Omata Kei, Yamazaki Yuto, Nakamura Yasuhiro, Anand Sharath K, Barletta Justine A, Sasano Hironobu, Rainey William E, Tomlins Scott A, Vaidya Anand
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109.
Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University, 980-0872 Sendai, Japan.
J Clin Endocrinol Metab. 2017 Jun 1;102(6):1792-1796. doi: 10.1210/jc.2016-4007.
Whether primary aldosteronism (PA) is the consequence of a monoclonal or multiclonal process is unclear.
A 48-year-old man with severe bilateral PA refractory to medical therapy underwent unilateral adrenalectomy of the dominant adrenal. Although computed tomography showed three left-sided cortical nodules, postsurgical histopathology and genetic analysis revealed five different adrenocortical adenomas. Two zona fasciculata (ZF)-like aldosterone-producing adenomas (APAs) each harbored distinct known somatic KCNJ5 mutations (L168R and T158A). A zona glomerulosa-like APA harbored a known CACNA1D G403R somatic mutation, whereas a zona reticularis-like adenoma, which was grossly black in pigmentation with histologic characteristics more associated with cortisol-producing adenomas, expressed CYP11B2, CYP17, and DHEA-ST by immunohistochemistry (IHC) and harbored no known somatic mutations. The fifth adenoma was ZF-type, negative for CYP11B2 and CYP17 IHC, and harbored no known somatic mutations.
This case highlights complex intertumor heterogeneity in histology, steroidogenesis, and somatic mutations in multiple adrenocortical adenomas arising in a single patient with PA. These findings suggest that the syndrome of PA can involve heterogeneous and multiclonal functional adrenal adenomas.
原发性醛固酮增多症（PA）是单克隆还是多克隆过程的结果尚不清楚。
一名48岁患有严重双侧PA且药物治疗无效的男性接受了优势肾上腺的单侧肾上腺切除术。尽管计算机断层扫描显示左侧有三个皮质结节，但术后组织病理学和基因分析发现了五个不同的肾上腺皮质腺瘤。两个束状带（ZF）样醛固酮生成腺瘤（APA）各自含有不同的已知体细胞KCNJ5突变（L168R和T158A）。一个球状带样APA含有已知的CACNA1D G403R体细胞突变，而一个网状带样腺瘤，其色素沉着呈黑色，组织学特征更与皮质醇生成腺瘤相关，免疫组织化学（IHC）显示表达CYP11B2、CYP17和脱氢表雄酮硫酸酯（DHEA - ST），且未发现已知的体细胞突变。第五个腺瘤为ZF型，CYP11B2和CYP17免疫组化阴性，也未发现已知的体细胞突变。
该病例突出了在一名PA患者中出现的多个肾上腺皮质腺瘤在组织学、类固醇生成和体细胞突变方面复杂的肿瘤间异质性。这些发现表明，PA综合征可能涉及异质性和多克隆功能性肾上腺腺瘤。
