Precursor lesions of the adrenal gland.

OBJECTIVE

To review the existing literature for evidence that adrenocortical and adrenomedullary tumours develop through a multistep process of carcinogenesis.

RESULTS

In the adrenal cortex hyperplasia and adenomas are frequently observed tumours or tumour-like conditions. In contrast, adrenocortical carcinomas are rare. Based on well-validated histopathological scoring systems, benign and malignant adrenocortical tumours can be separated, although a small subset of tumours remains hard to classify. Although extensive follow-up studies might argue against multistep carcinogenesis, analysis of chromosomal imbalances and gene expression profiling studies in these tumours are inconclusive and could give support for both multistep pathogenesis or de novo genesis of carcinomas. A major limit to most of these studies is the small sample size and the lack of extensive clinical (follow-up) data. In the adrenal medulla, pheochromocytomas (PCC) are the most frequent tumours in adults, with an incidence of 8 per million. They can be divided into benign and malignant PCC, but the distinction can only be made when metastases are present. Arbitrarily, lesions of less than 1 cm in diameter are called hyperplastic, but it should be expected that the majority of these are early lesions and if left in situ would grow to classify as PCC. In contrast to cortical tumours, the frequent 1p and 3q loss as an early event in tumourigenesis of benign PCC is verified in multiple studies. However, studies in malignant PCC yield divergent results, due to the small numbers analysed.

CONCLUSION

Taken together, there appears to be a relationship between cortical and medullary hyperplasia on the one hand and cortical adenomas and PCC on the other. However, whether there is a transition from benign to malignant tumours, both cortical and medullary, remains to be determined.