{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:37:41Z","timestamp":1792078661997,"version":"4.4.0"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinics and Practice"],"abstract":"<jats:p>Background: Malignant mixed corticomedullary adrenal tumors (MCMTs) are extremely rare, with limited cases reported in the literature. The pathophysiology of malignant MCMTs is not well understood; the most prevailing theories are that it is a composite tumor of embryologically derived mesodermal (adrenal cortex) and neural crest (medulla) origin, perpetuating as two distinct cell lines forming a singular mass. Clinical features and laboratory diagnosis are associated with hypersecretions of the adrenal cortex and medulla. Surgical resection is curative in an isolated tumor. We reviewed and compared cases in the literature highlighting the pathogenesis and genetics of benign and malignant MCMT. Methods: Comprehensive literature analysis was conducted on PubMed and all the cases of mixed corticomedullary adrenal tumor published in English were included. Results: Most patients were female (73.1%) with a median age of 49 in women and 50 in men. Surgery was performed in all patients, and in four patients with malignant disease, chemotherapy was used as well. Clinically, most patients presented with hypertension (69%) followed by Cushing syndrome (42%) and diabetes (19%). Tumors often produced cortisol (74%), catecholamines (50%), and adrenocorticotrophic hormone (ACTH) (38%), with lower incidence of aldosterone- (7%) or dopamine (4%)-producing tumors. Immunohistochemical staining of 96% of cases showed Chromogranin-A (73%) and Synaptophysin (62%), followed by Inhibin-\u03b1 (50%), Melan-A (31%), and S-100 (23%). Of the reported four cases with malignant disease, three showed a Ki-67 index of 40\u201350% with one showing less than 5%. Conclusion: Mixed corticomedullary adrenal tumors rarely present as a malignant disease requiring chemotherapy. Most MCMTs confer a good prognosis and respond well to surgical resection, though their pathogenesis is largely up to speculation because of limited data. Current theories regarding MCMT pathogenesis should be investigated further with genetic testing. Future research on MCMT may provide ways to guide physician diagnosis and subsequent treatment for refractory cases.<\/jats:p>","DOI":"10.3390\/clinpract12060096","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T04:30:52Z","timestamp":1668400252000},"page":"918-925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Current Understanding of \u201cMixed Corticomedullary Adrenal Tumor\u201d and an Insight into Genomic Profiling"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9435-9625","authenticated-orcid":false,"given":"Asad","family":"Ullah","sequence":"first","affiliation":[{"name":"Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah Ayman Elsaid","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine College of Medicine, Cairo University, Cairo 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaffar","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3273-3740","authenticated-orcid":false,"given":"Katharine","family":"Tracy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhabat","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Bolan Medical College, Sandman Provincial Hospital, Quetta 83700, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samiha","family":"Mohsen","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8146-1620","authenticated-orcid":false,"given":"Abdul Qahar Khan","family":"Yasinzai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Bolan Medical College, Sandman Provincial Hospital, Quetta 83700, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2093-6397","authenticated-orcid":false,"given":"Kaleemullah","family":"Badini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Bolan Medical College, Sandman Provincial Hospital, Quetta 83700, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9711-604X","authenticated-orcid":false,"given":"Philip T.","family":"Sobash","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh","family":"Heneidi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagla Abdel","family":"Karim","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Inova Schar Cancer Institute, University of Virginia, Fairfax, VA 22031, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/0002-9343(69)90193-4","article-title":"Cushing\u2032s syndrome with hypertensive crisis and mixed adrenal cortical adenoma-pheochromocytoma (Corticomedullary adenoma)","volume":"47","author":"Mathison","year":"1969","journal-title":"Am. 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