Current knowledge on diagnosis and staging of neuroendocrine tumors

Neuroendocrine tumors (NETs) consist of a heterogeneous group of malignancies with various clinical presentations and growth rates. The incidence has been estimated to 2.5–5 per 100,000 people per year and prevalence of 35 per 100,000. The largest group is the gastroenteropancreatic NETs. Small intestinal NETs are the most common followed by pancreatic NETs in the gastrointestinal tract. A classification system (World Health Organization) was established in year 2000 and recently updated in 2010, taking into consideration the histopathology and tumor biology of the tumors. To further refine the classification a “tumor node metastasis” staging has been suggested by the European Neuroendocrine Tumor Society. The same organization has also proposed a grading system (G1, G2, and G3). The diagnosis of a NET is based on histopathology on tumor specimens, circulating biomarkers as well as imaging. Traditional radiology, such as computerized tomography and magnetic resonance imaging, is still the basis but is complemented with somatostatin receptor scintigraphy and positron emission tomography with specific isotopes such 68Ga-DOTA-octreotate, F18-dopamine, or C11-5 hydroxytryptamine. Molecular imaging will increase in importance in the near future. There is still an unmet need for more sensitive biomarkers for diagnosis and follow-up.

[1]  E. Krenning,et al.  Role of somatostatins in gastroenteropancreatic neuroendocrine tumor development and therapy. , 2010, Gastroenterology.

[2]  Ahmed Essaghir,et al.  Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas , 2009, Modern Pathology.

[3]  B. Långstrom,et al.  Whole-body (11)C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and computed tomography. , 2005, The Journal of clinical endocrinology and metabolism.

[4]  A. Scarpa,et al.  TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system , 2007, Virchows Archiv.

[5]  M. Varas-Lorenzo,et al.  Gastrointestinal carcinoid tumors. , 2010, Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva.

[6]  B. Weinhold.  Epigenetics: The Science of Change , 2006, Virchows Archiv.

[7]  Kjell Öberg,et al.  Double-Detargeted Oncolytic Adenovirus Shows Replication Arrest in Liver Cells and Retains Neuroendocrine Cell Killing Ability , 2010, PloS one.

[8]  M. Bergström,et al.  Whole-Body 11C-5-Hydroxytryptophan Positron Emission Tomography as a Universal Imaging Technique for Neuroendocrine Tumors : Comparison with Somatostatin Receptor Scintigraphy and Computed Tomography , 2005 .

[9]  Michelle A. Anderson,et al.  Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas , 2000, American Journal of Gastroenterology.

[10]  D. Venzon,et al.  Somatostatin Receptor Scintigraphy: Its Sensitivity Compared with That of Other Imaging Methods in Detecting Primary and Metastatic Gastrinomas: A Prospective Study , 1996, Annals of Internal Medicine.

[11]  R. Jensen,et al.  Gastroenteropancreatic neuroendocrine tumours. , 2008, The Lancet. Oncology.

[12]  H. Friess,et al.  Clinical outcome and long‐term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas , 2008, The British journal of surgery.

[13]  Dr. O. Lubarsch.  Ueber den primären Krebs des Ileum nebst Bemerkungen über das gleichzeitige Vorkommen von Krebs und Tuberculose , 1888, Archiv für pathologische Anatomie und Physiologie und für klinische Medicin.

[14]  U. Hellman,et al.  Chromogranins--new sensitive markers for neuroendocrine tumors. , 1989, Acta oncologica.

[15]  M. Stridsberg,et al.  Tumor Markers in Neuroendocrine Tumors , 2000, Digestion.

[16]  E. D. de Vries,et al.  Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study. , 2006, The Lancet. Oncology.

[17]  I. Modlin,et al.  A 5‐decade analysis of 13,715 carcinoid tumors , 2003, Cancer.

[18]  K. Öberg.  Neuroendocrine gastrointestinal tumors - A condensed overview of diagnosis and treatment , 1999 .

[19]  S. Willich,et al.  Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors , 2008, Cancer.

[20]  G. Klöppel,et al.  The Gastroenteropancreatic Neuroendocrine Cell System and Its Tumors: The WHO Classification , 2004, Annals of the New York Academy of Sciences.

[21]  B. Skogseid,et al.  Prognostic Factors and Survival in 324 Patients with Pancreatic Endocrine Tumor Treated at a Single Institution , 2008, Clinical Cancer Research.

[22]  Hirotoshi Kikuchi,et al.  Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis. , 2008, Endocrine-related cancer.

[23]  L. Strauss,et al.  Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[24]  I. Modlin,et al.  Current status of gastrointestinal carcinoids. , 2005, Gastroenterology.

[25]  B. Eriksson,et al.  Tumour markers in neuroendocrine tumours. , 1999, Italian journal of gastroenterology and hepatology.

[26]  M. Memon,et al.  Gastrointestinal carcinoid tumors , 1997, Diseases of the colon and rectum.

[27]  K. Oberg,et al.  Somatostatin-receptor mediated diagnosis and treatment in gastrointestinal neuroendocrine tumours (GEP-NET's). , 2005, Roczniki Akademii Medycznej w Bialymstoku.

[28]  B. Skogseid,et al.  High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours. , 2004, European journal of endocrinology.

[29]  M. Stridsberg,et al.  A comparison between three commercial kits for chromogranin A measurements. , 2003, The Journal of endocrinology.

[30]  J. Reubi,et al.  Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[31]  K. Usadel,et al.  Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours , 1997, European Journal of Nuclear Medicine.

[32]  E. Nitzsche,et al.  Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[33]  R. Guillemin.  Hypothalamic hormones a.k.a. hypothalamic releasing factors. , 2005, The Journal of endocrinology.

[34]  R Guillemin,et al.  Hypothalamic releasing factors. , 1970, Annual review of biochemistry.