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The coexistence of benign and malignant masses has seldom been documented, leaving open the question of ACC progression from benign forms. We report a comprehensive genetic characterization of three adrenal cortical tumor samples obtained from a familial MEN1 patient, operated for the rapid progression of an initially stable nonfunctional adrenal incidentaloma. Histologically, the tumor consisted of a small ACA contiguous to a large ACC, which subsequently relapsed. Exome sequencing of ACC, ACA and recurrence evidenced a\n                    <jats:italic>MEN1<\/jats:italic>\n                    loss of heterozygosity (LOH) in ACC but not in ACA, where, however, a second hit driven by alternative mechanisms could not be excluded. The majority of the ACA variants were found to co-occurred in ACC (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200936\/42) and were benign, except for two of unknown significance in\n                    <jats:italic>KANK1<\/jats:italic>\n                    and\n                    <jats:italic>REN<\/jats:italic>\n                    genes, described as associated with renal cancer. Among variants shared between ACC and its recurrence (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200969), 11 were Tier III, while 2 affecting\n                    <jats:italic>TP53<\/jats:italic>\n                    and\n                    <jats:italic>NF1<\/jats:italic>\n                    genes were pathogenic. Bioinformatic clonal evolution analysis identified one clone \u2212 characterized by\n                    <jats:italic>TP53<\/jats:italic>\n                    and\n                    <jats:italic>NF1<\/jats:italic>\n                    mutations \u2212 absent in ACA but present in ACC and recurrence, as well as 2 clones shared between ACA and ACC but lost in the recurrence. In conclusion, comparative Whole Exome Sequencing (WES) analysis of three adrenal tumors in a MEN1 patient suggests a possible relationship between malignant and benign lesions occurring in MEN1 patients, without, however, demonstrating any causal adenoma-to-carcinoma progression driven by MEN1 LOH. Overall, these data further suggest an increased risk of MEN1 patients to develop adrenocortical malignancy.\n                  <\/jats:p>","DOI":"10.1007\/s12022-026-09908-0","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:15:21Z","timestamp":1773119721000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In-depth Genetic and Molecular Characterization of Unilateral Coexisting Adrenal Cortical Adenoma and Carcinoma in the Context of MEN1 Syndrome"],"prefix":"10.1007","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7718-6347","authenticated-orcid":false,"given":"Francesca","family":"Cioppi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Orioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9159-9199","authenticated-orcid":false,"given":"Giulia","family":"Cantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonino","family":"Ercolino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Cioppi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9590-0906","authenticated-orcid":false,"given":"Guillaume","family":"Assi\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-2065","authenticated-orcid":false,"given":"Anne","family":"Jouinot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Aurora","family":"Dedonno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5317-7533","authenticated-orcid":false,"given":"Raffaella","family":"Santi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6871-1296","authenticated-orcid":false,"given":"Ronald R.","family":"de Krijger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-4221","authenticated-orcid":false,"given":"Mario","family":"Maggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-356X","authenticated-orcid":false,"given":"Matteo","family":"Benelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4995-8108","authenticated-orcid":false,"given":"Letizia","family":"Canu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2614-944X","authenticated-orcid":false,"given":"Gabriella","family":"Nesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5186-064X","authenticated-orcid":false,"given":"Michaela","family":"Luconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"issue":"2","key":"9908_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1210\/endrev\/bnaa031","volume":"42","author":"ML Brandi","year":"2021","unstructured":"Brandi ML, Agarwal SK, Perrier ND, Lines KE, Valk GD, Thakker RV (2021) Multiple Endocrine Neoplasia Type 1: Latest Insights. 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