Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
Scand J Surg. 2020 Jun;109(2):133-142. doi: 10.1177/1457496918822622. Epub 2019 Jan 17.
Primary aldosteronism is a common cause of secondary hypertension. Primary aldosteronism is caused by an aldosterone-producing adenoma or bilateral hyperplasia that in some cases is asymmetrical with one adrenal dominating aldosterone secretion. Most patients with aldosterone-producing adenoma are biochemically cured by unilateral adrenalectomy, but patients with bilateral hyperplasia have a significant risk of residual or recurrent disease. Here, immunohistochemistry of CYP11B1 and B2 was used to investigate whether these markers could aid in the diagnostic workup of primary aldosteronism patients.
A total of 39 patients with primary aldosteronism who underwent unilateral adrenalectomy for a presumed adenoma during 2013-2016 were included. Immunohistochemistry using monoclonal antibodies identifying the enzymes CYP11B1 and B2 was part of routine histopathological workup in 6 cases; in 33 cases, it was applied retrospectively. The hyperplasia diagnosis was suggested when there was no dominating nodule but immunoreactivity for CYP11B2 was seen in several nodules, which were also seen on routine sections. To distinguish between adenoma and hyperplasia, a ratio between the largest and second largest CYP11B2-positive nodules was calculated.
In all, 22 patients had an aldosterone-producing adenoma, while 13 patients were judged to have hyperplasia. In four cases, a final diagnosis could not be established, thus these were judged equivocal. Among the 33 cases investigated retrospectively, the primary histopathological diagnosis was altered from hyperplasia to aldosterone-producing adenoma in 9 cases (27%) after immunohistochemistry, and the immunohistochemically rectified adenoma group displayed improved clinical cure rates compared to the routine H&E-diagnosed cohort. Moreover, the B2 ratio was significantly higher in adenoma than in hyperplasia and equivocal cases.
Immunohistochemistry detecting CYP11B1 and B2 expression is of great help in establishing a final histopathological diagnosis in patients with primary aldosteronism. This procedure should be part of the histopathological routine in all operated primary aldosteronism patients.
原发性醛固酮增多症是继发性高血压的常见病因。原发性醛固酮增多症由产生醛固酮的腺瘤或双侧增生引起,在某些情况下,增生是不对称的,一个肾上腺主导醛固酮分泌。大多数产生醛固酮的腺瘤患者通过单侧肾上腺切除术在生化上得到治愈,但双侧增生患者有残留或复发疾病的显著风险。在这里,我们使用 CYP11B1 和 B2 的免疫组织化学来研究这些标记物是否可以辅助原发性醛固酮增多症患者的诊断。
共纳入 2013-2016 年间因疑似腺瘤行单侧肾上腺切除术的 39 例原发性醛固酮增多症患者。6 例患者的常规组织病理学检查中使用了识别酶 CYP11B1 和 B2 的单克隆抗体进行免疫组织化学检查;33 例患者进行了回顾性应用。当没有主导性结节,但可见 CYP11B2 在几个结节中表达,且在常规切片中也可见到多个结节时,提示增生诊断。为了区分腺瘤和增生,计算了最大和第二大 CYP11B2 阳性结节之间的比值。
共有 22 例患者患有产生醛固酮的腺瘤,13 例患者被判断为增生。在 4 例患者中,无法确定最终诊断,因此这些病例被判断为不确定。在 33 例回顾性研究的病例中,在进行免疫组织化学检查后,有 9 例(27%)的患者的原始组织病理学诊断从增生改变为产生醛固酮的腺瘤,免疫组织化学修正后的腺瘤组与常规 H&E 诊断的队列相比,临床治愈率得到改善。此外,腺瘤的 B2 比值明显高于增生和不确定病例。
检测 CYP11B1 和 B2 表达的免疫组织化学在确定原发性醛固酮增多症患者的最终组织病理学诊断方面有很大帮助。该程序应成为所有接受手术治疗的原发性醛固酮增多症患者组织病理学常规的一部分。