Carney Complex with Adrenal Cortical Carcinoma

Context: Carney complex is a genetically heterogenous multiple neoplasia syndrome. Adrenal cortical carcinoma is a rare malignancy with a poor prognosis that is not recognized to be associated with this syndrome. Objective: We report a 22-yr-old female presenting with Carney complex who developed adrenal carcinoma. The response to adjunctive therapy is also described. Methods: We performed a detailed pathology review of the adrenal tumor to examine morphologic changes, Ki-67 labeling, and p53 expression. We also performed genetic testing of candidate genes and describe the response to radiation and kinase inhibition therapy. Results: The patient presented with an 8.5-cm adrenal mass with a MIB-1 labeling index of 20% and unequivocal angioinvasion classified as a T3NXM0 carcinoma. The nontumorous adrenal cortex revealed characteristic features of primary pigmented nodular adrenocortical disease. Genetic analysis revealed a novel PRKAR1 frame shift mutation resulting in a premature stop codon and a heterozygous p53 polymorphic substitution previously noted in other solid carcinomas. Disease recurrence in the liver showed partial response to combined stereotactic radiotherapy and sorafenib multikinase inhibition. Conclusion: This represents an initial characterization of a malignancy among patients with Carney complex. Our findings have implications for disease surveillance and management of individuals with this genetic syndrome. (J Clin Endocrinol Metab 97: E202-E206, 2012)