Pancreatic Cancer & Islet Cell Tumors

The pancreas is a critical organ with both endocrine and exocrine functions, making it susceptible to various pathologies. Chief among these are pancreatic adenocarcinomas and neuroendocrine tumors.

Pancreatic adenocarcinomas primarily arise from the exocrine pancreas, and typically develops in patients with chronic pancreatitis and smokers. Germline mutations in the tumor suppressor genes BRCA1 & BRCA2 are the most common cause of familial pancreatic adenocarcinoma. The CDKN2A and SMAD4 tumor suppressor genes are also risk factors. Mutations in the KRAS proto-oncogene is present in almost all cases of pancreatic adenocarcinoma.

The majority of pancreatic adenocarcinomas arise from the head of the pancreas, which can lead to obstruction of the common bile duct. These tumors often manifest with Courvoisier’s sign, as well as jaundice, light-colored stools, and dark urine. Epigastric pain radiating to the back and constitutional symptoms are also common. The tumor markers CA 19-9 and CEA are valuable diagnostic tools when combined with imaging and a thorough clinical history.

Pancreatic adenocarcinomas can metastasize to specific areas, such as the left supraclavicular node (Virchow's node), as well as to the umbilicus, forming a periumbilical mass, known as a Sister Mary Joseph Nodule. Paraneoplastic syndromes such as superficial migratory thrombophlebitis and Cushing syndrome can also occur with pancreatic adenocarcinomas.

Neuroendocrine tumors originate from the endocrine portion of the pancreas, specifically the Islets of Langerhans. Various subtypes exist, each secreting different hormones and presenting with unique symptoms.

Insulinomas are the most common type of pancreatic neuroendocrine tumors and are derived from the beta cells in the Islets of Langerhans. Excessive insulin secretion leads to hypoglycemia and symptoms such as tremors, diaphoresis, and confusion—often improving following a meal. Measurement of C-peptide levels can distinguish between endogenous (increased C-peptide) and exogenous (decreased C-peptide).

Glucagonomas are neuroendocrine tumors arising from the alpha cells of the Islets of Langerhans. The excessive glucagon secretion results in hyperglycemia and clinical manifestations such as diarrhea, weight loss, neuropsychiatric symptoms, and venous thromboembolism. A distinct skin condition, necrolytic migratory erythema, is also associated with glucagonomas.

Gastrinomas may originate in the pancreas or duodenum and produce excessive amounts of gastrin and. This leads to increased gastric acid secretion and Zollinger-Ellison Syndrome, characterized by the triad of islet cell tumors, gastric acid hypersecretion, and peptic ulcer disease. Other complications include ulcers in the duodenum or jejunum, GERD and malabsorption diarrhea. Diagnostic tools include upper GI endoscopy showing prominent thickening of gastric folds and the secretin stimulation test.

VIPomas secrete vasoactive intestinal peptide (VIP), resulting in a condition often termed ‘pancreatic cholera.’ This leads to large volume watery diarrhea, causing dehydration and hypokalemia. VIP also inhibits gastric acid secretion, leading to achlorhydria.

Somatostatinomas are derived from delta cells in the Islets of Langerhans and secrete somatostatin, which inhibits the secretion of various hormones including insulin, glucagon, and cholecystokinin. Clinical manifestations include malabsorption diarrhea, increased risk of gallstones, and hyperglycemia due to an increased inhibition of insulin relative to glucagon.

Lastly, multiple endocrine neoplasia 1 (MEN1) is an inherited syndrome resulting in tumors in multiple endocrine organs, including the pancreas.