<unk> s.<unk>  secretory protein-55, a member of the chromogranin family, is seen in pancreatic endocrine tumors but not intestinal<unk> s. Imaging For morphological imaging, CT-scans, MRIs, sonography (ultrasound), and endoscopy (including endoscopic ultrasound) are commonly used. Multiphase CT and MRI are typically used both for diagnostics and for evaluation of therapy. The multiphase CT should be performed before and after an intravenous injection of an iodine-based contrast agent, both in the late arterial phase and in the portal venous phase (triple-phase study). While MRI is generally superior to CT, both for detection of the primary tumor and for evaluation of metastases, CECT is more widely available, even at academic institutions. Therefore, multiphase CT is often the modality of choice. Advances in nuclear medicine imaging, also known as molecular imaging, have improved diagnostic and treatment paradigms in patients with<unk> s. This is because of its ability to not only identify sites of disease but also characterize them.<unk> rs express somatostatin receptors providing a unique target for imaging. Octreotide is a synthetic modification of somatostatin with a longer half-life. OctreoScan, also called somatostatin receptor scintigraphy (SRS or SSRS), utilizes intravenously administered octreotide that is chemically bound to a radioactive substance, often indium-111, to detect larger lesions with tumor cells that are avid for octreotide. Somatostatin receptor imaging can now be performed with positron emission tomography (PET) which offers higher resolution, three-dimensional and more rapid imaging. Gallium-68 receptor PET-CT is much more accurate than an Octreotide scan. Thus, octreotide scanning for<unk>  tumors is being increasingly replaced by gallium-68 DOTATOC scan. Imaging with fluorine-18 fluorodeoxyglucose (FDG) PET may be valuable to image some<unk> s. This scan is performed by injected radioactive sugar intravenously. Tumors that grow more quickly use more sugar. Using this scan, the aggressiveness of the tumor can be assessed. However,<unk> s are often slow growing and indolent, and these do not show well on FDG-PET. Functional imaging with gallium-labelled somatostatin analog and 18F-FDG PET tracers ensures better staging and prognostication of<unk>  neoplasms. The combination of somatostatin receptor and FDG PET imaging is able to quantify somatostatin receptor cell surface (SSTR) expression and glycolytic metabolism, respectively. The ability to perform this as a whole body study is highlighting the limitations of relying on histopathology obtained from a single site. This is enabling better selection of the most appropriate therapy for an individual patient. Histopathology Small intestinal<unk>  at bottom third of image, showing the typical intramural (within the wall) location, and overlying intact epithelium. H&E stain Features in common<unk> s, despite differing embryological origin, have common phenotypic characteristics.<unk> s show tissue immunoreactivity for markers of<unk>  differentiation (pan-neuroendocrine tissue markers) and may secrete various peptides and hormones. There is a lengthy list of potential markers in<unk> s; several reviews provide assistance in understanding these markers. Widely used<unk>  tissue markers are various chromogranins, synaptophysin and PGP9.5. Neuron-specific enolase (NSE) is less specific. The nuclear<unk>  marker insulinoma-associated protein-1 (INSM1) has proven to be sensitive as well as highly specific for<unk>  differentiation.<unk> s are often small, yellow or tan masses, often located in the submucosa or more deeply intramurally, and they can be very firm due to an accompanying intense desmoplastic reaction. The overlying mucosa may be either intact or ulcerated. Some GEP-NETs invade deeply to involve the mesentery. Histologically,<unk> s are an example of "small blue cell tumors," showing uniform cells which have a round to oval stippled nucleus and scant, pink granular cytoplasm. The cells may align variously in islands, glands or sheets. High power examination shows bland cytopathology. Electron microscopy can identify secretory granules. There is usually minimal pleomorphism but less commonly there can be anaplasia, mitotic activity, and necrosis. Some<unk>  cells possess especially strong hormone receptors, such as somatostatin receptors and uptake hormones strongly. This avidity can assist in diagnosis and may make some tumors vulnerable to hormone targeted therapies. Argentaffin and hormone secretion<unk> s from a particular anatomical origin often show similar behavior as a group, such as the foregut (which conceptually includes pancreas, and even thymus, airway and lung<unk> s), midgut and hindgut; individual tumors within these sites can differ from these group benchmarks: * Foregut<unk> s are argentaffin negative. Despite low serotonin content, they often secrete 5-hydroxytryptophan (5-HTP), histamine, and several polypeptide hormones. There may be associated atypical carcinoid syndrome, acromegaly, Cushing disease, other endocrine disorders, telangiectasia, or hypertrophy of the skin in the face and upper neck. These tumors can metastasize to bone. * Midgut<unk> s are argentaffin positive, can produce high levels of serotonin 5-hydroxytryptamine (5-HT), kinins, prostaglandins, substance P (SP), and other vasoactive peptides, and sometimes produce corticotropic hormone (previously adrenocorticotropic hormone ACTH). Bone metastasis is uncommon. * Hindgut<unk> s are argentaffin negative and rarely secrete 5-HT, 5-HTP, or any other vasoactive peptides. Bone metastases are not uncommon.
Neuroendocrine tumor
Pituitary adenoma
Metastatic insulinoma
Insulinoma
Glucagonoma
Granular cell tumor
Endocrine gland neoplasm
Glial tumor