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Islet Cell Tumor

Pancreatic Neuroendocrine Tumor

Islet cell tumors are a collective group of neoplasms that arise from the islet cells of the pancreas. The cell types of the pancreas play a role in the secretion of specific hormones. Hence, the clinical picture depends on which cell type is affected.

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Presentation

The functional tumors synthesize and release hormones that yield distinct clinical presentations related to the role of the hormone. The five neoplasms below are functional tumors.

Functional ICTs

Insulinomas

These are the most common of ICTs and are often benign. Insulinomas cause excessive secretion of insulin. The resultant hypoglycemia ultimately results in headaches, visual changes, confusion [13]. as well as irritability, weakness, tremors, ataxia, and seizures. Severe cases cause coma and even death.

Gastrinomas

Many of these tumors are typically either malignant or have malignant potential. They secrete elevated amounts of gastrin which cause gastric and duodenal ulcers. Collectively known as Zollinger-Ellison syndrome, the common symptoms are abdominal pain, diarrhea, steatorrhea, and gastric acid reflux. There are frequently found in the head of the pancreas although they can occur in the duodenum.

Glucagonomas

The majority of glucagonomas are malignant. They secrete excessive glucagon causing hyperglycemia and diabetes. Additionally, it leads to unintended weight loss, stomatitis, dermatitis, and anemia. Another severe complication of glucagonomas is thrombosis.

VIPomas

At the time of diagnosis, these tumors are likely to be malignant. They produce vasoactive intestinal polypeptide, which plays a role in the secretion of other hormones and causes gastrointestinal muscle relaxation. The symptoms of VIPomas include copious amounts of watery diarrhea, hypokalemia, and dehydration.

Somatostatinomas

These are large, malignant tumors that secrete somatostatin, which is a hormone that inhibits the release of others. Its sequelae include diabetes and cholelithiasis.

Non-functional ICTs

The tumors of this type are usually asymptomatic. They account for the minority of all ICTs. Almost 90% are malignant but usually diagnosed incidentally or in the later stages when their large sizes cause mechanical complication [14].

Weight Loss
  • The pancreatic tumor with central cyst formation was found on computerized tomographic examination of a 72-year-old man reporting appetite and weight loss.[ncbi.nlm.nih.gov]
  • loss Too little hydrochloric acid in the stomach, which can cause digestive problems and poor absorption of vitamins and nutrients Other symptoms Abdominal pain Jaundice, which is yellowing of the skin and whites of the eyes Vomiting blood Sweating Rapid[cancer.net]
  • The symptoms of low blood sugar are: a headache lightheadedness blurred vision weakness shaking irritability hunger Symptoms of a Glucagonoma The symptoms of a glucagonoma include: a rash on the stomach, legs, or face diarrhea unexplained weight loss[healthline.com]
Weakness
  • Possible mechanisms for explaining this apparent discrepancy include the production of immunoreactive molecules with weak or absent systemic biological activity.[ncbi.nlm.nih.gov]
  • A weak signal for GHRH receptor mRNA was detected in these somatotrophs. However, using in situ RT-PCR, GHRH receptor mRNA was more conclusively observed in most of the somatotrophs.[ncbi.nlm.nih.gov]
  • […] frequent urination, increased thirst, and increased hunger Rash that spreads on the face, abdomen, or lower extremities Symptoms of a VIPoma Watery diarrhea Too little potassium in the blood, which can cause an irregular heartbeat, muscle cramping and weakness[cancer.net]
  • The resultant hypoglycemia ultimately results in headaches, visual changes, confusion. as well as irritability, weakness, tremors, ataxia, and seizures. Severe cases cause coma and even death.[symptoma.com]
Weight Gain
  • gain or loss Inflamed mouth and tongue A mass or lump in the abdomen If you are concerned about any changes you experience, please talk with your doctor.[cancer.net]
  • gain (unintentional) Peptic ulcer pain Vomiting blood Diarrhea Abdominal pain Note: The symptoms depend upon the type of tumor and the hormone produced.[medicine.georgetown.edu]
  • Too much ACTH increases the production of steroids, which can lead to weight gain, depression, easy bruising, increased risk of infection, and darkened skin. Plus and Minus Icon There are few known risk factors for pancreatic neuroendocrine tumor.[mskcc.org]
  • Other general symptoms include episodic sweating, tremor and rapid heart rate, as well as hunger, nausea, weight gain, and sometimes even central nervous system symptoms (including rarely, seizures). Gastrinomas over-secrete the hormone gastrin.[pancreatica.org]
Anemia
  • A patient with a somatostatin (SRIH)-secreting islet cell tumor, whose only symptoms were dyspepsia and anemia, is described. The diagnosis of somatostatinoma was based on high plasma SRIH concentrations and immunocytochemical findings.[ncbi.nlm.nih.gov]
  • Additionally, it leads to unintended weight loss, stomatitis, dermatitis, and anemia. Another severe complication of glucagonomas is thrombosis. VIPomas At the time of diagnosis, these tumors are likely to be malignant.[symptoma.com]
  • […] and achlorhydria (Verner-Morrison syndrome, pancreatic cholera) VIP may also be secreted by neurogenic neoplasms 60% 5 year survival Somatostatinoma 2-3% of pancreatic endocrine neoplasms Diabetes mellitus, hypochlorhydria, cholelithiasis, diarrhea, anemia[surgpathcriteria.stanford.edu]
  • In addition, anemia, unintended weight loss, and inflammation or sores on the mucous membrane lining the inside of the mouth (stomatitis) have also been associated with glucagonomas.[rarediseases.org]
  • These symptoms may include muscular weakness, lethargy, and nausea. [12] Glucagonoma Glucagonomas secrete excessive amounts of glucagon and cause a syndrome characterized by the following [43] : Dermatitis Stomatitis Weight loss Anemia The dermatitis[emedicine.medscape.com]
Fatigue
  • Symptoms of a gastrinoma Ulcers, caused by too much stomach acid Diarrhea Symptoms of an insulinoma Hypoglycemia, which causes fatigue, nervousness and shakiness, dizziness or lightheadedness, seizures, and fainting episodes Confusion Symptoms of a glucagonoma[cancer.net]
  • He reported a three-month history of diffuse abdominal pain, fatigue, and blurred vision.[ncbi.nlm.nih.gov]
  • The following are common symptoms: Weakness Fatigue Headache Hunger Shaking Sweating Irritability and nervousness Rapid heart beat and sensations Fainting Seizure Coma or even death Patients with gastrinomas produce gastrin, which is the hormone that[symptoma.com]
  • Case Presentation Three years prior to the development of the current thoracic effusion, a 35-year-old man with a past medical history of hypertension, hydronephrosis, kidney stones, and desmoid tumor of the knee presented with fatigue, weakness, an unintentional[ncbi.nlm.nih.gov]
Diarrhea
  • They often experience severe abdominal pain, diarrhea, and gastrointestinal bleeding with potentially life-threatening consequences.[ncbi.nlm.nih.gov]
  • Symptoms of a gastrinoma Ulcers, caused by too much stomach acid Diarrhea Symptoms of an insulinoma Hypoglycemia, which causes fatigue, nervousness and shakiness, dizziness or lightheadedness, seizures, and fainting episodes Confusion Symptoms of a glucagonoma[cancer.net]
  • Symptoms of a Nonfunctional Tumor The symptoms of nonfunctional tumors include: indigestion increased gas diarrhea abdominal or back pain abdominal mass yellowing of the skin and the whites of the eyes, which is called “jaundice” or “icterus” Symptoms[healthline.com]
  • The symptoms are: Abdominal pain and discomfort Diarrhea Bloody vomit Glucagonomas produce glucagon, which is the hormone that normally increases the blood sugar level.[symptoma.com]
Abdominal Pain
  • They often experience severe abdominal pain, diarrhea, and gastrointestinal bleeding with potentially life-threatening consequences.[ncbi.nlm.nih.gov]
  • He reported a three-month history of diffuse abdominal pain, fatigue, and blurred vision.[ncbi.nlm.nih.gov]
  • pain Jaundice, which is yellowing of the skin and whites of the eyes Vomiting blood Sweating Rapid heart rate Anxiety Headache Convulsions Loss of consciousness Clouding of vision Unexplained weight gain or loss Inflamed mouth and tongue A mass or lump[cancer.net]
  • The symptoms are: Abdominal pain and discomfort Diarrhea Bloody vomit Glucagonomas produce glucagon, which is the hormone that normally increases the blood sugar level.[symptoma.com]
Vomiting
  • She complained of nausea, vomiting, and growing abdominal mass. Abdominal computed tomography showed multiple cysts in the whole pancreas and a calcified solid mass in the pancreatic head.[ncbi.nlm.nih.gov]
  • […] bad odor Diarrhea Weight loss Too little hydrochloric acid in the stomach, which can cause digestive problems and poor absorption of vitamins and nutrients Other symptoms Abdominal pain Jaundice, which is yellowing of the skin and whites of the eyes Vomiting[cancer.net]
  • Skin rash that migrates on the face, abdomen, perineum, buttocks, or lower extremities May be crusty and scaly May have raised lesions filled with clear fluid or pus Inflamed mouth and tongue Weight loss Weight gain (unintentional) Peptic ulcer pain Vomiting[medicine.georgetown.edu]
  • Symptoms may include: Abdominal pain Diarrhea Ulcers in the stomach and small bowel Vomiting blood (occasionally) Glucagonomas make the hormone glucagon, which helps the body raise blood sugar level.[medlineplus.gov]
Pelvic Mass
  • A 41-year-old woman presented with hirsutism, a pelvic mass, and Cushing's syndrome. Imaging studies revealed bilateral ovarian masses and a solid and cystic mass within the pancreas.[ncbi.nlm.nih.gov]
  • A large pelvic mass was found and thought to represent a recurrence. Serum insulin and C-peptide were undetectable. Morning cortisol was mildly elevated. Thyroid stimulating hormone, amylase, lipase, and renal and hepatic functions were normal.[ncbi.nlm.nih.gov]
Thrombosis
  • Another severe complication of glucagonomas is thrombosis. VIPomas At the time of diagnosis, these tumors are likely to be malignant.[symptoma.com]
  • […] and diarrhea insulinoma : [9] hypoglycemia occurs with concurrent elevations of insulin, proinsulin and C peptide [10] glucagonoma : the symptoms are not all due to glucagon elevations, [10] and include a rash, sore mouth, altered bowel habits, venous thrombosis[en.wikipedia.org]
  • Blood clots in extremities may cause deep vein thrombosis, a condition in which blood clots form in the legs causing the legs to become painful and swollen.[rarediseases.org]
  • Gastrinoma triangle" (common bile duct, duodenum, pancreatic head) Duodenum affected more than pancreas 20 - 30% of gastrinomas are associated with MEN1 Malignant in 80% Glucagonoma: 4Ds: diabetes, dermatitis (necrolytic migratory erythema), deep vein thrombosis[pathologyoutlines.com]
  • […] can be significant, even when the tumors are small and not metastatic. [45] In addition, as many as a third of patients with glucagonoma syndrome have secondary thromboembolic phenomena; therefore, they may have a history consistent with deep venous thrombosis[emedicine.medscape.com]
Hypertension
  • A 22-year-old woman presented with lump in the left hypochondrium, refractory high-protein ascites and evidence of left-sided portal hypertension.[ncbi.nlm.nih.gov]
  • Case Presentation Three years prior to the development of the current thoracic effusion, a 35-year-old man with a past medical history of hypertension, hydronephrosis, kidney stones, and desmoid tumor of the knee presented with fatigue, weakness, an unintentional[ncbi.nlm.nih.gov]
  • Affected individuals may have a round, moon-shaped face, thin, fragile skin that bruises easily, high blood pressure (hypertension), generalized muscle weakness, behavioral changes, facial flushing, and weakened bones that fracture easily (osteoporosis[rarediseases.org]
Blurred Vision
  • He reported a three-month history of diffuse abdominal pain, fatigue, and blurred vision.[ncbi.nlm.nih.gov]
  • The symptoms of low blood sugar are: a headache lightheadedness blurred vision weakness shaking irritability hunger Symptoms of a Glucagonoma The symptoms of a glucagonoma include: a rash on the stomach, legs, or face diarrhea unexplained weight loss[healthline.com]
  • This can cause blurred vision, headache, and feeling lightheaded, tired, weak, shaky, nervous, irritable, sweaty, confused, or hungry. Fast heartbeat. Too much glucagon may cause: Skin rash on the face, stomach, or legs. High blood sugar.[cancer.gov]
Back Pain
  • Symptoms of a Nonfunctional Tumor The symptoms of nonfunctional tumors include: indigestion increased gas diarrhea abdominal or back pain abdominal mass yellowing of the skin and the whites of the eyes, which is called “jaundice” or “icterus” Symptoms[healthline.com]
  • Signs and symptoms [ edit ] Some PanNETs do not cause any symptoms, in which case they may be discovered incidentally on a CT scan performed for a different purpose. [6] : 43–44 Symptoms such as abdominal or back pain or pressure, diarrhea, indigestion[en.wikipedia.org]
  • Too much gastrin may cause: Stomach ulcers that keep coming back. Pain in the abdomen, which may spread to the back. The pain may come and go and it may go away after taking an antacid.[cancer.gov]
Muscle Weakness
  • Affected individuals may have a round, moon-shaped face, thin, fragile skin that bruises easily, high blood pressure (hypertension), generalized muscle weakness, behavioral changes, facial flushing, and weakened bones that fracture easily (osteoporosis[rarediseases.org]
  • This can cause muscle weakness, aching, or cramps, numbness and tingling, frequent urination, fast heartbeat, and feeling confused or thirsty. Cramps or pain in the abdomen. Weight loss for no known reason.[cancer.gov]
Dermatitis
  • Additionally, it leads to unintended weight loss, stomatitis, dermatitis, and anemia. Another severe complication of glucagonomas is thrombosis. VIPomas At the time of diagnosis, these tumors are likely to be malignant.[symptoma.com]
  • These symptoms may include muscular weakness, lethargy, and nausea. [12] Glucagonoma Glucagonomas secrete excessive amounts of glucagon and cause a syndrome characterized by the following [43] : Dermatitis Stomatitis Weight loss Anemia The dermatitis[emedicine.medscape.com]
  • Patients with glucagonomas tend to present with mild diabetes and a severe dermatitis. These tumors are frequently fairly large by the time of diagnosis, sometimes greater than two inches in diameter. Approximately 70% of these tumors are malignant.[pancreatica.org]
  • Glucagonomas can cause a distinct skin rash (dermatitis) usually on the face, stomach or legs. Mild diabetes may also develop.[rarediseases.org]
  • (peptic ulcers, gastroesophageal reflux, diarrhea) "Gastrinoma triangle" (common bile duct, duodenum, pancreatic head) Duodenum affected more than pancreas 20 - 30% of gastrinomas are associated with MEN1 Malignant in 80% Glucagonoma: 4Ds: diabetes, dermatitis[pathologyoutlines.com]
Hirsutism
  • A 41-year-old woman presented with hirsutism, a pelvic mass, and Cushing's syndrome. Imaging studies revealed bilateral ovarian masses and a solid and cystic mass within the pancreas.[ncbi.nlm.nih.gov]
Withdrawn
  • Organizations Islet Cell Tumor Trials Acromegaly Islet Cell Tumor Pancreatic Cancer Pancreatic Diseases Pituitary Neoplasm Any 17 and under 18 - 34 35 - 50 51 - 69 70 Available Active, not recruiting Not yet recruiting Recruiting Completed Terminated Suspended Withdrawn[patientwing.com]
Confusion
  • Because of its scarcity and the cytomorphologic similarity between plasma cells and endocrine cells, EMP of the pancreas may be confused with neuroendocrine (islet cell) tumors of the pancreas.[ncbi.nlm.nih.gov]
  • Symptoms of a gastrinoma Ulcers, caused by too much stomach acid Diarrhea Symptoms of an insulinoma Hypoglycemia, which causes fatigue, nervousness and shakiness, dizziness or lightheadedness, seizures, and fainting episodes Confusion Symptoms of a glucagonoma[cancer.net]
  • Symptoms Sweating Tremor Rapid heart rate Anxiety Hunger Dizziness Headache Clouding of vision Confusion Behavioral changes Convulsions Loss of consciousness Skin rash that migrates on the face, abdomen, perineum, buttocks, or lower extremities May be[medicine.georgetown.edu]
  • This rare cancer is often confused with the more aggressive pancreatic cancer, the cancer which took the lives of celebrities Patrick Swayze, Luciano Pavarotti, Michael Landon, and Jack Benny.[carcinoid.org]
Seizure
  • An 11 year-old boy with AIDS, cerebral palsy and seizure disorder presented with intractable hypoglycemia 12 days after diagnosis of Burkitt's lymphoma.[ncbi.nlm.nih.gov]
  • Symptoms of a gastrinoma Ulcers, caused by too much stomach acid Diarrhea Symptoms of an insulinoma Hypoglycemia, which causes fatigue, nervousness and shakiness, dizziness or lightheadedness, seizures, and fainting episodes Confusion Symptoms of a glucagonoma[cancer.net]
  • The resultant hypoglycemia ultimately results in headaches, visual changes, confusion. as well as irritability, weakness, tremors, ataxia, and seizures. Severe cases cause coma and even death.[symptoma.com]
  • Feeling tired or weak Shaking or sweating Headache Hunger Nervousness, anxiety, or feeling irritable Unclear thinking or feeling uneasy Double or blurry vision Fast or pounding heartbeat If your blood sugar level gets too low, you may faint, have a seizure[medlineplus.gov]
Headache
  • The symptoms of low blood sugar are: a headache lightheadedness blurred vision weakness shaking irritability hunger Symptoms of a Glucagonoma The symptoms of a glucagonoma include: a rash on the stomach, legs, or face diarrhea unexplained weight loss[healthline.com]
  • […] hydrochloric acid in the stomach, which can cause digestive problems and poor absorption of vitamins and nutrients Other symptoms Abdominal pain Jaundice, which is yellowing of the skin and whites of the eyes Vomiting blood Sweating Rapid heart rate Anxiety Headache[cancer.net]
  • The resultant hypoglycemia ultimately results in headaches, visual changes, confusion. as well as irritability, weakness, tremors, ataxia, and seizures. Severe cases cause coma and even death.[symptoma.com]
  • Symptoms Sweating Tremor Rapid heart rate Anxiety Hunger Dizziness Headache Clouding of vision Confusion Behavioral changes Convulsions Loss of consciousness Skin rash that migrates on the face, abdomen, perineum, buttocks, or lower extremities May be[medicine.georgetown.edu]
Irritability
  • The resultant hypoglycemia ultimately results in headaches, visual changes, confusion. as well as irritability, weakness, tremors, ataxia, and seizures. Severe cases cause coma and even death.[symptoma.com]
  • The symptoms of low blood sugar are: a headache lightheadedness blurred vision weakness shaking irritability hunger Symptoms of a Glucagonoma The symptoms of a glucagonoma include: a rash on the stomach, legs, or face diarrhea unexplained weight loss[healthline.com]
  • Symptoms may include: Feeling tired or weak Shaking or sweating Headache Hunger Nervousness, anxiety, or feeling irritable Unclear thinking or feeling uneasy Double or blurry vision Fast or pounding heartbeat If your blood sugar level gets too low, you[medlineplus.gov]
  • Irritable Bowel Syndrome (IBS) and Crohn’s disease are the two most common misdiagnosed conditions with midgut carcinoid. NET cancers typically spread to the liver and lymph nodes.[carcinoid.org]
Dizziness
  • She reported dizziness and had recorded low capillary blood glucose despite discontinuing her diabetic medication prior to admission.[ncbi.nlm.nih.gov]
  • Symptoms of a gastrinoma Ulcers, caused by too much stomach acid Diarrhea Symptoms of an insulinoma Hypoglycemia, which causes fatigue, nervousness and shakiness, dizziness or lightheadedness, seizures, and fainting episodes Confusion Symptoms of a glucagonoma[cancer.net]
  • Symptoms Sweating Tremor Rapid heart rate Anxiety Hunger Dizziness Headache Clouding of vision Confusion Behavioral changes Convulsions Loss of consciousness Skin rash that migrates on the face, abdomen, perineum, buttocks, or lower extremities May be[medicine.georgetown.edu]
  • Insulinomas can cause low blood sugar, which leads to symptoms such as dizziness and light-headedness. Glucagonomas These tumors may interfere with the production of glucose in the blood, causing an elevation of blood sugar and diabetes.[mskcc.org]

Workup

In addition to the evaluation of the clinical picture, the clinical assessment consists of a full personal and family history, physical examination, and appropriate testing. Laboratory studies include the measurement of the hormones, polypeptides, prostaglandins, tumor markers, and radioimmunoassays.

Laboratory tests

In the evaluation of insulinomas, investigation includes the fasting serum glucose, serum insulin level, and C-peptide suppression test.

Studies for the assessment of gastrinomas include the measurement of gastric acid secretion including the hormone's basal and maximum acid output. Furthermore, the secretion stimulation test is also useful.

Finally, a fasting serum glucagon level is used to diagnose glucagonomas.

Imaging

The primary imaging technique for localization and staging of ICTs is the CT scan with oral and intravenous contrast [15] [16]. This tool reveals the involvement of peri-pancreatic lymph node, the presence of liver metastases, as well as the blood supply. Very importantly, the CT scan guides the surgical and treatment planning.

Further testing involves angiography, which offers a closer investigation of the pancreatic arterial blood supply. This modality is used as the next step when the CT scan does not detect the tumor [17].

Another advantageous technique is the endoscopic ultrasonography, which displays the tumor and allows for a biopsy [18] [19]. One study reported that ultrasonography demonstrated more sensitivity than the combination of CT and angiography [19].

Magnetic resonance imaging (MRI) with gadolinium-enhancement is helpful as it offers key details.

Somatostatin receptor scintigraphy is beneficial. The associated radionuclide scan detects the somatostatin receptors on the primary ICTs [20]. as well as the metastatic lesions.

In a few cases where the above imaging tools cannot visualize the small tumors, selective transhepatic portal venous hormone sampling can be performed [21] [22].

Fasting Hypoglycemia
  • The work-up of fasting hypoglycemia may be difficult but is crucially important because a wrong diagnosis can lead to either unnecessary pancreatectomy or a missed pancreatic tumor.[ncbi.nlm.nih.gov]
  • We report a 22-yr-old male patient with chronic hepatitis B and a large, well differentiated hepatoma who developed episodes of symptomatic fasting hypoglycemia, which were caused by paraneoplastic secretion of unprocessed "big" insulin-like growth factor-II[ncbi.nlm.nih.gov]
  • Fasting hypoglycemia was believed to be the cause of the movements. A computed tomographic scan showed a large mass in the left inferior hemithorax.[ncbi.nlm.nih.gov]
  • Abstract Non-islet cell tumor hypoglycemia (NICTH) is one of major causes of fasting hypoglycemia. In some patients with NICTH, insulin-like growth factor II (IGF-II) produced by and secreted from the tumors is thought to be a hypoglycemic agent.[ncbi.nlm.nih.gov]
  • Non-islet cell tumor-induced hypoglycemia (NICTH), a major cause of fasting hypoglycemia, is caused by the overproduction of incompletely processed, high molecular-weight insulin-like growth factor-II (IGF-II), termed "big" IGF-II.[ncbi.nlm.nih.gov]
Cortisol Increased
  • Cortisol increases blood pressure and blood sugar and inhibits the immune system. ACTHomas can result in Cushing’s syndrome, a disorder characterized by excessive amounts of weight gain (central obesity).[rarediseases.org]

Treatment

The therapeutic approach depends on the tumor's size, location, and it metastatic status. It also reflects the overall clinical presentation and presence of co-morbidities [23]. The management of the patient involves multidisciplinary coordination between oncology, surgery, primary care, gastroenterology, endocrinology, and other relevant specialties.

Surgery

Surgical intervention is the treatment of choice. In cases with syndromic ICTs without metastasis, complete surgical resection is warranted. When the tumor is located in the pancreatic tail or body, surgical procedures include distal pancreatectomy. If the lesion is located in the pancreatic head, the Whipple procedure is the preferred procedure. Small single masses can be enucleated. If there is liver metastasis, surgical resection [24]. and debulking may be beneficial.

Ablation through radiofrequency and cryosurgery are alternative procedures for metastatic cases.

Chemotherapy

In patients with extensive metastasis, chemotherapy drugs have produced variable results [25] [26]. Examples of anti-neoplastic agents include cisplatin, 5-fluorouracil, and streptozotocin. Newer drugs are undergoing evaluation in current drug trials.

Chemoembolization

The management of liver metastasis may warrant embolization of the hepatic artery in order to obstruct blood supply to the liver tumor [27].

Hormone therapy

Octreotide, a somatostatin analogue, can be used in cases where the lesion is not resectable or when there is a residual tumor.

Other

Addressing the clinical manifestations of these tumors is paramount to prevent serious complications. For example, supportive therapy for peptic ulcers includes proton-pump inhibitor drugs and histamine blocking medications. Additionally, antidiarrheal drugs and intravenous (IV) fluids with electrolytes are other important considerations. Finally, there are medications regarding the management of blood glucose abnormalities.

Lifestyle modifications such as dietary restrictions, smoking cessation, and abstinence from alcohol are all recommended for patients with these tumors.

Prognosis

If the tumor is detected prior to metastasis, the outcome is typically better. The disease is likely curable if complete surgical removal is possible. For example, if the tumor is resectable, the 5-year survival rate is 55% whereas the rate is 15% when the lesion is not resectable [3]. In cases with advanced disease, aggressive treatment may prolong survival.

A significant predictor of the tumor's behavior is the tumor size which is found to be proportional to the probability of metastasis, invasion, and aggressiveness [11] [12]. Furthermore, the prognosis depends on factors such as the type of islet cell, tumor location, metastatic status, the patient's clinical profile, and if cancer has relapsed. Another pertinent prognostic factor is whether the patient has multiple endocrine neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), or neurofibromatosis type I (NF-1).

Note that the percentage of malignant cases is lowest in insulinomas (10%) but is significantly higher in gastrinomas (60%) and glucagonomas (80%). The other types of functional ICTs are also mostly malignant as are the non-functional ones as well.

Etiology

The etiology is not fully understood. The majority of islet cell tumors develop sporadically. Furthermore, it is believed that some patients have a genetic predisposition in conjunction with an environmental trigger.

Epidemiology

ICTs comprise 3% to 5% of all pancreatic malignancies [2] [3]. The incidence of these neoplasms is about 1 per population of 100,000. Furthermore, in the United States, there are approximately 1,000 new cases annually [2].

With regards to patient demographics, ICTs have a slight predilection for women. Additionally, sporadic cases occur between the age of 30 and 60 years while the genetic forms develop in childhood or early adulthood.

Sex distribution
Age distribution

Pathophysiology

Endocrine cells account for less than 5% of the pancreatic mass. These cells are distributed in clusters known as the islet of Langerhans. The three chief types of islet cells are the beta, alpha, and delta cells which secrete insulin, glucagon, and somatostatin, respectively. Furthermore, other hormones are also produced from the minor cells.

Islet cells have access to the bloodstream due to their extensive blood supply as they receive up to 15% of the pancreatic perfusion. Moreover, these cells have neural innervation from the parasympathetic and sympathetic nervous system which modulate the hormonal mechanisms of insulin and glucagon secretion.

Pathophysiology of ICTs

The pancreatic islet cells are a component of the neuroendocrine system of the pancreas and the gut. Since these cells contain high levels of amine and are capable of amine precursor uptake with decarboxylation, they are termed as APUD cells [4] [5]. These cells are pluripotent neuroendocrine cells found in the gastrointestinal tract, pulmonary mucosa, and the nervous system [6]. The APUD cells differentiate into distinct endocrine tissues [5] [7].

Since there are numerous pancreatic cell types, there are at least five different cancers. When functional, each type yields a particular metabolic and clinical picture reflecting the characteristic effects of the specific polypeptide released from the tumor cells. This is in contrast to the non-functional tumors that produces non-specific symptomatology secondary to the tumor bulk or metastases [8]. While 85% these tumors are considered functional, the remaining non-functional cases resemble the clinical picture of the exocrine adenocarcinomas [9] [10].

Histologic evaluation

ICTs display well-differential cells that are arranged in a pattern of nets, trabeculae, or ribbon. It is difficult to predict the behavior of pancreatic neoplasms based on histology. With regards to malignancy, the most remarkable histologic finding is the invasion of neighboring organs and large vasculature, and spread to lymph nodes or elsewhere. However, benign and malignant tumors may resemble each other histologically hence adding to the difficulty in differentiating between the two.

Prevention

There are no preventive measures for ICTs.

Summary

Islet cell tumors (ICTs), also known as pancreatic neuroendocrine tumors, refer to the rare neuroendocrine tumors that stem from the cells of the pancreas. These well-differentiated neoplasms either develop as isolated lesions or arise from genetic syndromes [1]. There are numerous types of islet cells and each produces key hormones that play an integral role in the regulation of metabolic functions.

The main tumors are insulinomas, glucagonomas, and gastrinomas. The clinical presentation reflects the distinctive metabolic effects of these hormones. The former are all functional tumors. In contrast, there are non-functioning tumors which do not cause symptoms until late stages. The etiology of ICTs is not fully elucidated. Some are sporadic and others are likely to develop as a result of genetic and environmental interplay.

ICTs can be detected through a clinical assessment comprised of a physical exam, laboratory tests, and various imaging modalities. Laboratory tests such as measurement of hormone levels, tumor markers, and biochemical studies are key for diagnosis of the disease. Imaging techniques such as computed tomography (CT), endoscopic ultrasonography, and scintigraphy are among the diagnostic modalities that are likely to identify the presence of a lesion.

The therapeutic approach in patients with ICTs is dependent on the location and size of the mass, presence of distant metastasis, presence of co-morbidities, overall clinical picture, and other factors as well. Surgical resection is the preferred therapy, which is the only curative treatment. Furthermore, chemotherapy, hormone therapy, chemoembolization and supportive care may be used in conjunction with surgery as an adjunctive treatment or it may be used as a combination treatment strategy.

An early diagnosis and the absence of metastatic lesions is associated with a good prognosis. The presence of distant metastasis influences the outcome.

Patient Information

What are islet cell tumors?

These are rare tumors that develop in the pancreas. There are numerous types of pancreatic cells called the islet cells. Each type produces a certain hormone that regulates important metabolic functions. For example, the A cells make insulin, the B cells makes glucagon, and the D cells make gastrin. There are other types as well. Some of the tumors are benign while other are malignant. If they are malignant, they spread to other organs such as the liver as well as the lymph nodes.

What are the causes?

The causes are unknown. Some occur sporadically while others develop from a combination of genetic and environmental triggers. Also, these tumors may occur alone or part of genetic syndromes.

What are signs and symptoms?

Each type of tumor produces its own symptoms. In the case of insulinomas, they increase insulin levels in the body, which in turn causes low blood sugar. The following are common symptoms:

Patients with gastrinomas produce gastrin, which is the hormone that releases acid in the stomach. Therefore, it causes stomach and duodenal ulcers. The symptoms are:

Glucagonomas produce glucagon, which is the hormone that normally increases the blood sugar level. These patients experience:

How are these tumors diagnosed?

After assessing the patient's symptoms, the physician will obtain the personal and family history of the patient, perform a full physical examination, and order the appropriate blood tests and imaging studies.

Laboratory test include:

  • Levels of specific hormones such as insulin, glucagon, or gastrin
  • Tumor markers
  • Radioimmunoassays

Imaging techniques include:

  • Endoscopic ultrasonography with biopsy
  • CT scan
  • MRI
  • Angiography

How are they treated?

There are numerous ways to treat these tumors. Surgical resection of the tumor may cure the disease. The therapeutic approach depends on factors such as the location of the tumor and whether it has spread. The doctor will also assess if the patient is a good surgical candidate on the basis of age and presence of other diseases.

  • Surgery: the specific procedure depends on the location of the tumor and whether it has spread
  • Chemotherapy: drugs are used to either kill the cancer cells or stop their growth. There are current drug trials testing out new chemotherapy medications
  • Embolization: this causes blood to stop flowing to the liver
  • Hormone therapy: this can block the effects of the hormone and stop the cancer's growth

Since there are complications caused by these tumors, supportive therapy is important in these patients. For example, patients with ulcers need antacid medications. Also, those with diabetes require insulin or other sugar lowering drugs.

All patients are advised to adhere to healthy diets and to quit smoking.

What is the prognosis?

The earlier the diagnosis, the better the prognosis. Surgical removal of the tumor before it spreads helps the patient achieve long-term survival.

The prognosis also depends on the type of tumor. For example, only 10% of insulinomas are malignant however 60% of gastrinomas and 80% of glucagonomas are malignant.

References

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Last updated: 2019-07-11 21:43