Islet cell tumors

ALSO KNOWN AS: Neuroendocrine tumors of the pancreas, pancreatic neuroendocrine tumors,

RELATED CONDITIONS: Multiple endocrine neoplasia type 1, von Hippel–Lindau disease, Zollinger-Ellison syndrome, Verner-Morrison syndrome, Gastrinoma, Insulinoma, VIPoma, Somatostatinoma, Glucagonoma

DEFINITION: Islet cell tumors are abnormal cell masses that develop in the islet cells (islets of Langerhans) of the pancreas. These tumors can be either malignant (cancerous) or benign. Types include insulinomas, gastrinomas, glucagonomas, somatostatinomas, vasoactive intestinal peptide tumors, and nonfunctioning tumors.

Risk factors: Between 5 and 8 percent of insulinomas and 16 to 35 percent of gastrinomas are associated with the inherited disorder multiple endocrine neoplasia type 1 (MEN 1), but most islet cell tumors arise spontaneously with no known risk factors.

Etiology and the disease process: The pancreas is a digestive organ on the right side of the abdomen near where the stomach joins the small intestine. It is composed of two cell types. About 95 percent of pancreas cells (the exocrine pancreas) secrete digestive juices that flow into ducts that empty into the small intestine. The remaining cells (the endocrine pancreas) release hormones, mostly insulin and glucagon, directly into the bloodstream. These hormones regulate the use of glucose (sugar) in the body.

Some islet cell tumors produce excess amounts of hormones. These are called functioning tumors. Islet cell tumors that do not produce excess hormones are called nonfunctioning tumors. The percentage of islet cell tumors that are nonfunctioning is uncertain, as these tumors are often difficult to detect. Estimates range from approximately 15 percent to 50 percent or more. Either type of tumor can be malignant or benign. Nonfunctioning tumors are more likely than functioning tumors to be malignant.

Islet cell tumors arise from different islet cells and are named for the primary hormone they secrete. Insulinomas produce insulin, which decreases the amount of glucose in the blood and increases the amount of glucose stored in the body. Insulinomas are the most common of all islet cell tumors. Gastrinomas are the second-most common islet cell tumors; they produce gastrin, which causes the stomach to secrete acid. Excess acid leads to stomach and intestinal ulcers. Glucagonomas produce glucagon, which releases stored glucose and increases the glucose level in the blood, causing high blood sugar (hyperglycemia). Somatostatinomas produce somatostatin, which helps regulate the production of other hormones. Vasoactive intestinal peptide tumors, also called VIPomas, produce vasoactive intestinal peptide, which relaxes smooth muscles in the digestive system and increases the amount of water in the stool, causing severe diarrhea.

Although islet cell tumors can occur in people of any age, most are diagnosed in middle-aged individuals. In most, especially those who do not have MEN 1, these tumors tend to develop slowly.

Incidence: Islet cell tumors are rare. Only about one to three thousand cases are diagnosed annually in the United States. However, the incidence increased over time because of imaging and other diagnostic technology advances. Islet cell cancers constitute 1 to 2 percent of all pancreatic neoplasms, and five to ten people per million develop these cancers annually. Most diagnoses are in those between the age of thirty and sixty.

Symptoms: Nonfunctioning tumors produce few symptoms. Symptoms of functioning tumors depend on the type of hormone secreted. Insulinomas cause low blood sugar (hypoglycemia), hunger, weight gain, sweating, and nausea. Glucagonomas cause high blood sugar or mild diabetes accompanied by severe skin inflammation (dermatitis). Gastrinomas cause stomach pain and ulcers. VIPomas cause severe watery diarrhea. Somatostatinomas cause weight loss and diarrhea.

Screening and diagnosis: Diagnosis of a suspected islet cell tumor is difficult. Various blood and urine tests are used to determine the level of specific hormones in the body. Once a tumor is suspected, an array of imaging studies, including (MRI), computed (CT) scans, ultrasound, and arteriography, are used to locate the tumor. In the case of functioning tumors, the diagnosis is confirmed by testing for the hormonal or other biochemical markers secreted by the tumor.

The American Joint Committee on Cancer recommends staging islet cell tumors as follows:

  • Stage 0: Carcinoma in situ.
  • Stage IA: Tumor is only in the pancreas and is 2 centimeters (cm) or less in diameter.
  • Stage IB: Tumor is only in the pancreas and is greater than 2 cm in diameter.
  • Stage IIA: Tumor has spread beyond the pancreas but has not reached regional lymph nodes and does not involve the celiac axis or the superior mesenteric artery.
  • Stage IIB: Tumor may be only in pancreas or may have spread beyond the pancreas but does not involve the celiac axis or the superior mesenteric artery; cancer has spread to regional lymph nodes.
  • Stage III: Tumor involves the celiac axis or the superior mesenteric artery; lymph nodes may or may not be involved.
  • Stage IV: Tumor has metastasized to other parts of the body.

Treatment and therapy: Primary treatment involves removing the tumor and sometimes the surrounding tissue, often followed by chemotherapy. When surgery is not an option, is often given, followed by hormone therapy to slow the cancer's growth. Radiofrequency or cryosurgical ablation is another option for inoperable tumors. If the tumor is mainly affecting the liver and causing severe symptoms, chemoembolization or hepatic arterial occlusion may be performed, with or without chemotherapy. Other treatment options include peptide receptor radionuclide therapy (PRRT), targeted therapy, and hormone therapy.

Prognosis, prevention, and outcomes: The prognosis and outcome of islet cell cancer are highly variable because of the different tumors involved. Large nonfunctioning tumors produce the worst outcome. In functioning tumors, tumor size is unrelated to outcome. Many tumors grow slowly, and patients may survive for years. The overall five-year survival rate is 50 percent. Those with localized cancer have a 90 percent survival rate, but in those whose cancer has spread to the lungs or liver, the survival rate is 20 percent. Islet cell cancer most often metastasizes to the liver and lymph nodes. If metastasis occurs, the outcome is poor. There is no known way to prevent this cancer.

Bibliography

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Isayama, Hiroyuki, et al. Management of Pancreatic Cancer and Cholangiocarcinoma. Springer, 2021.

Miles, Carly B., and Timothy B. Gardner. "Expanding Indications for Pancreatic Islet Cell Transplantation." Current Opinion in Gastroenterology, vol. 36, no. 5, 2020, pp. 452-455. doi:10.1097/MOG.0000000000000660.

Neoptolemos, John, et al. Pancreatic Cancer. Springer, 2020. 

"Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ)." National Cancer Institute, 7 Oct. 2022, www.cancer.gov/types/pancreatic/patient/pnet-treatment-pdq. Accessed 20 June 2024.

Pisegna, Joseph R., editor. Management of Pancreatic Neuroendocrine Tumors. Springer, 2015.

Raymond, Eric, et al., editors. Management of Neuroendocrine Tumors of the Pancreas and Digestive Tract: From Surgery to Targeted Therapies; A Multidisciplinary Approach. Springer, 2014.

Siddiqui, Mahwash, et al. "Pasireotide: A Novel Treatment for Tumor-induced Hypoglycemia Due to Insulinoma and Non-islet Cell Tumor Hypoglycemia." Journal of the Endocrine Society, vol. 5, no. 1, 2021. doi:10.1210/jendso/bvaa171.

Tahbaz, Meghan, and Eiji Yoshihara. "Immune Protection of Stem Cell-derived Islet Cell Therapy for Treating Diabetes." Frontiers in Endocrinology, vol. 12, 2021. doi.org/10.3389/fendo.2021.716625.