Endocrine tumours of the pancreas

Endocrine tumours of the pancreas arise from the pancreatic islet cells and include a number of distinct tumours that match the cell type of origin. 

Terminology

Pancreatic endocrine tumours 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.

Epidemiology

Most tumours 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.

There are also associations between pancreatic endocrine tumours and von Hippel Lindau and tuberous sclerosis.

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.

Clinical presentation

Syndromic tumours tend to present earlier, with clinical signs and symptoms related to their cell type and biological activity. 

Non-syndromic tumours tend to present later and are often larger in size.

Pathology

These tumours can broadly be divided according to whether or not they secrete enough active compounds to be syndromic or not:

Individual functional tumours are discussed in more detail separately. 

The term "syndromic" is preferred over "functioning", since it is becoming increasingly clear that most tumours 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.

Neuroendocrine tumorus are classified histologically by the presence of neurosecretory granules, which stain positively for:

  • chromogranin
  • synaptophysin
  • Gremilius stains
  • neuron-specific enolase

Radiographic features

Overall these endocrine tumours of the pancreas tend to be highly vascular and well circumscribed, often displacing adjacent structures. They can demonstrate calcific or cystic change.

Ultrasound
  • well-circumscribed with smooth margins
  • round or oval
  • hypoechoic

Liver metastases may be hyperechoic or targetoid.

CT

Smaller tumours:

  • hypervascular
  • tend to be homogenous and well circumscribed

Larger tumours:

  • may appear heterogenous 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 tumours of the pancreas show peak contrast enhancement in the early arterial phase (25-35 secs) rather than in late arterial phase (35-45 secs) 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 tumour will appear isointense with enhancing pancreatic parenchyma.

75% of patients with neuroendocrine tumors have metastatic disease at presentation, most commonly in the liver and less frequently in bone.

MRI

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+ (Gad): hyperintense/hypervascular relative to pancreas
Nuclear medicine

May be useful to localize or confirm a functioning tumour and look for metastases.

  • 111In-octreotide:
    • planar or SPECT
    • sensitivity is ~80%, although limited by the somatostatin receptor characteristics of the tumour
      • reported sensitivity is highest with gastrinomas >2 cm
      • reported sensitivity is lowest with insulinomas
  • FDG-PET
    • 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 behaviour also depends on cell of origin:

Differential diagnosis

  • metastasis to the spleen (e.g. renal cell carcinoma)
  • intrapancreatic splenule (if in the tail of the pancreas)
  • mostly-solid serous cystadenoma

Related articles

Pancreatic pathology

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