ADRENOCORTICAL TUMORS: FOR CLINICIANS & RESEARCHERS

Related Syndromes

 

Some patients with adrenocortical tumors (ACT) are genetically predisposed to cancer and consequently have a higher risk of developing certain types of malignancies than those in the general public. For children with ACT, the chance that the disease was inherited is high.

Hereditary cancer syndromes

A hereditary cancer syndrome is a tendency to develop tumors caused by germline (inherited) mutations, especially at younger ages. Most hereditary cancer syndromes are inherited in an autosomal dominant way. Everyone in the family who inherits the mutation will have an increased chance of developing cancer. 

About 50% of children with ACT test positive for a germline TP53 mutation. This also explains the relative increase of ACT seen in childhood. Pediatric ACT is a core malignancy of Li-Fraumeni syndrome (LFS), a rare disorder that increases the risk of development of several different tumor types.  A similar disorder, Li-Fraumeni-like syndrome, shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers, beginning in childhood; however, the pattern of specific tumor type seen in affected family members is different. Up to 10% of LFS-associated cancers are ACTs, suggesting that germline TP53 mutations infer a significant relative risk increase. Therefore, TP53 germline testing should be considered for any patient with a diagnosis of ACT, independent of a family history of cancer.

Associated conditions

Other constitutional disorders that have been associated with an increase in pediatric ACT occurrence include:

Another set of clinical diagnosis has been proposed to identify affected families that fall outside the classical clinical criteria for LFS, including Li-Fraumeni-like syndrome, Chompret criteria, Birch criteria or Eeles criteria

LFS is rare, but with the introduction of these criteria, more families with LFS have been identified. It was previously estimated that fewer than 400 families had been diagnosed with LFS worldwide. We now believe that LFS may be as frequent as one in 5,000 to one in 20,000. A diagnosis of LFS and performing TP53 gene mutation testing is recommended for anyone with a personal or family history that meets one of these criteria.

Carney complex is an autosomal dominant syndrome associated with spotty pigmentation of the skin, endocrinopathy, and endocrine and non-endocrine tumors, including myxomas of the skin, heart, breast and other sites. It has also been associated with primary pigmented nodular adrenocortical disease, Psammomatous melanotic schwannomas, pituitary adenomas and testicular Sertoli-cell tumors and possibly, other benign and malignant neoplasms and conditions. Tumors of the thyroid gland and ductal adenomas of the breast, as well as acromegaly due to somatomammotroph hyperplasia and adenomas not dependent on growth hormone–releasing hormone have also been linked. Mutations in PRKAR1A or PDE11A were identified and associated to this disorder.