Neuroendocrine tumor ( NETs ) is a neoplasm that arises from endocrine cells (hormonal) and nervous system. Many are benign, while some are malignant. They occur most often in the intestines, where they are often called carcinoid tumors, but they are also found in the pancreas, lungs and whole body.
Although there are many types of NET, they are treated as a group of tissues because these neoplasm cells share a common feature, as they look similar, have special secretory grains, and often produce biogenic amines and polypeptide hormones.
Video Neuroendocrine tumor
Classification
WHO
The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize tumor rates rather than the origin of anatomy:
- well-differentiated neuroendocrine tumors, subsequently subdivided into benign tumors and those with uncertain behavior
- undifferentiated (low degrees) neuroendocrine carcinoma with low-grade malignant behavior
- undifferentiated (high-grade) neuroendocrine carcinoma, which is a large cell neuroendocrine and small cell carcinoma.
In addition, the WHO scheme recognizes a mixed tumor with neuroendocrine and epithelial carcinoma features, such as goblet cell cancer, a rare gastrointestinal tract tumor.
Placing a given tumor into one of the categories depends on a well-defined histologic picture: size, lymphovascular invasion, mitotic number, Ki-67 labeling index, adjacent organ invasion, presence of metastases and whether they produce hormones.
Anatomical distribution
Traditionally, neuroendocrine tumors have been classified by their anatomical site of origin. NET can appear in different areas of the body, and most often located in the intestines, pancreas or lungs. Different types of cells that can cause NETs are present in the endocrine glands and are also distributed diffusely throughout the body, most often Kulchitsky cells or similar enterochromaffin-like cells, which are relatively more common in gastrointestinal and pulmonary systems.
NET includes certain tumors of the gastrointestinal tract and pancreatic islet cells, certain thymus and lung tumors, and medullary carcinoma of the parafolicular cells of the thyroid. Tumors with similar cellular characteristics in the pituitary, parathyroid, and adrenomedullary glands are sometimes included or excreted.
In the broad category of neuroendocrine tumors there are many different types of tumors: this outline is presented to facilitate the retrieval of information. Neuroendocrine tumors are rare in many of these areas, and often represent only a small part of the tumor or cancer in this location.
- Pituitary gland: Neuroendocrine heel from the anterior pituitary
- Thyroid gland: Neuroendocrine thyroid tumor, especially medullary carcinoma
- Parathyroid tumor
- Thymus tumor and mediastinal carcinoid tumor
- Pulmonary neuroendocrine tumor
- bronchus
- pulmonary carcinoid tumor: typical carcinoid (TC; low level); atypical carcinoid (AC; middle class)
- small cell lung cancer (SCLC)
- large cell lung neuroendocrine carcinoma (LCNEC)
- Extraculmonary small cell carcinoma (ESCC or EPSCC) GEP-NET foregut (forepse tumor may conceptually include not only the NETs of the stomach and the proximal duodenum, but also the pancreas, and even thymus, lung and bronchial)
- Pancreatic endocrine tumor (if considered separate from GEP-NET foregut)
- Midgut GEP-NET (from the distal portion of the 2nd part of the duodenum to the two thirds of the proximal portion of the transverse colon)
- attachments, including well-differentiated NETs (benign); Well-differentiated NET (uncertain malignant potential); well-differentiated neuroendocrine carcinoma (with low malignant potential); mixed exocrine-neuroendocrine carcinoma (goblet cell carcinoma, also called adenocarcinoid and adenocarcinoid mucus)
- Hindgut GEP-NET
- Schwannoma
- paraganglioma
- neuroblastoma
- urinary tract carcinoid tumors and neuroendocrine carcinoma
- ovaries
- neuroendocrine tumors of the cervix
- testis
- multiple endocrine neoplasia type 1 (MEN1)
- multiple endocrine neoplasia type 2 (MEN2)
- von Hippel-Lindau (VHL) disease
- type 1 neurofibromatosis
- tuberous sclerosis
- The Carney Complex
Grading
Neuroendocrine lesions are measured histologically according to cell proliferation markers, not cellular polymorphisms. The following grading scheme is currently recommended for all gastroenteropancreatic neuroendocrine neoplasms by the World Health Organization:
If the number of mitosis and ki67 do not match, then the number that gives the highest value is used.
Neoplasm neo-endocrine G1 and G2 are called neuroendocrine tumors (NET) - formerly called carcinoid tumors. Neoplasm G3 is called neuroendocrine carcinoma (NEC).
It has been suggested that the current G3 category is further separated into histologically differentiated and differentiated neoplasms to better reflect the prognosis.
Staging
There is currently no single staging system for all neuroendocrine neoplasms. Well-differentiated lesions generally have their own staging systems based on anatomical locations, whereas poorly differentiated and blended lesions are staged as the carcinoma of the site. For example, NEC gastric and adenoneuroendocrine cancer mixtures staged as a major carcinoma of the stomach.
TNM staging of neuroendocrine tumors Class 1 and Class 2 gastroenteropancreatic are as follows:
Maps Neuroendocrine tumor
Signs and symptoms
gastroenteropancreatic neuroendocrine tumors (GEP-NET)
Conceptually, there are two main types of NET in this category: emerging from the gastrointestinal (GI) system and emerging from the pancreas. In use, the term "carcinoid" has often been applied to both, although sometimes it is limited to NETs of GI origin (as herein), or alternatives to tumors that secrete functional hormones or polypeptides associated with clinical symptoms, as discussed.
Carcinoid tumor
Carcinoid most commonly affects the small intestine, especially ileum, and is the most common malignancy of the appendix. Many carcinoids are asymptomatic and found only after surgery for unrelated causes. These accidental carcinoids are common; one study found that one in ten people had it. Many tumors cause no symptoms even when they have metastasized. Other tumors even if very small can produce adverse effects by secreting hormones.
Ten percent (10 percent) or less of carcinoids, especially some midgut carcinoids, secrete excess hormone levels, especially serotonin (5-HT) or P substance, causing a constellation of symptoms called carcinoid syndrome:
- redness
- diarrhea
- asthma or wheezing
- congestive heart failure (CHF)
- abdominal cramp
- peripheral edema
- heart palpitation
Carcinoid crisis with deep rinsing, bronchospasm, tachycardia, and blood pressure that fluctuate widely and quickly can occur when large amounts of hormone are secreted acutely, which is sometimes triggered by factors such as diet, alcohol, surgical chemotherapy, embolization or ablation therapy radio frequency.
Chronic exposure to high levels of serotonin causes thickening of the heart valves, especially the tricuspid and pulmonary valves, and in the long run can cause congestive heart failure. However, valve replacement is rarely needed. The excessive flow of serotonin can lead to tryptophan thinning leading to a deficiency of niacin, and thus pellagra, which is associated with dermatitis, dementia, and diarrhea. Many other hormones can be secreted by some of these tumors, most often growth hormones that can cause acromegaly, or cortisol, which can cause Cushing's syndrome.
Occasionally, bleeding or mass tumor effects are symptoms that appear. Intestinal obstruction may occur, sometimes due to the fibrosing effect of the NET secretory product with intense desmoplastic reactions at the site of the tumor, or mesenterium.
Pancreatic neuroendocrine tumor
Pancreatic neuroendocrine tumors (Pannet) are often referred to as "islet cell tumors", or "pancreatic endocrine tumors"
The PanNet denomination is in line with current WHO guidelines. Historically, PanNet has also been referred to by various terms, and is still often called "islet cell tumor" or "pancreatic endocrine tumor". comes from the pancreas. Pannet is quite different from the usual form of pancreatic cancer, adenocarcinoma, which appears in the exocrine pancreas. Approximately 95 percent of pancreatic tumors are adenocarcinoma; only 1 or 2% of clinically significant pancreatic neoplasms are GEP-Net.
Good or moderated differentiated PanNET is sometimes called islet cell tumor; neuroendocrine cancer (NEC) (identical to islet cell carcinoma) is more aggressive. Up to 60% of non-secretory or nonfunctional Pannets, which do not secrete, or quantities or types of products such as pancreatic polypeptides (PPOMs), chromogranine A, and neurotensin do not cause clinical syndromes, although blood levels may be high. Functional tumors are often classified by the most powerful hormone secreted by pancreatic neuroendocrine tumors, as discussed in the main article.
More
In addition to the two main categories of GEP-NET, there are more rare forms of neuroendocrine tumors that appear anywhere in the body, including inside the lungs, thymus and parathyroid. Carcinoid bronchi may cause airway obstruction, pneumonia, pleuritis, difficulty breathing, cough, and haemoptysis, or may be associated with weakness, nausea, weight loss, night sweats, neuralgia, and Cushing's syndrome. Some have no symptoms.
Animal neuroendocrine tumors include neuroendocrine liver cancer in dogs, and devil face tumor disease in Tasmanian devils.
familial syndrome
Most NET pancreas is sporadic. However, neuroendocrine tumors can be seen in some of the inherited family syndromes, including:
- multiple endocrine neoplasia type 1 (MEN1)
- multiple endocrine neoplasia type 2 (MEN2)
- von Hippel-Lindau (VHL) disease
- type 1 neurofibromatosis
- tuberous sclerosis
- The Carney Complex
In view of this association, recommendations in the NET include family history evaluation, evaluation for a second tumor, and under certain circumstances to test germline mutations such as for MEN1.
Pathophysiology
NET is believed to be derived from a variety of neuroendocrine cells that function normally to serve in the neuroendocrine interface. Neuroendocrine cells present not only in the endocrine glands throughout the body that produce hormones, but are found in all body tissues.
Diagnosis
Marker
The symptoms of secreted hormones can encourage the measurement of appropriate hormones in their blood or associated urinary products, for early diagnosis or to assess changes in tumor intervals. The secretory activity of tumor cells is sometimes different from tissue immunoreactivity for certain hormones.
Given the variety of NET secretory activities, there are many other potential markers, but the limited panel is usually sufficient for clinical purposes. Apart from secretory tumor hormones, the most important markers are:
- chromogranine A (CgA), present in 99% metastatic carcinoid tumor
- urine 5-hydroxyindoleacetic acid (5-HIAA)
- the specific enelase neuron (NSE, gamma-gamma dimer)
- synaptophysin (P38)
New markers include N-terminally truncated variants of Hsp70 present in NETs but none in normal pancreatic islets. High levels of CDX2, a homeobox gene product that is essential for bowel development and differentiation, is seen in intestinal NET. Neuroendocrine secretory protein-55, a member of the chromogranine family, is seen in pancreatic endocrine tumors but not gut NETs.
Imaging
CT-scan, MRI, sonography (ultrasound), and endoscopy (including ultrasound endoscopy) are common diagnostic tools. CT-scans using contrast media can detect 95 percent of tumors over 3 cm, but generally not tumors below 1 cm.
Advances in nuclear medicine imaging, also known as molecular imaging, have enhanced the diagnostic and treatment paradigm in patients with neuroendocrine tumors. This is because of its ability to not only identify disease sites but also their characteristics. Neuronocrine tumors express somatostatin receptors that provide unique targets for imaging. Octreotide is a synthetic modification of somatostatin with a longer half-life. OctreoScan, also called somatostatin receptor scintigraphy (SRS or SSRS), uses chemically-bound intravenous octotides with radioactive substances, often indium-111, to detect larger lesions with diluted tumor cells for octerotides.
Somatostatin receptor imaging can now be performed with positron emission tomography (PET) that offers higher resolution, three-dimensional imaging and faster. Gallium-68 receptor PET-CT is much more accurate than OctreoScan.
Imaging with fluorine-18 fluorodeoxyglucose (FDG) PET may be useful for describing some neuroendocrine tumors. This scan is done by intravenously injecting radioactive sugars. Tumors that grow faster use more sugar. By using this scan, tumor aggressiveness can be assessed.
The combination of somatostatin receptors and PET FDG imaging is capable of measuring the surface of somatostatin receptor cell surface (SSTR) and glycolytic metabolism. The ability to do this as a whole-body study highlights the limitations of relying on histopathology obtained from one site. This allows a more precise selection of the most appropriate therapy for a patient.
Histopathology
Same feature
Neuroendocrine tumors, although distinct from embryology, have general phenotypic characteristics. NET shows tissue immunoreactivity for markers of neuroendocrine differentiation (a marker of pan-neuroendocrine tissue) and may excrete various peptides and hormones. There is a long list of potential markers on neuroendocrine tumors; some reviews provide help in understanding these markers. Widely used neuroendocrine tissue markers of various chromogranins, synaptophysin and PGP9.5. Specific enolase neurons (NSE) are less specific.
NET is often small, yellow or tan mass, often located in the submucosa or deeper intramural, and they can be very firm because of the intense desmoplastic reaction that accompanies it. The mucosa on it can be intact or ulcerated. Some GEP-NET attacks in depth to involve mesentery. Histologically, NET is an example of a "small blue cell tumor," showing uniform cells that have rounded nuclei to oval and a small pink granular cytoplasm. These cells may line up diversely on the island, glands or sheets. High power check shows cytopathology bland. Electron microscopy can identify secretory granules. There is usually minimal pleomorphism but there is less rarely anaplasia, mitotic activity, and necrosis.
Some neuroendocrine tumor cells have very strong hormone receptors, such as somatostatin receptors and take hormones strongly. This oddity can help in diagnosis and can make some tumors susceptible to hormone-targeted therapy.
Argentaffin and hormone secretions
NET from a particular anatomic origin often exhibits the same behavior as a group, such as foregut (which conceptually includes the pancreas, and even the thymus, respiratory and lung nets), midgut and hindgut; Individual tumors within these sites may differ from this group's benchmarks:
- Net Foregut is a negative argentaffin. Although serotonin levels are low, they often excrete 5-hydroxytryptophan (5-HTP), histamine, and some polypeptide hormones. There may be associated atypical carcinoid syndrome, acromegaly, Cushing's disease, other endocrine disorders, telangiectasia, or skin hypertrophy on the face and upper neck. These tumors can metastasize to the bone.
- Midgut NETs argentaffin is positive, can produce serotonin 5-hydroxytryptamine (5-HT), quinine, prostaglandin, P (SP), and other vasoactive peptides, and sometimes produce corticotropic hormone (previous adrenocorticotropic hormone [ACTH] ). Bone metastasis is rare.
- Hindgut NETs are negative argentaffin and rarely secrete 5-HT, 5-HTP, or other vasoactive peptides. Bone metastasis is not uncommon.
Treatment
Some problems help determine the proper treatment for neuroendocrine tumors, including its location, invasion, hormonal secretion, and metastasis. Treatment may be aimed at curing diseases or relieving symptoms (palliation). Observation may be appropriate for low-grade neuroendocrine tumors that do not work. If the tumor develops locally or has metastasized, but the growth is slow, symptomatic relief of the treatment is often preferred over the challenging surgery immediately.
Middle and high-grade tumors (noncarcinoids) are usually best handled by early interventions (active therapy) rather than observation (wait-and-see approach).
Treatments have improved over the last few decades, and the results have improved. In malignant carcinoid tumors with carcinoid syndrome, the median survival has increased from two years to more than eight years.
Detailed guidelines for managing neuroendocrine tumors are available from ESMO, NCCN and UK panels. NCI has guidelines for several categories of NET: pancreatic islet cell tumor, gastrointestinal carcinoid, Merkel cell tumor and pheochromocytoma/paraganglioma.
Surgery
Even if the tumor has developed and metastasizes, making curative surgery improper, surgery often has a role in neuroendocrine cancer to relieve symptoms and the likelihood of increased lifespan.
Cholecystectomy is recommended if there is long-term treatment consideration with somatostatin analogues.
Symptomatic Help
In secretor tumors, analog somatostatin is given subcutaneous or intramuscular relief of symptoms by blocking the release of hormones. A consensus review has reported the use of analog somatostatin for GEP-Net.
These drugs may also anatomically stabilize or shrink tumors, as suggested by the PROMID study (a randomized, placebo-controlled prospective study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDGut tumors): at least in the NET subset, average was 14.3 months compared with 6 months for placebo.
The CLARINET study (a randomized, double-blind, placebo-controlled study on the antiproliferative effects of lanreotide in patients with enteropancreatic neuroendocrine tumors) further demonstrates the antiproliferative potential of lanreotide, analog somatostatin and FDA treatment recently approved for GEP-NETS. In this study, lanreotide showed statistically significant improvement in progression-free survival, meeting its primary endpoint. Diseases in sixty-five percent of patients treated with lanreotide in the study did not develop or cause death at 96 weeks, the same was true in 33% of patients with placebo. This represents a 53% reduction in the risk of developing disease or death with lanreotide based on a hazard ratio of 0.47.
Lanreotide is the first and only FDA-approved antitumor therapy that demonstrates the statistically significant development-free survival advantage in the combined population of patients with GEP-NETS.
Other drugs that block the effects of certain secretions can sometimes relieve symptoms.
Chemotherapy
Interferon is sometimes used to treat GEP-Net. Its effectiveness is somewhat uncertain, but low doses can be titrated in everyone, often considering the effect on the number of blood leukocytes; Interferon is often used in combination with other agents, especially analog somatostatin such as octreotide.
Gastrointestinal neuroendocrine tumor
Most gastrointestinal carcinoid tumors tend to not respond to chemotherapeutic agents, suggesting a 10 to 20% response rate that is usually less than 6 months. Combining chemotherapy drugs usually does not show significant improvement that shows a 25 to 35% response rate that is usually less than 9 months.
The exception is a poorly differentiated (high or anaplastic) metastasis disease, in which cisplatin with etoposide can be used and a negative tumor of Somatostatin Receptor Scintigraphy (SSRS) that has a response rate greater than 70% compared with 10% in highly positive SRSS carcinoids. tumor.
PanNet
Targeted therapy with everolimus (Afinitor) and sunitinib (Sutent) are approved by the FDA at non-operable, locally advanced or metastatic PanNETs. Some PanNETs are more responsive to chemotherapy than gastroenteric carcinoid tumors. Some agents have demonstrated activity and incorporating several drugs, especially doxorubicin with streptozocin and fluorouracil (5-FU or f5U), often more effectively. Although slightly effective in well-differentiated PET, cisplatin with active etoposide in poorly differentiated neuroendocrine cancer (PDNECs).
radionuclide therapy
Peptide receptor radionuclide therapy (PRRT) is a type of radioisotope (RIT) therapy in which a peptide or conjugated hormone to a radionuclide or radioligand is given intravenously, peptide or neuroamine hormones which have previously shown good dosage of tracer absorbance, using the Somatostatin imaging receptor as described in on. This type of radiotherapy is systemic therapy and will have a positive effect on somatostatin. The peptide receptors may be bound to luteium-177, yttrium-90, indium-111 and other isotopes including alpha emitters. This is a highly targeted and effective therapy with minimal side effects on tumors with high levels of somatostatin cell surface expression, since radiation is absorbed at the site of the tumor, or excreted in the urine. Radioactive-labeled hormones enter tumor cells that, together with nearby cells, are damaged by radiation attached. Not all cells are killed instantly; cell death can last up to two years.
PRRT was originally used for low-level NET. It is also very useful in more aggressive NET like Grade 2 and 3 Net as long as they show high retrieval on SSTR imaging to suggest benefits.
Hepatic artery
Metastases to the liver can be treated with some type of liver artery treatment based on the observation that tumor cells get almost all of their nutrients from the hepatic arteries, while normal liver cells get about 70-80 percent of their nutrients and 50% of their oxygen supply from the veins portals, and thus can survive with hepatic arteries that are effectively blocked.
- Hepatic artery embolization (HAE) blocks blood flow to the tumor, achieving significant tumor shrinkage in more than 80%. In hepatic arterial chemotherapy, chemotherapeutic agents are administered to the hepatic artery, often with a stable infusion for hours or even days. Compared with systemic chemotherapy, a higher proportion of chemotherapy agents (in theory) are sent to lesions in the liver.
- Chemoembolization of the hepatic artery (HACE), sometimes called transarterial chemoembolization (TACE), combines hepatic artery embolization with hepatic artery hepatocyte chemoinfusion: embospheres bound to chemotherapeutic agents, injected into the hepatic artery, downstream capillaries. The ball not only blocks blood flow to the lesions, but by stopping the chemotherapy agents around the lesions, they provide much better targeting targeting than chemoinfusion. Selective internal radiation therapy (SIRT) for neuroendocrine metastases to the liver provides radioactive microsphere therapy (RMT) with injections into the hepatic artery, lodging (as with HAE and HACE) downstream of the capillaries. In contrast to radiotherapy given hormones, the lesions do not need overexpress peptide receptors. Mechanical targeting radiates from yttrium microspheres selectively labeled to tumors without overly affecting the normal liver. This type of treatment is FDA approved for liver metastases secondary to colorectal colorectal and is being investigated for the treatment of other liver malignancies, including neuroendocrine malignancies.
Other therapies
Radiofrequency ablation (RFA) is used when the patient has relatively little metastasis. In RFA, the needle is inserted into the center of the lesion and is currently applied to generate heat; tumor cells are killed by cooking.
Cryoablation is similar to RFA; the endothermic substance is injected into the tumor to kill by freezing. Cryoablation has been less successful for GEP-NETs than RFA.
AdVince, a type of gene therapy using genetically modified oncolytic adenovirus and supported by the iCancer crowdfunding campaign used in Phase 1 trials against NET in 2016.
Incident
Although estimates vary, the annual incidence of clinically significant neuroendocrine tumors is about 2.5-5 per 100,000; two thirds are carcinoid tumors and one-third are other NETs.
Prevalence has been estimated as 35 per 100,000, and may be much higher if clinically silent tumors are included. A study of pancreatic autopsy in people dying of unrelated causes found a very high incidence of asymptomatic JB. Routine microscopic studies of three pancreatic random sections found NETs in 1.6%, and some parts identified NETs in 10%. Because diagnostic imaging increases sensitivity, such as endoscopic ultrasonography, is very small, clinically insignificant NETS can be accidentally discovered; not associated with symptoms, such neoplasms may not require excision surgery.
History
Small bowel neuroendocrine tumors were first distinguished from other tumors in 1907. They were named carcinoid tumors because their slow growth was considered "cancer-like" rather than completely cancerous.
However, in 1938, it was known that some small bowel tumors could become malignant. Regardless of the differences between these two original categories, and further complexity due to the inclusion of NETs of pancreas and other pulmonary origin, all NET is sometimes (incorrectly) incorporated into the term "carcinoid".
Enterochromaffin cells, which give rise to carcinoid tumors, were identified in 1897 by Nikolai Kulchitsky and their serotonin secretion was established in 1953 when the "rinsing" effects of serotonin have been clinically recognized. Carcinoid heart disease was identified in 1952, and carcinoid fibrosis in 1961.
Neuroendocrine tumors are sometimes called APUDomas because these cells often show a mining p (L-DOPA and 5- hydroxytryptophan) u ptake and d equilibrate to produce biogenic amines such as catecholamines and serotonin. Although this behavior is also part of the unproved hypothesis that these cells may be embryologically derived from neuralendocrine crystals, occasionally produce different types of hormones and amines, and they can also have strong receptors for other hormones they respond to.
There are several nomenclature systems for this tumor, and the distinction between these schemes is often confusing. However, these systems all distinguish between differentiated (low and middle) and bad (high-level) NET. The rate of cellular proliferation is very important in this prognostic assessment.
References
External links
- Neuroendocrine Cancer Awareness Network (NCAN)
- Neuroendocrine Tumor in Curlie (based on DMOZ)
- Neuroendocrine Tumor Research Foundation
Source of the article : Wikipedia
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