Endocrine neoplasms of the pancreas: pathologic and genetic features.
BACKGROUND
Pancreatic endocrine neoplasms (PENs) are diagnostically challenging tumors whose natural history is largely unknown. Histopathology allows the distinction of 2 categories: poorly differentiated high-grade carcinomas and well-differentiated neoplasms. The latter include more than 90% of PENs whose clinical behavior varies from indolent to malignant and cannot be predicted by their morphology.


OBJECTIVE
To review the literature and report on additional primary material about the clinicopathologic features, classification, staging, grading, and genetic features of PENs.


METHODS
Literature review of relevant articles indexed in PubMed (US National Library of Medicine) and primary material from the authors' institution.


CONCLUSIONS
The diagnosis of PEN is generally easy, but unusual features may induce misdiagnosis. Immunohistochemistry solves the issue, provided that the possibility of a PEN has been considered. Morphology allows the distinction of poorly differentiated aggressive carcinomas from well-differentiated neoplasms. The World Health Organization classification criteria allow for the discernment of the latter into neoplasms and carcinomas with either benign or uncertain behavior. The recently proposed staging and grading systems hold great promise for permitting a stratification of carcinomas into clinically significant risk categories. To date, inactivation of the MEN1 gene remains the only ascertained genetic event involved in PEN genesis. It is inactivated in roughly one-third of PENs. The degree of genomic instability correlates with the aggressiveness of the neoplasm. Gene silencing by promoter methylation has been advocated, but a formal demonstration of the involvement of specific genes is still lacking. Expression profiling studies are furnishing valuable lists of mRNAs and noncoding RNAs that may advance further the research to discover novel markers and/or therapeutic targets.
Capelli
Paola
P
Department of Pathology, Section ofAnatomical Pathology, Policlinico G. B. Rossi, 37134 Verona, Italy. paola.capelli@azosp.vr.it
Martignoni
Guido
G
Pedica
Federica
F
Falconi
Massimo
M
Antonello
Davide
D
Malpeli
Giorgio
G
Scarpa
Aldo
A
D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism
C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins