Tumores Endocrinos d e Pancreas

Endocrinol Metab Clin N Am 35 (2006) 431–447

Endocrine Tumors of the Pancreas
Peter Simon, MD, Elisabeth Spilcke-Liss, MD, Henri Wallaschofski, MD*
Department of Gastroenterology, Endocrinology and Nutrition, Ernst-Moritz-Arndt-University, Friedrich Loeffler Strasse 23A, D-17487 Greifswald, Germany

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that originate from acommon precursor cell population that share a number of antigens with nerve elements, like neuron-specific enolase, chromogranins, and synaptophysin. NETs affect endocrine glands (eg, pituitary gland, parathyroids, or the neuroendocrine adrenal gland) and endocrine islets within glandular tissues (eg, thyroid or pancreatic) and cells dispersed between exocrine cells (digestive or respiratory tract).The pancreatic endocrine tumors (PETs) are rare NETs of the pancreas originating from totipotential stem cells or differentiated mature endocrine cells within the exocrine gland. PETs have been frequently called ‘‘islet cell tumors,’’ whereas it is uncertain that they all originate from pancreatic islets. In case of nonfunctioning PETs this name is a misnomer, and in tumors with a typical pattern ofhormones (gastrinoma, VIPoma, and so forth) that originate from the gastrointestinal tract outside the pancreas [1,2]. Most patients without typical symptoms are not investigated routinely for the full spectrum of possibly released peptides or hormones and might be miscategorized. It is commonly assumed that hormone or peptide release influences tumor behavior and outcome. PETs releasing insulinshow a lower risk of behaving aggressively than those releasing pancreatic polypeptide, somatostatin, glucagon, adrenocortocotropin hormone, calcitonin, or growth hormone–releasing hormone (Table 1). The diagnosis of NETs mainly relies on the positive assessment of markers of neuroendocrine differentiation by immunohistochemistry. The most commonly used markers are general neuroendocrine markers(applicable to all neuroendocrine cells),
H.W. received payments for services from Novartis (Basel, Switzerland) and Ipsen (Paris, France). Various passages have been adapted from an outstanding review in this field by GA Kaltsas et al [1]. * Corresponding author. E-mail address: henri.wallaschofski@uni-greifswald.de (H. Wallaschofski). 0889-8529/06/$ - see front matter Ó 2006 Elsevier Inc. Allrights reserved. doi:10.1016/j.ecl.2006.02.011 endo.theclinics.com

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Table 1 Classification of pancreatic endocrine tumours Well differentiated neuroendocrine tumor Benign behavior Confined to pancreas No angioinvasion !20 mm in size !2 mitosis per 10 HPF !2% Ki-67 proliferation/10 HPF Nonfunctioning Insulin producing Tumors Uncertain behavior Confirmed to pancreas AngioinvasionO20 mm in size O2 mitosis per 10 HPF O2% Ki-67 proliferation/10 HPF Nonfunctioning Functioning (gastrin, insulin, VIP, glucagon, somatostatin, ACTH, GH, PTHrP) Low-grade malignant Local invasion/metastases Angioinvasion/perineural invasion 2–9 mitosis per 10 HPF 2%–10% Ki-67 proliferation/10 HPF Nonfunctioning Functioning (gastrin, insulin, VIP, glucagon, somatostatin, ACTH, GH, PTHrP) Poorlydifferentiated neuroendocrine carcinoma High-grade malignant tumours with atypical cells Undifferentiated carcinoma Prominent angioinvasion O10 mitosis per 10 HPF O10% Ki-67 proliferation/10 HPF Abbreviations: ACTH, adrenocorticotropic hormome; GH, growth hormone; HPF, highpower field; PTHrP, parathormone related peptide; VIP, vasoactive intestinal polypeptide.

either in the cytosol, such asneuron-specific enolase and the protein gene product 9.5, or granular markers, such as chromogranin A and synaptophysin [3–7]. Histologic and hormonal features of specific cell types are integrated in a so-called ‘‘morphofunctional’’ classification to predict the natural course of the tumor. Currently, the World Health Organization included both histopathologic and functional parameters into a widely...