Islet Cell Tumor
Disease Details
Family Health Simplified
- Description
- Islet cell tumor, also known as pancreatic neuroendocrine tumor (PNET), is a rare type of tumor originating from the hormone-producing cells of the pancreas which can be either benign or malignant and potentially cause various hormonal imbalances.
- Type
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Islet cell tumors, also known as pancreatic neuroendocrine tumors (PNETs), are a type of cancer that arises from the hormone-producing islet cells of the pancreas. They can be either benign or malignant.
Type of genetic transmission: While most islet cell tumors occur sporadically without an identifiable hereditary pattern, a subset of these tumors may be associated with genetic syndromes such as Multiple Endocrine Neoplasia type 1 (MEN1) and Von Hippel-Lindau syndrome, which follow an autosomal dominant inheritance pattern. - Signs And Symptoms
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Some PanNETs do not cause any symptoms, in which case they may be discovered incidentally on a CT scan performed for a different purpose.: 43–44 Symptoms such as abdominal or back pain or pressure, diarrhea, indigestion, or yellowing of the skin and whites of the eyes can arise from the effects of a larger PanNET tumor, either locally or at a metastasis. About 40% of PanNETS have symptoms related to excessive secretion of hormones or active polypeptides and are accordingly labeled as "functional"; the symptoms reflect the type of hormone secreted, as discussed below. Up to 60% of PanNETs are nonsecretory or nonfunctional, in which there is no secretion, or the quantity or type of products, such as pancreatic polypeptide (PPoma), chromogranin A, and neurotensin, do not cause a clinical syndrome although blood levels may be elevated. In total, 85% of PanNETs have an elevated blood marker.Functional tumors are often classified by the hormone most strongly secreted, for example:
gastrinoma: the excessive gastrin causes Zollinger–Ellison syndrome (ZES) with peptic ulcers and diarrhea
insulinoma: hypoglycemia occurs with concurrent elevations of insulin, proinsulin and C peptide
glucagonoma: the symptoms are not all due to glucagon elevations, and include a rash, sore mouth, altered bowel habits, venous thrombosis, and high blood glucose levels
VIPoma, producing excessive vasoactive intestinal peptide, which may cause profound chronic watery diarrhea and resultant dehydration, hypokalemia, and achlorhydria (WDHA or pancreatic cholera syndrome)
somatostatinoma: these rare tumors are associated with elevated blood glucose levels, achlorhydria, cholelithiasis, and diarrhea
less common types include ACTHoma, CRHoma, calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone–related peptide tumorIn these various types of functional tumors, the frequency of malignancy and the survival prognosis have been estimated dissimilarly, but a pertinent accessible summary is available. - Prognosis
- Islet cell tumors, also known as pancreatic neuroendocrine tumors (PNETs), have varying prognoses depending on several factors, including the type of tumor (benign or malignant), its size, whether it has metastasized, and how well it responds to treatment. Generally, benign tumors tend to have a better prognosis, while malignant tumors can have a more guarded outlook. Early detection and treatment typically improve the chances of a favorable outcome.
- Onset
- Islet cell tumors, also known as pancreatic neuroendocrine tumors (PanNETs), typically have a variable onset. These tumors can develop at any age but are most commonly diagnosed in adults between the ages of 30 and 60. They can be either functional, producing hormones that cause various clinical syndromes, or nonfunctional, presenting with nonspecific symptoms or discovered incidentally on imaging.
- Prevalence
- The prevalence of islet cell tumors, also known as pancreatic neuroendocrine tumors (PNETs), is relatively low. These tumors are rare, with an incidence rate of about 1 in 100,000 people per year. Though they account for only 1-2% of all pancreatic cancers, the actual prevalence in the population may be slightly higher due to their often slow-growing nature and potential for late diagnosis.
- Epidemiology
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For islet cell tumor, also known as pancreatic neuroendocrine tumor (PNET):
**Epidemiology:**
- Incidence: Relatively rare, with an estimated incidence of 1-2 cases per 100,000 people per year.
- Age: Can occur at any age but most commonly diagnosed in individuals between 40 and 60 years old.
- Gender: Slightly more common in males than females.
- Risk Factors: Include multiple endocrine neoplasia type 1 (MEN1), von Hippel-Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis.
**Prevalence:**
- Represents about 1-2% of all pancreatic tumors.
- Can be functional (hormone-producing) or non-functional (non-hormone-producing) with non-functional tumors being more common.
Given the specialized nature of PNETs, it's important to consult medical literature or a healthcare provider for more detailed and specific information. - Intractability
- Islet cell tumors, also known as pancreatic neuroendocrine tumors (PNETs), vary in their level of intractability. The prognosis and management depend on factors such as the type of tumor (functioning or non-functioning), its size, malignancy, and whether it has metastasized. Some can be effectively treated with surgery, medications, and targeted therapies, making them potentially manageable. Others, particularly malignant or metastatic tumors, may be more challenging to treat, requiring a combination of therapies and having less favorable outcomes. Early detection and personalized treatment plans are crucial in managing the disease effectively.
- Disease Severity
- Islet cell tumor severity can vary based on whether the tumor is benign or malignant. Benign islet cell tumors generally have a good prognosis and are often surgically removable with minimal complications. Malignant islet cell tumors, however, are more serious and can spread to other parts of the body (metastasize), leading to significant health issues and requiring more aggressive treatments. Early detection and treatment are crucial for managing the severity of both types.
- Healthcare Professionals
- Disease Ontology ID - DOID:1799
- Pathophysiology
- Islet cell tumors, also known as pancreatic neuroendocrine tumors (PNETs), originate from the hormone-producing islet cells in the pancreas. The pathophysiology involves abnormal proliferation of these cells, leading to either functional or non-functional tumors. Functional tumors secrete excess hormones, causing specific clinical syndromes like insulinomas (excess insulin), gastrinomas (excess gastrin), or glucagonomas (excess glucagon). Non-functional tumors do not produce hormones but may cause symptoms by mass effect. Genetic mutations, such as those in the MEN1 gene, are often implicated.
- Carrier Status
- Carrier status is not typically applicable to islet cell tumors, as these tumors generally arise due to sporadic mutations rather than inherited genetic changes. They are a type of neuroendocrine tumor that develops in the hormone-producing islet cells of the pancreas.
- Mechanism
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Islet cell tumors, also known as pancreatic neuroendocrine tumors (PNETs), originate from the hormone-producing islet cells of the pancreas.
**Mechanism:**
The development of an islet cell tumor typically follows from abnormal growth and proliferation of islet cells. These tumors can be functional (producing hormones) or non-functional (not producing hormones).
**Molecular Mechanisms:**
1. **Genetic Mutations:** Several genetic mutations are associated with islet cell tumors:
- **MEN1:** Mutation in the MEN1 gene (encoding menin) is commonly seen in multiple endocrine neoplasia type 1 (MEN1) syndrome and can lead to PNETs.
- **DAXX/ATRX:** Loss-of-function mutations in DAXX (death-domain associated protein) and ATRX (alpha-thalassemia/mental retardation syndrome X-linked protein) are often observed.
- **mTOR Pathway:** Activation of the mTOR (mechanistic target of rapamycin) pathway due to mutations in genes like TSC2 (tuberous sclerosis complex 2) and PTEN (phosphatase and tensin homolog) can promote tumor growth.
2. **Epigenetic Changes:** Abnormal methylation patterns and histone modifications can lead to dysregulated gene expression, contributing to tumor development and progression.
3. **Hormonal Factors:** Functional islet cell tumors may secrete excess levels of hormones such as insulin, glucagon, or gastrin, leading to clinical syndromes like insulinoma, glucagonoma, or gastrinoma, respectively.
Understanding these molecular mechanisms helps in the diagnosis, classification, and development of targeted therapies for islet cell tumors. - Treatment
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In general, treatment for PanNET encompasses the same array of options as other neuroendocrine tumors, as discussed in that main article. However, there are some specific differences, which are discussed here.In functioning PanNETs, octreotide is usually recommended prior to biopsy: 21 or surgery: 45 but is generally avoided in insulinomas to avoid profound hypoglycemia.: 69 PanNETs in Multiple endocrine neoplasia type 1 are often multiple, and thus require different treatment and surveillance strategies.Some PanNETs are more responsive to chemotherapy than are gastroenteric carcinoid tumors. Several agents have shown activity. In well differentiated PanNETs, chemotherapy is generally reserved for when there are no other treatment options. Combinations of several medicines have been used, such as doxorubicin with streptozocin and fluorouracil (5-FU) and capecitabine with temozolomide. Although marginally effective in well-differentiated PETs, cisplatin with etoposide has some activity in poorly differentiated neuroendocrine cancers (PDNECs), particularly if the PDNEC has an extremely high Ki-67 score of over 50%.: 30 Several targeted therapy agents have been approved in PanNETs by the FDA based on improved progression-free survival (PFS):
everolimus (Afinitor) is labeled for treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease. The safety and effectiveness of everolimus in carcinoid tumors have not been established.
sunitinib (Sutent) is labeled for treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Sutent also has approval from the European Commission for the treatment of 'unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults'. A phase III study of sunitinib treatment in well differentiated pNET that had worsened within the past 12 months (either advanced or metastatic disease) showed that sunitinib treatment improved progression-free survival (11.4 months vs. 5.5 months), overall survival, and the objective response rate (9.3% vs. 0.0%) when compared with placebo. - Compassionate Use Treatment
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Compassionate use, also known as expanded access, allows patients with serious or life-threatening conditions to access investigational treatments outside of clinical trials. For islet cell tumors, compassionate use treatments might include:
1. **Peptide Receptor Radionuclide Therapy (PRRT)**: This treatment involves targeting tumors with radioactive substances linked to peptides. PRRT is mainly used for neuroendocrine tumors that express specific receptors.
2. **Everolimus (Afinitor)**: An mTOR inhibitor that is approved for pancreatic neuroendocrine tumors, but may also be available through compassionate use for other types of islet cell tumors.
3. **Sunitinib (Sutent)**: An anti-angiogenic tyrosine kinase inhibitor that may also be available via compassionate use if standard treatments are not effective.
Off-label or experimental treatments could include:
1. **Immunotherapy**: Drugs like pembrolizumab (Keytruda) and nivolumab (Opdivo) which are approved for other cancers but could be used off-label for islet cell tumors based on the tumor's characteristics.
2. **Chemotherapeutic Agents**: Off-label use of chemotherapies, such as capecitabine and temozolomide, which might not be specifically approved for islet cell tumors but can be used based on physician judgement.
3. **Targeted Therapy**: Investigational drugs targeting specific mutations or pathways in the tumor cells, which are being tested in clinical trials, may be available experimentally.
Patients interested in these options should discuss with their healthcare providers to understand eligibility, potential benefits, and risks. - Lifestyle Recommendations
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For individuals with an islet cell tumor, lifestyle recommendations generally focus on overall health and supporting treatment efficacy. These may include:
1. **Balanced Diet**: Maintain a well-balanced diet rich in fruits, vegetables, lean proteins, and whole grains. Depending on the tumor's effect on hormone production, specific adjustments might be needed.
2. **Regular Exercise**: Engage in regular physical activity to support general health, maintain a healthy weight, and improve energy levels.
3. **Regular Monitoring**: Frequent medical check-ups to monitor the condition and adjust treatment as necessary.
4. **Stress Management**: Practice stress-reducing activities such as yoga, meditation, or deep-breathing exercises.
5. **Avoid Alcohol and Tobacco**: Limiting or avoiding alcohol and quitting smoking can support overall well-being and reduce potential complications.
6. **Blood Sugar Management**: Due to possible effects on insulin production, closely monitor and manage blood sugar levels as directed by a healthcare provider.
Discussing and tailoring these recommendations with a healthcare provider is crucial. - Medication
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Islet cell tumors, also known as pancreatic neuroendocrine tumors (PNETs), are rare tumors that arise from the islet cells of the pancreas. The main types of medications used to manage these tumors include:
1. **Somatostatin Analogues**: Drugs like octreotide and lanreotide help control symptoms by inhibiting hormone release.
2. **Targeted Therapy**: Everolimus and sunitinib can inhibit tumor growth.
3. **Chemotherapy**: Agents such as streptozocin, often combined with other drugs like doxorubicin or 5-fluorouracil, are used, especially for more aggressive tumors.
4. **Peptide Receptor Radionuclide Therapy (PRRT)**: This involves using radiolabeled somatostatin analogues to target and destroy tumor cells.
Specific treatment plans should be tailored based on the type, stage of the tumor, and individual patient factors. - Repurposable Drugs
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For islet cell tumors (a type of neuroendocrine tumor affecting the pancreas), some drugs originally developed for other conditions have shown potential effectiveness. These repurposable drugs include:
1. **Everolimus**: Originally developed as an immunosuppressant for organ transplant patients, it also has anti-cancer properties through inhibition of the mTOR pathway.
2. **Sunitinib**: A tyrosine kinase inhibitor initially used for renal cell carcinoma and gastrointestinal stromal tumors, it has proven beneficial in treating pancreatic neuroendocrine tumors.
3. **Metformin**: Commonly prescribed for type 2 diabetes, it has shown potential anti-cancer effects in various studies by inhibiting cell proliferation and inducing apoptosis.
These drugs may be used under specific circumstances and should be administered under professional medical guidance. - Metabolites
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Islet cell tumors, also known as pancreatic neuroendocrine tumors (PNETs), can affect the production of various metabolites depending on whether the tumor is functional (hormone-producing) or non-functional. Some common metabolites associated with functional islet cell tumors include:
1. **Insulin** - Excess production can lead to hypoglycemia.
2. **Gastrin** - Increased levels can cause Zollinger-Ellison syndrome, leading to peptic ulcers.
3. **Glucagon** - Overproduction can cause hyperglycemia and a characteristic rash called necrolytic migratory erythema.
4. **Somatostatin** - Excess can inhibit other hormone secretions, causing diabetes, gallstones, and diarrhea.
5. **VIP (Vasoactive Intestinal Peptide)** - Overproduction can lead to Verner-Morrison syndrome, causing severe watery diarrhea and electrolyte imbalance.
Non-functional islet cell tumors typically do not produce hormones and, therefore, do not manifest with hormone-related symptoms but may still alter metabolism indirectly through mass effects on pancreatic function. - Nutraceuticals
- There is limited evidence supporting specific nutraceuticals for treating islet cell tumors, which are a type of neuroendocrine tumor found in the pancreas. Standard treatments typically include surgery, medication, and sometimes chemotherapy or radiation. It's crucial to consult a healthcare professional for personalized advice.
- Peptides
- Islet cell tumors, also known as pancreatic neuroendocrine tumors (PNETs), can secrete various peptides including insulin, gastrin, glucagon, vasoactive intestinal peptide (VIP), and somatostatin. These peptides can cause distinct clinical syndromes depending on which hormone is overproduced.