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.

Fig. 1

Magnetic resonance images demonstrate a left adrenal mass (arrows) with solid and cystic components. The solid component shows no significant loss of signal intensity in T1-w out-of phase sequence, which meanss that the lesion does not contain a significant amount of intracellular lipids (A). The arterial phase demonstrates dishomogeneous enhancement of the lesion and a lack of enhancement of the cystic component, a finding more frequently observed in pheocromocytoma (B). The diferential diagnosis includes lipid poor adenoma and pheocromocytoma

Fig. 2

Mixed corticomedullary tumor. External appearance of the resection specimen (A) whose section (B) showed a yellowish tumor with interspersed pink and brownish areas and cystification. Microscopically, a combination of cells with eosinophilic cytoplasm with a central nucleus (cortical adenoma type) was observed, along with another tumor cell component displaying granular basophilic to amphophilic cytoplasm (pheochromocytoma type) (C and D). Tumor cells with a cortical phenotype were positive for inhibin (E) and melan-A (F), while those with a chromaffin phenotype stained for chromogranin (G)