{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T12:42:06Z","timestamp":1760618526207,"version":"build-2065373602"},"reference-count":18,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant disorder commonly associated with tumor development in the parathyroid glands, pancreas, and pituitary gland. While pituitary adenomas are frequently observed in MEN1 patients, the presence of additional tumors within the pituitary gland is unusual. Moreover, the co-occurrence of a pituitary adenoma with an atypical teratoid\/rhabdoid tumor (ATRT) has not been previously documented. ATRT is a rare, aggressive neoplasm predominantly affecting young children and is typically associated with inactivating mutations in the SMARCB1 or SMARCA4 tumor suppressor genes. These mutations result in uncontrolled cellular proliferation, which underlies the malignancy\u2019s rapid progression. In adults, ATRT is exceedingly rare, making this case particularly noteworthy for its uniqueness in both tumor type and patient demographics. ATRTs are now classified into three molecular subgroups\u2014MYC, SHH, and TYR\u2014each with distinct epigenetic and clinical features, further refining diagnostic and prognostic assessments. In this case report, we describe a case of a female patient with MEN1 who experienced several recurrences of pituitary adenoma, ultimately necessitating surgical resection. Detailed pathological evaluation of the resected tissue revealed two distinct neoplasms within the pituitary gland: one typical of a pituitary adenoma, and the other confirmed as ATRT. The diagnosis of ATRT was established through extensive workup including immunohistochemical analysis, next-generation sequencing and methylation profiling, which served as essential tools in distinguishing ATRT from other potential differential diagnoses. This case illustrates the complex diagnostic journey and challenges encountered in identifying ATRT in the context of MEN1, underscoring the importance of using advanced molecular and immunohistochemical techniques in atypical presentations. Furthermore, it expands the understanding of potential tumor associations within MEN1, providing insight for pathologists and clinicians into the rare possibility of concurrent tumors in addition to pituitary adenoma in MEN1 patients. Raising awareness of such co-occurrences could prompt earlier diagnostic considerations by refining the differential diagnosis in patients with MEN1 presenting with unusual tumor types.<\/jats:p>","DOI":"10.3390\/ijms262010065","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T12:17:02Z","timestamp":1760617022000},"page":"10065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unusual Dual Brain Tumor Morphologies in an MEN1 Patient: A Case Report of Diagnostic Challenges and Methylation Insights"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-6982","authenticated-orcid":false,"given":"Viharkumar","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Pathology, University of California Davis Health System, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7916-1629","authenticated-orcid":false,"given":"Orwa","family":"Aboud","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Surgery, University of California Davis Health System, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4605-4935","authenticated-orcid":false,"given":"Abdelrahman","family":"Barakat","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S272","DOI":"10.4103\/2230-8210.104058","article-title":"Multiple endocrine neoplasia type 1","volume":"16","author":"Thakker","year":"2012","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"944","DOI":"10.21037\/atm-21-1165","article-title":"A narrative review of multiple endocrine neoplasia syndromes: Genetics, clinical features, imaging findings, and diagnosis","volume":"9","author":"Hu","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5030","DOI":"10.1158\/1078-0432.CCR-16-0452","article-title":"Novel genetic causes of pituitary adenomas","volume":"22","author":"Caimari","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e27418","DOI":"10.1016\/j.heliyon.2024.e27418","article-title":"PDP type brain tumor in association with multiple endocrine neoplasia type 1","volume":"10","author":"Einarsson","year":"2024","journal-title":"Heliyon"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"43","DOI":"10.6061\/clinics\/2012(Sup01)09","article-title":"Pituitary tumors in patients with MEN1 syndrome","volume":"67","author":"Syro","year":"2012","journal-title":"Clinics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ccell.2016.02.001","article-title":"Atypical Teratoid\/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes","volume":"29","author":"Johann","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1210\/endrev\/bnaa031","article-title":"Multiple Endocrine Neoplasia Type 1: Latest Insights","volume":"42","author":"Brandi","year":"2020","journal-title":"Endocr. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1158\/1078-0432.CCR-23-3308","article-title":"A cohort study of CNS tumors in Multiple Endocrine Neoplasia Type 1","volume":"30","author":"Graillon","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1191040","DOI":"10.3389\/fendo.2023.1191040","article-title":"Cutaneous lesions and other non-endocrine manifestations of Multiple Endocrine Neoplasia type 1 syndrome","volume":"14","author":"Pierotti","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11060-022-03959-z","article-title":"Atypical teratoid\/rhabdoid tumor in adults: A systematic review of the literature with meta-analysis and additional reports of 4 cases","volume":"157","author":"Broggi","year":"2022","journal-title":"J. Neuro-Oncol."},{"key":"ref_11","first-page":"CASE23287","article-title":"Sellar atypical teratoid\/rhabdoid tumor in adults: Survival analysis of treatment strategies. Illustrative case","volume":"6","author":"Zohdy","year":"2023","journal-title":"J. Neurosurg. Case Lessons"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1510439","DOI":"10.3389\/fonc.2025.1510439","article-title":"Case report: Molecular characterization of adult atypical teratoid rhabdoid tumor and review of the literature","volume":"15","author":"Connor","year":"2025","journal-title":"Front. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ijpam.2020.06.004","article-title":"Atypical teratoid rhabdoid tumors (ATRT): King Faisal specialist hospital and research centre experience","volume":"8","author":"Mousa","year":"2021","journal-title":"Int. J. Pediatr. Adolesc. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lindsay, H., and Huang, A. (2019). Atypical Teratoid Rhabdoid Tumors. Oncology of CNS Tumors, Springer.","DOI":"10.1007\/978-3-030-04152-6_33"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1093\/neuonc\/nou090","article-title":"The descriptive epidemiology of atypical teratoid\/rhabdoid tumors in the United States, 2001\u20132010","volume":"16","author":"Ostrom","year":"2014","journal-title":"Neuro-Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Calandrelli, R., Massimi, L., Pilato, F., Verdolotti, T., Ruggiero, A., Attin\u00e0, G., Gessi, M., and Colosimo, C. (2023). Atypical Teratoid Rhabdoid Tumor: Proposal of a Diagnostic Pathway Based on Clinical Features and Neuroimaging Findings. Diagnostics, 13.","DOI":"10.3390\/diagnostics13030475"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e12967","DOI":"10.1111\/bpa.12967","article-title":"Histopathological patterns in atypical teratoid\/rhabdoid tumors are related to molecular subgroup","volume":"31","author":"Zin","year":"2021","journal-title":"Brain Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/neuonc\/noz235","article-title":"Molecular subgrouping of atypical teratoid\/rhabdoid tumors-a reinvestigation and current consensus","volume":"22","author":"Ho","year":"2020","journal-title":"Neuro-Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T12:22:04Z","timestamp":1760617324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":18,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010065"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010065","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]}}}