Diagnosis & Discussion

Diagnosis

Well-differentiated pancreatic neuroendocrine tumor (PanNET), WHO grade 1, with multiple associated microadenomas.

Discussion 

PanNETs are low-grade malignant neoplasms of intrapancreatic neuroendocrine cells that occur most commonly between the ages of 30-60 years. They make up less than 2% of pancreatic tumors, but there is an increased diagnosis of asymptomatic tumors in recent times due to improved sensitivity of modern imaging techniques.

PanNETs can be classified based on hormone production and the resulting syndrome, or the lack thereof, into functional and non-functional types, respectively. Functional tumors may secrete pancreatic hormones like insulin (causing hypoglycemia), glucagon (causing necrolytic migratory erythema), pancreatic polypeptides, and somatostatin, or ectopic peptides like gastrin (as occurs in the Zollinger-Ellison syndrome), and vasoactive intestinal peptide (causing profuse diarrhea). Non-functional tumors are usually asymptomatic but may come to clinical attention from compression of surrounding structures (e.g., jaundice from bile duct obstruction or pancreatitis from pancreatic duct obstruction).

Most PanNETs are sporadic, but a minority occurs as part of hereditary disorders like MEN1 and the von Hippel Lindau syndrome. Features of MEN1-associated PanNETs include younger patient age, multiple tumors, and concurrent microadenomas. Microadenomas are benign non-functional neuroendocrine neoplasms less than 0.5 cm in size (Figures 6-9).

The diagnosis of PanNETs is by morphology supported by immunohistochemistry. The gross tumor is white-yellow, well-demarcated, and firm. On microscopy, tumor cells are monotonous and display finely granular (“salt and pepper”) chromatin, distinct nucleoli, and a moderate amount of cytoplasm (Figure 2). The tumor cells are positive for neuroendocrine markers like synaptophysin (Figure 3), chromogranin (Figure 4), and CD56, and also positive for pan-cytokeratin.

WHO grade is assigned based on the Ki-67 index and mitotic rate. In this tumor, there were <2 mitoses/2mm² and a Ki-67 index <3% (Figure 5), consistent with a grade 1 well-differentiated neuroendocrine tumor. Tumors confined to the pancreas are treated with surgical resection; patients with metastatic tumors receive long-acting somatostatin analogs.

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References

Joo Young Kim and Seung-Mo Hong. Recent updates on neuroendocrine tumors from the gastrointestinal and pancreatobiliary tracts. Archives of pathology & laboratory medicine: May 2016, Vol. 140, No. 5, pp. 437-448.

Lamps, L. W., & Kakar, S. Diagnostic pathology: Hepatobiliary and pancreas. Elsevier, 2017

Mills SE, Greenson JK, Hornick JL, Longacre TA, Reuter VE, Sternberg SS. Sternberg's diagnostic surgical pathology. Philadelphia: Wolters Kluwer Lippincott Williams & Wilkins, 2015.