Approximately one-tenth of the general population exhibit adrenal cortical nodules, and the incidence has increased. Afflicted patients display a multifaceted symptomatology—sometimes with rather spectacular features. Given the general infrequency as well as the specific clinical, histological, and molecular considerations characterizing these lesions, adrenal cortical tumors should be investigated by endocrine pathologists in high-volume tertiary centers. Even so, to distinguish specific forms of benign adrenal cortical lesions as well as to pinpoint malignant cases with the highest risk of poor outcome is often challenging using conventional histology alone, and molecular genetics and translational biomarkers are therefore gaining increased attention as a possible discriminator in this context. In general, our understanding of adrenal cortical tumorigenesis has increased tremendously the last decade, not least due to the development of next-generation sequencing techniques. Comprehensive analyses have helped establish the link between benign aldosterone-producing adrenal cortical proliferations and ion channel mutations, as well as mutations in the protein kinase A (PKA) signaling pathway coupled to cortisol-producing adrenal cortical lesions. Moreover, molecular classifications of adrenal cortical tumors have facilitated the distinction of benign from malignant forms, as well as the prognostication of the individual patients with verified adrenal cortical carcinoma, enabling high-resolution diagnostics that is not entirely possible by histology alone. Therefore, combinations of histology, immunohistochemistry, and next-generation multi-omic analyses are all needed in an integrated fashion to properly distinguish malignancy in some cases. Despite significant progress made in the field, current clinical and pathological challenges include the preoperative distinction of non-metastatic low-grade adrenal cortical carcinoma confined to the adrenal gland, adoption of individualized therapeutic algorithms aligned with molecular and histopathologic risk stratification tools, and histological confirmation of functional adrenal cortical disease in the context of multifocal adrenal cortical proliferations. We herein review the histological, genetic, and epigenetic landscapes of benign and malignant adrenal cortical neoplasia from a modern surgical endocrine pathology perspective and highlight key mechanisms of value for diagnostic and prognostic purposes.

大约十分之一的普通人群表现出肾上腺皮质结节，并且发病率有所增加。受折磨的患者表现出多方面的症状——有时具有相当惊人的特征。考虑到这些病变的普遍罕见性以及特定的临床、组织学和分子学方面的考虑，肾上腺皮质肿瘤应由大容量三级中心的内分泌病理学家进行调查。即便如此，单独使用传统组织学来区分特定形式的良性肾上腺皮质病变以及查明预后不良风险最高的恶性病例通常具有挑战性，因此分子遗传学和转化生物标志物作为一种可能的鉴别器而受到越来越多的关注。这个上下文。一般来说，在过去十年中，我们对肾上腺皮质肿瘤发生的理解大大增加，尤其是由于下一代测序技术的发展。综合分析有助于建立良性产生醛固酮的肾上腺皮质增殖与离子通道突变之间的联系，以及与产生皮质醇的肾上腺皮质病变相关的蛋白激酶 A (PKA) 信号通路突变。此外，肾上腺皮质肿瘤的分子分类有助于区分良性和恶性形式，以及对确诊的肾上腺皮质癌个体患者的预后，从而实现仅靠组织学无法实现的高分辨率诊断。因此，结合组织学、免疫组化、和下一代多组学分析都需要以集成的方式在某些情况下正确区分恶性肿瘤。尽管在该领域取得了重大进展，但当前的临床和病理挑战包括术前区分局限于肾上腺的非转移性低级别肾上腺皮质癌，采用与分子和组织病理学风险分层工具一致的个体化治疗算法，以及组织学确认多灶性肾上腺皮质增生背景下的功能性肾上腺皮质疾病。我们在此从现代外科内分泌病理学的角度回顾了良性和恶性肾上腺皮质肿瘤的组织学、遗传学和表观遗传学特征，并强调了对诊断和预后目的有价值的关键机制。