Neuroendocrine Tumors
This article on neuroendocrine tumors (NET) discusses cancers that are very rare. The total number of new cancers in the US in 2023 was almost two million, with 300,000 from breast cancer. There were only 12,000 new cases of NE cancers, affecting only 200,000 total people in the US.
Neuroendocrine tumors are unusual and uncommon, comprising less than 1% of all cancers but are uniformly malignant. They occur predominantly in the gastrointestinal tract, pancreas, and lung, but there are numerous subtypes, with each secreting a hormone specific to that tumor. As a result, each presents with its own symptomatology, hormone markers, treatment protocols, and prognosis. Because there are a diverse number of NECs and so few patients in each category, large clinical studies offering substantial information and data for treatment guidelines are unavailable. Treatments that will be discussed are the current approaches being used for evaluation and staging, but only the most common types will be mentioned, and for each, a brief summary.
These tumors can develop wherever there are endocrine cells in the body, which produce hormones. In normal situations, hormone secretion is tightly regulated, but in these tumors, often, their secretion and the downstream effects are unchecked, potentially influencing the regulation of growth, metabolism, and reproduction.
The typical staging and grading systems used in the categorizations of other tumors have been difficult to apply in NET. Normally, for example, colon cancer is found in a specific organ and is of a specific type of cell. Symptoms are generally abdominal pain, bleeding, changes in weight and appetite, etc., and can be staged based on its location.
Introduction
In neuroendocrine tumors, tissue sampling requires not only the histologic or microscopic appearance of the abnormal cells and their location via imaging, as in other cancers but uniquely must be integrated with the laboratory determination of the hormone that is secreted. So, while a specific organ is involved, the hormones being produced vary, requiring treating the tumor itself as well as controlling the hormone effects created by the tumor. So, because of the complexity of each cancer and its signs and symptoms, clinical expertise is needed to diagnose and treat these conditions, which means most patients are followed at large medical centers that have the most experience with NETs.
The cellular microscopic classifications include:
Well-differentiated neuroendocrine cancer, with behavior that is characterized by slow growth with a low risk of metastasis.
Well-differentiated neuroendocrine cancer whose behavior is uncertain.
Poorly differentiated neuroendocrine cancer or high-grade carcinoma, often related to small cell lung cancers, with rapid progression and poor long-term survival.
Currently, the addition of the Ki67 laboratory marker is used to indicate the percentage of positive cancer cells that are rapidly replicating, based on cellular nuclear division. It allows improvement in the overall discrimination of disease aggressiveness.
Further considerations that must also be integrated include the specific hormones produced and secreted by the tumor, each of which can affect treatment and prognosis. Some tumors, however, produce hormones that are nonfunctional.
Recently, the definition of these diseases has undergone changes in terminology, with a neuroendocrine tumor (NET) being regarded as a well-differentiated tumor while a neuroendocrine carcinoma (NEC) is considered a poorly differentiated type.
Evaluation and treatment of neuroendocrine tumors require establishing their location, determining the organ involved, the size and number of tumors, testing to discover the endocrine hormones being produced, and deciding on the management either through surgery, medical pharmaceuticals, or both.
Known Risks for NET
There are systematic reviews of dozens of studies of neuro-endocrine tumors (NET) and their association with:
A higher incidence of NEC if there are other family members that have had one.
Elevated BMI, body mass index
Diabetes
Long-term heavy smoking for lung
Association with Other Diseases
Overall, the majority of these tumors arise spontaneously for reasons unknown,
but there are diseases that appear to predispose to the development of these tumors.
These include:
Multiple Endocrine Neoplasia, Type 1 is an extremely rare hereditary disease which presents most commonly with neuroendocrine tumors of the pituitary, parathyroid gland or pancreas but organs may also develop tumors.
Von Hippel Lindau Syndrome is a rare condition that can produce cancerous and non-cancerous tumors in various parts of the body. There is a VHL genetic variant that affects a tumor suppressor gene.
Both diseases listed below are recognized in early childhood or adolescence
Neurofibromatosis is another rare genetic disease with different skin lesions and pigmented spots, benign nerve sheath tumors, and cognitive developmental issues.
and Tuberous Sclerosis is a genetically inherited disease with brain issues. These include benign tumors, neurodevelopmental, and psychiatric issues.
Neuroendocrine Gastroenteropancreatic Tumors (GEP-NETs)
These tumors require evaluations to determine not only its origin as well as the type of hormone being produced. As discussed above, the complexity of the hormones produced requires an in-depth understanding of the symptoms each can produce and how to regulate and manage their secretion.
The hormones possibly secreted by these GEP-NETs are:
In intestinal NETs, approximately half are carcinoid tumors, secreting the hormone serotonin. If the tumor spreads to the liver, which happens in one-third, these are the people who present with the characteristic symptoms associated with carcinoid syndrome. These include asthmatic wheezing, diarrhea and cramps, scarring of the heart lining, and flushing.
Pancreatic neuroendocrine tumors account for ⅓ of gastro GEP-NETs, with one half functional, the other half non functional
Calcitoninoma
Calcitonin normally acts as a counterbalance to parathyroid hormone. Calcitonin decreases calcium while parathyroid hormone increases it. It is the classic hormone released in medullary thyroid cancer but can be secreted in other cancers, lung, breast, prostate, and colon. It is extremely rare in pancreatic cancers.
GRFoma (Growth Hormone Releasing Factor)
ACTHoma
Somatostatinoma
Gastrinoma
Insulinoma
Glucagonoma
VIPoma( Vasoactive Intestinal Peptide Secreting Tumor)
CRHoma,( Corticotropin- Releasing Hormone Secreting Tumor)
Parathyroid hormone-peptide hormone is a rare NET of the pancreas that causes increases in calcium levels that are aggressive and difficult to control
Neurotensinoma
PPoma
Location of Neuroendocrine Tumors
Gastrointestinal /HepatoBiliary Tumors
Pancreas
Colon
Rectum
Hepatopancreatic Duct
Appendix
Lung Neuroendocrine Tumors Include:
Carcinoid Tumors
Small Cell Lung Cancer
Large Cell Neuroendocrine Lung Cancer
Imaging of Tumors
The imaging of neuroendocrine tumors utilizes CT, MRI, ultrasound, and PET scans to Determine The Location and Extent of disease. Using these modalities, small intestine tumors can be seen in 50% of cases and pancreatic lesions in >80%, while 90% of lung tumors can be seen on x-rays, but other modalities are often used for more detailed information.
Neuroendocrine Neoplasms (NEN’s) often express somatostatin receptors. Somatostatin is a hormone that can slow the production of insulin, glucagon, growth hormone, ACTH, and serotonin, making it useful as a medical treatment in many NENs. Since many NENs secrete these hormones, PET scans can use analogs, which are pharmaceutically synthesized forms of somatostatin, to assess both the number of tumor receptors and the potential controlling the hormone secretion from the tumor.
Staging
While these tumors are characterized by location and the hormones they are producing they are still staged.
Gastrointestinal endocrine tumors (NETs) are generally staged according to the depth of invasion into the tissue until in extends beyond the organ into adjacent tissue
Carcinoid Tumor of the Lung is generally described in stages related to the size of the lesion and the total number of tumors and if invasion of adjacent tissues has occurred. There are also carcinoid tumors of the gastrointestinal/liver-biliary system.
Pancreatic Neuroendocrine Tumors are staged according to the size of the tumor until it invades other areas and adjacent organs.
Common Gastroenteropancreatic Neuroendocrine Tumors
Carcinoid Tumors
For many years, all neuroendocrine tumors (NET) were generally labeled carcinoid tumors. It was a generic term that designated tumors in the digestive tract, intestines and pancreas, lungs, and uncommonly in the kidney and ovary.
These tumors can also be categorized by their original embryologic location. The digestive system starts as a closed tube, the top or foregut ( thymus, stomach, lung, and first part of duodenum, midgut (lower segments of the small intestine and initial portion of the colon, and hindgut, the end of the tube (colon and rectum)
The current designation as a carcinoid NET is that it secretes serotonin. Many of these tumors do not produce the characteristic “carcinoid syndrome”, which occurs only in only 10% of cases, because the excess hormone is metabolized or neutralized in the liver unless liver metastasis has occurred, and then metabolism is impaired allowing serotonin levels to increase.
Carcinoids produce serotonin so the diagnosis is directed at the metabolites of serotonin called biogenic amines.
The most common include:
(5-HIAA) 5-hydroxy-indole-acetic acid is the final product in the metabolism of serotonin, which is 100% specific for carcinoid if it is present in a 24 hr. urine
(CgA) Chromogranin A represents the storage vesicles of serotonin and glucagon. The level is indicative of the amount of tumor.
Symptoms of carcinoid tumors generally appear when levels of serotonin increase from metastasis. They include:
Right-sided valvular heart disease
GI symptoms of vomiting, nausea and diarrhea
Enlarged liver
Skin flushing
Respiratory - cough, wheezing and shortness of breath
Scarring of tissues in the back of the abdominal cavity
Treatment
Carcinoid tumors are rare, slow growing and often nonfunctional, don't secrete serotonin.
In oncology practices, carcinoid tumors account for < 1% of patients.
If possible, surgery to remove the tumor is the best option, and if successful, is often curative.
Somatostatin analogs can medically control hypersecretion of serotonin
If metastatic, laser or radiofrequency ablation can be used
Combination chemotherapies are also treatment options
Insulinoma
Insulinoma is so extremely rare that many physicians have no experience in treating it, so, as mentioned, most people are evaluated and treated at large centers. It occurs almost equally in men and women and is usually discovered in older adults over 50.
Normal Insulin Secretion
Insulin is a complex protein(51 amino acids) that is secreted by the Beta cells of the pancreas and by a small concentration in specific neurons in the central nervous system. Normally, blood sugar levels are controlled and sustained within a very tight range, based on real-time blood levels, with increases caused by the production of sugars from the diet and a lowering using storage in the liver, muscles, and adipose tissues.
Abnormal Insulin Secretion
An insulinoma is commonly a benign functioning neuroendocrine tumor of the pancreas that secretes insulin. While normal regulation is based on physiologic needs,in an insulinoma, there is uncontrolled, often excessive secretion causing hypoglycemia.
Symptoms of low blood sugar were recognized in the nineteenth century, but in the 1920, Drs Banting and Best purified insulin from cattle and saved a young boy with diabetes. They received the nobel prize for their work, ushering in a new era of treatment for diabetes. It was also noted that overtreatment with too much insulin causes low blood sugar.
The discovery of insulinomas occurred when people presented with symptoms of low blood sugar, but did not take insulin for diabetes. It was speculated that these people were making excess insulin, and diagnosed as having hyperinsulinemia of unknown cause. Several years after insulin was introduced, a patient with severe episodes of low blood sugar was shown to have a malignant pancreatic islet cell tumor, and when the pancreas tumor tissue was injected into rabbits, it caused hypoglycemia.
The result of excess insulin production from an NET or inappropriately high insulin dosage used in diabetes results in symptoms of hypoglycemia, seen clinically involving both systemic reactions as well as its effects on the brain.
These include:
A sympathetic/adrenal response including, sweating, dizziness, palpitations, and shaking
Neurologic symptoms including, seizure, confusion, visual changes and altered mood
Short-term impaired memory
Most commonly, insulinomas are benign, single or multiple neuroendocrine tumors of the pancreas,with ninety percent being localized in the pancreas and non-metastatic. Those that are considered malignant usually spread outside the pancreas.
The other 10% of these tumors are associated with Multiple Endocrine Neoplasia type 1 (MEN-1)
A hereditary genetic cancer in which there is a mutation of the MEN gene, a tumor suppressor gene that normally controls cell growth and division.
They are primary tumors that occur in the parathyroid glands, anterior pituitary, digestive/pancreas endocrine cells, but can occur in the thymus or bronchi, carcinoid tumor or gastric tumor.
Diagnosis is defined as having two of the three primary tumors or a family history of MEN-1.
Clinical Diagnosis of Insulinoma
Diagnosis is based on high insulin levels occurring associated with fasting or during unprompted hypoglycemic situations.
Documentation of low glucose levels (<45-50) after a 2-hour fasting combined with markers of elevated insulin including: elevated serum insulin, C peptide and proinsulin
Almost three-quarters of people will present with fasting hypoglycemia or low sugar after eating. Clinically, many of these people have low blood glucose and hypoglycemic symptoms which diminishes when the blood sugar goes up.
Laboratory Diagnosis Using Biochemical Testing are:
Increased insulin,
Increased proinsulin
Increased C peptide, which is a byproduct of insulin production and can reliably indicate the amount of insulin being made in the pancreas.
Diagnostic Imaging
Is utilized to locate the tumor and to determine the appropriate treatment
Radiology Imaging with CT or MR
Selective arterial calcium stimulation can stimulate insulin secretion as measured by liver blood samples
During exploratory surgery, using real-time Ultrasound examination
Surgical Intervention can be used to
Remove the tumor
Surgery is an option if the tumor is localized to the pancreas and is accessible. It is smaller and has few additional tumors. A single nonhereditary non-cancerous tumor is curable if removed.
Remove a portion of the pancreas
And if the tumor is obstructing the flow of bile and pancreatic enzymes, a radical whipple procedure may be necessary, requiring removal of the head of the pancreas, the duodenum, and part of the stomach, and reconfiguring and connecting them.
Medical Therapy is designed to control symptoms of hypoglycemia
Diet:
Several small meals a day
whole grains( complex carbohydrates), nuts and seeds, vegetables, proteins, eggs, clean meat, fish and poultry, all of which slow digestion digest to help maintain sugar balance and avoid hypoglycemia.
avoidance of concentrated sugars, from juices, candy, soda, sugary snacks and processed foods·
Medications
Drug therapies are often used prior to surgery, or in situations where there is a recurrence or malignant disease to control blood sugar ranges.
These include
Diazoxide Is used to decrease or inhibit insulin release and is indicated for benign or malignant islet cell tumors and those not surgical candidates.
The side effect profile percentages are limited due to the small number of people taking it
Common side effects:
The most concerning are excessive hair growth face, chest, thighs and back primarily in women and marked swelling
Tachycardia, heart failure, elevated BP, low white count and platelets, diarrhea
Octreotide is similar to somatostatin, inhibits growth hormone but in therapeutic doses, also inhibits thyroid stimulating hormone (TSH ), glucagon, which raises blood sugar, and, while limited in its effect, insulin. It is generally used in other NE tumors, but if the person doesn't tolerate Diazoxide, it is sometimes used.
Metastatic Disease
Spread of disease is generally to the liver and local lymph nodes but can involve the peritoneal lining of the abdomen and the lungs.
Liver metastasis, if limited, and function is normal disease can be treated with removal of the tumor or with
Hepatic embolization in which a catheter is placed in the hepatic artery to eliminate the blood supply to the cancer.
Other Common Pancreatic Neuroendocrine Tumors
Ppomas are silent neuroendocrine tumors that secrete pancreatic polypeptides or proteins. While they do not cause hormonal issues, they grow slowly, reaching a large size, often causing blockages of the pancreatic and bile ducts and associated symptoms of abdominal pain, jaundice, and weight loss. At the time of diagnosis, they are malignant and have commonly metastasized to the liver. Laboratory markers of polypeptides and chromogranin can help delineate what kind of tumor mass is present. Surgery is used to relieve symptoms as the tumor is spread to the liver. Chemotherapy is also an option for treatment, but uniformly the expected length of survival is short.
VIPomas secrete vasoactive intestinal peptide, which can occur in adults and children, presenting commonly with severe watery diarrhea. Confirmation is via laboratory peptide measurement. Initially, rehydration and electrolyte replacement are needed, followed by somatostatin analogs to reduce symptoms. While surgery is the first option, when possible, but >50% have metastasized at the time of diagnosis. Treatment then often adds chemotherapy or molecular targeted therapy.
Glucagonoma
This is a rare neuroendocrine tumor that originates in the pancreas, which secretes excessive glucagon. Glucagon is a hormone utilized by the body to regulate blood sugar when it is low. Glucose is the primary carbohydrate stored in the liver and muscles as glycogen. In situations of low blood sugar, glucagon is secreted by the pancreas and it acts to release this stored sugar for energy. Glucagon secretion, normally, is inhibited by elevated blood sugar and the presence of insulin.
These tumors are usually cancerous and are often discovered late, with half already having spread outside the pancreas. They are generally single, relatively large tumors, but only one-quarter can be cured by removing the tumor, but because of its tendency to spread, treatment is indicated to reduce a greater risk of metastasis.
Glucagonoma Syndrome
The over-secretion of glucagon from the tumor results in the symptoms of:
A specific dermatitis called necrolytic migratory erythema which causes plaques and raised lesions that join together as large fluid lesions and inflammation of tongue and mucous membranes in the mouth
Weight loss
These two symptoms occur in 90% of patients.
Almost three-quarters of people develop diabetes
And half of people develop significant depression,
Deep vein clots
Diarrhea
Making a Diagnosis
Very high fasting blood sugar
Skin biopsy
Sophisticated methods to evaluate glucagon levels
Imaging using CT, MRI, PET scans and the tumors having somatostatin receptors an octreotide scan.
Management Initially
Surgical reception, if possible
Somatostatin analogs, octreotide and lanreotide help inhibit glucagon actions and glucagon secretion.
Anticoagulation to prevent deep vein clots
Metastatic Therapies
Liver spread is common and treatments include:
Hepatic artery embolism to shut of the tumor blood supply
Radiofrequency tumor destruction
Chemotherapy
Targeted molecular therapies
Peptide receptor radionuclide therapy combines a protein that binds to specific tumor cell receptors that carry radiation to destroy the tumor.
These tumors are slow-growing but many have already spread at the time of diagnosis, so the determination of long-term survival depends upon the patient’s immune status, the aggressiveness of the tumor and if there is distant metastasis.
Gastrinoma
When the subjective feeling of hunger occurs or someone starts to eat, the vagus nerve stimulates the release of a hormone, gastrin, from G cells, at the far end of the stomach at the duodenum. It is released into the bloodstream, binds at the upper part of the stomach, and stimulates histamine, which results in the production of stomach acid, activates pepsin, an enzyme to help digest protein, as well as the release of vitamin B12. Normally, when the pH acid level reaches the correct level for digestion, gastrin secretion stops.
Zollinger Ellison Syndrome is a neuroendocrine tumor, found in the small intestine or pancreas that produces excess acid. The effects of excess acid secretion are peptic or stomach ulcers and sometimes bleeding, nausea, weight loss, diarrhea, esophageal inflammation and scarring from reflux of acid and abdominal pain.
Diagnosis specifically measures serum gastrin levels.
Treatments include:
Surgical removal of the tumor
Block the blood supply to the tumor via embolization
Radio Wave destruction of the tumor
chemotherapy
Somatostatinoma
This is an extremely rare NEC that secretes the hormone somatostatin. Its origin is either in the body or the head of the pancreas, where it connects to the small intestine at the duodenum. Its action is to inhibit the secretion of insulin, glucagon, growth hormone and gastrin.
Approximately one-third are associated with the hereditary multiple endocrine neoplasia-1 (MEN-1)
Interestingly, many do not present because of excess hormone production but rather with abdominal issues, pain, GI bleeding, and diarrhea, or if metastatic to the liver, with jaundice.
If it inhibits insulin, which is produced in the pancreas, diabetes can potentially occur.
They are usually discovered when imaging, CT or MRI, is done because of the above-mentioned symptoms.
Treatment
Surgery is a consideration, in a limited number of cases as generally 75-80% are metastatic at the time of discovery.
GRFoma (Growth Hormone Releasing Factor)
These tumors secrete growth hormone originating in carcinoid tumors, pancreatic cell tumors, small cell lung cancer, adrenal adenomas, endometrial tumors (the uterus) and the outer adrenal gland, called a pheochromocytoma.
Normally growth hormone tumors are associated with acromegaly, giant people, related to the pituitary losing its regulatory ability. This does not happen with these NEC, and they are the only types in which growth hormone measurements can be used for diagnosis.
Non-Surgical Therapies for Neuroendocrine Gastroenteropancreatic Tumors Using Somatostatin
Many of these tumors secrete a hormone called somatostatin. It is a regulatory hormone, made in the body with a wide distribution in tissues and the brain. It acts as a neurotransmitter able to send information and messaging that control the release or inhibition of growth hormone, thyroid stimulating hormone, gastrin, serotonin, insulin, glucagon, gastrin and pancreatic enzymes. Because many neuroendocrine tumors secrete these different hormones, treatment with a somatostatin analog, a pharmaceutically developed drug that is structurally similar to somatostatin, can be used to bind to the same receptors and control and regulate the excess secretion of these hormones. This makes them useful in symptomatic disease or in people who are not surgical candidates.
The Analog Drugs used are: (both are injected in treatment)
Octreotide
Side effects include:
27% Gallstones
24% Gallbladder sludge
30% Headache
12% Low thyroid function or hair loss
25% Auto antibodies to the drug
Lanreotide, a long-acting analog
Side effects include:
Similar risk of gallstones or sludge
18% abnormally slow heartbeat
30% itching 19% musculoskeletal pain
Management of Neuroendocrine Gastroenteropancreatic Tumors that are unresectable, implying they cannot be removed using surgery.
Grading of the tumor is important, and low grade and intermediate grade are
tumors that are more amenable to medical therapies, while more aggressive tumors with rapid replication measured via mitosis index and Ki67, indicating aggressiveness and invasiveness, are less likely to respond long-term.
Asymptomatic people with low amount of tumor burden are watched and followed closely
In symptomatic people or with increased tumor quantity:
1. Those that have somatostatin receptors (SSTR) on the tumor cells benefit from long acting somatostatin created analogs that act to decrease symptoms and tumor growth.
2. Those with low or intermediate-grade disease that have liver involvement that is unresectable can be treated with embolization or disrupting the blood supply to the tumor.
3. For people with SSTR receptors but aggressive or large tumors, somatostatin analogs plus peptide receptor radionuclide therapy is beneficial. This is delivering radiative material to the tumor.
Common Lung Neuroendocrine Tumors Include:
Carcinoid Tumors
These are rare, accounting for only a few percent of lung tumors, but in perspective, they are one-quarter of NETs.
These tumors are:
Typical carcinoid tumors are slow-growing, tend to be located in the central lung area and remain there and do not metastasize. They are difficult to reach surgically, and since chemotherapy and radiation are designed to destroy rapidly dividing cells, their effect is limited.
Atypical Carcinoid Tumors are found in the lung periphery, and can be slow or aggressively growing. When growing rapidly, half metastasize to lymph nodes and bone. Because of the rapid growth they are usually very responsive to treatment.
Neuroendocrine Lung Cancers
The recent recommendations that long-term cigarette smokers be screened with regular lung CAT scans appear justified in that multiple types of lung cancers, including NETs, can often be discovered early, providing the best opportunity for successful treatment.
These are markedly abnormal cells that behave aggressively and metastasize to the bones, adrenals and often the brain. Genetically only 5% originate from a hereditary genetic mutation, the MEN-1, multiple endocrine neoplasia.
They include:
Small Cell Lung Cancer (SCLC)
These tumors account for 15% of all tumors in the lung and are divided into 2 subtypes.
Oat cell combination, composed of SCLC and either adenocarcinoma or squamous cell carcinoma. It is highly associated with heavy cigarette smoking.
Its development is related to a mutation inhibiting the inability to perform DNA repair and effect tumor suppression.
Without any treatment the life expectancy is only a few months. But regardless of the extent of disease, chemotherapy can be effective.This NET of the Lung reveals markedly abnormal cells that have aggressive behavior and frequently metastasize to the adrenals, bone, and often the brain.
Symptoms for this and LCNEC, listed below, are respiratory-related, with a persistent cough, sometimes producing blood, shortness of breath, and frequent lung infections. The systemic symptom of fatigue is also common.
Imaging is initiated based on symptoms with a chest x-ray or lung CT. When abnormal, tissue is obtained either via bronchoscopy, which is a scope to visualize the inside of the airways, or by surgery to perform a needle biopsy or with large tumors a removal of a section of the lung.
Staging: Length of survival is improved with
Limited disease, localized to one area of the lung and associated lymph nodes or
Initially limited to a single side of the lung, and centrally located. The 2-year survival is 80% but 15% at 5 years
Current Therapy:
Initial Therapy:
Cisplatin and Etoposide (Toposar and Etopophus)
Extensive Disease
is treated with Atezolizumab, a PD-1 inhibitor in combination with carboplatin and etoposide
Large Cell Neuroendocrine Carcinoma (LCNEC) of the Lung
Large-cell neuroendocrine carcinoma is a rare pulmonary cancer. Using genetic sequencing the cellular appearances observed are mixed, with cells commonly having characteristics of both small cell, and a subtype squamous cell carcinoma and non-small cell cancer but also adenocarcinoma and adenocarcinoma, the commonest form of lung cancer.
It is characterized by the large cell size which appears atypical or undifferentiated indicating aggressive behavior, and having the appearance and lab testing that are seen in neuroendocrine tumors.
Because it is so rare and there are no controlled trials of treatment oncologists have approached therapies based on what is currently available for non-small cell and small cell lung cancers.
Risk factors
The primary risk is being a smoker with a long history and a large number of packs/day and as result there is increased risk for those exposed to secondhand smoke.
Environmental exposures including asbestos, air pollution and radon. Radon is a naturally occurring radioactive gas that can be tested for in homes and remediated.
Beer was a significant risk for lung cancer and subtypes. In addition, eating a low beef, high cereal fiber, and high nonoily fish diet lowered the risk of lung cancer, as did eating dried fruit.
Presentation
The symptoms of lung cancer are similar for the different types, with fatigue, shortness of breath, referred pain causing shoulder or chest pain,and weight loss. Lung cancer can be diagnosed by a variety of techniques from needle biopsy, to inserting a scope in the bronchus, the large airway, and obtaining a sample, to opening an area on the chest and taking a piece of lung. With LCNEC, the tumors are at the outer edges of the lung and diagnosis often requires removing a larger area of tissue to confirm the diagnosis.
Treatment
Stage 1 or 2
Because symptoms develop early, diagnosis in Stage 1 or 2 occurs more frequently. If the tumor is localized, the treatment is surgical removal, but rather than observing for progression, proactive chemotherapy is also given.
Stage 3
This implies that that there is a spread to lymph nodes in the central chest and the mediastinum, and whether or not surgery can be performed; the recommendation is for both chemotherapy and radiation simultaneously, followed by continued additional chemotherapy.
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