Capelli Paola, Martignoni Guido, Pedica Federica, Falconi Massimo, Antonello Davide, Malpeli Giorgio, Scarpa Aldo
Department of Pathology, Section ofAnatomical Pathology, Policlinico G. B. Rossi, 37134 Verona, Italy.
Arch Pathol Lab Med. 2009 Mar;133(3):350-64. doi: 10.5858/133.3.350.
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.
To review the literature and report on additional primary material about the clinicopathologic features, classification, staging, grading, and genetic features of PENs.
Literature review of relevant articles indexed in PubMed (US National Library of Medicine) and primary material from the authors' institution.
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.
胰腺内分泌肿瘤（PENs）是诊断具有挑战性的肿瘤，其自然病史很大程度上未知。组织病理学可区分两类：低分化高级别癌和高分化肿瘤。后者包括超过90%的PENs，其临床行为从惰性到恶性不等，无法通过形态学预测。
回顾文献并报告关于PENs临床病理特征、分类、分期、分级和基因特征的额外原始资料。
对美国国立医学图书馆PubMed索引的相关文章进行文献综述以及作者所在机构的原始资料。
PEN的诊断通常容易，但不寻常特征可能导致误诊。免疫组织化学可解决该问题，前提是已考虑到PEN的可能性。形态学可区分低分化侵袭性癌和高分化肿瘤。世界卫生组织的分类标准有助于将后者区分为行为良性或不确定的肿瘤和癌。最近提出的分期和分级系统有望将癌分层为具有临床意义的风险类别。迄今为止，MEN1基因失活仍然是唯一确定参与PEN发生的遗传事件。大约三分之一的PENs中该基因失活。基因组不稳定程度与肿瘤的侵袭性相关。有人主张通过启动子甲基化进行基因沉默，但仍缺乏特定基因参与的正式证据。表达谱研究提供了有价值的mRNA和非编码RNA列表，可能进一步推动发现新标志物和/或治疗靶点的研究。
