Adrenal mixed corticomedullary tumors: report of a case with molecular characterization and systematic review

Abstract

Adrenal mixed corticomedullary tumors (MCMTs) are rare lesions showing a mixture of two cell populations of cortical and medullary lineage. We describe an MCMT case presented in a 56-year-old woman with a history of arterial hypertension and high levels of aldosterone, accompanied by a review of the literature. The adrenalectomy specimen showed a well-circumscribed nodule of 30 mm in size, containing 60% of cells with a cortical phenotype (positive for α-inhibin and melan-A) and 40% of cells with a medullary phenotype (positive for chromogranin-A, GATA-3 and somatostatin receptor 2). There was no significant mitotic activity, necrosis, nor lymphovascular invasion. The GNAS p.(Arg844Cys) mutation, as well as variants of uncertain significance AKAP13 p.(His641Pro) and EPAS1 p.(Ser478del) were detected in the tumor. MCMT is more common in women (75%) with a mean age of 46.6 years (range 16-78). Most patients present with hypertension (79%), frequently associated with Cushing's syndrome, (39%), diabetes (21%), aldosteronism (15%), and/or hyperandrogenism (6%). Laboratory data showed elevated levels of both cortisol and cathecholamines and/or their metabolites in more than 50% of cases, supporting the dual nature of the tumor. Most MCMTs are benign, but aggressive behavior was detected in four (12%) cases, all of them showing large size (80-220 mm), poor delimitation, venous invasion, necrosis, and/or high proliferation rates. The pathogenesis is unknown, but our findings suggest a tumor histogenesis from the cortical cellular component through the regulation of the protein kinase A pathway and secondary proliferation of the medullary component.

Keywords: AKAP13; EPAS1; GNAS; Adrenal tumor; Arterial hypertension; Mixed corticomedullary tumor.