Recent advances in molecular genetics and genomics have led to increased understanding of the aetiopathogenesis of pheochromocytomas and paragangliomas (PPGLs). Thus, pan-genomic studies now provide a comprehensive integrated genomic analysis of PPGLs into distinct molecularly defined subtypes concordant with tumour genotypes. In addition, new embryological discoveries have refined the concept of how normal paraganglia develop, potentially establishing a developmental basis for genotype–phenotype correlations for PPGLs. The challenge for modern pathology is to translate these scientific discoveries into routine practice, which will be based largely on histopathology for the foreseeable future. Here, we review recent progress concerning the cell of origin and molecular pathogenesis of PPGLs, including pathogenetic mechanisms, genetic susceptibility and molecular classification. The current roles and tools of pathologists are considered from a histopathological perspective, including differential diagnoses, genotype–phenotype correlations and the use of immunohistochemistry in identifying hereditary predisposition and validating genetic variants of unknown significance. Current and potential molecular prognosticators are also presented with the hope that predictive molecular biomarkers will be integrated into risk stratification scoring systems to assess the metastatic potential of these intriguing neoplasms and identify potential drug targets.

分子遗传学和基因组学的最新进展使人们对嗜铬细胞瘤和副神经节瘤 (PPGL) 的发病机制有了更多的了解。因此，泛基因组研究现在提供了将 PPGL 综合分析为与肿瘤基因型一致的不同分子定义的亚型。此外，新的胚胎学发现完善了正常副神经节如何发育的概念，可能为 PPGL 的基因型-表型相关性建立发育基础。现代病理学面临的挑战是将这些科学发现转化为常规实践，在可预见的未来，这将主要基于组织病理学。在这里，我们回顾了关于 PPGLs 的起源细胞和分子发病机制的最新进展，包括发病机制，遗传易感性和分子分类。从组织病理学的角度考虑病理学家当前的作用和工具，包括鉴别诊断、基因型-表型相关性以及免疫组织化学在鉴定遗传易感性和验证未知意义的遗传变异中的应用。目前和潜在的分子预后因素也被提出，希望预测分子生物标志物将被整合到风险分层评分系统中，以评估这些有趣的肿瘤的转移潜力并确定潜在的药物靶点。基因型-表型相关性以及免疫组织化学在鉴定遗传易感性和验证未知意义的遗传变异中的应用。目前和潜在的分子预后因素也被提出，希望预测分子生物标志物将被整合到风险分层评分系统中，以评估这些有趣的肿瘤的转移潜力并确定潜在的药物靶点。基因型-表型相关性以及免疫组织化学在鉴定遗传易感性和验证未知意义的遗传变异中的应用。目前和潜在的分子预后因素也被提出，希望预测分子生物标志物将被整合到风险分层评分系统中，以评估这些有趣的肿瘤的转移潜力并确定潜在的药物靶点。