review of literature on clinical pancreatology - The Pancreapedia

ENDOCRINE PANCREATIC TUMORSHistoryA search on PubMed using the keywords “neuroendocrine”, “pancreas” and “carcinoid” wasperformed to identify relevant <strong>literature</strong> over the last 30 years. The introduction <strong>of</strong> a revisedclassification <strong>of</strong> neuroendocrine tumours by the World Health Organisation (WHO) in 2000significantly changed our understanding <strong>of</strong> and approach to the management <strong>of</strong> thesetumours. Advances in laboratory and radiological techniques have also led to an increaseddetection <strong>of</strong> PNETs. Surgery remains the only treatment that <strong>of</strong>fers a chance <strong>of</strong> cure withincreasing number <strong>of</strong> non-surgical options serving as beneficial adjuncts. The betterunderstanding <strong>of</strong> the behaviours <strong>of</strong> PNETs together with improvements in tumour localisationhas resulted in a more aggressive management strategy with a concomitant improvement insymptom palliation and a prolongation <strong>of</strong> survival. Due to their complex nature and the widerange <strong>of</strong> therapeutic options, the involvement <strong>of</strong> specialists from all necessary disciplines in amultidisciplinary team setting is vital to provide optimal treatment <strong>of</strong> this disease [662].Reported cases <strong>of</strong> diffuse nesidioblastosis have had common clinical features: postprandialhyperinsulinemic hypoglycemia, no abnormal findings in radiological examinations, and thepresence <strong>of</strong> the ductulo-insular complex on histological examination. Surgical resection isrecommended, but the extent <strong>of</strong> surgery is controversial. Our case had some clinical features<strong>of</strong> insulinoma but was diagnosed as diffuse nesidioblastosis according to histopathologiccriteria. Because arterial stimulation and veneous sampling showed that the pancreatic bodyand tail had a lesion producing insulin abnormally, we performed a distal pancreatectomy tocure the hypoglycemia. Clinically, it is very difficult to distinguish diffuse nesidioblastosis frominsulinkoma [663].GeneticsPancreatic endocrine neoplasms (PENs) are diagnostically challenging tumors whose naturalhistory is largely unknown. Histopathology allows the distinction <strong>of</strong> two categories: poorlydifferentiated high-grade carcinomas and well-differentiated neoplasms. The latter includemore than 90percent <strong>of</strong> PENs whose clinical behavior varies from indolent to malignant andcannot be predicted by their morphology. The diagnosis <strong>of</strong> PEN is generally easy, butunusual features may induce misdiagnosis. Immunohistochemistry solves the issue, providedthat the possibility <strong>of</strong> a PEN has been considered. Morphology allows the distinction <strong>of</strong> poorlydifferentiated aggressive carcinomas from well-differentiated neoplasms. The World HealthOrganization classification criteria allow for the discernment <strong>of</strong> the latter into neoplasms andcarcinomas with either benign or uncertain behavior. The recently proposed staging andgrading systems hold great promise for permitting a stratification <strong>of</strong> carcinomas into clinicallysignificant risk categories. To date, inactivation <strong>of</strong> the MEN1 gene remains the onlyascertained genetic event involved in PEN genesis. It is inactivated in roughly one-third <strong>of</strong>PENs. The degree <strong>of</strong> genomic instability correlates with the aggressiveness <strong>of</strong> the neoplasm.Gene silencing by promoter methylation has been advocated, but a formal demonstration <strong>of</strong>the involvement <strong>of</strong> specific genes is still lacking. Expression pr<strong>of</strong>iling studies are furnishingvaluable lists <strong>of</strong> mRNAs and noncoding RNAs that may advance further the research todiscover novel markers and/or therapeutic targets [664].Gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs) originate from cells <strong>of</strong>the diffuse endocrine system. Most GEP-NETs are sporadic, however, some <strong>of</strong> them,especially pancreatic endocrine tumors, may occur as part <strong>of</strong> familial syndromes. Thegenetic and molecular pathology <strong>of</strong> neuroendocrine tumor development is incomplete andremains largely unknown. However, the WHO classification introduced in clinical practice will