New pathology classification of endocrine and neuroendocrine tumours is currently being updated as one of WHO classification of tumours version 5. Not only pathologists but also clinicians involved in the clinical management of those patients should be familiar with novel classification including their new concepts. Therefore in this presentation, we will introduce newly updated concepts of adrenocortical diseases associated with Cushing's syndrome and primary aldosteronism.
In Cushing's syndrome, primary bilateral nodular adrenal cortical disease has turned out to harbor multiple independent clonal proliferations and the term hyperplasia should not be used in these adrenocortical disorders. Hyperplasia should be only reserved for those associated with ACTH overproduction from pituitary or others. Various somatic and/or genomic mutations of the genes involved in intracellular signaling pathways have been reported in almost all bilateral micronodular adrenal cortical disease and the great majority of bilateral macronodular adrenal cortical disease associated with Cushing's syndrome.
For instance, bilateral micronodular adrenocortical disease harbors pathogenic germline mutations resulting in the activation of the protein kinase A or PKA pathway including PRKAR1A, PRKAR1A, PRKACA, PDE11A, PDE8B and 2p16 CNC2 locus alterations. On the other hand, bilateral macronodular adrenal cortical disease has been linked to several germline alterations including ARMC5, MEN1, FH, APC and others.Clinical significance of those genetic abnormalities above including potential therapeutic manipulation is being studied at this juncture.
In primary aldosteronism, the introduction of CYP11B2 has enormously contributed to the establishment of new concept of adrenocortical pathology. Primary aldosteronism can be generally classified into two categories. The one in which aldosterone production diffusely occurs in the hyperplastic zona glomerulosa and the other harboring localized aldosterone production. The former is generally bilateral and the latter unilateral or bilateral. The latter category also includes both nodule and adenoma, which could be differentiated according to the status of intra-lesional distribution of CYP11B2. CYP11B2 positive localized proliferation of the zona glomerulosa cells is frequently detected in non hypertensive subject and should be termed aldosterone producing nodules (APN) rather than aldosterone producing cell clusters (APCC). The potential cascade from these aldosterone producing nodules in normal subject to those associated with clinically overt primary aldosteronism is being investigated including the possible concept of pre- or subclinical primary aldosteronism.