Anlauf Martin, Wieben Daniel, Perren Aurel, Sipos Bence, Komminoth Paul, Raffel Andreas, Kruse Marie L, Fottner Christian, Knoefel Wolfram T, Mönig Heiner, Heitz Philipp U, Klöppel Günter
Department of Pathology, University of Kiel, Kiel, Germany.
Am J Surg Pathol. 2005 Apr;29(4):524-33. doi: 10.1097/01.pas.0000151617.14598.ae.
Persistent hyperinsulinemic hypoglycemia (PHH) in adults that is not caused by an insulinoma is a rare and not well-characterized disease that has been named nesidioblastosis. In this study, we defined and scrutinized criteria for its histologic diagnosis, assessed its relative incidence, and discussed its pathogenesis. In pancreatic specimens from 15 adult patients with PHH in whom no insulinoma was detected and in 18 adult control patients, the endocrine tissue was screened for islet and beta-cell changes. The diagnostic reliability of the findings was checked by an interobserver analysis. The relative frequency of the disease was assessed in a series of 232 patients with PHH. Finally, genetic analysis of the menin gene was performed. Among the various indicators of islet changes, beta-cell hypertrophy characterized by enlarged and hyperchromatic beta-cell nuclei was the most significant and diagnostic finding in patients with PHH. The interobserver analysis revealed 100% specificity and 87.7% sensitivity. The hyperfunctional state of the beta-cells was not associated with changes in the subcellular distribution of insulin and proinsulin, proliferative activity, or mutations of the menin gene. Our results indicate that diffuse nesidioblastosis in adult patients with PHH resembles that seen in neonates suffering from PHH. The most important criterion for the diagnosis is the beta-cell hypertrophy. As approximately 4% of adult patients with PHH are affected by diffuse nesidioblastosis, this disease is not as rare as it has been thought to be. Pathogenetically, the defective insulin secretion could be based on a molecular defect.
成人非胰岛素瘤所致的持续性高胰岛素血症性低血糖症（PHH）是一种罕见且特征不明的疾病，已被命名为胰岛细胞增殖症。在本研究中，我们定义并详细审查了其组织学诊断标准，评估了其相对发病率，并讨论了其发病机制。在15例未检测到胰岛素瘤的成人PHH患者及18例成人对照患者的胰腺标本中，筛查内分泌组织的胰岛和β细胞变化。通过观察者间分析检查结果的诊断可靠性。在一系列232例PHH患者中评估该疾病的相对发生率。最后，对Menin基因进行基因分析。在胰岛变化的各种指标中，以β细胞核增大和染色质增多为特征的β细胞肥大是PHH患者最显著的诊断性发现。观察者间分析显示特异性为100%，敏感性为87.7%。β细胞的高功能状态与胰岛素和胰岛素原的亚细胞分布变化、增殖活性或Menin基因突变无关。我们的结果表明，成人PHH患者中的弥漫性胰岛细胞增殖症类似于新生儿PHH患者中的情况。诊断的最重要标准是β细胞肥大。由于约4%的成人PHH患者受弥漫性胰岛细胞增殖症影响，该疾病并不像人们认为的那样罕见。在发病机制上，胰岛素分泌缺陷可能基于分子缺陷。
