Endocrine tumors of the pancreas, also known as pancreatic neuroendocrine tumors (pNET), arise from the pancreatic islet cells and include some distinct tumors that match the cell type of origin.
Pancreatic endocrine tumors have commonly been referred to as "islet cell tumors", referring to the islets of Langerhans, from which they were thought to derive. It has since been shown that these tumors derive from ductal pluripotent stem cells, and "endocrine tumor" is now preferred 3.
Overall, pancreatic endocrine tumors have an incidence of 0.001% and account for 1-2% of pancreatic neoplasms. They occur most commonly at ages 30-60, with no clear gender predilection.
Most tumors are isolated. 1-2% are associated with the multiple endocrine neoplasia type I (MEN I), which is characterized by the triad of parathyroid, pituitary, and pancreatic lesions.
Syndromic tumors tend to present earlier, with clinical signs and symptoms related to their cell type and biological activity:
- insulinoma: Whipple triad
- gastrinoma: Zollinger-Ellison syndrome
- glucagonoma: 4D syndrome
- non-functioning tumors: tend to present late and often larger in size
These tumors can broadly be divided according to whether or not they secrete enough active compounds to be syndromic or not:
- syndromic tumors
- non-syndromic tumors: third most common
Individual functional tumors are discussed in more detail separately.
The term "syndromic" is preferred over "functioning" since it is becoming increasingly clear that most tumors are functional (i.e. produce hormones), but either do not produce enough hormone or produce an ineffective variant of the hormone, so that they may not produce a clinical syndrome.
According to the 2017 World Health Organization (WHO) classification, these tumors are histologically graded as 5,6:
- well-differentiated status
- grade 1 (G1): tumor expressing < 2 mitoses/2mm2 and ≤ 2% Ki-67 index
- grade 2 (G2): tumor expressing between 2 to 20 mitoses/2mm2 and 3 to 20% Ki-67 index
- grade 3 (G3): more than 20 mitoses/2mm2 and more than 20% Ki-67 index
- poorly-differentiated and containing components of adenocarcinoma - they are named pancreatic neuroendocrine carcinoma (pNEC) and divided into two types
- small cell type
- large cell type
Overall these endocrine tumors of the pancreas tend to be highly vascular and well-circumscribed, often displacing adjacent structures. They can demonstrate calcific or cystic change.
- well-circumscribed with smooth margins
- round or oval
Liver metastases may be hyperechoic or targetoid.
- tend to be homogenous and well-circumscribed
- may appear heterogeneous and contain areas of cystic or necrotic change
- can occasionally manifest as primarily cystic lesions and are distinguishable from other cystic neoplasms by their hypervascular rim
Since usually have a distinct capsule which means they displace rather than invade surrounding structures as they grow in size. As a result, they less frequently present with biliary obstruction, which is a classic mode of presentation for pancreatic adenocarcinomas.
Endocrine tumors of the pancreas show peak contrast enhancement in the early arterial phase (25-35 s) rather than in late arterial phase (35-45 s) which is normally used for pancreatic imaging. This is particularly important when considering that small lesions may be missed in late arterial phase when the tumor will appear isointense with enhancing pancreatic parenchyma.
Sensitivity is similar to CT
- T1: hypointense relative to pancreas
- T2: typically hyperintense relative to pancreas, but there is a range of signal intensities
- T1 C+ (Gd): hyperintense/hypervascular relative to pancreas
May be useful to localize or confirm a functioning tumor and look for metastases.
- planar or SPECT
- sensitivity is ~80%, although limited by the somatostatin receptor characteristics of the tumor
- reported sensitivity is highest with gastrinomas >2 cm
- reported sensitivity is lowest with insulinomas
- sensitivity limited unless poorly-differentiated
Treatment and prognosis
If diagnosed early enough (before metastases), then complete surgical resection may be curable. Even patients with advanced disease can have reasonable long-term survival. Biological behavior also depends on the cell of origin:
- insulinoma: 10% malignant
- gastrinoma: 60% malignant
- glucagonoma: 80% malignant
- VIPoma: 75% malignant
- somatostatinoma: 75% malignant
- non-functional: 85-100% malignant
- metastasis (e.g. renal cell carcinoma)
- intrapancreatic splenule (if in the tail of the pancreas)
- mostly-solid serous cystadenoma
check for concomitant metastatic disease: neuroendocrine tumors most commonly give metastases in the liver and, less frequently, in the bones
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- 5. Guido Rindi, David S. Klimstra, Behnoush Abedi-Ardekani, Sylvia L. Asa, Frederik T. Bosman, Elisabeth Brambilla, Klaus J. Busam, Ronald R. de Krijger, Manfred Dietel, Adel K. El-Naggar, Lynnette Fernandez-Cuesta, Günter Klöppel, W. Glenn McCluggage, Holger Moch, Hiroko Ohgaki, Emad A. Rakha, Nicholas S. Reed, Brian A. Rous, Hironobu Sasano, Aldo Scarpa, Jean-Yves Scoazec, William D. Travis, Giovanni Tallini, Jacqueline Trouillas, J. Han van Krieken, Ian A. Cree. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. (2018) Modern Pathology. 31 (12): 1770. doi:10.1038/s41379-018-0110-y - Pubmed
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