Final Diagnosis -- Well-differentiated pancreatic neuroendocrine neoplasm

FINAL DIAGNOSIS:

WELL-DIFFERENTIATED PANCREATIC NEUROENDOCRINE NEOPLASM OF UNCERTAIN BEHAVIOR, INVOLVING PANCREATIC TAIL, 5.0 CM.

DISCUSSION:

Histologically, this case is fairly characteristic for a pancreatic neuroendocrine neoplasm. These neoplasms are usually positive for chromogranin and synaptophysin. In this case, the tumor was chromogranin negative; however, staining for chromogranin is often weaker than staining for synaptophysin in pancreatic neuroendocrine tumors (1). The absence of mitosis and nuclear pleomorphism favor a more benign neoplasm, but the presence of angiolymphatic invasion increases the risk for recurrence and metastasis. The five peripancreatic lymph nodes were examined and were negative for tumor.

Pancreatic neuroendocrine tumors (aka. pancreatic endocrine tumors) are uncommon tumors occurring in approximately 1 in 100,000 and representing only 1-2% of pancreatic neoplasms (2). They are separated into functioning versus non-functioning based on the clinical manifestations. Functioning tumors include insulinomas, glucagonomas, somatostatinomas, gastrinomas, and VIPomas. These tumors are recognized clinically based on symptoms related to the particular hormone (3). There are also glucagonomas which do not stain for glucagon. In this patient, her diabetes improved to the point that she was able to decrease her daily doses of insulin; however, her diabetes did not resolve.

Non-functioning tumors, like the one present in this case, are usually diagnosed when they become symptomatic due to increasing size, invasion into adjacent structures, or metastasis; however, with the increasing use of CT scans, somewhat smaller neoplasms can be found incidentally. The WHO set forth criteria to classify pancreatic endocrine tumors into three types: well-differentiated endocrine tumor, well-differentiated endocrine carcinoma, and poorly-differentiated endocrine carcinoma. The well-differentiated endocrine tumors are further divided into "benign behavior" and "uncertain behavior". Those with uncertain behavior, like this case, are confined to the pancreas, > 2 cm in size, show 2-10 mitosis/10 HPF, show presence of angio- or perineural invasion, or have > 2 percent Ki-67 positivity (see Table 1). Non-functioning tumors are usually >2 cm in size (3). Those that are 5cm or greater have been shown to have an increased risk of malignancy (1). In this particular case, based on the size of the neoplasm and presence of angioinvasion, the tumor falls in to the category of well-differentiated endocrine tumor of uncertain behavior.

Table 1. Adapted from WHO Classification of Tumours.
Pathology and Genetics of Tumours of Endocrine Organs.

REFERNCES:

1. Odze RD, Goldblum JR, and Crawford JM (eds): Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas. Saunders: Philadelphia, 2004.
2. Sheehan M, Latona C, Aranha G, and Pickleman J. "Functioning and nonfunctioning neuroendocrine tumors of the pancreas." Curr Opinion in Oncology 2007; 19:30-35.
3. DeLellis RA, Lloyd RV, Heitz PU, and Eng C (eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Organs. IARC Press: Lyon 2004.

Contributed by Deborah Marks-Jones, MD, Smiljana Istvanic-Zdravkovic, MD and Jagjit Singh, MD