Department of Diagnostic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan.
Department of Pathology, Iwate Medical University, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan.
Diagn Pathol. 2023 Oct 20;18(1):115. doi: 10.1186/s13000-023-01403-y.
Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH), also known as adult-onset nesidioblastosis, is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. This disease is characterized by diffuse hyperplasia of pancreatic endocrine cells and is diagnosed by a pathological examination. While diagnostic criteria for this disease have already been proposed, we established more quantitative criteria for evaluating islet morphology.
We measured the number, maximum diameter, total area, and circularity (representing how closely islets resemble perfect spheres) of islets contained in representative sections of ANHH (n = 4) and control cases (n = 5) using the NIS-Elements software program. We also measured the average cell size, percentage of cells with enlarged nuclei, and percentage of cells with recognizable nucleoli for each of three representative islets. We also assessed the interobserver diagnostic concordance of ANHH between five experienced and seven less-experienced pathologists.
There was no significant difference in the number, maximum diameter, or total area of islets between the two groups, even after correcting for these parameters per unit area. However, the number of islets with low circularity (< 0.71) per total area of the pancreatic parenchyma was significantly larger in ANHH specimens than in controls. We also found that the percentage of cells with recognizable nucleoli was significantly higher in the ANHH group than in the controls. There were no significant differences in the average cell size or the number of cells with enlarged nuclei between the groups. The correct diagnosis rate with the blind test was 47.5% ± 6.12% for experienced pathologists and 50.0% ± 8.63% for less-experienced pathologists, with no significant differences noted.
Low circularity, which indicates an irregular islet shape, referred to as "irregular shape and occasional enlargement of islets" and "lobulated islet structure" in a previous report, is a useful marker for diagnosing ANHH. An increased percentage of recognizable nucleoli, corresponding to "macronucleoli in β-cells," has potential diagnostic value.
成人非肿瘤性高胰岛素血症性低血糖（ANHH），又称成人发病的胰岛细胞增生症，是成人内源性高胰岛素血症性低血糖的罕见病因。该病的特征为胰腺内分泌细胞弥漫性增生，通过病理检查进行诊断。虽然已经提出了该病的诊断标准，但我们建立了更定量的胰岛形态评估标准。
我们使用 NIS-Elements 软件程序测量了 ANHH（n=4）和对照组（n=5）代表性切片中胰岛的数量、最大直径、总面积和圆形度（代表胰岛与完美球体的接近程度）。我们还测量了每个胰岛的 3 个代表性胰岛的平均细胞大小、核增大细胞的百分比和可识别核仁的细胞百分比。我们还评估了 5 名经验丰富的病理学家和 7 名经验较少的病理学家之间对 ANHH 的诊断一致性。
即使校正了胰岛的单位面积参数，两组间的胰岛数量、最大直径或总面积均无显著差异。然而，ANHH 标本中胰岛圆形度（<0.71）较低的数量与对照组相比显著增加。我们还发现 ANHH 组的可识别核仁的细胞百分比显著高于对照组。两组间的平均细胞大小或核增大细胞的数量均无显著差异。盲法测试的正确诊断率为经验丰富的病理学家 47.5%±6.12%，经验较少的病理学家为 50.0%±8.63%，无显著差异。
低圆形度，提示胰岛形状不规则，在之前的报告中称为“胰岛形状不规则和偶尔增大”和“胰岛分叶状结构”，是诊断 ANHH 的有用标志物。可识别核仁的百分比增加，对应于“β 细胞中的巨核仁”，具有潜在的诊断价值。
