Neuroendocrine neoplasms – Overview

Tumors of the endocrine pancreas are a collection of tumor cell types collectively referred to as pancreatic neuroendocrine neoplasms. These tumors originate in islet cells, that belong to the gastro-entero-pancreatic endocrine system. Click here for more information about islet cells. They are uncommon neoplasms with an incidence of 4-5 cases per 100000 people. However, recent data indicate an increasing incidence.  

From an epidemiological standpoint, pancreatic neuroendocrine neoplasms are divided into two groups:

  • Sporadic neoplasms. These are more common and are not inherited neoplastic conditions
  • Neoplasms associated with genetic syndromes: These neoplasms are in connection with genetic syndromes such as multiple endocrine neoplasia type 1 (MEN1), Von Hippel-Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis

Pancreatic neuroendocrine neoplasms are clinically classified into two groups on the basis of hormone production:

  • Functional neuroendocrine neoplasms. Functional neoplasms cause an increase in hormone levels, and are associated to hormone syndromes. The most common functional neoplasms are insulinoma and gastrinoma
  • Non-functional neuroendocrine neoplasms. Non-functional neoplasms do not produce hormones associated with clinical syndromes. Therefore, they do not cause specific symptoms, but more that 50% are malignant. They are more common than functional neoplasms
Furthermore, pancreatic neuroendocrine neoplasms are graded on the basis of a scale system (G1 to G3) proposed by the World Health Organization (WHO) in 2010. Grading is assigned by a Pathologist after examining biopsy samples or surgical specimen. Tumor grade is based on morphologic characteristics of the neoplastic cells, mitotic count or measurement of the proliferation index Ki-67.
  • Well-differentiated pancreatic neuroendocrine neoplasms (G1/G2) are made up of cells that closely resemble healthy cells of the pancreas, and have low mitotic count or low Ki-67. Well-differentiated tumors are also less likely to be aggressive. 90% of pancreatic neuroendocrine neoplasms are well differentiated.
  • Poorly differentiated pancreatic neuroendocrine neoplasms (G3) are made up of cells that less closely resemble healthy cells of the pancreas, and display high mitotic count or elevated Ki-67. Poorly differentiated tumors are aggressive.

The European Neuroendocrine Tumor Society (ENETS) proposed a TNM classification system for neuroendocrine neoplasms. The tumor/node/metastasis system evaluates the size of the primary tumor, whether the tumor has spread to nearby organs or vessels, whether the tumor has spread to nearby lymph nodes, and whether the tumor has spread (metastasized) to distant organs. The ENETS staging system has been shown to well correlate with patient prognosis, and is currently applied in the clinical practice.

Because of their rarity and heterogeneity, pancreatic neuroendocrine neoplasms are particularly challenging to treat, and require an expert multidisciplinary team. The plaNET is the multidisciplinary team that, within the University of Verona Hospital Trust, focuses on gastro-entero-pancreatic neuroendocrine neoplasms. This group comprises Surgeons, Oncologists, Radiologists, Nuclear Medicine Physicians, Endocrinologists, and Gastroenterologists who meet periodically and predispose the best available diagnostic and care plan for each patient. To learn more about pancreatic neuroendocrine neoplasms, visit the specific sections.