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Neuroendocrine Tumors of Pancreas

MCQ - Pancreatic Neuroendocrine Tumors (PanNETs)

Explanation:

  • PanNEC does not represent genetic progression from a lower-grade PanNET.
  • Most PanNETs do not involve the main pancreatic duct.
  • Most PanNETs are hypercellular and stroma poor.
  • The frequency of pancreatic NET is very high in MEN1 (30%-80%) and VHL (17%), but they are extremely rare in NF1 and TSC.

MCQ - Variant of Pancreatic NET Arising from Pancreatic Duct

Answer: B

Explanation:

  • A variant of serotonin-producing PanNET has been described that arises from the pancreatic duct with associated fibrosis, similar to the mesenteric fibrosis seen in NETs of the small intestine.

MCQ - Hereditary Pancreatic Neuroendocrine Tumor Syndromes

Answer: C

Explanation:

  • Hereditary Pancreatic Neuroendocrine Tumor Syndromes inherited as autosomal dominant:
    • MEN-1/4
    • VHL disease
    • Neurofibromatosis type 1 (NF1)
    • Tuberous sclerosis (TSC)
  • Mahvash disease is inherited as an autosomal recessive condition.

MCQ - Duodenal and Ampullary Somatostatinoma

Answer: A

Explanation:

  • Somatostatinoma symptoms include diarrhea, cholelithiasis, dyspepsia, and diabetes. Somatostatinoma of the duodenum is almost never functional.
  • The presence of psammoma calcification is associated with 100% of NF1-associated tumors and 60% of sporadic somatostatinomas.

MCQ - Mahvash Disease

Answer: C

Explanation:

  • Mahvash disease is an autosomal recessive hereditary condition caused by homozygous or biallelic heterozygous mutation of the gene encoding glucagon receptor.
  • The patients present with asymptomatic hyperglucagonemia and can develop multiple glucagonomas. Penetrance is 100% by 60 years of age.
  • Glucagon-producing precursor microadenomas can present in Mahvash disease.
  • Precursor microadenomas are present in MEN-1 (predominantly insulin- and glucagon-producing in the pancreas and gastrin-producing in the duodenum) and in Mahvash disease (glucagon-producing).

MCQ - Multiple Pancreatic NETs

Answer: D

Explanation:

  • Multiple PanNETs are often observed in MEN-1, VHL, and Mahvash disease.

MCQ - Genetic Syndrome and Pancreatic Tumors

Answer: A

Explanation:

  • Patients with VHL (Von Hippel-Lindau syndrome) can develop serous cystadenomas that can coexist with pancreatic neuroendocrine tumors (PanNETs).
  • Frequently mutated genes in sporadic PanNETs include MEN1 (44%) and DAXX/ATRX (43%).
  • PanNETs with MEN1/DAXX/ATRX mutant genotype have a worse clinical prognosis than tumors with the wildtype genotype.

MCQ - Pancreatic Neuroendocrine Carcinomas (PNEC) Ki67 Index

Answer: B

Explanation:

  • Pancreatic neuroendocrine carcinomas (PNEC) are inevitably high grade with a proliferative index (Ki67) of:
    • Greater than 80% for the small-cell subtype
    • More than 20% for the large-cell subtype

MCQ - Pancreatic Neuroendocrine Tumors (PanNETs)

Answer: C

Explanation:

  • The most commonly mutated genes in PNECs are the tumor suppressors p53 (95%) and Rb (74%).
  • PanNETs can occur anywhere in the pancreas.
  • Functional tumors are associated with better survival than nonfunctional PanNETs.
  • Approximately 60% of PanNET cases have distant metastases at presentation.

MCQ - Pancreatic Manifestations in VHL

Answer: B

Explanation:

  • VHL (Von Hippel-Lindau) is an autosomal dominant syndrome that predisposes patients to several cancers including:
    • Renal cell carcinoma
    • Pheochromocytoma
    • Cerebellar and spinal hemangioblastoma
    • Retinal angioma
    • Endolymphatic sac neoplasms
    • Epididymal cystadenoma
    • Cystic and solid pancreatic neoplasms
  • The most common pancreatic manifestation of VHL is serous cystadenoma.

MCQ - Whipple's Triad

Answer: D

Explanation:

  • Whipple's triad includes:
    • Plasma glucose less than 40 mg/dL
    • Symptoms of hypoglycemia
    • Resolution of symptoms with a meal
  • Insulinomas typically produce higher levels of insulin and proinsulin, but this is not part of Whipple's triad.

MCQ - Factitious Hypoglycemia

Answer: A

Explanation:

  • Factitious hypoglycemia is more commonly seen in women.
  • It is suspected in individuals with access to insulin or oral hypoglycemic drugs.
  • Urinary sulfonylurea concentration should be measured by gas chromatography-mass spectroscopy to detect the abuse of oral hypoglycemic drugs.
  • Anti-insulin antibodies should not be detectable in patients with insulinoma.
  • An increased serum concentration of proinsulin or C-peptide during hyp

oglycemia effectively excludes the diagnosis of factitious hypoglycemia.

MCQ - Diagnosis of Insulinoma

Answer: B

Explanation:

  • The diagnosis of insulinoma includes:
    • Serum glucose level lower than 45 mg/dL
    • Concomitant serum level of insulin higher than 5 µU/mL
    • Elevated serum levels of C-peptide (>0.7 ng/mL)
  • 60% of patients with insulinoma develop symptoms within 24 hours after fasting, and almost all patients develop symptoms within 72 hours.
  • Diazoxide inhibits insulin release in approximately 50% of patients with insulinoma; calcium channel blockers or phenytoin may suppress insulin production.
  • Surgery is the only curative therapy for insulinoma.

MCQ - Hallmark of Gastrinoma

Answer: D

Explanation:

  • Gastrinoma is characterized by:
    • Recurrent peptic ulcers
    • Chronic diarrhea
    • Thickened gastric mucosal folds
  • All of the above are hallmarks of gastrinoma.

MCQ - MEN 1 Syndrome

Which of the following statements is false regarding MEN 1 syndrome?

  • A. Genetic defect in MEN 1 is linked to muscle glycogen phosphorylase gene
  • B. Gene defect is localized to the short arm of chromosome 11
  • C. In MEN 1, parathyroidectomy should be done before pancreas surgery
  • D. All the above are true

Answer: B

Explanation:

  • MEN 1 syndrome:
    • The genetic defect in patients with MEN 1 has been localized to the long arm of chromosome 11, not the short arm.
    • It is linked to the skeletal muscle glycogen phosphorylase gene.
    • In MEN 1, primary hyperparathyroidism (three and one-half gland parathyroidectomy) should be performed prior to pancreatic surgery because correction of the hypercalcemia will greatly ameliorate the signs and symptoms of Zollinger-Ellison syndrome.

MCQ - Most Common Location of GRFoma

Answer: A

Explanation:

  • GRFomas (Growth Hormone-Releasing Factoromas) occur most frequently in the lung (bronchus), followed by the pancreas, jejunum, adrenal glands, and retroperitoneum.
  • Pancreatic GRFomas are typically large (>6 cm).
  • Approximately 50% of patients with GRFomas also have Zollinger-Ellison syndrome and 33% have MEN-1.
  • Patients present with acromegaly and a pancreatic mass.

MCQ - Homology with Motilin

Answer: A

Explanation:

  • Ghrelin has significant homology with motilin.
  • Ghrelin promotes growth hormone release, increases appetite and food intake, modulates insulin secretion, and stimulates gastric contractility and acid secretion.

MCQ - Functional and Nonfunctional Pancreatic NETs

Answer: D

Explanation:

  • Insulinoma and gastrinoma are the two most common functioning endocrine neoplasms of the pancreas.
  • The most common functional pancreatic NET is insulinoma.
  • The most common pancreatic NET overall is nonfunctional NET.
  • The most common functional malignant pancreatic NET is gastrinoma.

MCQ - Gastrinoma in MEN 1

Answer: A

Explanation:

  • Gastrinomas in MEN 1 are typically small, multiple, and most likely found in the duodenum (>85%).
  • Recurrent peptic ulcers, diarrhea, reflux esophagitis, and thickened mucosal folds in the stomach are hallmarks of the disease.
  • Confirmatory for gastrinoma: gastrin level > 10 times normal and gastric pH < 2.

MCQ - Boundaries of Passaro Triangle (Gastrinoma Triangle)

Answer: A

Explanation:

  • Boundaries of Passaro triangle (Gastrinoma triangle):
    • Junction of cystic duct and common bile duct (CBD)
    • Junction of 2nd and 3rd part of duodenum
    • Junction of head and body of pancreas

  • The junction of the duodenum and pancreas is not a boundary of Passaro triangle. The attached image provides visual confirmation.

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MCQ - Migratory Necrolytic Erythema

Answer: D

Explanation:

  • Migratory necrolytic erythema (NME) is a characteristic manifestation of glucagonoma.

MCQ - Characteristics of Migratory Necrolytic Erythema

Answer: C

Explanation:

  • Migratory necrolytic erythema (NME):
    • It can be the first manifestation in glucagonoma.
    • Starts in the perineum and extends to the trunk and extremities.
    • The lesions exhibit centrifugal growth with central healing and peripheral expansion, associated with waxing and waning.
    • The rash can be completely reversed with total parenteral nutrition.

Additional Information on Glucagonoma and NME:

  • Glucagonomas are almost always malignant.
  • The migratory rash (NME) is often the first manifestation.
  • The rash is migratory, red, scaling, and associated with intense pruritus, commonly occurring in intertriginous areas, including the groin and lower extremities.
  • NME is pathognomonic for glucagonoma.
  • The rash is related to markedly decreased plasma levels of amino acids.
  • Approximately 20% of patients with glucagonoma do not present with hyperglycemia.
  • Plasma glucagon levels greater than 1000 pg/mL are diagnostic of glucagonoma.
  • Glucagonomas are almost always found within the body and tail of the pancreas.

MCQ - Components of Pancreatic Cholera

Answer: B

Explanation:

  • Verner-Morrison syndrome (WDHA syndrome/VIPoma) includes:
    • Large-volume diarrhea
    • Severe hypokalemia with muscle weakness
    • Hypercalcemia
    • Hypochlorhydria
    • Diarrhea that is persistent during a fast (secretory diarrhea)
    • VIPomas typically occur in adults, with approximately half being benign.
    • The diarrhea is typically large in volume (>5 L/day) and occurs in 70% of patients.

MCQ - Somatostatinoma

Answer: A

Explanation:

  • Somatostatinoma:
    • Contrary to their duodenal counterparts, pancreatic somatostatinomas are not associated with von Recklinghausen syndrome.
    • Despite equal distribution of islet D cells throughout the pancreas, two-thirds of the tumors are located in the head of the pancreas, with the remainder found in the duodenum, at the ampulla, or small intestine.

MCQ - Pancreatic NET Associated with NF1

Answer: C

Explanation:

  • Somatostatinoma is the most common pancreatic NET associated with Neurofibromatosis type 1 (NF1).

MCQ - Triad of Somatostatinoma

Answer: D

Explanation:

  • The classic triad of somatostatinoma includes:
    • Diabetes mellitus
    • Cholelithiasis
    • Steatorrhea

MCQ - Pancreatic NET Imaging and Characteristics

Answer: D

Explanation:

  • 68Ga-PET/CT is the preferred functional imaging of choice over OctreoScan.
  • 68Ga-PET/CT will detect both functional and nonfunctional PNETs.
  • Somatostatinoma associated with glucose intolerance, cholelithiasis, weight loss, diarrhea, steatorrhea, or anemia
  • Duodenal somatostatinoma associated with NF1 are less likely to be malignant.
  • PPoma in the context of MEN1 tends to be multifocal and malignant.
  • PNETs with uptake on 18FDG PET are more likely to have early disease progression than those who are 18FDG PET negative.

MCQ - Somatostatin Receptor on Well Differentiated NET

Answer: B

Explanation:

  • The frequently expressed somatostatin receptor on well-differentiated NET is SSTR 2.

OctreoScan:

  • Uses the radiotracer indium-111-DTPA-octreotide, with dark spots indicating where the radiotracer has bound to SSTR2 (and to a lesser extent, SSTR5 and SSTR3).

68Ga-PET/CT:

  • Preferred functional imaging of choice over OctreoScan.
  • Detects both functional and nonfunctional PNETs.

MCQ - Side Effect of Temozolomide

Answer: C

Explanation:

  • The most notable toxicity with temozolomide is myelosuppression.
  • Lethal toxicities of dacarbazine include septic shock and myocardial infarctions.
  • The chemotherapy regimen for advanced PNET includes temozolomide in combination with capecitabine (CAPETEM).

Peptide Receptor Radionuclide Therapy (PRRT)

  • Radionuclides used for PRRT therapy:
    • Gamma-emitting: 111Indium
    • Beta-emitting: 90Yttrium (90Y)
    • Beta-emitting: 177Lutetium (177Lu)
  • Notable toxicities of PRRT:
    • Myelosuppression
    • Nephrotoxicity

MCQ - Noninsulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS)

Explanation

Insulinoma is the most common cause of hyperinsulinemic hypoglycemia. However, NIPHS (Nesidioblastosis) can cause similar symptoms.

  • NIPHS is characterized by excessive pancreatic beta cell function, with associated pathological changes including pancreatic islet hyperplasia and dysplasia, and histologic identification of beta cells budding from and in apposition to pancreatic ductal structures.
  • Nesidioblastosis is usually a disease of infancy but can occur in adults, making it difficult to differentiate from insulinoma.

Key Differentiation

  • Postprandial hypoglycemia (within 4 hours of a meal) is the hallmark of NIPHS and helps differentiate it from insulinoma, which does not have this feature.
  • Patients with NIPHS may have a positive 72-hour fast with episodes of hypoglycemia associated with inappropriate elevation of insulin, C-peptide, and proinsulin levels.

Diagnosis and Treatment

  • Clinical diagnosis of exclusion is based on the exclusion of insulinoma.
  • The final diagnosis is confirmed by a pathologic examination of the pancreas and clinical response to treatment.
  • Treatment of NIPHS includes pancreatectomy (most commonly 95% distal pancreatectomy), dietary control, and medical therapy with diazoxide and somatostatin analogues.

MCQ - Postgastric Bypass Noninsulinoma Pancreatogenous Hypoglycemia Syndrome

Explanation

Postgastric Bypass NIPHS is recognized as a complication of bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB).

  • NIPHS includes a constellation of postprandial neuroglycopenic symptoms similar to insulinoma but often more severe, such as confusion, disorientation, unconsciousness, syncope, shakiness, tremors, abnormal behavior, anxiety, weakness, blurred vision, and seizures.
  • The etiology in the setting of RYGB is theorized to be due to obesity-induced beta cell hypertrophy not reversed after RYGB, inappropriate growth factor release, or persistent altered gut hormonal signaling.

Treatment

  • First-line treatment: Dietary modifications and medication.
  • Medical management strategies include continuous glucose monitoring, acarbose, calcium channel blockade, diazoxide, and somatostatin analogues.
  • Surgical intervention: Considered in refractory cases. Options include RYGB reversal or distal pancreatectomy, taking into account perioperative risk, long-term outcome, potential for weight regain, and effects on obesity-related comorbidity.
  • Pancreatic resection is the most common surgical procedure, but the appropriate extent of resection is controversial, and symptoms often recur.

MCQ Questions

Answer: B

Answer: D

Answer: D

Answer: B

Answer: B