Pérez Béliz, EdurneThorpe Plaza, Benjamín AlfonsoDíaz-López, Everardo JosuéLoidi, LourdesVillalba Martín, CarmenAbdulkader Nallib, IhabCameselle Teijeiro, José Manuel2025-07-102025-07-102025-04-02Pérez-Béliz, E., Thorpe-Plaza, B.A., Díaz-López, E.J. et al. Adrenal mixed corticomedullary tumors: report of a case with molecular characterization and systematic review. Virchows Arch (2025). https://doi.org/10.1007/s00428-025-04091-90945-6317https://hdl.handle.net/10347/42437Adrenal 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.eng© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holderAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Mixed corticomedullary tumorAdrenal tumorGNASAKAP13EPAS1Arterial hypertensionjournal article10.1007/s00428-025-04091-9open access