Neuroendocrine tumor
Neuroendocrine tumor | |
---|---|
Micrograph of a neuroendocrine tumor. H&E stain. | |
Specialty | Endocrine oncology |
Neuroendocrine tumors (NETs) are
Although there are many kinds of NETs, they are treated as a group of tissue because the cells of these neoplasms share common features, including a similar histological appearance, having special
The term "neuro" refers to the dense core granules (DCGs), similar to the DCGs in the serotonergic neurons storing monoamines. The term "endocrine" refers to the synthesis and secretion of these monoamines. The neuroendocrine system includes endocrine glands such as the pituitary, the parathyroids and the neuroendocrine adrenals, as well as endocrine islet tissue embedded within glandular tissue such as in the pancreas, and scattered cells in the exocrine parenchyma. The latter is known as the diffuse endocrine system.[2][3]
Classification
WHO
The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize the tumor grade rather than the anatomical origin:[4][5]
- well-differentiated neuroendocrine tumors, further subdivided into tumors with benign and those with uncertain behavior
- well-differentiated (low grade) neuroendocrine carcinomas with low-grade malignant behavior
- poorly differentiated (high grade) neuroendocrine carcinomas, which are the large cell neuroendocrine and small cell carcinomas.
Additionally, the WHO scheme recognizes mixed tumors with both neuroendocrine and
Placing a given tumor into one of these categories depends on well-defined histological features: size, lymphovascular invasion, mitotic count, Ki-67 labelling index, invasion of adjacent organs, presence of metastases and whether they produce hormones.[4][5]
The
Neuroendocrine carcinomas are poorly differentiated high-grade neuroendocrine neoplasms and a designation of tumor grade is therefore redundant.[7] Lung and thymic neuroendocrine neoplasms are classified in a similar manner, including typical and atypical carcinoids, small cell and large cell neuroendocrine carincomas.[7]
Furthermore, the 2022 WHO classification introduces a two-tiered grading system for medullary thyroid carcinomas based on mitotic count, Ki-67 index and the absence or presence of tumor necrosis. Here, it may be noted that different cut-offs than with tumors of gastrointestinal, aerodigestive and lung origin are applied.[7]
Anatomic distribution
Traditionally, neuroendocrine tumors have been classified by their anatomic site of origin. NETs can arise in many different areas of the body, and are most often located in the
NETs include certain tumors of the gastrointestinal tract and of the pancreatic
Within the broad category of neuroendocrine tumors there are many different tumor types,[10] representing only a small proportion of the tumors or cancers in most of these tissues[citation needed]:
- pituitary
- Thyroid gland: Neuroendocrine thyroid tumors, particularly medullary carcinoma
- Parathyroid tumors
- Thymus and mediastinal carcinoid tumors[11][12]
- Pulmonary neuroendocrine tumors[13][14]
- bronchus[12]
- pulmonary carcinoid tumors: typical carcinoid (TC; low-grade); atypical carcinoid (AC; intermediate-grade)
- small-cell lung cancer (SCLC)
- large cell neuroendocrine carcinoma of the lung (LCNEC)[15]
- Extrapulmonary small cell carcinomas (ESCC or EPSCC)
- Gastroenteropancreatic neuroendocrine tumors (GEP-NET)[16][17]
- Foregut GEP-NET (foregut tumors can conceptually encompasses not only NETs of the stomach and proximal duodenum, but also the pancreas, and even thymus, lung and bronchus)[citation needed]
- Pancreatic endocrine tumors (if considered separately from foregut GEP-NET)[18]
- Midgut GEP-NET (from distal half of 2nd part of the duodenum to the proximal two-thirds of the transverse colon)
- appendix,[19] including well differentiated NETs (benign); well differentiated NETs (uncertain malignant potential); well differentiated neuroendocrine carcinoma (with low malignant potential); mixed exocrine-neuroendocrine carcinoma (goblet cell carcinoma, also called adenocarcinoid and mucous adenocarcinoid)
- Hindgut GEP-NET[20][21]
- Foregut GEP-NET (foregut tumors can conceptually encompasses not only NETs of the stomach and proximal duodenum, but also the pancreas, and even thymus, lung and bronchus)[citation needed]
- Liver[22][23][24] and gallbladder[25]
- Adrenal tumors, particularly adrenomedullary tumors
- Pheochromocytoma
- Peripheral nervous system tumors, such as:
- Breast[26]
- Genitourinary tract
- urinary tract carcinoid tumor and neuroendocrine carcinoma[27][28]
- ovary
- neuroendocrine tumor of the cervix[29]
- Prostate tumor with neuroendocrine differentiation[30][31]
- testes
- carcinomaof skin (trabecular cancer)
- Inherited conditions:[32]
- multiple endocrine neoplasia type 1 (MEN1)
- multiple endocrine neoplasia type 2 (MEN2)
- von Hippel-Lindau (VHL) disease[32]
- neurofibromatosis type 1[33][34]
- tuberous sclerosis[34][35]
Grading
Neuroendocrine lesions are graded histologically according to markers of cellular proliferation, rather than cellular polymorphism. The following grading scheme is currently recommended for all gastroenteropancreatic neuroendocrine neoplasms by the World Health Organization:[38]
G | Mitotic count (per 10 HPF) | Ki-67 index (%) |
---|---|---|
GX | Grade cannot be assessed | |
G1 | < 2 | < 3% |
G2 | 2 to 20 | 3–20% |
G3 | > 20 | > 20% |
If mitotic count and Ki-67 are discordant, the figure which gives the highest grade is used.
G1 and G2 neuroendocrine neoplasms are called neuroendocrine tumors (NETs) – formerly called carcinoid tumours. G3 neoplasms are called neuroendocrine carcinomas (NECs).[citation needed]
It has been proposed that the current G3 category be further separated into histologically well-differentiated and poorly-differentiated neoplasms to better reflect prognosis.[39]
Staging
Currently there is no one staging system for all neuroendocrine neoplasms. Well-differentiated lesions generally have their own staging system based on anatomical location, whereas poorly differentiated and mixed lesions are staged as carcinomas of that location. For example, gastric NEC and mixed adenoneuroendocrine cancers are staged as primary carcinoma of the stomach.[40]
TNM staging of gastroenteropancreatic Grade 1 and Grade 2 neuroendocrine tumors are as follows:
Primary Tumor (T) | |
---|---|
T Category | Tumor Criteria |
TX | Primary tumour cannot be assessed |
T0 | No evidence of primary tumour |
T1 | Invades the lamina propria or submucosa, and less than or equal to 1 cm in size |
T2 | Invades the muscularis propria, or greater than 1 cm in size |
T3 | Invades through the muscularis propria into subserosal tissue without penetration of overlying serosa |
T4 | Invades visceral peritoneum (serosal) or other organs or adjacent structures |
Regional Lymph Node (N) | |
N Category | N Criteria |
NX | Regional lymph nodes cannot be assessed |
N0 | No regional lymph node metastasis |
N1 | Regional lymph node metastasis |
Distant Metastasis (M) | |
M Category | M Criteria |
M0 | No distant metastasis |
M1 | Distant metastasis |
M1a | Metastasis confined to liver |
M1b | Metastasis in at least one extra-hepatic site |
M1c | Both hepatic and extra-hepatic metastases |
AJCC Prognostic Stage Groups | |
Stage | Criteria |
I | T1, N0, M0 |
II | T2 or T3, N0, M0 |
III | Any T, N1, M0; T4, N0, M0 |
IV | Any T, any N, M1 |
Primary Tumor (T) | |
---|---|
T Category | Tumor Criteria |
TX | Primary tumour cannot be assessed |
T1 | Invades the mucosa or submucosa only, and less than or equal to 1 cm in size (duodenal tumors) Confined within the sphincter of Oddi, and less than or equal to 1 cm in size (ampullary tumors) |
T2 | Invades the muscularis propria, or is > 1 cm (duodenal) Invades through sphincter into duodenal submucosa or muscularis propria, or is > 1 cm (ampullary) |
T3 | Invades the pancreas or peripancreatic adipose tissue |
T4 | Invades visceral peritoneum (serosal) or other organs |
Regional Lymph Node (N) | |
N Category | N Criteria |
NX | Regional lymph nodes cannot be assessed |
N0 | No regional lymph node metastasis |
N1 | Regional lymph node metastasis |
Distant Metastasis (M) | |
M Category | M Criteria |
M0 | No distant metastasis |
M1 | Distant metastasis |
M1a | Metastasis confined to liver |
M1b | Metastasis in at least one extra-hepatic site |
M1c | Both hepatic and extra-hepatic metastases |
AJCC Prognostic Stage Groups | |
Stage | Criteria |
I | T1, N0, M0 |
II | T2 or T3, N0, M0 |
III | T4, N0, M0; Any T, N1, M0 |
IV | Any T, any N, M1 |
Primary Tumor (T) | |
---|---|
T Category | Tumor Criteria |
TX | Primary tumour cannot be assessed |
T0 | No evidence of primary tumour |
T1 | Invades the lamina propria or submucosa, and less than or equal to 1 cm in size |
T2 | Invades the muscularis propria, or greater than 1 cm in size |
T3 | Invades through the muscularis propria into subserosal tissue without penetration of overlying serosa |
T4 | Invades visceral peritoneum (serosal) or other organs or adjacent structures |
Regional Lymph Node (N) | |
N Category | N Criteria |
NX | Regional lymph nodes cannot be assessed |
N0 | No regional lymph node metastasis |
N1 | Regional lymph node metastasis less than 12 nodes |
N2 | Large mesenteric masses (> 2 cm) and / or extensive nodal deposits (12 or greater), especially those that encase the superior mesenteric vessels |
Distant Metastasis (M) | |
M Category | M Criteria |
M0 | No distant metastasis |
M1 | Distant metastasis |
M1a | Metastasis confined to liver |
M1b | Metastasis in at least one extra-hepatic site |
M1c | Both hepatic and extra-hepatic metastases |
AJCC Prognostic Stage Groups | |
Stage | Criteria |
I | T1, N0, M0 |
II | T2 or T3, N0, M0 |
III | Any T, N1 or N2, M0; T4, N0, M0; |
IV | Any T, any N, M1 |
Primary Tumor (T) | |
---|---|
T Category | Tumor Criteria |
TX | Primary tumour cannot be assessed |
T0 | No evidence of primary tumour |
T1 | 2 cm or less in greatest dimension |
T2 | Tumor more than 2 cm but less than or equal to 4 cm |
T3 | Tumor more than 4 cm or with subserosal invasion or involvement of the mesoappendix |
T4 | Perforates the peritoneum or directly invades other organs or structures (excluding direct mural extension to adjacent subserosa of adjacent bowel) |
Regional Lymph Node (N) | |
N Category | N Criteria |
NX | Regional lymph nodes cannot be assessed |
N0 | No regional lymph node metastasis |
N1 | Regional lymph node metastasis |
Distant Metastasis (M) | |
M Category | M Criteria |
M0 | No distant metastasis |
M1 | Distant metastasis |
M1a | Metastasis confined to liver |
M1b | Metastasis in at least one extra-hepatic site |
M1c | Both hepatic and extra-hepatic metastases |
AJCC Prognostic Stage Groups | |
Stage | Criteria |
I | T1, N0, M0 |
II | T2 or T3, N0, M0 |
III | Any T, N1, M0; T4, N1, M0 |
IV | Any T, any N, M1 |
Primary Tumor (T) | |
---|---|
T Category | Tumor Criteria |
TX | Primary tumour cannot be assessed |
T0 | No evidence of primary tumour |
T1 | Invades the lamina propria or submucosa, and less than or equal to 2 cm |
T1a | Less than 1 cm in greatest dimension |
T1b | 1–2 cm in greatest dimension |
T2 | Invades the muscularis propria, or greater than 2 cm in size with invasion of the lamina propria or submucosa |
T3 | Invades through the muscularis propria into subserosal tissue without penetration of overlying serosa |
T4 | Invades visceral peritoneum (serosal) or other organs or adjacent structures |
Regional Lymph Node (N) | |
N Category | N Criteria |
NX | Regional lymph nodes cannot be assessed |
N0 | No regional lymph node metastasis |
N1 | Regional lymph node metastasis |
Distant Metastasis (M) | |
M Category | M Criteria |
M0 | No distant metastasis |
M1 | Distant metastasis |
M1a | Metastasis confined to liver |
M1b | Metastasis in at least one extra-hepatic site |
M1c | Both hepatic and extra-hepatic metastases |
AJCC Prognostic Stage Groups | |
Stage | Criteria |
I | T1, N0, M0 |
IIA | T2, N0, M0 |
IIB | T3, N0, M0 |
IIIA | T4, N0, M0 |
IIIB | Any T, N1, M0 |
IV | Any T, any N, M1 |
Primary Tumor (T) | |
---|---|
T Category | Tumor Criteria |
TX | Primary tumour cannot be assessed |
T1 | Limited to the pancreas, less than or equal to 2 cm in size |
T2 | Limited to the pancreas, 2–4 cm in size |
T3 | Limited to the pancreas, > 4 cm; or invading the duodenum or bile duct |
T4 | Invading adjacent organs or the wall of large vessels |
Regional Lymph Node (N) | |
N Category | N Criteria |
NX | Regional lymph nodes cannot be assessed |
N0 | No regional lymph node involvement |
N1 | Regional lymph node involvement |
Distant Metastasis (M) | |
M Category | M Criteria |
M0 | No distant metastasis |
M1 | Distant metastasis |
M1a | Metastasis confined to liver |
M1b | Metastasis in at least one extra-hepatic site |
M1c | Both hepatic and extra-hepatic metastases |
AJCC Prognostic Stage Groups | |
Stage | Criteria |
I | T1, N0, M0 |
II | T2 or T3, N0, M0 |
III | Any T, N1, M0; T4, N0, M0 |
IV | Any T, any N, M1 |
Signs and symptoms
Gastroenteropancreatic
Conceptually, there are two main types of NET within the gastroenteropancreatic neuroendocrine tumors (GEP-NET) category: those which arise from the
Carcinoid tumors
Ten per cent (10%)[50] or less of carcinoids, primarily some midgut carcinoids, secrete excessive levels of a range of hormones, most notably serotonin (5-HT) or substance P,[51] causing a constellation of symptoms called carcinoid syndrome:[citation needed]
- flushing
- diarrhea
- asthma or wheezing
- congestive heart failure(CHF)
- abdominal cramping
- peripheral edema
- heart palpitations
A carcinoid crisis with profound flushing, bronchospasm, tachycardia, and widely and rapidly fluctuating blood pressure[1] can occur if large amounts of hormone are acutely secreted,[51] which is occasionally triggered by factors such as diet,[51] alcohol,[51] surgery[1][51] chemotherapy,[51] embolization therapy or radiofrequency ablation.[1]
Chronic exposure to high levels of serotonin causes thickening of the
Occasionally,
Pancreatic neuroendocrine tumors
Pancreatic neuroendocrine tumors (PanNETs) are often referred to as "islet cell tumors",[54][55] or "pancreatic endocrine tumors"[4]
The PanNET denomination is in line with current
Well or intermediately differentiated PanNETs are sometimes called
Other
In addition to the two main categories of GEP-NET, there are rarer forms of neuroendocrine tumors that arise anywhere in the body, including within the
Familial syndromes
Most pancreatic NETs are sporadic.[54] However, neuroendocrine tumors can be seen in several inherited familial syndromes, including:[32]
- multiple endocrine neoplasia type 1 (MEN1)
- multiple endocrine neoplasia type 2 (MEN2)
- von Hippel-Lindau (VHL) disease[32]
- neurofibromatosis type 1[33]
- tuberous sclerosis[34][35]
Given these associations, recommendations in NET include family history evaluation, evaluation for second tumors, and in selected circumstances testing for germline mutations such as for MEN1.[1]
Pathophysiology
NETs are believed to arise from various
Diagnosis
This section needs additional citations for verification. (November 2020) |
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.[60]
Given the diverse secretory activity of NETs there are many other potential markers, but a limited panel is usually sufficient for clinical purposes.[1] Aside from the hormones of secretory tumors, the most important markers are:
- chromogranin A (CgA), present in 99% of metastatic carcinoid tumors[61]
- urine 5-hydroxyindoleacetic acid(5-HIAA)
- neuron-specific enolase(NSE, gamma-gamma dimer)
- synaptophysin (P38)
Newer markers include
Imaging
For morphological imaging,
Advances in nuclear medicine imaging, also known as molecular imaging, have improved diagnostic and treatment paradigms in patients with neuroendocrine tumors. This is because of its ability to not only identify sites of disease but also characterize them. Neuroendocrine tumours express somatostatin receptors providing a unique target for imaging. Octreotide is a synthetic modification of somatostatin with a longer half-life.[
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.[64] Thus, octreotide scanning for NET tumors is being increasingly replaced by gallium-68 DOTATOC scan.[65]
Imaging with fluorine-18 fluorodeoxyglucose (FDG) PET may be valuable to image some neuroendocrine tumors.[66] 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.[citation needed] However, neuroendocrine tumors 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 neuroendocrine neoplasms.[67]
The combination of somatostatin receptor and FDG PET imaging is able to quantify somatostatin receptor cell surface (SSTR) expression and glycolytic metabolism, respectively.[66] 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.[68]
Histopathology
Features in common
Neuroendocrine tumors, despite differing
NETs 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.[72] Histologically, NETs 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.[citation needed]
Some neuroendocrine tumor 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.[citation needed]
Argentaffin and hormone secretion
NETs 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 NETs), midgut and hindgut; individual tumors within these sites can differ from these group benchmarks:[citation needed]
- Foregut NETs are 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.[73]These tumors can metastasize to bone.
- Midgut NETs 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 NETs are argentaffin negative and rarely secrete 5-HT, 5-HTP, or any other vasoactive peptides. Bone metastases are not uncommon.
Treatment
Several issues help define appropriate treatment of a neuroendocrine tumor, including its location, invasiveness, hormone secretion, and metastasis. Treatments may be aimed at curing the disease or at relieving symptoms (
Intermediate and high grade tumors (noncarcinoids) are usually best treated by various early interventions (active therapy) rather than observation (wait-and-see approach).[74]
Treatments have improved over the past several decades, and outcomes are improving.[49] In malignant carcinoid tumors with carcinoid syndrome, the median survival has improved from two years to more than eight years.[75]
Detailed guidelines for managing neuroendocrine tumors are available from ESMO,[76] NCCN[77] and a UK panel.[1] The NCI has guidelines for several categories of NET: islet cell tumors of the pancreas,[78] gastrointestinal carcinoids,[79] Merkel cell tumors[80] and pheochromocytoma/paraganglioma.[81] However, effective predictive biomarkers are yet to be discovered. Similarly, recent advances in understanding neuroendocrine tumor's molecular and genomic alterations still have to find their ways into a definitive management strategy.[82]
Surgery
Even if the tumor has advanced and metastasized, making curative surgery infeasible, surgery often has a role in neuroendocrine cancers for
Cholecystectomy is recommended if there is a consideration of long-term treatment with somatostatin analogs.[83]: 46
Symptomatic relief
In secretory tumors, somatostatin analogs given subcutaneously or intramuscularly alleviate symptoms by blocking hormone release. A consensus review has reported on the use of somatostatin analogs for GEP-NETs.[84]
These medications may also anatomically stabilize or shrink tumors, as suggested by the PROMID study (Placebo-controlled prospective randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumors): at least in this subset of NETs, average tumor stabilization was 14.3 months compared to 6 months for placebo.[85]
The CLARINET study (a randomized, double-blind, placebo-controlled study on the antiproliferative effects of lanreotide in patients with enteropancreatic neuroendocrine tumors) further demonstrated the antiproliferative potential of lanreotide, a somatostatin analog and recently approved FDA treatment for GEP-NETS. In this study, lanreotide showed a statistically significant improvement in progression-free survival, meeting its primary endpoint. The disease in sixty-five percent of patients treated with lanreotide in the study had not progressed or caused death at 96 weeks, the same was true of 33% of patients on placebo. This represented a 53% reduction in risk of disease progression or death with lanreotide based on a hazard ratio of .47.[86]
Lanreotide is the first and only FDA approved antitumor therapy demonstrating a statistically significant progression-free survival benefit in a combined population of patients with GEP-NETS.[citation needed]
Other medications that block particular secretory effects can sometimes relieve symptoms.[52]
Chemotherapy
Gastrointestinal neuroendocrine tumors
Most gastrointestinal carcinoid tumors tend not to respond to chemotherapy agents,[52] showing 10 to 20% response rates that are typically less than 6 months. Combining chemotherapy medications has not usually been of significant improvement[52] showing 25 to 35% response rates that are typically less than 9 months.
The exceptions are poorly
PanNETs
Radionuclide therapy
PRRT was initially used for low grade NETs. It is also very useful in more aggressive NETs such as Grade 2 and 3 NETs[91][92] provided they demonstrate high uptake on SSTR imaging to suggest benefit.
Hepatic artery
Metastases to the liver can be treated by several types of hepatic artery treatments based on the observation that tumor cells get nearly all their nutrients from the hepatic artery, while the normal cells of the liver get about 70–80 percent of their nutrients and 50% their oxygen supply from the portal vein, and thus can survive with the hepatic artery effectively blocked.[49][93]
- Hepatic artery embolization (HAE) occludes the blood flow to the tumors, achieving significant tumor shrinkage in over 80%.[51] In hepatic artery chemotherapy, the chemotherapy agents are given into the hepatic artery, often by steady infusion over hours or even days. Compared with systemic chemotherapy, a higher proportion of the chemotherapy agents are (in theory) delivered to the lesions in the liver.[93]
- Hepatic artery chemoembolization (HACE), sometimes called transarterial chemoembolization (TACE), combines hepatic artery embolization with hepatic artery chemoinfusion: embospheres bound with chemotherapy agents, injected into the hepatic artery, lodge in downstream capillaries. The spheres not only block blood flow to the lesions, but by halting the chemotherapy agents in the neighborhood of the lesions, they provide much better targeting leverage than chemoinfusion provides.[citation needed]
- radiotherapy, the lesions need not overexpress peptide receptors. The mechanical targeting delivers the radiation from the yttrium-labeled microspheres selectively to the tumors without unduly affecting the normal liver.[96] This type of treatment is FDA approved for liver metastases secondary to colorectal carcinoma and is under investigation for treatment of other liver malignancies, including neuroendocrine malignancies.[94]
Other therapies
AdVince, a type of gene therapy using a genetically modified oncolytic adenovirus[97] and supported by the crowdfunding campaign iCancer[98] was used in a Phase 1 trial against NET in 2016.[99]
Further efforts towards more
Epidemiology
Although estimates vary, the annual incidence of clinically significant neuroendocrine tumors is approximately 2.5–5 per 100,000;[103] two thirds are carcinoid tumors and one third are other NETs.
The
History
Small intestinal neuroendocrine tumors were first distinguished from other tumors in 1907.[105][48] They were named carcinoid tumors because their slow growth was considered to be "cancer-like" rather than truly cancerous.[48]
However, in 1938 it was recognized that some of these small bowel tumors could be malignant.[105][48] Despite the differences between these two original categories, and further complexities due to subsequent inclusion of other NETs of pancreas and pulmonary origin, all NETs are sometimes (incorrectly) subsumed into the term "carcinoid".[citation needed]
Neuroendocrine tumors were sometimes called
There have been multiple nomenclature systems for these tumors,[4] and the differences between these schema have often been confusing. Nonetheless, these systems all distinguish between well-differentiated (low and intermediate-grade) and poorly differentiated (high-grade) NETs. Cellular proliferative rate is of considerable significance in this prognostic assessment.[4]
References
- ^ PMID 15888809.
- PMID 21976424.
- PMID 29091800.
- ^ S2CID 3735444.
- ^ PMID 21603312.
- S2CID 20185589.
- ^ S2CID 247455289.
- ^ S2CID 24740130.
- ^ PMID 16762613.
- PMID 15053292.
- PMID 10550713.
- ^ PMID 18456740.
- PMID 15898407.
- S2CID 22143641.
- PMID 1317668.
- PMID 18803349.
- S2CID 46127116.
- PMID 18703061.
- PMID 21160597.
- PMID 20380002.
- PMID 21160865.
- PMID 12636090.
- PMID 18333038.
- PMID 8348490.
- PMID 12725316.
- PMID 11890336.
- PMID 17076534.
- PMID 7511278.
- PMID 11718210.
- S2CID 131934021.
- S2CID 4732323.
- ^ PMID 18798544.
- ^ PMID 11573632.
- ^ PMID 20833335.
- ^ PMID 18978035.
- ^ a b "Carney Complex, type 1; CNC1". OMIM - Online Mendelian Inheritance in Man. OMIM 160980.
- ^ a b "Carney Complex, type 2; CNC2". OMIM - Online Mendelian Inheritance in Man. OMIM 605244.
- ISBN 978-92-832-2432-7.
- PMID 25723112.
- ISBN 978-3-319-40617-6.
- ISBN 978-3-319-40617-6.
- ISBN 978-3-319-40617-6.
- ^ AJCC, 8th edition: Klimstra DS, Yang Z (29 October 2019). "Pathology, classification, and grading of neuroendocrine neoplasms arising in the digestive system". UpToDate.
- ISBN 978-3-319-40617-6.
- ISBN 978-3-319-40617-6.
- ISBN 978-3-319-40617-6.
- S2CID 20567425. "[In] 800 autopsy cases, ... incidence of tumor was 10% (6/60) in individuals having histiological studies of all sections of the pancreas"
- ^ ISBN 978-3-540-43462-7.
- ^ a b c d Pommier R (October 2003). The role of surgery and chemoembolization in the management of carcinoid. California Carcinoid Fighters Conference. Archived from the original on 2015-09-15.
- ^ "Carcinoid Tumor Overview". Health Communities. Archived from the original on 2012-03-03.
- ^ a b c d e f g h Kvols LK (2002). "Carcinoid Tumors and the Carcinoid Syndrome: What's New in the Therapeutic Pipeline". Carcinoid Symposium 2002. The Carcinoid Cancer Foundation. Archived from the original on 2015-01-05.
- ^ ISBN 978-0-615-41824-7. Archived from the originalon 2011-05-15., cancernetwork.com; accessed November 8, 2015.
- ^ "Cushing's Syndrome". The Lecturio Medical Concept Library. Retrieved 28 September 2021.
- ^ PMID 26389309.
- S2CID 7329783.
- S2CID 54100368.
The tumors [of Devil facial tumor disease] have been characterized as a neuroendocrine cancer
- ^ Kinver M (January 1, 2010). "Tasmanian devil facial cancer origins 'identified'". BBC. Archived from the original on January 2, 2010.
- ^ Walsh B (January 1, 2010). "Decoding the Tasmanian Devil's Deadly Cancer". Time. Archived from the original on January 8, 2010.
- ^ S2CID 33139633.
- ^ S2CID 25108086.
- ^ McMorran J, Crowther DC, McMorran S, Prince C, YoungMin S, Pleat J, Wacogne I. "investigations – General Practice Notebook". www.gpnotebook.co.uk. Archived from the original on 24 February 2017. Retrieved 23 February 2017.
- ^ S2CID 208286399.
- S2CID 40129404.
- S2CID 21843609.
- PMID 30096273.
- ^ PMID 22846204. Retrieved November 8, 2015.
- PMID 31555796.
- PMID 26922350.
- PMID 17699847.
- PMID 20036951.
- S2CID 52110673.
- ^ "Definition of Mesentery". MedicineNet. Retrieved 2018-04-21.
- ^ Tebbi CK, Windle ML, Cripe TP, Sakamoto KM (1 April 2014). Coppes MJ (ed.). "Carcinoid Tumor". Medscape.com. WebMD LLC. Archived from the original on 15 December 2014. Retrieved 3 September 2014.
- ^ PMID 15887158.
- ^ PMID 10388123.
- PMID 20555086.
- PMID 19635226.
- ^ "Islet Cell Tumors (Endocrine Pancreas)". National Cancer Institute. Archived from the original on 2011-06-07.
- ^ "Gastrointestinal Carcinoid Tumors Treatment". National Cancer Institute. Archived from the original on 2011-06-27.
- ^ "Merkel cell tumors". National Cancer Institute. 21 February 2006. Archived from the original on 2011-06-07.
- ^ "Pheochromocytoma and Paraganglioma". National Cancer Institute. Archived from the original on 2011-06-07.
- S2CID 232172557.
- ^ "Neuroendocrine tumors, NCCN Guidelines Version 1.2015" (PDF). NCCN Guidelines. National Comprehensive Cancer Network, Inc. November 11, 2014. Retrieved December 25, 2014.
- PMID 15151956.
- PMID 19704057.
- PMID 25014687.
- ^ a b Öberg K. Neuroendocrine Gastroenteropancreatic Tumours: Current Views on Diagnosis and Treatment. Business Briefing. European Oncology Review 2005; pp. 1–6.
- PMID 19336011.
- PMID 28076709.
- PMID 25070685.
- S2CID 20740102.
- S2CID 207407820.
- ^ a b Fong T, Schoenfield LJ. "Arterial Chemotherapy Infusion of the Liver (and) Chemoembolization of the Liver (TACE)". medicinenet.com. Archived from the original on 2014-12-24. Retrieved 8 November 2015.
- ^ PMID 16979443.
- PMID 19521311.
- PMID 12354840.
- ^ Masters A (2014-10-14). "A plutocratic proposal". Mosaic. The Wellcome Trust. Archived from the original on 2016-05-29. Retrieved 2016-07-03.
- ^ "iCancer web site". icancer.org.uk. Archived from the original on 2016-07-14. Retrieved 2016-07-03.
- ^ Masters A (2016-07-02). "Can crowdfunding really cure cancer? Alexander Masters investigates a pioneering new project". The Telegraph. Archived from the original on 2016-07-03. Retrieved 2016-07-03.
- PMID 32615560.
- PMID 38429350.
- S2CID 214768622.
- ^ S2CID 29720754.
- S2CID 20567425.
- ^ PMID 15619202.
External links
- Neuroendocrine tumor at Curlie