Fact-checked by Grok 2 weeks ago

Carcinoid

Carcinoid tumors, also known as carcinoids, are a type of rare, slow-growing neuroendocrine tumor that originates from neuroendocrine cells, which are specialized cells capable of producing hormones such as serotonin and insulin.^[1] These tumors typically develop in the gastrointestinal tract, most commonly in the small intestine, appendix, or rectum, but can also arise in the lungs or other sites throughout the body.^[2] The term "carcinoid" is a historical designation for what are now more broadly classified as well-differentiated neuroendocrine tumors (NETs), reflecting their indolent growth pattern and potential for hormone secretion.^[3] Often asymptomatic in early stages, carcinoid tumors may go undetected for years until they metastasize, particularly to the liver, where they can trigger the release of bioactive substances into the bloodstream.^[1] They are more prevalent in adults, with an incidence of approximately 4 cases per 100,000 people annually that has been increasing over time to 2-5 cases per 100,000 as of 2021, and show a slight predominance in females and older individuals.^[3]^[4] Risk factors include a family history of multiple endocrine neoplasia type 1 (MEN 1), a genetic condition that predisposes individuals to various endocrine tumors, though the exact causes remain largely unknown and are linked to acquired DNA mutations in neuroendocrine cells.^[1] When symptomatic, carcinoid tumors can lead to carcinoid syndrome, characterized by episodic flushing of the skin, chronic diarrhea, abdominal pain, and wheezing due to excess hormone production.^[2] Additional complications may include carcinoid heart disease, where fibrous deposits damage heart valves, or, in cases involving lung-based tumors, Cushing syndrome from overproduction of cortisol-like substances.^[1] Diagnosis typically involves imaging studies such as CT or MRI scans, blood and urine tests for hormone markers, and biopsy confirmation, while treatment often centers on surgical resection for localized disease, with options like somatostatin analogs or targeted therapies for advanced cases.^[3]

Definition and Classification

Definition

Carcinoid tumors are rare, slow-growing neuroendocrine tumors (NETs) that arise from neuroendocrine cells of the diffuse neuroendocrine system, such as enterochromaffin cells in the gastrointestinal tract and Kulchitsky cells in the lungs, which are specialized for hormone production.^[5]^[1] These tumors originate from the diffuse neuroendocrine system, where enterochromaffin cells function in both neural and endocrine capacities, often leading to their indolent behavior despite malignant potential.^[6] The term "carcinoid" represents a historical classification for well-differentiated NETs, coined in 1907 by German pathologist Siegfried Oberndorfer to denote tumors that resembled carcinomas in appearance but exhibited more benign characteristics.^[7] The term "carcinoid" derives from "carcinoma" and the suffix "-oid," meaning "carcinoma-like," reflecting their resemblance to carcinomas but with more benign characteristics.^[8] Under the World Health Organization (WHO) classifications, including the 2019 edition for digestive system tumors and the 2022 edition for endocrine and neuroendocrine tumors, "carcinoid" is now largely supplanted by the broader term "neuroendocrine tumor" to emphasize differentiation and grading; however, it remains in use for specific low-grade (grade 1 or 2) cases in gastrointestinal and pulmonary sites, such as typical and atypical carcinoids in the lung.^[9] Unlike higher-grade or poorly differentiated NETs and neuroendocrine carcinomas, carcinoids are typically indolent, well-differentiated lesions (grades 1-2) with low proliferative activity, though they retain the capacity for hormone secretion that may precipitate syndromes like carcinoid syndrome in metastatic settings.^[6]

Classification and Subtypes

Carcinoid tumors, now more precisely termed well-differentiated neuroendocrine tumors (NETs) under the World Health Organization (WHO) classification, are categorized based on their differentiation, proliferative activity, and anatomical origin. The 2019 and 2022 WHO updates for digestive system and endocrine tumors emphasize a unified framework for neuroendocrine neoplasms (NENs), distinguishing well-differentiated NETs from poorly differentiated neuroendocrine carcinomas (NECs).^[10]^[11]^[12] Grading of NETs relies on two key proliferation markers: mitotic count per 2 mm² and Ki-67 index, which measures the percentage of tumor cells in active cell cycle phases. The system divides NETs into three grades:

Grade	Mitotic Rate (per 2 mm²)	Ki-67 Index (%)
G1	<2	<3
G2	2–20	3–20
G3	>20	>20

The higher value between mitotic rate and Ki-67 determines the grade. The term "carcinoid" is retained specifically for G1 and G2 well-differentiated NETs, particularly those arising in the gastrointestinal tract and lungs, reflecting their indolent behavior compared to G3 NETs or NECs.^[10]^[11]^[12]^[13] Staging for carcinoid tumors employs tumor-node-metastasis (TNM) systems adapted for NETs, with the European Neuroendocrine Tumor Society (ENETS) providing site-specific guidelines and the American Joint Committee on Cancer (AJCC) offering adaptations for gastrointestinal sites. The T category assesses tumor size and depth of invasion (e.g., T1 for tumors ≤1 cm confined to mucosa/submucosa), N evaluates regional lymph node involvement (N0 absent, N1 present), and M indicates distant metastases (M0 none, M1 present). These systems incorporate functional status and grade for prognostic refinement, differing slightly by primary site such as the pancreas or appendix.^[14]^[15]^[16] Carcinoid tumors are subclassified by their embryological origin in the gut, influencing clinical behavior and hormone production. Foregut carcinoids, originating from the esophagus, stomach, duodenum, pancreas, or lungs, often exhibit atypical features with higher mitotic rates and potential for serotonin precursors like 5-hydroxytryptophan, leading to less common syndromes. Midgut carcinoids, from the distal ileum, appendix, and proximal colon, represent the classic form associated with serotonin-mediated effects and are typically indolent when low-grade. Hindgut carcinoids, arising in the distal colon and rectum, are usually non-functioning, with rare hormone secretion and a lower metastatic potential.^[17]^[18]^[19] Special variants include goblet cell adenocarcinomas (formerly goblet cell carcinoids), primarily in the appendix, which are amphicrine neoplasms blending neuroendocrine and glandular features and behave more aggressively than pure NETs. Atypical carcinoids, frequently pulmonary, are distinguished by elevated mitotic activity (>2 per 2 mm²) and necrosis, conferring a worse prognosis than typical counterparts despite well-differentiated morphology.^[20]^[21]^[22]

Epidemiology

Incidence and Prevalence

Carcinoid tumors, now classified under neuroendocrine tumors (NETs), exhibit a steadily increasing incidence, with global age-adjusted rates of approximately 2 cases per 100,000 population annually.^[23] In the United States, SEER data show rates rising from 1.64 per 100,000 in 1975 to 8.52 per 100,000 in 2021, corresponding to approximately 28,000 new cases annually based on 2021 population estimates, with trends continuing into the mid-2020s.^[4] This increase is largely attributed to advancements in diagnostic imaging, endoscopy, and awareness. These tumors are more prevalent in adults over 50 years of age and represent a significant portion of gastrointestinal NETs.^[24] Prevalence has also increased due to improved survival, with an estimated 248,000 individuals living with an NET diagnosis in the US as of 2021.^[4] Primary sites show a distribution of approximately 50-60% in the gastrointestinal tract (including small intestine ~16-20%, rectum ~15%, appendix ~10-15%), 20-25% in the lungs, ~15% in the pancreas, and the remainder in other sites such as the thymus or genitourinary tract.^[4] Within the gastrointestinal tract, the small intestine has become the most common site, surpassing the appendix in recent decades due to enhanced detection of non-incidental cases.^[4] This trend underscores the importance of continued epidemiological surveillance to track the evolving burden of these neoplasms.^[25]

Risk Factors and Demographics

Carcinoid tumors predominantly affect individuals in their sixth or seventh decade of life, with an average age at diagnosis of around 61 years.^[24] There is a slight female predominance, with approximately 54% of cases occurring in women, corresponding to a female-to-male ratio of about 1.2:1.^[26] Regarding race, the majority of cases—around 80%—occur in Caucasian individuals, though incidence rates vary by population subgroup, with higher rates among African Americans for gastrointestinal sites.^[24]^[26] Genetic factors play a role in a minority of cases, with most carcinoid tumors arising sporadically and fewer than 10% linked to hereditary syndromes overall. Multiple endocrine neoplasia type 1 (MEN1) syndrome, caused by mutations in the MEN1 gene, is associated with 5-10% of neuroendocrine tumors, including foregut carcinoids such as those in the thymus or bronchi, where the risk reaches about 10%.^[27]^[28] Neurofibromatosis type 1 (NF1), due to defects in the NF1 gene, increases the risk of small intestinal neuroendocrine tumors, including carcinoids, though the association is uncommon, affecting 1-5% of NF1 patients.^[27]^[28] Familial isolated primary hyperparathyroidism, often related to MEN1 or hyperparathyroidism type 2 (HRPT2), is linked to pancreatic neuroendocrine tumors that may include carcinoid subtypes.^[28] Rarer hereditary associations include von Hippel-Lindau (VHL) syndrome, with VHL gene mutations conferring a 12% risk of pancreatic neuroendocrine tumors, and tuberous sclerosis complex (TSC), where TSC1 or TSC2 defects are tied to 1-5% of malignant islet cell tumors.^[27]^[28] Environmental risk factors are not well-established for most carcinoid tumors, with no strong links to infectious agents. Smoking is associated with increased risk for certain subtypes, including an odds ratio of 1.50 for pulmonary carcinoids and 1.59 for small intestinal tumors.^[29] Dietary factors may contribute modestly, as higher intake of saturated fats has been suggested to elevate risk for small intestinal carcinoids.^[30]

Pathophysiology

Cellular Origin

Carcinoid tumors, now more precisely termed well-differentiated neuroendocrine tumors (NETs), originate from specialized neuroendocrine cells within the diffuse neuroendocrine system. These cells, known as Kulchitsky cells or enterochromaffin cells, are primarily located in the crypts of Lieberkühn in the gastrointestinal (GI) tract.^[31] In the respiratory system, they arise from similar Kulchitsky-like cells embedded in the bronchial and bronchiolar epithelium.^[32] These progenitor cells belong to the amine precursor uptake and decarboxylation (APUD) system, characterized by their ability to synthesize and store biogenic amines and peptides.^[33] The diffuse neuroendocrine system comprises these cells scattered throughout various mucosal sites, including the GI mucosa from esophagus to rectum, bronchial epithelium, pancreas, and other endocrine organs.^[34] This widespread distribution explains the diverse primary sites of carcinoid tumors, with the majority originating in the GI tract (particularly the small intestine) and lungs. The cells maintain a basal state of low activity but can respond to environmental stimuli, contributing to the indolent nature of the resulting neoplasms. Tumor initiation typically begins with hyperplasia of these neuroendocrine cells, often triggered by chronic overstimulation such as in conditions like diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) in the lungs or hypergastrinemia in the stomach.^[35] This hyperplasia progresses to dysplastic changes and formation of microscopic tumorlets, eventually leading to monoclonal expansion of a neoplastic clone.^[36] The tumors exhibit slow proliferation, reflected in a low Ki-67 proliferation index, usually less than 3% in grade 1 NETs, which correlates with their indolent growth and favorable prognosis compared to higher-grade neuroendocrine carcinomas.^[37] Multi-centric occurrence is common, with up to 40% of patients with small intestinal NETs presenting multiple synchronous primary tumors, supporting a model of field cancerization where a shared genetic or environmental predisposition affects broad mucosal fields.^[38]^[39] This pattern underscores the multifocal independent clonal origins within predisposed tissues, consistent with field cancerization, rather than widespread metastasis at diagnosis.

Molecular Mechanisms and Hormone Production

Carcinoid tumors, as well-differentiated neuroendocrine neoplasms, exhibit specific genetic alterations that drive their pathogenesis and functional behavior. Somatic mutations in the MEN1 gene (11q13) occur in approximately 15-20% of non-pancreatic foregut carcinoid tumors and up to 44% of pancreatic NETs, a major subset of foregut carcinoids, leading to loss of function in the menin protein and dysregulation of cell proliferation.^[40] Similarly, mutations in DAXX and ATRX genes, involved in telomere maintenance through chromatin remodeling, are present in approximately 20-40% of pancreatic neuroendocrine tumors (combined), promoting genomic instability and alternative lengthening of telomeres.^[41]^[42] In cases of progression to higher-grade forms, alterations in TP53 and RB1 tumor suppressor genes become prominent, facilitating dedifferentiation and aggressive tumor behavior.^[43] Hormone production in carcinoid tumors arises from the specialized neuroendocrine cells that retain enterochromaffin-like properties, enabling the synthesis and secretion of bioactive amines and peptides. Midgut carcinoid tumors predominantly produce serotonin (5-hydroxytryptamine, 5-HT) through the action of the rate-limiting enzyme tryptophan hydroxylase 1 (TPH1), which converts tryptophan to 5-hydroxytryptophan; this serotonin is subsequently metabolized to 5-hydroxyindoleacetic acid (5-HIAA), detectable in urine as a diagnostic marker.^[44] Foregut variants may secrete gastrin, contributing to Zollinger-Ellison syndrome characterized by excessive acid production, while other tumors release somatostatin, which inhibits gastrointestinal hormone secretion, and chromogranin A, a general marker of neuroendocrine activity stored in secretory granules.^[45] Key signaling pathways underpin these molecular processes, with activation of the PI3K/AKT/mTOR pathway commonly observed in carcinoid tumors, promoting cell survival, growth, and angiogenesis through phosphorylation of downstream targets like mTOR.^[46] Epigenetic modifications, including promoter hypermethylation of tumor suppressor genes such as RASSF1A, further contribute to gene silencing and tumor progression across various carcinoid subtypes.^[47] The metastatic potential is enhanced when tumors spread to the liver, allowing secreted hormones to evade hepatic first-pass metabolism and enter the systemic circulation, thereby amplifying endocrine effects.^[48]

Clinical Presentation

Symptoms by Primary Site

Carcinoid tumors most commonly arise in the gastrointestinal tract, accounting for approximately 65% of cases. In the appendix, these tumors are frequently incidental findings during appendectomy for suspected appendicitis and are often asymptomatic, particularly when small and confined to the organ. Small bowel carcinoids, particularly in the ileum, typically present with abdominal pain due to local tumor growth or intermittent bowel obstruction caused by a desmoplastic reaction in the mesentery, affecting 20-30% of patients at diagnosis.^[49]^[50]^[51] Pulmonary carcinoids represent about 25% of all cases and are often located centrally in the bronchi. Common symptoms include cough, hemoptysis, and wheezing, which may mimic asthma or chronic obstructive pulmonary disease; atypical carcinoids tend to be more symptomatic than typical ones due to higher aggressiveness. Bronchial obstruction occurs in 10-20% of cases, leading to recurrent pneumonia or dyspnea.^[52]^[53] Carcinoid tumors in other sites are less common but produce site-specific symptoms. Ovarian carcinoids may cause pelvic pain from mass effect and, in some instances, estrogen-related effects such as postmenopausal bleeding due to hormone production by the tumor. Thymic carcinoids can lead to superior vena cava syndrome, manifesting as facial swelling, dyspnea, and venous distension from mediastinal compression.^[54]^[55] Local effects from carcinoid tumors at any primary site include gastrointestinal bleeding from mucosal ulceration or diarrhea due to direct secretion of bioactive substances into the lumen. Many tumors are detected incidentally during routine endoscopy or colonoscopy, especially in the gastrointestinal tract, before symptoms develop.^[51]^[56]

Carcinoid Syndrome and Metastatic Effects

Carcinoid syndrome, a paraneoplastic manifestation of neuroendocrine tumors, develops in approximately 10-20% of patients, most commonly in those with midgut-origin tumors that have metastasized to the liver, allowing systemic release of bioactive substances into the circulation.^[57]^[48] This syndrome is characterized by episodic symptoms driven by excess secretion of serotonin, histamine, and other mediators. Flushing, the most prevalent symptom affecting 80-90% of cases, presents as transient reddening of the skin, often on the face and upper trunk, lasting from minutes to hours and mediated by histamine and serotonin release.^[58]^[48] Diarrhea occurs in about 70% of patients, resulting from serotonin's stimulatory effect on gastrointestinal motility and secretion, leading to watery, frequent stools that can cause dehydration and electrolyte imbalances.^[58] Bronchospasm, manifesting as wheezing or shortness of breath, affects 10-20% during flushing episodes due to prostaglandin and bradykinin involvement.^[58]^[48] A significant complication is carcinoid heart disease, seen in up to 60-70% of patients with longstanding syndrome, primarily involving fibrosis of the right-sided heart valves (tricuspid and pulmonic), leading to regurgitation and potential heart failure from serotonin-induced endocardial damage.^[48] Additionally, pellagra-like symptoms arise in approximately 5% of cases due to diversion of tryptophan—the precursor to niacin—toward excessive serotonin production, resulting in niacin deficiency that causes dermatitis, further diarrhea, and occasionally dementia.^[58] Common triggers for symptom exacerbation include emotional or physical stress, alcohol consumption, and selective serotonin reuptake inhibitors (SSRIs), which can provoke massive hormone release.^[58]^[48] Metastatic spread contributes to additional systemic effects beyond the syndrome. Liver metastases are present in about 50% of patients at diagnosis, often leading to portal hypertension through mass effect, fibrosis, or vascular compression, which can result in ascites, varices, and gastrointestinal bleeding.^[58]^[59] Bone metastases, occurring in 10-12% of neuroendocrine tumor cases, typically cause localized pain and are associated with pathological fractures in around 9% of affected individuals, as well as spinal cord compression in 10%.^[60]^[61] A particularly severe metastatic complication is carcinoid crisis, a life-threatening event triggered by anesthesia, surgery, or procedures like biopsy, characterized by profound hypotension, tachycardia, and exacerbated flushing, diarrhea, and bronchospasm from abrupt tumor hormone secretion.^[58]^[48] The goblet cell variant of appendiceal carcinoid tumors, now termed goblet cell adenocarcinoma, exhibits aggressive behavior with a high propensity for peritoneal dissemination, often resulting in mucinous ascites and pseudomyxoma peritonei—a condition involving progressive accumulation of gelatinous mucin in the peritoneal cavity that can lead to bowel obstruction and malnutrition.^[62]^[63] Biochemical markers such as urinary 5-hydroxyindoleacetic acid (5-HIAA) levels are elevated in most syndrome cases but are addressed in diagnostic contexts.^[58]

Diagnosis

Clinical Evaluation

The clinical evaluation of suspected carcinoid tumors begins with a detailed history and physical examination to identify characteristic symptoms and signs suggestive of the condition or its associated carcinoid syndrome. Patients often report episodic flushing, affecting up to 85% of those with carcinoid syndrome, which may manifest as salmon-pink to dark-red discoloration of the face, neck, and upper chest, lasting from minutes to hours and triggered by stress, certain foods, alcohol, or exercise.^[48] Diarrhea is another common complaint, occurring in approximately 80% of cases, characterized by chronic, watery stools that can reach up to 30 episodes per day and lead to malabsorption or electrolyte imbalances.^[48] Inquiry should also include family history, as carcinoid tumors may associate with multiple endocrine neoplasia type 1 (MEN1) syndrome, particularly in cases involving foregut or pancreatic primaries.^[64] Additional symptoms to elicit include abdominal pain, wheezing or bronchospasm (in 10-20% of patients), palpitations, fatigue, and unexplained weight loss.^[48]^[65] On physical examination, clinicians should assess for palpable abdominal masses, particularly in the right lower quadrant for midgut tumors, hepatomegaly due to liver metastases, and wheezing indicative of bronchial involvement.^[64] Cutaneous findings such as facial telangiectasias or pellagra-like lesions from niacin deficiency may be evident in advanced cases with chronic diarrhea.^[48] Cardiac auscultation is crucial, as up to 60-70% of patients with long-standing carcinoid syndrome develop right-sided heart murmurs from valvular fibrosis resembling endocarditis, including tricuspid regurgitation or pulmonic stenosis.^[48]^[65] Pallor suggesting anemia or signs of volume depletion from diarrhea should prompt further scrutiny. Differential diagnosis for carcinoid-related symptoms is broad and requires careful consideration to avoid misattribution. Gastrointestinal symptoms like chronic diarrhea and abdominal pain may mimic irritable bowel syndrome (IBS) or other motility disorders, while wheezing and dyspnea can resemble asthma or allergic reactions.^[48] Flushing episodes raise suspicion for pheochromocytoma, mastocytosis, or medication side effects, necessitating targeted questioning about triggers and associated hypertension.^[64] Other considerations include anaphylaxis, celiac disease, or even menopausal hot flashes in women, with the episodic and multisystem nature of symptoms helping to differentiate carcinoid.^[48] Red flags warranting urgent evaluation include unexplained weight loss, which signals possible metastatic disease or malabsorption, and anemia potentially arising from occult gastrointestinal bleeding in tumors of the small bowel or appendix.^[48] Incidental discovery of masses or lesions on routine imaging, such as during abdominal scans for unrelated issues, should heighten suspicion, particularly in asymptomatic patients.^[64] These findings underscore the indolent yet potentially aggressive behavior of carcinoid tumors. Given the complexity of carcinoid tumors, early referral to a multidisciplinary team is essential, including endocrinologists for hormonal aspects and oncologists for tumor management, to coordinate care and optimize outcomes.^[66] This approach facilitates prompt transition to confirmatory imaging and laboratory investigations as needed.^[66]

Imaging and Laboratory Tests

Laboratory tests play a central role in diagnosing carcinoid tumors by detecting biochemical markers of neuroendocrine activity. The 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) test measures the primary metabolite of serotonin, which is often elevated in patients with functioning carcinoid tumors, particularly those causing carcinoid syndrome; this test has a sensitivity of 70-90% and specificity of 70-90% for such cases.^[67] Serum chromogranin A (CgA) is another key biomarker, a glycoprotein released by neuroendocrine cells, with a sensitivity of approximately 73% and specificity of 95% for detecting neuroendocrine tumors; it is elevated in 50-90% of patients with carcinoid tumors, particularly those that are metastatic or functioning.^[48]^[68] These tests are particularly useful for initial screening and monitoring tumor burden, though false elevations in 5-HIAA can occur with certain foods or medications, and CgA levels may be influenced by renal function or proton pump inhibitors.^[48] Imaging modalities are essential for localizing carcinoid tumors, assessing staging, and identifying metastases, given their often indolent growth and hypervascular nature. Computed tomography (CT) scans, especially multiphase protocols that capture arterial and venous phases, are widely used for detecting primary tumors and liver metastases due to the tumors' enhancement patterns, with reported sensitivities around 78-85% for neuroendocrine tumors.^[69] Magnetic resonance imaging (MRI) complements CT with superior soft-tissue contrast, achieving sensitivities of 75-95% for pancreatic and gastrointestinal neuroendocrine tumors, and is particularly effective for liver lesion characterization.^[70] Somatostatin receptor scintigraphy (SRS), also known as Octreoscan using indium-111 pentetreotide, targets somatostatin receptors overexpressed on carcinoid cells, offering a sensitivity of 75-100% for detecting well-differentiated neuroendocrine tumors and aiding in whole-body staging.^[71] More advanced functional imaging with gallium-68 DOTATATE positron emission tomography (PET) has become the preferred modality for somatostatin receptor-positive tumors, providing higher spatial resolution and sensitivity greater than 90% for localizing carcinoid tumors and metastases compared to traditional SRS or conventional CT/MRI.^[72] This tracer binds specifically to somatostatin receptor subtype 2, which is present in over 90% of neuroendocrine tumors, enabling earlier detection of small lesions.^[73] Endoscopic procedures are valuable for direct visualization and biopsy of accessible carcinoid tumors. Upper and lower gastrointestinal endoscopy allows inspection of the mucosa for submucosal lesions in the stomach, small bowel, or colon, guiding tissue sampling for suspected primary sites.^[74] Bronchoscopy is the primary tool for evaluating pulmonary carcinoids, revealing characteristic vascular, polypoid endobronchial masses in up to 75% of central lung cases and facilitating biopsy despite bleeding risks.^[75] In patients with carcinoid syndrome, echocardiography is recommended to assess for valvular heart disease, a complication affecting up to 60% of cases due to serotonin-induced fibrosis. Transthoracic echocardiography identifies thickening and regurgitation of the tricuspid and pulmonary valves with high reliability, serving as the cornerstone for diagnosing carcinoid heart disease and grading severity.^[76]

Pathological Confirmation

Pathological confirmation of carcinoid tumors, now more precisely termed well-differentiated neuroendocrine tumors (NETs), relies on tissue sampling followed by microscopic examination and immunohistochemical analysis. Biopsy techniques vary by tumor location but prioritize minimizing procedural risks, particularly in patients with functional tumors prone to carcinoid crisis—a potentially life-threatening release of bioactive substances. Endoscopic biopsy is preferred for accessible gastrointestinal lesions, such as those in the small intestine or rectum, allowing direct visualization and sampling with forceps.^[77] For deeper or submucosal tumors, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or fine-needle biopsy (FNB) provides targeted access, often using a 22- or 25-gauge needle to obtain cytologic or histologic material while avoiding excessive manipulation that could provoke a crisis.^[78] Surgical biopsy, including wedge resection or laparotomy, is reserved for cases where less invasive methods are infeasible or yield nondiagnostic results, though it carries higher risks in metastatic disease.^[79] Fine-needle techniques are generally safe, with studies reporting low rates of carcinoid crisis (near 0% in percutaneous approaches), but prophylactic octreotide is often administered in high-risk patients.^[80] Histologically, carcinoid tumors exhibit characteristic neuroendocrine architecture, consisting of uniform, polygonal to spindled cells arranged in organoid nests, trabeculae, or rosettes, supported by a vascular stroma.^[81] The nuclei are round to oval with finely dispersed "salt-and-pepper" chromatin, inconspicuous nucleoli, and minimal pleomorphism, reflecting their low-grade nature.^[82] Cytoplasm is typically eosinophilic and granular, with rare mitoses and no necrosis in typical cases. These features distinguish them from higher-grade malignancies, though crush artifacts in small biopsies can mimic more aggressive tumors. Immunohistochemical staining is essential for confirmation, demonstrating neuroendocrine differentiation. Tumor cells are typically positive for synaptophysin (a synaptic vesicle protein, sensitive in >95% of cases), chromogranin A (a granule protein, specific but less sensitive in small biopsies), and CD56 (neural cell adhesion molecule, membranous staining in most well-differentiated NETs).^[83] These markers, used in panels, achieve diagnostic accuracy exceeding 90%, with synaptophysin often serving as the most reliable single stain.^[84] Additional hormone-specific stains (e.g., serotonin for midgut carcinoids) may support functional correlation but are not required for diagnosis. Grading assesses proliferative activity to subclassify tumors as grade 1 (G1), grade 2 (G2), or grade 3 (G3) well-differentiated NETs, guiding prognosis and management. This is based on mitotic count (mitoses per 2 mm² of viable tumor) and Ki-67 proliferation index (percentage of nuclei positive for Ki-67 via immunohistochemistry).^[85] G1 tumors show <2 mitoses/2 mm² and Ki-67 <3%; G2 have 2–20 mitoses/2 mm² or Ki-67 3–20%; G3 exhibit >20 mitoses/2 mm² or Ki-67 >20% but retain well-differentiated morphology.^[86] Ki-67 is particularly valuable on limited biopsy material, correlating strongly with mitotic rate and outperforming it as a prognostic marker in some series.^[87] Historical silver stains, such as Grimelius argyrophil or Fontana-Masson argentaffin, which highlighted neuroendocrine granules, are now obsolete due to nonspecificity and replacement by reliable IHC.^[88] Differential diagnosis includes adenocarcinoma and small cell carcinoma, which may overlap morphologically in limited samples. Adenocarcinomas feature glandular formation, mucin production, and positivity for cytokeratins (e.g., CK7/CK20) with negativity for neuroendocrine markers, unlike the diffuse synaptophysin/chromogranin expression in carcinoids.^[89] Small cell carcinomas show high-grade features—hyperchromatic nuclei, molding, crush artifact, numerous mitoses (>50/2 mm²), and Ki-67 >50%—plus TTF-1 positivity, contrasting the low-grade, salt-and-pepper chromatin of carcinoids.^[90] In ambiguous cases, a full IHC panel resolves most distinctions.

Management and Treatment

Surgical Approaches

Surgery remains the cornerstone of treatment for localized carcinoid tumors, offering the potential for cure when the disease is resectable. For tumors confined to the primary site without distant metastases, complete surgical excision is pursued, tailored to the anatomical location to achieve negative margins and address regional lymph node involvement. In cases of metastatic disease, particularly to the liver, cytoreductive procedures aim to reduce tumor burden and alleviate symptoms, though they are not curative. For appendiceal carcinoid tumors smaller than 2 cm, a simple appendectomy is typically sufficient and curative, with low risk of lymph node metastasis. Tumors exceeding 2 cm or those with adverse features such as invasion of the mesoappendix may require a right hemicolectomy to ensure adequate lymphadenectomy and margin control. In the small bowel, particularly the ileum, segmental resection of the affected bowel segment along with regional lymphadenectomy is the standard approach, often extending to the mesentery to remove involved nodes. For midgut carcinoids originating in the distal ileum, a right hemicolectomy is commonly performed to encompass the primary tumor, lymph nodes, and potential multicentric lesions in this region. Pancreatic and duodenal carcinoids demand specialized resections based on location; for tumors in the pancreatic head or periampullary duodenum, the Whipple procedure (pancreaticoduodenectomy) is employed to remove the tumor en bloc with adjacent structures including the duodenum, pancreatic head, and regional nodes. In metastatic settings with liver involvement, cytoreductive surgery—such as wedge resections, hemihepatectomy, or extended hepatectomy—can remove a substantial portion of tumor burden, leading to symptom improvement in 80-90% of patients with carcinoid syndrome. Preoperative prophylaxis with octreotide, administered as 100-200 μg subcutaneously three times daily for at least two weeks prior to surgery, is recommended to mitigate the risk of intraoperative carcinoid crisis, characterized by hemodynamic instability from hormone release. Surgical access may involve laparoscopic techniques for favorable sites like the appendix or early small bowel lesions, offering reduced recovery time compared to open surgery, though open approaches are preferred for complex cases involving extensive mesenteric involvement or liver debulking to ensure oncologic adequacy. Pulmonary carcinoids are managed with parenchyma-sparing resections such as sleeve lobectomy or segmentectomy when feasible; pneumonectomy is reserved for rare instances of extensive central disease where lesser resections are not possible.

Pharmacological and Targeted Therapies

Pharmacological therapies for carcinoid tumors, particularly neuroendocrine tumors (NETs) with carcinoid syndrome, primarily aim to control hormonal symptoms and slow tumor progression in unresectable or metastatic cases. Somatostatin analogs (SSAs) represent the cornerstone of medical management, binding to somatostatin receptors on tumor cells to inhibit hormone secretion and exert antiproliferative effects.^[91] Octreotide and lanreotide, administered as long-acting formulations, achieve symptom control in approximately 50-70% of patients with carcinoid syndrome, including reductions in flushing and diarrhea.^[92] These agents are equally efficacious in symptom relief and biomarker reduction, with lanreotide offering convenience through less frequent dosing.^[93] Dose escalation, such as increasing octreotide to 40-60 mg or shortening lanreotide intervals, can further improve control in refractory cases.^[94] Peptide receptor radionuclide therapy (PRRT) extends SSA-based approaches by delivering targeted radiation to somatostatin receptor-positive tumors. Lutetium-177 DOTATATE (177Lu-DOTATATE), approved for progressive somatostatin receptor-positive midgut NETs, significantly prolongs progression-free survival (PFS) compared to high-dose octreotide, with a median PFS of 28.4 months versus 8.4 months in the phase 3 NETTER-1 trial.^[95] This therapy also improves quality of life and is well-tolerated, with stable disease as the most common outcome post-treatment.^[96] Chemotherapy plays a limited role in carcinoid management due to the indolent nature of most NETs and modest response rates, reserved for rapidly progressive or poorly differentiated cases. The combination of streptozocin and 5-fluorouracil (5-FU) is recommended for pancreatic NETs, achieving a disease control rate of about 80% and objective response rate of 33% in well-differentiated tumors.^[97] For progressive disease, temozolomide-based regimens, often combined with capecitabine, demonstrate improved PFS over temozolomide alone, with median PFS around 18 months in advanced NETs.^[98] Targeted therapies inhibit key signaling pathways to halt tumor growth. Everolimus, an oral mTOR inhibitor, is approved for advanced, progressive pancreatic NETs and non-functional NETs of gastrointestinal or lung origin, extending median PFS to 11.0 months versus 4.6 months with placebo (investigator assessment) in the RADIANT-3 trial.^[99] Sunitinib, a multi-tyrosine kinase inhibitor, is indicated for unresectable pancreatic NETs, improving median PFS to 11.4 months compared to 5.5 months with placebo and showing durable benefits in long-term analyses.^[100] Cabozantinib, an oral multi-tyrosine kinase inhibitor, was approved by the FDA in March 2025 for adult patients with previously treated advanced NETs regardless of primary tumor site, including carcinoid tumors.^[101] These agents are often sequenced after SSAs and can synergize with surgical debulking to enhance symptom palliation.^[102] As of 2025, emerging therapies focus on improving SSA convenience and efficacy. Paltusotine, an investigational oral non-peptide somatostatin receptor type 2 agonist from Crinetics Pharmaceuticals, is under evaluation in the phase 3 CAREFNDR trial for carcinoid syndrome associated with NETs, offering once-daily dosing for long-term hormonal control without injections.^[103] Following its FDA approval for acromegaly in September 2025, paltusotine demonstrates rapid and durable effects on hormone levels, with ongoing data supporting its potential expansion to NET management.^[104]

Prognosis and Follow-up

Survival Outcomes

The 5-year relative survival rate for gastrointestinal carcinoid tumors, a common subtype of neuroendocrine tumors (NETs), is approximately 94% across all stages (based on SEER data from 2015–2021), with rates of 97% for localized disease, 96% for regional spread, and 68% for distant metastases.^[105] For pulmonary carcinoid tumors, the overall 5-year survival is around 78-95%, with 98% for localized cases, 87% for regional involvement, and 49% for distant disease.^[106] These figures reflect improvements in detection and management, though survival declines significantly with advanced disease. Survival outcomes also differ markedly by tumor grade, as defined by the World Health Organization classification for NETs. Well-differentiated grades G1 and G2 tumors exhibit 5-year overall survival rates exceeding 90%, often approaching 100% for G1, due to their indolent behavior.^[107] In contrast, poorly differentiated G3 tumors have 5-year survival rates below 50%, typically 26-44%, reflecting their aggressive nature and poorer response to therapy.^[108] Site-specific variations further influence prognosis. Appendiceal carcinoids, frequently localized at diagnosis, achieve 5-year survival rates of 90-97.5% with surgical resection.^[109] Small bowel carcinoids, prone to metastasis, show 5-year survival of 60-80% overall, with localized disease 70-100% and distant cases around 35-60%.^[81] Pulmonary carcinoids maintain favorable outcomes at 70-90% for 5 years, particularly for typical variants.^[110] In metastatic settings, liver involvement from carcinoid tumors yields 5-year survival rates of 40-80%, with well-selected patients achieving up to 70% through multimodal approaches.^[111] The presence of carcinoid syndrome, often linked to hepatic metastases, further reduces 5-year survival to 30-67%, primarily due to associated cardiac complications.^[112] Over time, overall 5-year survival for carcinoid tumors has improved from approximately 50-70% in the 1990s to over 90% for common subtypes (based on SEER data from 2015–2021), attributed to earlier detection via advanced imaging and therapies like peptide receptor radionuclide therapy (PRRT), which extends progression-free survival in advanced cases.^[26]^[113] Factors influencing these outcomes, such as age and comorbidities, are detailed in subsequent discussions on prognosis.

Factors Influencing Prognosis and Monitoring

The prognosis of carcinoid tumors, also known as well-differentiated neuroendocrine tumors, is influenced by several key factors including disease stage, tumor grade, patient age, and functional status. Localized disease generally carries a favorable outlook with 5-year survival exceeding 90%, whereas metastatic involvement, particularly to distant sites like the liver, is associated with substantially poorer outcomes, often below 50%.^[114] Tumor grade, determined primarily by the Ki-67 proliferation index, serves as a critical predictor; indices greater than 10% correlate with aggressive behavior and reduced survival rates.^[115] Advanced age over 65 years independently worsens prognosis across neuroendocrine tumor subtypes, including carcinoid, due to diminished physiologic reserve and treatment tolerance.^[116] Similarly, poor performance status, such as an Eastern Cooperative Oncology Group score of 2 or higher, is linked to inferior overall survival, reflecting the impact of baseline health on therapeutic response and disease control.^[117] Comorbidities further modify prognosis, with carcinoid heart disease representing a major adverse factor that significantly reduces survival compared to patients without cardiac involvement (e.g., mean survival of 1.6 years vs. 4.6 years in historical data), primarily through right-sided valvular fibrosis leading to heart failure.^[118] Multifocal tumors, often arising in the small intestine or multiple sites, are associated with worse overall survival than unifocal lesions, likely due to increased metastatic potential and diagnostic challenges.^[115] Post-treatment monitoring is essential for early detection of progression or recurrence, typically involving serial biochemical assessments of chromogranin A (CgA) and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels to track tumor burden and secretory activity.^[119] Imaging with contrast-enhanced CT or somatostatin receptor-based PET/CT is recommended annually, with more frequent evaluations every 3-6 months in the initial post-treatment period for high-risk cases, transitioning to yearly surveillance thereafter to balance detection efficacy with patient burden.^[120] Recurrence affects 20-40% of patients following curative-intent resection, with liver metastases predominating as the site of relapse due to the hematogenous spread pattern of these indolent tumors.^[121] Liver transplantation remains a rare option, generally limited to carefully selected young patients with extensive, unresectable hepatic metastases and low tumor grade, offering potential long-term control in otherwise refractory cases.^[122]

History

Early Discoveries

The earliest reports of what are now recognized as carcinoid tumors date back to 1888, when German pathologist Otto Lubarsch described multiple small tumors in the distal ileum of two patients discovered at autopsy, though these were initially misclassified as benign adenomas or multiple carcinomas without appreciating their distinct histological features.^[123] Lubarsch's observations, published in Virchows Archiv, marked the first documented gastrointestinal cases but failed to distinguish them as a unique entity separate from typical adenomatous growths.^[114] In 1907, Siegfried Oberndorfer, a prominent German pathologist, provided a pivotal advancement by coining the term "Karzinoide" (carcinoma-like tumors) to describe a series of small, submucosal tumors primarily in the small intestine, including the appendix, which appeared benign and exhibited slow growth without aggressive infiltration.^[123] Oberndorfer's seminal paper, "Karzinoide Tumoren des Dünndarms," published in Frankfurter Zeitschrift für Pathologie, emphasized their carcinoma-mimicking yet less malignant behavior, distinguishing them from conventional adenocarcinomas and resolving earlier debates over their classification as adenomyomas or ectopic pancreatic tissue.^[7] This nomenclature highlighted their indolent nature, though Oberndorfer later acknowledged their potential for metastasis in subsequent works.^[124] During the 1920s, Pierre Masson further elucidated the cellular origins of these tumors, demonstrating in 1928 that carcinoids arose from enterochromaffin cells in the gastrointestinal mucosa, which exhibited argentaffin properties detectable via silver impregnation staining.^[125] Masson's studies, including his work on appendiceal mucosa, established these cells as the source of the tumors' distinctive histology and laid the groundwork for understanding their neuroendocrine characteristics, later linked to serotonin production.^[126] The clinical significance of carcinoid tumors became clearer in the 1950s with the description of carcinoid syndrome by Åke Thorson and colleagues, who in 1954 reported a series of patients with small intestinal carcinoids and liver metastases presenting with episodic flushing, diarrhea, bronchoconstriction, and right-sided valvular heart disease.^[127] This observation, detailed in Acta Medica Scandinavica, connected the syndrome to hepatic bypass of tumor-secreted vasoactive substances like serotonin, transforming the understanding of these tumors from primarily pathological curiosities to clinically impactful entities.^[125]

Key Developments and Terminology Evolution

In the 1960s, A.G.E. Pearse introduced the APUD (amine precursor uptake and decarboxylation) concept, proposing that neuroendocrine cells, including those giving rise to carcinoid tumors, shared a common embryologic origin from neural crest-derived cells capable of amine handling and polypeptide hormone production.^[128] This framework unified the understanding of diffuse neuroendocrine systems but was later refined as evidence showed varied embryologic origins for many such cells.^[129] The discovery of somatostatin in 1973 by Paul Brazeau and colleagues at the Salk Institute marked a pivotal biochemical advancement, identifying this tetradecapeptide as a key inhibitor of growth hormone and other hormones relevant to neuroendocrine regulation.^[130] By the 1980s, synthetic somatostatin analogs like octreotide were developed, offering stable, long-acting options to control hormone hypersecretion in carcinoid syndrome, with octreotide first synthesized in 1979 and entering clinical use for symptom management.^[131] The 1990s and 2000s saw standardization in staging and grading, with the European Neuroendocrine Tumor Society (ENETS) proposing the first tumor-node-metastasis (TNM) staging systems in 2006 for pancreatic neuroendocrine tumors and 2007 for gastrointestinal ones, tailored to their indolent biology and improving prognostic accuracy over general cancer frameworks.^[132] Ki-67 proliferative index standardization emerged prominently in the 2010 World Health Organization (WHO) classification, defining grades as G1 (<3% Ki-67), G2 (3-20%), and initially lumping higher-proliferating cases with carcinomas, though this evolved to better stratify well-differentiated tumors.^[37] From the 2010s to 2025, WHO classifications progressively phased out the term "carcinoid" in favor of "neuroendocrine tumor" (NET) to reflect a spectrum of malignancy, with the 2010 edition classifying all GI and pancreatic NETs as potentially malignant and emphasizing Ki-67-based grading; the 2019 update introduced NET G3 as a distinct well-differentiated category separate from poorly differentiated neuroendocrine carcinomas (NECs); and the 2022 edition unified nomenclature across organ systems under a common framework for all neuroendocrine neoplasms.^[133] Therapeutically, the 2017 NETTER-1 phase 3 trial validated peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE, demonstrating significantly prolonged progression-free survival (28.4 months vs. 8.4 months with high-dose octreotide) in somatostatin receptor-positive midgut NETs, leading to its regulatory approval.^[134] By 2025, Crinetics Pharmaceuticals reported phase 2 progression-free survival data for paltusotine, an oral nonpeptide somatostatin receptor type 2 agonist, showing 74% one-year PFS in carcinoid syndrome associated with NETs, advancing toward phase 3 completion for potential oral therapy alternatives.^[135] Imaging advancements paralleled these developments, evolving from computed tomography (CT) scans in the 1980s, which provided anatomical detection but limited functional insight, to gallium-68 DOTATATE positron emission tomography (PET) in the 2010s, achieving over 95% sensitivity and specificity for detecting somatostatin receptor-expressing NETs and transforming staging and response assessment.^[136]

Occurrence in Other Organisms

Animal Models and Research

Animal models have been instrumental in elucidating the pathogenesis of carcinoid tumors, which are a subset of neuroendocrine tumors (NETs), and in evaluating therapeutic interventions. These models replicate key aspects of human disease, such as tumor development, hormone secretion, and response to treatments, facilitating preclinical studies that inform clinical translation. Rodent-based systems, in particular, offer controllable genetic manipulations to study tumor initiation and progression, while xenograft approaches allow testing of human-derived cells in vivo.^[137]^[138] The RIP-Tag mouse model, engineered with the SV40 T-antigen under the control of the rat insulin promoter (RIP), develops insulinomas resembling pancreatic NETs akin to carcinoids, providing insights into multistage tumorigenesis from hyperplasia to invasive carcinoma. This model exhibits predictable tumor progression with a short latency period, enabling the identification of genes involved in angiogenesis and metastasis, and has been validated through cross-species comparisons with human PanNETs.^[139]^[140] Complementing this, MEN1 knockout mice mimic hereditary forms of multiple endocrine neoplasia type 1 (MEN1), which predisposes to carcinoid-like NETs in the pancreas, parathyroid, and pituitary; heterozygous mutants develop multifocal tumors by 6-8 months, recapitulating hypercalcemia and hypophosphatemia observed in human patients. These mice have been used to explore menin loss-of-function effects on endocrine tumor formation, including β-cell-specific ablation leading to insulinomas.^[141]^[142]^[143] Xenograft models utilizing human carcinoid cell lines, such as BON-1 derived from a pancreatic metastasis, implanted into immunodeficient nude mice, serve as platforms for drug testing, particularly for mTOR inhibitors like everolimus. BON-1 xenografts exhibit constitutive Akt/mTOR pathway activation due to an autocrine IGF-I loop, allowing evaluation of pathway-targeted therapies that reduce tumor growth and serotonin secretion, mirroring human NET responses. Bioluminescent variants of BON-1 and similar lines (e.g., QGP-1) enhance imaging for longitudinal studies of tumor burden and metastasis.^[144]^[145]^[146] Genetic models in lower vertebrates, such as zebrafish harboring men1 mutations, facilitate studies of neuroendocrine hyperplasia and early tumorigenesis. The zebrafish men1 ortholog shares high conservation with human MEN1, including residues affected by patient missense mutations, enabling functional analysis of gene inactivation in islet development and potential precursor lesions. Additionally, spontaneous pulmonary carcinoids in dogs and cats provide translational research opportunities, as these naturally occurring tumors share histologic and molecular features with human counterparts, supporting comparative oncology studies on tumor biology and therapy resistance.^[147]^[148]^[149] More recently, a 2024 mouse model with combined deletion of Men1, Atrx, and Pten in pancreatic islet cells has been developed, triggering aggressive PanNET formation and offering a platform for studying mutation synergies and novel therapies.^[150] These models underpin key research applications, including the evaluation of peptide receptor radionuclide therapy (PRRT) efficacy. In SSTR-positive xenograft models, 177Lu-DOTATATE and novel α-particle emitters like 212Pb-DOTAMTATE demonstrate significant antitumor effects and prolonged survival compared to controls, informing dosimetry and combination strategies for clinical PRRT. Similarly, modulation of the serotonin pathway—central to carcinoid syndrome—has been tested in these systems; inhibition of peripheral serotonin synthesis via TPH1 blockade reduces tumor growth and metastasis in mouse models, highlighting its role in immune evasion and as a therapeutic target.^[151]^[152]^[153]^[144]^[154]

Veterinary Cases

Carcinoid tumors, a subset of neuroendocrine neoplasms, occur spontaneously in various domestic animals, though they are less common than in humans and often diagnosed incidentally or postmortem. In veterinary medicine, these tumors are documented across species, providing comparative pathology insights into gastrointestinal and pulmonary manifestations.^[155] In ferrets, neuroendocrine tumors constitute a significant portion of neoplasms, with endocrine-origin tumors accounting for 39.7% to 53% of cases in surveyed populations; however, well-differentiated carcinoids are rarer, typically involving the gastric or pancreatic regions. Case reports describe gastric carcinoid with metastasis to lymph nodes and peritoneum, presenting with nonspecific signs like lethargy and weight loss rather than overt serotonin-mediated syndrome. Hepatic neuroendocrine carcinomas have also been noted, often in middle-aged ferrets.^[156]^[157]^[158] Intestinal carcinoids have been reported in horses, particularly in the small intestine, which can lead to chronic colic due to obstruction or inflammation. These tumors are reported in the gastrointestinal tract and occasionally in nasal cavities or maxillary sinuses, causing exophthalmos or respiratory issues. Nasal and retrobulbar carcinoids have been histologically confirmed in multiple cases, highlighting their potential for local invasion.^[159]^[160] In dogs, pulmonary carcinoids are rare but have been reported as primary lung tumors, comprising neuroendocrine variants that may cause cough, dyspnea, or nonspecific respiratory distress. Gastrointestinal and hepatic locations are also reported, with tumors often metastasizing to lymph nodes or lungs; primary lung carcinoids have been successfully resected in some cases, with no recurrence noted up to 11 months post-surgery.^[155]^[161]^[162] Carcinoid tumors are rare in ruminants such as cattle and sheep, typically discovered incidentally at slaughter as small appendiceal or rectal masses without clinical signs. In cattle, poorly differentiated rectal carcinoids adjacent to the anorectal junction have been documented as solitary lesions. No widespread epidemiological data exist for sheep, but overall neoplasm surveys indicate low incidence of neuroendocrine types.^[163]^[164] Clinical presentation in affected animals mirrors human patterns to some extent, with potential for carcinoid syndrome including flushing or diarrhea in cases of serotonin secretion, though this is infrequently reported in veterinary literature; in ferrets, episodic flushing has been anecdotally associated with advanced gastric cases. Treatment approaches are analogous, emphasizing surgical resection for localized tumors, with somatostatin analogs like octreotide used palliatively for symptomatic control in metastatic disease.^[165]^[157] These veterinary cases pose no zoonotic risk, as carcinoid tumors do not transmit between species. Spontaneous occurrences in companion and livestock animals serve as natural models for studying aging-related gastrointestinal carcinogenesis in veterinary oncology, informing management strategies beyond experimental settings.^[155]

References

[1]
Carcinoid tumors - Symptoms and causes - Mayo Clinic
Jan 22, 2025 · Carcinoid tumors are a type of slow-growing cancer that can arise in several places throughout your body.
[2]
Definition of carcinoid tumor - NCI Dictionary of Cancer Terms
A slow-growing type of tumor usually found in the gastrointestinal system (most often in the small intestine and rectum), and sometimes in the lungs or other ...
[3]
Neuroendocrine Tumor - NCI - National Cancer Institute
Jul 30, 2020 · Neuroendocrine tumor used to be called carcinoid tumor. ... Carcinoid syndrome is a problem that develops from the tumors making hormones.How Common Is Net? · How Is Net Diagnosed? · How Is Net Treated?
[4]
Carcinoid tumors - PubMed - NIH
Dec 17, 2008 · Carcinoid tumors are rare, slow-growing neuroendocrine tumors arising from the enterochromaffin cells disseminated throughout the gastrointestinal and ...
[5]
Neuroendocrine Tumors and Carcinoid Tumors
Sep 25, 2025 · Carcinoid tumor is an older name for a subset of well-differentiated NETs. They are most often found in the digestive system or lungs.
[6]
Siegfried Oberndorfer: origins and perspectives of carcinoid tumors
Although the enterochromaffin cell, the carcinoid cell of origin, had been identified as early as 1897 by N. Kulchitsky (1856-1925), it was not until 1953 that ...
[7]
Gastrointestinal neuroendocrine (carcinoid) tumours
Jul 5, 2010 · The term carcinoid (carcinoma-like) was introduced by Oberndorfer in 1907 to describe a tumour of the gastrointestinal tract that was less ...<|separator|>
[8]
Overview of the 2022 WHO Classification of Neuroendocrine ...
Mar 16, 2022 · In this review, we detail the changes and the relevant features that are applied to neuroendocrine neoplasms (NENs) in the 2022 WHO Classification of Endocrine ...
[9]
Well differentiated neuroendocrine tumor - Pathology Outlines
Oct 2, 2025 · The 5th edition of the WHO 2019 Digestive Tumors Classification definition of neuroendocrine tumor (NET): well differentiated, grade 1, 2 or 3 ...
[10]
Pathology and classification of gastroenteropancreatic ...
May 19, 2025 · INTRODUCTION. Neuroendocrine cells are distributed widely throughout the body. Neuroendocrine neoplasms (NENs), defined as epithelial ...
[11]
What is New in the 2019 World Health Organization (WHO ... - NIH
In the current WHO classification, neuroendocrine carcinomas (NECs) are all considered high-grade ... Grading of neuroendocrine neoplasms: mitoses and ki-67 are ...Appendiceal Serrated Lesions... · Appendiceal Mucinous... · Appendiceal Goblet Cell...
[12]
Histopathologic and genetic distinction of well-differentiated grade 3 ...
Mar 4, 2025 · The term carcinoid has been repeatedly criticized10; it is now replaced with well-differentiated neuroendocrine tumor for all organ systems ...
[13]
TNM staging of foregut (neuro)endocrine tumors: a consensus ... - NIH
We report the tumor–node–metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at ...
[14]
Neuroendocrine Tumors Guidelines - Medscape Reference
Jun 19, 2025 · The AJCC uses separate staging systems for carcinoids of the ... (TNM) classification created by the ENETS and the 2010 WHO grading system.
[15]
Gastrointestinal Neuroendocrine Tumor Stages
Aug 8, 2025 · The staging system most often used for GI neuroendocrine tumors is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 ...
[16]
Gastrointestinal Neuroendocrine Tumors and the Carcinoid Syndrome
Aug 25, 2023 · The carcinoid syndrome is the quintessential hormonal syndrome in gastrointestinal neuroendocrine tumors, particularly those of midgut origin.
[17]
[PDF] CARCINOID TUMORS | Endotext
The foregut includes tumors arising from the lungs, stomach, liver, biliary tract, pancreas, and first portion of the duodenum. The midgut includes the distal ...
[18]
Carcinoid Tumor: Practice Essentials, Background, Pathophysiology
Feb 29, 2024 · Carcinoid tumors are of neuroendocrine origin and derived from primitive stem cells in the gut wall, especially the appendix.
[19]
Gastrointestinal Neuroendocrine Tumors (Health Professionals)
May 9, 2025 · Neuroendocrine tumors are rare, slow-growing tumors that originate in cells of the diffuse neuroendocrine system.
[20]
Current management of gastrointestinal carcinoid tumors
Foregut carcinoid tumors produce low amounts of serotonin and are usually associated with atypical carcinoid syndromes. Adrenocorticotropic hormone–producing ...
[21]
Updates on lung neuroendocrine neoplasm classification
Oct 4, 2023 · Based on the grade of differentiation, the four entities TC, AC, SCLC and LCNEC can be separated into two classes: carcinoids/neuroendocrine ...
[22]
Malignant Carcinoid Syndrome - Medscape Reference
Dec 2, 2024 · The incidence of clinical carcinoid tumors is estimated to be 1.5-1.9 cases per 100,000 population; the actual frequency is almost certainly ...<|control11|><|separator|>
[23]
Types of Neuroendocrine Tumors - Penn Medicine
about 12,000 new cases annually and around 170,000 people living ...Experience With The Full... · Gastroenteropancreatic... · Well-Differentiated...
[24]
Key Statistics About Gastrointestinal Neuroendocrine Tumors
Aug 8, 2025 · The recorded annual incidence of neuroendocrine tumors is approximately 1 to 2 cases per 100,000 people. The number of diagnosed NETs has been ...
[25]
An analysis of 8305 cases of carcinoid tumors - Modlin - 1997 - Cancer
Feb 15, 1997 · The most frequent sites for carcinoids were the gastrointestinal (GI) tract (73.7%) and the bronchopulmonary system (25.1%). Within the GI tract ...
[26]
Epidemiology of Neuroendocrine Neoplasms in the US | Oncology
Jun 24, 2025 · In SEER 17, the highest incidences were 1.40 per 100 000 persons in the lung, 4.27 per 100 000 persons in gastroenteropancreatic sites (1.41 per ...Missing: global | Show results with:global
[27]
Epidemiology of Neuroendocrine Neoplasms in the US - PMC - NIH
Jun 24, 2025 · In this cross-sectional study evaluating 145 477 NEN cases in the US, age-adjusted incidence rates increased 5.2-fold between 1975 and 2021.
[28]
Updated Population-Based Review of Carcinoid Tumors - PMC - NIH
We determined that the overall incidence of carcinoid tumors has markedly increased and most recently was 38.5 per million persons (in 1997). To put this into ...
[29]
Gastrointestinal Neuroendocrine Tumor Risk Factors
Aug 8, 2025 · Gastrointestinal Neuroendocrine Tumor Risk Factors · Genetic syndromes · Race and sex · Age · Other stomach conditions · Family history of any cancer.
[30]
Familial syndromes associated with neuroendocrine tumours - PMC
Neuroendocrine tumours may be associated with familial syndromes. At least eight inherited syndromes predisposing to endocrine neoplasia have been identified.
[31]
https://pmc.ncbi.nlm.nih.gov/articles/PMC3311499/
[32]
Causes of Carcinoid Tumors - News-Medical
Saturated fats: Some studies suggest that the intake of more saturated fat increases the risk for carcinoid in the small intestine in comparison with intake of ...<|control11|><|separator|>
[33]
Carcinoid and Other Neuroendocrine Tumors of the Colon and ... - NIH
Neuroendocrine tumors (NETs) are found throughout the intestinal tract and arise from the Kulchitsky cells located in the crypts of Lieberkühn.
[34]
Advances in Endoscopic Management of Endobronchial Carcinoid
Aug 16, 2023 · Histologically, they arise in the bronchial and bronchiolar epithelium and their origin cell type is either Kulchitsky cells (neuroendocrine ...
[35]
Neuroendocrine syndrome in bronchial carcinoid tumors - PMC
Oct 14, 2020 · Carcinoid tumors are part of the neuroendocrine tumors APUD ... Kulchitsky cells (agent affine cells). Pulmonary carcinoid tumors ...
[36]
CT/MRI of neuroendocrine tumours - PMC - PubMed Central
Histologically, the tumour comprises sheets of uniform round cells arising from the enterochromaffin cells, which are APUD cells of the diffuse endocrine system ...
[37]
Not only stem cells, but also mature cells, particularly ... - NIH
May 27, 2018 · Studies of gastric carcinogenesis demonstrate that mature neuroendocrine (NE) cells upon long-term overstimulation may develop through stages of hyperplasia, ...
[38]
Morphologic and molecular classification of lung neuroendocrine ...
Combined adenocarcinoma-atypical carcinoid of the lung. Targeted next-generation sequencing (NGS) suggests a monoclonal origin of the two components. Diagn ...<|separator|>
[39]
Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative ...
Feb 17, 2023 · Ki67 index was found to be higher in parathyroid tumors and hyperplasia than in normal glands [59] and, among tumors, in carcinoma than in ...
[40]
Primary small intestinal neuroendocrine tumors are highly ... - PubMed
Oct 7, 2019 · There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease.
[41]
Whole genome sequencing reveals the independent clonal origin of ...
Aug 3, 2022 · The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. ... field cancerization.<|control11|><|separator|>
[42]
Mutations and Allelic Deletions of the MEN1 Gene Are Associated ...
16 Indeed, the frequencies of mutations in foregut and mid/hindgut tumors were very similar (15.2% versus 16.6%), despite the fact that the number of ...
[43]
ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors ...
Oct 12, 2018 · Molecular studies have identified mutations in MEN1, ATRX, and DAXX to be the most commonly found in PanNETs (found in approximately 40, 10, and ...
[44]
Progression of Low-Grade Neuroendocrine Tumors (NET) to High ...
Nov 18, 2024 · Our data demonstrate that low-grade NET can progress via the acquisition of both TP53 and RB1 alteration, similar to NEC.
[45]
A Luminescent Sensor for Investigating Serotonin Metabolism in ...
Oct 31, 2023 · Peripheral serotonin biosynthesis is catalyzed by the rate-limiting enzyme tryptophan hydroxylase 1 (Tph1). Dysregulated serotonin metabolism is ...
[46]
Carcinoid Tumor | Johns Hopkins Medicine
Fewer than 10% of people with carcinoid tumors develop symptoms. The incidence of symptoms, however, may vary based on the location of the tumor. Because ...
[47]
PI3K/AKT/mTOR pathway in pulmonary carcinoid tumours - PMC - NIH
The present study examined the expression of mammalian target of rapamycin (mTOR) and mutations in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway in 54 ...
[48]
Neuroendocrine tumours: cracking the epigenetic code in
Epigenetic marks such as DNA methylation at RASSF1A are frequent findings in NETs of all origins and may be associated with worse prognosis. MicroRNA signatures ...Epigenetic modifications · Key epigenetic findings in cancer · DNA methylation in...
[49]
Carcinoid Syndrome - StatPearls - NCBI Bookshelf - NIH
Carcinoid syndrome is a clinical condition caused by metastatic, well-differentiated neuroendocrine tumors, most commonly arising from the midgut with liver ...Pathophysiology · History and Physical · Evaluation · Treatment / Management
[50]
Current Status of Gastrointestinal Carcinoids - Gastroenterology
Carcinoids are classified based on organ site and cell of origin and occur most frequently in the GI (67%) where they are most common in small intestine (25%), ...
[51]
Carcinoid tumor of the appendix: A case report - PMC - NIH
In general, appendiceal carcinoids are either asymptomatic or present as acute appendicitis, which is then diagnosed incidentally as appendiceal carcinoids ...
[52]
Intestinal Carcinoid Tumor - Medscape Reference
Dec 20, 2021 · Intestinal carcinoid tumors are gastrointestinal neuroendocrine tumors (GI-NETs). They are conventionally considered to originate from the serotonin-secreting ...Missing: growing | Show results with:growing
[53]
Lung Carcinoids: A Comprehensive Review for Clinicians - PMC
Nov 16, 2023 · Typical carcinoids account for 2% and atypical carcinoids for 0.2% of all lung tumors; adenocarcinomas constitute 40%, squamous cell carcinomas ...
[54]
Carcinoid Lung Tumors Clinical Presentation - Medscape Reference
May 13, 2024 · In symptomatic patients, the most common clinical findings are those associated with bronchial obstruction, such as persistent cough, hemoptysis ...
[55]
Ovarian neuroendocrine tumor metastases can induce estrogen ...
We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations.Abstract · Introduction · Results · Discussion
[56]
Thymic carcinoid - ScienceDirect
About 50% of patients with this tumor exhibit local symptoms (chest pain, cough, dyspnea, or superior vena cava syndrome). Carcinoid syndrome is exceedingly ...
[57]
Carcinoid Tumors - AAFP
Aug 1, 2006 · There are three main areas of origin for carcinoid tumors: foregut carcinoid tumors start in the lungs, bronchi, or stomach; midgut carcinoid ...
[58]
The frequency of carcinoid syndrome at neuroendocrine tumor ...
Jul 30, 2018 · Since nearly 1 in every 5 patients with NETs has CS, ameliorating the symptoms should be an important aspect of patient care. Additionally, our ...Missing: effects | Show results with:effects
[59]
Carcinoid Syndrome: A Review - PMC - NIH
Mar 5, 2020 · CS is associated with several common symptoms. Classically, patients complain of flushing (90%), diarrhea (70%), and wheezing (15%) [1,18]. The ...Missing: prevalence | Show results with:prevalence
[60]
Carcinoid heart disease and carcinoid syndrome - PubMed
... carcinoid heart disease, which can cause postsinusoidal portal hypertension, thereby increasing the risk of death from hemorrhage during hepatic resection. W …
[61]
Palliative Radiation Therapy for Bone Metastases in ... - NIH
Bone metastases are reported in 10% to 12% of patients with neuroendocrine neoplasms (NENs) and can lead to pain and skeletal-related events (SREs), resulting ...Palliative Radiation Therapy... · Study Population · Outcomes Analyses In All...<|control11|><|separator|>
[62]
Bone metastases and skeletal-related events from neuroendocrine ...
At time of detection of bone metastases, 60% reported symptoms, including pain; 10% developed cord compression, 9% suffered a pathological fracture, and 4% ...Results · Bone Metastases Presentation... · Overall Survival
[63]
Appendiceal Goblet Cell Carcinoma: Role of Cytoreductive Surgery ...
May 25, 2023 · GCC of the appendix is an aggressive type of tumour with a high risk of peritoneal and systemic dissemination. ... neuroendocrine and mucinous ...
[64]
Appendiceal Neoplasms - PMC - PubMed Central - NIH
Another point of confusion with regard to histologic classification is the goblet cell “carcinoid.” Previously thought of as an aggressive variant of ...
[65]
Carcinoid Tumor Clinical Presentation: History - Medscape Reference
Feb 29, 2024 · Signs and symptoms of carcinoid tumors vary greatly and depend on the location and size of the tumor and on the presence of metastases.Missing: physical | Show results with:physical
[66]
Malignant Carcinoid Syndrome Clinical Presentation
Dec 2, 2024 · Carcinoid tumors present as acute appendicitis or chronic pain in the lower right abdominal quadrant. For this reason, the condition is frequently misdiagnosed ...
[67]
Multidisciplinary Reference Centers: The Care of Neuroendocrine ...
The purpose of this study was to review the need for and benefits of multidisciplinary care in patients with cancer, to describe our experience setting up a ...
[68]
PROGNOSTIC UTILITY OF 24-HOUR URINARY 5-HIAA DOUBLING ...
Serotonin secretion is the main cause for the carcinoid syndrome; hence, it is not surprising that urinary 5-HIAA has 70 to 90% sensitivity and specificity ...
[69]
Imaging in neuroendocrine tumors: an update for the clinician - PMC
A study comparing MRI, CT and standard somatostatin receptor-based imaging (OctreoScan) reported 95.2% sensitivity for MRI, 78.5% sensitivity for CT and 49.3% ...
[70]
Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms
MRI has a 75%–95% sensitivity in detecting pNENs, with lower performance rates in cases degraded by respiratory motion. Tumor size also impacts its sensitivity, ...
[71]
Octreotide Scan - StatPearls - NCBI Bookshelf
May 4, 2025 · An octreotide scan, also known as somatostatin receptor scintigraphy (SRS), is valuable for detecting carcinoid tumors and various neuroendocrine tumors (NETs).
[72]
Diagnostic Efficiency of 68Ga-DOTATATE PET/CT as Compared to ...
However, in the current study, the sensitivity and specificity of CT/MRI was 83.3% and 100%, respectively, for GI tract tumors, similar to 68Ga-DOTATATE PET/CT.
[73]
68Ga-DOTATATE Compared with 111In-DTPA-Octreotide and ... - NIH
Ga-DOTATATE estimated sensitivity, 90.9% (95% confidence interval, 81.4%–96.4%), and specificity, 90.6% (95% confidence interval, 77.8%–96.1%), were high. Five ...
[74]
Carcinoid tumors - Diagnosis and treatment - Mayo Clinic
Jan 22, 2025 · Tests and procedures used to diagnose carcinoid tumors include: Blood tests. If you have a carcinoid tumor, your blood may contain high levels ...Missing: history differential
[75]
Bronchoscopic diagnosis and treatment of endobronchial carcinoid
Bronchoscopy is the mainstay of diagnostic evaluation for pulmonary carcinoids. In 75% of cases, bronchoscopy highlights budding well-vascularised, well-rounded ...
[76]
Valvular Disorders in Carcinoid Heart Disease - PMC - NIH
Carcinoid heart disease is a rare cause of right-side heart valve disease. Echocardiography remains a reliable method for the definite diagnosis. Valve ...
[77]
Role of Advanced Gastrointestinal Endoscopy in ... - PubMed Central
Aug 19, 2023 · EUS-FNA should be performed for diagnosis or when there is a question about tumor grade. Although FNA is most frequently performed, the addition ...
[78]
Endoscopic Ultrasound-Guided Fine Needle Aspiration and Biopsy ...
Jul 30, 2019 · EUS-FNA/B is a minimally invasive and effective diagnostic method that plays an important role in the diagnosis of gastrointestinal SETs, which, ...
[79]
Percutaneous Image-Guided Core Needle Biopsy of ... - PubMed
Feb 16, 2021 · Percutaneous image-guided core biopsy of NETs is safe, with low complication rate and no definite carcinoid crisis in the current cohort.
[80]
Percutaneous Image-Guided Core Needle Biopsy of ...
Percutaneous image-guided core biopsy of NETs is safe, with low complication rate and no definite carcinoid crisis in the current cohort.Clinical Study · Abstract · Introduction
[81]
Neuroendocrine tumor - Small intestine & ampulla
Oct 6, 2025 · Neuroendocrine tumor of the small intestine involves well differentiated duodenal, jejunal and ileal epithelial neoplasms with ...
[82]
Top 10 Histological Mimics of Neuroendocrine Carcinoma You ...
Mar 20, 2023 · In this review, the top ten morphological and/or immunohistochemical mimics of NEC are detailed in terms of histology, immunohistochemistry, and molecular ...
[83]
Role of Synaptophysin, Chromogranin and CD56 in ... - BMC Cancer
May 1, 2021 · Synaptophysin, chromogranin and CD56 are recommended markers to identify pulmonary tumors with neuroendocrine differentiation.
[84]
Role of Synaptophysin, Chromogranin and CD56 in ... - PubMed
May 1, 2021 · Background: Synaptophysin, chromogranin and CD56 are recommended markers to identify pulmonary tumors with neuroendocrine differentiation.
[85]
Usefulness of Ki-67, Mitoses, and Tumor Size for Predicting ... - NIH
The author concluded that the proliferation rate in carcinoid tumors is generally very low but increased in AC and can be related to worse prognosis. Arbiser et ...
[86]
Grades and stages of neuroendocrine cancer
The higher the mitotic rate or Ki67%, the faster the growth. There are 3 grades of neuroendocrine tumours (NETs) – grade 1, 2 and 3a: Grade 1 cancers grow ...
[87]
A comparison of Ki-67 and mitotic count as prognostic markers for ...
Apr 11, 2013 · There is a lack of concordance between Ki-67 and MC in assigning tumour grade. Grade according to Ki-67 was a better prognostic marker than MC ...<|separator|>
[88]
[PDF] carcinoid) tumours gastroenteropancreatic neuroendocrine ...
Histochemical stains, such as the Grimelius silver stain, are non-specific and not recommended. ... Three subtypes of gastric argyrophil carcinoid and the gastric ...
[89]
Distinguishing Carcinoid Tumor From Small Cell Carcinoma of the ...
May 1, 2005 · Carcinoids, atypical carcinoids, and small cell carcinomas of the lung: differential diagnosis of fine-needle aspiration biopsy specimens.Missing: adenocarcinoma | Show results with:adenocarcinoma
[90]
Distinguishing carcinoid tumor from small cell carcinoma of the lung
Nevertheless, some carcinoids may be difficult to distinguish from small cell carcinomas. ... Diagnosis, Differential; Diagnostic Errors / prevention & control ...
[91]
Targeting neuroendocrine tumors with octreotide and lanreotide
Octreotide and lanreotide have demonstrated firstly to provide a control over hormonal cell secretion and then they have shown also an anti-proliferative effect ...
[92]
Carcinoid Syndrome Treatment - NETRF
Both Octreotide and Lanreotide have similar effectiveness and provide symptom relief in 50% to 70% of people with carcinoid syndrome.3 Additionally, multiple ...
[93]
Treatment of carcinoid syndrome: a prospective crossover ... - PubMed
Lanreotide and octreotide are equally efficacious in terms of symptom control and reduction in tumor cell markers for patients with carcinoid syndrome.
[94]
https://www.onclive.com/view/dose-escalation-with-somatostatin-analogs-remains-an-important-element-of-gep-net-management
[95]
2L: NETTER-1 | LUTATHERA® (lutetium Lu 177 dotatate) | HCP
NETTER-1: ~3x longer PFS in patients after progression on an SSA1-3. Statistically significant improvement in PFS (primary end point).
[96]
Therapy With 177 Lu-DOTATATE: Clinical Implementation and ...
The NETTER-1 study also showed a significant quality-of-life benefit for patients with midgut NETs who received 177Lu-DOTATATE versus those treated with high- ...
[97]
The efficacy of streptozotocin in managing pancreatic ...
For doublet chemotherapy, 13 studies reported a DCR of 80 % and an ORR of 33 % for the STZ plus 5-FU regimen, while seven studies reported a DCR of 61 ...
[98]
Randomized Study of Temozolomide or ... - ASCO Publications
Oct 19, 2022 · The combination of capecitabine/temozolomide was associated with a significant improvement in PFS compared with temozolomide alone in patients with advanced ...
[99]
Everolimus for Advanced Pancreatic Neuroendocrine Tumors
Feb 10, 2011 · Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors.
[100]
Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine ...
Feb 10, 2011 · Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as ...
[101]
Sunitinib in pancreatic neuroendocrine tumors: updated progression ...
In summary, our current results confirm the benefit of sunitinib and show that the efficacy findings are robust after longer term analysis. BICR confirmed the ...
[102]
Paltusotine, Oral SST2 Agonist - Crinetics
Paltusotine is also in clinical development for carcinoid syndrome associated with neuroendocrine tumors (NETs) as part of a global Phase 3 pivotal trial.
[103]
Crinetics Announces FDA Approval of PALSONIFY™ (paltusotine ...
Sep 25, 2025 · Paltusotine is also being evaluated for the treatment of carcinoid syndrome in the pivotal Phase 3 CAREFNDR trial. Conference Call and Webcast
[104]
Survival Rates for Gastrointestinal Carcinoid Tumors
Aug 8, 2025 · The SEER database tracks 5-year relative survival rates for GI neuroendocrine ... Accessed at https://seer.cancer.gov/explorer/ on June 13, 2025.
[105]
Survival Rates for Lung Carcinoid Tumors - American Cancer Society
Jun 26, 2025 · The SEER database tracks 5-year relative survival rates for lung carcinoid tumor in the United States, based on how far the cancer has spread.
[106]
Factors Affecting Survival in Neuroendocrine Tumors: A 15-Year ...
In the study by Ma et al., (2017) the 5-year survival rate was 58.4% while survival rates in G1, G2 and G3 were 100%, 71.4% and 44.4%, respectively. In our ...
[107]
Long-term survival in patients with gastroenteropancreatic ...
Five-year OS was 81% (95%CI: 79–83), 78% (95%CI: 72–84) and 26% (95%CI: 22–30) in patients with non-metastatic G1, G2 and G3 NENs, respectively (Table 2 and Fig ...Original Research · 3. Results · 3.2. Overall And Relative...
[108]
Appendiceal neuroendocrine tumor | Radiology Reference Article
Sep 1, 2025 · Appendiceal NETs have a more benign course than other gastrointestinal carcinoids, rarely metastasizing, with a 5-year survival rate of >90% 2,3 ...<|separator|>
[109]
Carcinoid Lung Tumors - Medscape Reference
May 13, 2024 · Between 25% and 39% of patients with a carcinoid pulmonary tumor are asymptomatic. The vast majority of symptomatic patients have symptoms ...
[110]
Treatment of Liver Metastases of Carcinoid Tumors - PubMed
In a consecutive series of 64 patients with the midgut carcinoid syndrome we thus attained a 5-year survival rate of 70%. Fourteen of the patients underwent ...
[111]
Long-term prognostic factors for PRRT in neuroendocrine tumors - NIH
Jun 9, 2023 · PRRT is an effective and well-tolerated treatment option for patients with neuroendocrine tumors (NETs) that prolongs progression-free survival (PFS).
[112]
Carcinoid Tumors - PMC - PubMed Central - NIH
Carcinoid tumors are rare, slow-growing neuroendocrine tumors arising from the enterochromaffin cells disseminated throughout the gastrointestinal and ...Introduction · Tumor Biology · Surgical Treatment
[113]
Prognostic differences in grading and metastatic lymph node pattern ...
Jun 19, 2023 · Remission after surgery was less often achieved in patients with higher Ki67 index (> 10%). Lymph node metastases (N +) were present in 174 ( ...Material And Methods · Table 4 · Table 2<|control11|><|separator|>
[114]
Characteristics and long-term prognosis of patients with rectal ... - NIH
In those with tumors ≥ 2 cm with muscular or serosal invasion, the 5-year survival rate was 50% (3/6), and in those with distant metastasis, the 5-year survival ...
[115]
Treatment Approaches and Outcome of Patients with ...
May 31, 2022 · Median overall survival for the entire cohort was 31 months. Stage, performance status and Ki67 were significant prognostic factors in ...
[116]
Carcinoid heart disease: presentation, diagnosis, and management
Carcinoid heart disease is a rare, but interesting and important cause of intrinsic tricuspid and pulmonary valve disease leading to significant morbidity and ...Aetiology And... · Diagnosis · Carcinoid Heart Disease: Key...
[117]
Current best practice in the management of neuroendocrine tumors
The prognosis of siNENs depends on histopathological grade and TNM staging and 5-year OS ranges between 50% and 60%. In siNENs with locally advanced disease 5- ...
[118]
Consensus Guidelines for the Management and Treatment of ...
Follow-up for advanced disease is recommended every 3-6 months; can lengthen interval to every 6 months for patient with long duration (>12 month) of stable ...
[119]
SEOM-GETNE clinical guidelines for the diagnosis and treatment of ...
May 19, 2023 · The relapse rate in lung NET ranges between 4 and 26%, in SI-NET between 23 and 58% and in panNET between 12 and 69% [80, 81]. Nevertheless, ...
[120]
Liver transplantation for metastatic neuroendocrine tumors - PMC
Five-year recurrence-free survival rates ranged from 20 to 30% in largest series [9,11,12]. In Coppa et al.'s study comparing liver resection and LT; recurrence ...
[121]
The eminent German pathologist Siegfried Oberndorfer (1876-1944 ...
Carcinoid tumors of the gastrointestinal tract belong to the group of neuroendocrine tumors of epithelial origin. 19th century pathologists used to divide the ...
[122]
Siegfried Oberndorfer and the Evolution of Carcinoid Disease
Feb 1, 2007 · His unique observations regarding multiple small-intestinal tumors were presented at the German Pathological Society convention (Dresden, ...
[123]
Carcinoid Tumors: Past, Present, and Future - PMC - NIH
May 9, 2020 · Carcinoid tumors, now more specifically referred to as small bowel neuroendocrine tumors (SBNETs), were previously rare tumors which were ...Diagnosis · Radiology · TreatmentMissing: definition | Show results with:definition
[124]
Chapter 19. Carcinoid Tumors - AccessSurgery - McGraw Hill Medical
Carcinoid tumors were first described in a 1907 paper titled "Karzinoide Tumoren des Dünndarms," or "Cancer-like Tumors of the Gut," by the German pathologist ...
[125]
Malignant carcinoid of the small intestine with metastases ... - PubMed
Malignant carcinoid of the small intestine with metastases to the liver, valvular disease of the right side of the heart (pulmonary stenosis and tricuspid ...
[126]
NEUROENDOCRINE EMBRYOLOGY AND THE APUD CONCEPT
Pearse, A.G.E. & Polak, J.M. (1971b) Neural crest origin of the endocrine polypeptide (APUD) cells of the gastrointestinal tract and pancreas. Gut, 12, 783 ...Missing: tumors history
[127]
The origin of neuroendocrine tumors and the neural crest saga
Apr 1, 2011 · Although the possible endocrine nature of Kultschitsky's cells and the relationship of these cells to carcinoid tumors had been suggested by ...
[128]
Inhibition of Growth Hormone Secretion in the Rat by Synthetic ...
Cite. PAUL BRAZEAU, JEAN RIVIER, WYLIE VALE, ROGER GUILLEMIN, Inhibition of Growth Hormone Secretion in the Rat by Synthetic Somatostatin, Endocrinology ...
[129]
Somatostatin analogues in acromegaly and gastroenteropancreatic ...
After its discovery in 1979, octreotide became the first synthetic biologically stable somatostatin analogue with a short-acting formulation of octreotide ...
[130]
The ENETS and AJCC/UICC TNM classifications of the ...
Apr 27, 2010 · In 2006 a working group of the European Neuroendocrine Tumor Society (ENETS) developed and published a proposal for a TNM staging ...
[131]
The new WHO classification of gastrointestinal neuroendocrine ...
The 2019 World Health Organization (WHO) classification of gastrointestinal tumors defines well-differentiated grade 3 neuroendocrine tumors, the mixed ...Missing: 2022 | Show results with:2022
[132]
Phase 3 Trial of 177 Lu-Dotatate for Midgut Neuroendocrine Tumors
Jan 12, 2017 · We report here results from the phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial, which evaluated the efficacy and safety of 177Lu ...
[133]
https://pmc.ncbi.nlm.nih.gov/articles/PMC8406677/
[134]
Current Concepts in 68Ga-DOTATATE Imaging of Neuroendocrine ...
Nov 1, 2017 · Ga-DOTATATE PET/CT showed high sensitivity (>94%) and specificity (>92%) for NEN lesion localization, with the highest accuracy being for ...
[135]
An update on genetically engineered mouse models of pancreatic ...
Nov 2, 2022 · An update on genetically engineered mouse models of pancreatic neuroendocrine neoplasms ... RIP-Tag models are unique models of early-onset ...Missing: carcinoid | Show results with:carcinoid
[136]
An update on genetically engineered mouse models of pancreatic ...
Nov 2, 2022 · In this review, we present the state of the art of the most relevant PanNEN GEMMs available and correlate their findings with the human neoplasms' counterparts.
[137]
Alleles of Insm1 determine whether RIP1-Tag2 mice produce ...
Feb 22, 2019 · This is partly due to the fact that PanNETs are produced by the RIP1-Tag2 tumor model (RT2), which was one of the very first transgenic mouse ...
[138]
A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors ...
Integrated mRNA and miRNA profiling of mouse and human pancreatic neuroendocrine tumors (PanNET) identifies distinct subtypes and validates the RIP1-Tag2.
[139]
Exploring the tumors of multiple endocrine neoplasia type 1 in ... - NIH
The frequency of MEN1 germline mutation is much lower in MEN1 index cases without a family history of MEN1 (1–10%) [2]. MEN1 is rare but the sporadic ...
[140]
A mouse model of multiple endocrine neoplasia, type 1, develops ...
Men1 Gene Targeting. To target the mouse gene by homologous recombination in ES cells, an intended conditional knockout construct was developed that contained ...
[141]
Multiple endocrine neoplasia type 1 knockout mice ... - PubMed
Multiple endocrine neoplasia type 1 knockout mice develop parathyroid, pancreatic, pituitary and adrenal tumours with hypercalcaemia, hypophosphataemia and ...
[142]
Carcinoid Syndrome: Preclinical Models and Future Therapeutic ...
BON-1 cells represent the best characterized and used in vitro experimental model for drug testing in NETs. A dose dependent cytotoxic effect of the tyrosine ...
[143]
Predictive factors of response to mTOR inhibitors in neuroendocrine ...
This cell line, the BON1 cells, displays constitutive activation of the Akt/mTOR pathway due to an autocrine IGF-I loop (von Wichert et al. 2000). Zitzmann also ...
[144]
Establishment and characterization of a human carcinoid in nude ...
The authors have established a long-term tissue culture cell line (BON) derived from a metastatic human carcinoid tumor of the pancreas. The cells have been ...Missing: mTOR inhibitors
[145]
Zebrafish as an innovative model for neuroendocrine tumors in
Amino acids affected by inactivating missense mutations in MEN1 patients in this region are completely conserved between human and zebrafish. Such a high ...
[146]
Isolation, characterization, expression and functional analysis of the ...
Feb 5, 2014 · Of the 81 missense mutations and in-frame deletions reported in MEN1 patients, 72 occur in residues that are identical in zebrafish, suggesting ...
[147]
Spontaneous tumors in dogs and cats: models for the study of ...
Spontaneous tumors in dogs and cats are appropriate and valid model tumor systems available for testing cancer therapeutic agents or studying cancer biology.
[148]
In Vivo Efficacy Testing of Peptide Receptor Radionuclide Therapy ...
Feb 1, 2023 · Peptide receptor radionuclide therapy (PRRT) is a form of internal radiation to treat patients with metastasized neuroendocrine tumors (NETs).
[149]
Enhancing the anti-tumour activity of 177 Lu-DOTA-octreotate ...
Jun 23, 2020 · PRRT holds great promise for the treatment of NET and our studies using a well characterised SSTR2-expressing preclinical tumour model ...
[150]
Preclinical Investigation of 212 Pb-DOTAMTATE for Peptide ...
Further studies showed that PRRT could be combined with chemotherapeutics to enhance efficacy (10–14). The studies presented here further support the use of ...<|separator|>
[151]
Attenuation of peripheral serotonin inhibits tumor growth and ...
Sep 15, 2021 · Serotonin promotes tumor growth in mouse models via enhanced PD-L1 ... Reporting of mouse studies followed the Animal Research Guidelines.
[152]
Carcinoids in Animals - Endocrine System - Merck Veterinary Manual
Carcinoids are a heterologous group of neuroendocrine tumors that occur in various regions of the GI tract, liver, lung, and occasionally heart.
[153]
Neoplastic diseases in ferrets: 574 cases - AVMA Journals
Sixty-one ferrets had multiple tumor types. Primary tumors were found in every system; endocrine (254; 39.7%).
[154]
Gastric neuroendocrine carcinoma (carcinoid) in a ferret (Mustela ...
Veterinary practitioners and diagnosticians should include neuroendocrine carcinoma as a differential diagnosis when encountering gastric neoplasms in ferrets ...
[155]
Hepatic neuroendocrine carcinoma in a ferret - Vetjournal
Sep 13, 2024 · Other endocrine tumors are infrequently reported including a single case of gastric neuroendocrine carcinoma (carcinoid).
[156]
an etiologic consideration for chronic colic in horses - PubMed
Intestinal carcinoid, or argentaffinoma, should be an etiologic consideration for horses with chronic colic. A mare was referred with a history of chronic ...
[157]
Three cases of carcinoid in the equine nasal cavity and ... - PubMed
Three cases of carcinoid tumor in horses are described. The tumors originated from the maxillary sinuses and the retrobulbar region and caused exophthalmos.
[158]
Cytologic and immunohistochemical characterization of a lung ...
With these findings the tumor was diagnosed as a primary lung carcinoid. Eleven months after resection, there was no evidence of tumor regrowth or metastasis.
[159]
Conference 20 - 2018 Case: 1 20180404
Apr 6, 2018 · In dogs, hepatic, gastrointestinal and pulmonary carcinoids have been reported. Carcinoid tumors are reported in both sexes, several ...
[160]
Poorly differentiated rectal carcinoid in a cow - PubMed
A carcinoid tumor was found as a solitary soft mass in the wall of the rectum adjacent to the anorectal junction in an adult Holstein cow.Missing: sheep appendiceal
[161]
Neoplasms in Domestic Ruminants and Swine: A Systematic ... - NIH
Feb 18, 2023 · The most frequent neoplasms were squamous cell carcinomas for cattle, goats, and sheep, while melanoma was the most frequent for pigs.
[162]
Neuroendocrine Tumors | VCA Animal Hospitals
Carcinoids in the intestine can cause symptoms like gastrinomas. As they grow in size, they can lead to an intestinal obstruction.