Tumors of the Adrenal Glands; Pathology and Genetics

Abstract

Adrenal cortical carcinomas (ACCs) are malignant epithelial neoplasms arising from the mesodermal-derived adrenal cortex, while pheochromocytomas and paragangliomas (PPGLs) are neurally derived tumors originating from the adrenal medulla and extra-adrenal paraganglia. It is the current thinking as stated in 2017 WHO classification of endocrine neoplasia that PPGLs have some metastatic potential. The pioneering studies from the Cancer Genome Atlas project (TCGA) have recently added to rapid developments in molecular genetics of PPGL and ACC. The former carries the highest degree of heritability among all human neoplasms and is characterized by a low mutational load, while the latter by significant copy number alterations with whole genome doubling as hallmark mechanism for disease progression. The TCGA studies elucidated the landscape of both tumor types by providing a comprehensive integrated genomic analysis into distinct molecularly defined groups and led to fundamental advances in endocrine molecular pathology. In this chapter, we provide an update on advances in pathology and genetics with an emphasis on various aspects of PPGL and ACC tumorigenesis, including the changes introduced in the recent WHO classification and advances stemming from the TCGA analyses, relevant to all endocrine-related specialists. In particular, we discuss the epidemiology, histopathology, molecular pathology and genetics, microenvironment, staging, grading as well as prognostic and predictive biomarkers in ACCs and PPGLs.