Pancreas chapter

Pancreatic Endocrine Neoplasms (PanNETs)

Characteristics of PanNETs

• Distinction from Cystic Neoplasms: PanNETs must be differentiated from degenerative changes in secondary pancreatic cystic neoplasms.

• Growth Patterns: Some may show primary intraductal patterns of growth, indicating abnormal growth within pancreatic ducts.

• Microscopic Features: Composed of small, uniform cuboidal cells with:

  • Centrally located nuclei

  • Cytoplasm that is either acidophilic or amphophilic and finely granular.

  • Potential for marked nuclear enlargement and pleomorphism.

• Location: Can occur anywhere in the pancreas; often solitary with a homogeneous appearance lacking well-defined capsules.

• Gross Appearance: Tumoral cut surfaces vary in color from tan-yellow to red and can resemble the spleen or congested lymph nodes.

  • May also show signs of hemorrhage, necrotic foci, and in rare cases, calcifications and bone formation.

  • A small number of tumors can have a predominantly cystic appearance, particularly in patients with Multiple Endocrine Neoplasia (MEN) syndrome.

Morphological Variants and Findings

• Unusual Findings:

  • Mucin production

  • Black pigmentation from lipofuscin granules

  • Spindling of tumor cells

  • Psammoma bodies (often linked to somatostatinomas)

  • Rhabdoid features and focal sarcomatoid transformation in rare cases.

• Vascularity: PanNETs are highly vascular, with structures surrounding nests of neoplastic cells. The presence of dense stroma may vary from tumor to tumor, and significant stromal abundance can occur but does not affect clinical outcomes.

Architectural Growth Patterns

• Various patterns of growth have been observed, including:

  • Solid nests

  • Trabecular patterns

  • Rosettes

• Specific variants like clear cell and oncocytic PanNETs may mimic other types of tumors such as renal cell carcinoma and hepatocellular carcinoma respectively.

Functional PanNETs

Types of Functional Tumors

• Insulinomas:

  • Most common, typically seen in adults with a slight female predominance.

  • Characterized by symptoms relating to insulin secretion such as hypoglycemia.

  • Classic symptom triad known as Whipple triad:

    1. Mental confusion, weakness, fatigue, convulsions.

    2. Fasting blood glucose levels <50 mg.

    3. Relief of symptoms with glucose administration.

  • Usually solitary tumors approximately 1.5 cm or less.

• Gastrinomas:

  • Produce excessive gastrin leading to Zollinger-Ellison syndrome.

  • Often located in the duodenum and pancreas; can lead to ulcers and digestive issues.

  • Significant percentage associated with MEN 1 syndrome.

• Glucagonomas:

  • Associated with the glucagonoma syndrome, which manifests with symptoms like skin rash and severe weight loss.

• VIPomas and Somatostatinomas:

  • VIPomas linked with severe diarrhea; somatostatinomas typically asymptomatic but may cause diabetes and gallbladder issues.

Multiple Endocrine Neoplasia (MEN) Syndromes

MEN 1 (Werner Syndrome)

• Features pancreatic endocrine tumors (PanNETs), including insulinomas and gastrinomas.

• Associated with anterior pituitary adenomas and primary hyperparathyroidism.

MEN 2 (Sipple and Gorlin Syndromes)

• Characterized by medullary thyroid carcinoma, pheochromocytomas, and hyperparathyroidism (MEN 2a);

• MEN 2b includes mucosal neuromas, marfanoid habitus, and other features distinctive to the syndrome.

Diagnosis and Management of PanNETs

• Imaging and Diagnostics:

  • CT, MRI, and endoscopic ultrasound are crucial for localization pre-surgery.

  • Angiography with stimulation venous sampling can accurately locate insulinomas.

• Surgical Treatment:

  • Primary treatment approach for localized tumors; ranging from enucleation to more extensive resection based on tumor characteristics.

  • Nonfunctional tumors and those found incidentally may also be evaluated for surgical options.

Grading and Prognosis

• WHO Classification: PanNETs graded based on mitotic count and Ki-67 index:

  • Grade 1 (G1): Mitoses <2/10 HPF, Ki-67 <3%

  • Grade 2 (G2): Mitoses 2-20/10 HPF, Ki-67 3%-20%

  • Grade 3 (G3): Mitoses >20/10 HPF, Ki-67 >20%

• Factors influencing prognosis include patient age, tumor size, and presence of metastases.