Cellular and Molecular Pathology of Adrenocortical Carcinoma

Abstract

Information molecular and genetic alterations as well as about morphological stages of adrenocortical tumorigenesis is sparse in comparison with our understanding of the development of more common neoplasms like those arising in breast or colon tissue. Breast and colon cancer have well-defined pre-cancerous or cancerous precursor lesions, carcinoma in situ, and adenoma, respectively. Stages and related genetic and epigenetic alterations are well defined. In contrast, adrenocortical tumorigenesis is less well defined. It is still a matter of debate whether adrenocortical carcinomas (ACCs) arise from normal tissue via the stages of hyperplasia or adenoma. It is certainly known that some hereditary diseases predispose to the development of ACC and, in fact, some of the alterations caused by these genetic syndromes can also be found in sporadic ACCs (see Chapter 10). The contributions of p53, IGF2, and WNT/β-catenin signaling pathway to adrenocortical tumorigenesis are discussed in chapters in this book dedicated to hereditary syndromes and their underlying genetic changes. This chapter will focus on the contributions of other known or suggested pathways, genomic and genetic alterations, as well as common principles of carcinogenesis, such as aneuploidy and clonal origin.