Pancreatic neuroendocrine tumors
Citation, DOI & article data
Pancreatic neuroendocrine tumors (pNET), also known as endocrine tumors of the pancreas, arise from pancreatic ductal stem cells and include some distinct tumors that match the cell type of origin.
Pancreatic neuroendocrine 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 "neuroendocrine tumor" is now preferred 3.
Overall, pancreatic neuroendocrine 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. Approximately 1-2% are associated with multiple endocrine neoplasia type 1 (MEN1), 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:
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:
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 form 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:
grade 1 (G1): tumor expressing <2 mitoses/2 mm2 and ≤2% Ki-67 index
grade 2 (G2): tumor expressing between 2 to 20 mitoses/2 mm2 and 3 to 20% Ki-67 index
grade 3 (G3): more than 20 mitoses/2 mm2 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 neuroendocrine 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 pNETs usually have a distinct capsule, this means that 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.
Neuroendocrine tumors of the pancreas show peak contrast enhancement in the early arterial phase (25-35 s) rather than in the 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 the 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 the pancreas, but there is a range of signal intensities
T1 C+ (Gd): hyperintense/hypervascular relative to pancreas
DWI/ADC: restricted diffusion is usually present and tends to correlate to the degree of tumor differentiation
Nuclear medicine studies play an important role in the staging of neuroendocrine tumors.
superior to octreotide scan
F-18 FDG PET-CT
sensitivity limited unless poorly-differentiated
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
has been largely replaced by PET-CT in most centers
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
- 1. Demos TC, Posniak HV, Harmath C et-al. Cystic lesions of the pancreas. AJR Am J Roentgenol. 2002;179 (6): 1375-88. AJR Am J Roentgenol (full text) - Pubmed citation
- 2. Raman SP, Hruban RH, Cameron JL et-al. Pancreatic imaging mimics: part 2, pancreatic neuroendocrine tumors and their mimics. AJR Am J Roentgenol. 2012;199 (2): 309-18. doi:10.2214/AJR.12.8627 - Pubmed citation
- 3. Lewis RB, Lattin GE, Paal E. Pancreatic endocrine tumors: radiologic-clinicopathologic correlation. Radiographics. 2010;30 (6): 1445-64. doi:10.1148/rg.306105523 - Pubmed citation
- 4. Horton KM, Hruban RH, Yeo C et-al. Multi-detector row CT of pancreatic islet cell tumors. Radiographics. 2006;26 (2): 453-64. doi:10.1148/rg.262055056 - Pubmed citation
- 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
- 6. Inzani F, Petrone G, Rindi G. The New World Health Organization Classification for Pancreatic Neuroendocrine Neoplasia. (2018) Endocrinology and metabolism clinics of North America. 47 (3): 463-470. doi:10.1016/j.ecl.2018.04.008 - Pubmed