{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:34:04Z","timestamp":1755225244981,"version":"3.43.0"},"reference-count":28,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome caused by genomic alterations in the tumor protein p53 (TP53) gene. The lifetime risk of developing cancer is very high, and carriers of germline TP53 pathogenic variants must be closely monitored starting from a young age. LFS is particularly associated with specific tumors, such as breast cancer, soft tissue and bone sarcomas, primary central nervous system cancers, acute leukemia, and adrenocortical carcinoma. Despite its association with a broad spectrum of malignancies, pheochromocytoma\/paraganglioma (PCC\/PGL) is an unusual manifestation of LFS and has only rarely been reported. Here, we present a case of a 57-year-old female patient who is a carrier of a deleterious germline TP53 pathogenic variant and developed a PCC; several years later, she had lung and bone lesions compatible with metastatic PCC. We also discuss the most recent literature regarding the genomic landscape of PCCs\/PGLs and their pathogenesis in connection with TP53 pathogenic variants.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf166","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T07:39:39Z","timestamp":1751355579000},"source":"Crossref","is-referenced-by-count":0,"title":["Metastatic Pheochromocytoma in a Patient With Li-Fraumeni Syndrome"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9875-7479","authenticated-orcid":false,"given":"Sotiris","family":"Loizidis","sequence":"first","affiliation":[{"name":"Medical Oncology Department, Bank of Cyprus Oncology Center , Nicosia 2006 ,","place":["Cyprus"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiana","family":"Matthaiou","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Bank of Cyprus Oncology Center , Nicosia 2006 ,","place":["Cyprus"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efrosini","family":"Iacovou","sequence":"additional","affiliation":[{"name":"Independent Histopathology Services, ECCLabs-IHCS , Nicosia 2020 ,","place":["Cyprus"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3541-3767","authenticated-orcid":false,"given":"Karel","family":"Pacak","sequence":"additional","affiliation":[{"name":"Center for Adrenal Endocrine Tumors, AKESO , Prague 155 00 ,","place":["Czech Republic"]},{"name":"Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Rockville, MD 20847 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1176-6186","authenticated-orcid":false,"given":"Ashley","family":"Grossman","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London , London EC1M 6BQ ,","place":["UK"]},{"name":"Green Templeton College, University of Oxford , Oxford OX2 6HG ,","place":["UK"]},{"name":"ENETS Centre of Excellence, Royal Free Hospital , London NW3 2QG ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"issue":"4","key":"2025081304271083300_luaf166-B1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.7326\/0003-4819-71-4-747","article-title":"Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome?","volume":"71","author":"Li","year":"1969","journal-title":"Ann Intern Med"},{"issue":"4985","key":"2025081304271083300_luaf166-B2","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1126\/science.1978757","article-title":"Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms","volume":"250","author":"Malkin","year":"1990","journal-title":"Science"},{"volume-title":"GeneReviews: Li-Fraumeni Syndrome","year":"1993","author":"Schneider","key":"2025081304271083300_luaf166-B3"},{"issue":"5","key":"2025081304271083300_luaf166-B4","doi-asserted-by":"crossref","first-page":"a026062","DOI":"10.1101\/cshperspect.a026062","article-title":"Tumor-suppressor functions of the TP53 pathway","volume":"6","author":"Aubrey","year":"2016","journal-title":"Cold Spring Harb Perspect 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pheochromocytomas","volume":"33","author":"Mete","year":"2022","journal-title":"Endocr Pathol"},{"issue":"1","key":"2025081304271083300_luaf166-B9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s12020-017-1310-9","article-title":"Routine genetic screening with a multi-gene panel in patients with pheochromocytomas","volume":"59","author":"Sbardella","year":"2018","journal-title":"Endocrine"},{"issue":"2","key":"2025081304271083300_luaf166-B10","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ccell.2017.01.001","article-title":"Comprehensive molecular characterization of pheochromocytoma and paraganglioma","volume":"31","author":"Fishbein","year":"2017","journal-title":"Cancer Cell"},{"issue":"3","key":"2025081304271083300_luaf166-B11","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/cen.12530","article-title":"Testing for germline mutations in sporadic pheochromocytoma\/paraganglioma: a systematic review","volume":"82","author":"Brito","year":"2015","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"2","key":"2025081304271083300_luaf166-B12","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1210\/endrev\/bnab019","article-title":"Personalized management of pheochromocytoma and paraganglioma","volume":"43","author":"N\u00f6lting","year":"2022","journal-title":"Endocr Rev"},{"issue":"1","key":"2025081304271083300_luaf166-B13","doi-asserted-by":"crossref","first-page":"20221","DOI":"10.1038\/srep20221","article-title":"Genetic and functional analysis of a Li Fraumeni syndrome family in China","volume":"6","author":"Hu","year":"2016","journal-title":"Sci Rep"},{"issue":"4","key":"2025081304271083300_luaf166-B14","doi-asserted-by":"crossref","first-page":"dgz269","DOI":"10.1210\/clinem\/dgz269","article-title":"Simultaneous occurrence of germline mutations of SDHB and TP53 in a patient with metastatic pheochromocytoma","volume":"105","author":"Gniado","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025081304271083300_luaf166-B15","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3803\/EnM.2020.756","article-title":"Whole exome sequencing identifies novel genetic alterations in patients with pheochromocytoma\/paraganglioma","volume":"35","author":"Seo","year":"2020","journal-title":"Endocrinol Metab (Seoul)"},{"issue":"10","key":"2025081304271083300_luaf166-B16","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.3390\/cancers13102389","article-title":"Mutation profile of aggressive pheochromocytoma and paraganglioma with comparison of TCGA data","volume":"13","author":"Choi","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"1","key":"2025081304271083300_luaf166-B17","first-page":"e220091","article-title":"Germline genetic variants in pheochromocytoma\/paraganglioma: single-center experience","volume":"3","author":"Lima","year":"2023","journal-title":"Endocr Oncol"},{"key":"2025081304271083300_luaf166-B18","first-page":"6699698","article-title":"Li-fraumeni syndrome with six primary tumors-case report","volume":"2024","author":"Stojiljkovi\u0107","year":"2024","journal-title":"Case Rep Oncol Med"},{"issue":"4","key":"2025081304271083300_luaf166-B19","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/modpathol.3801013","article-title":"Frequent loss of 17p, but no p53 mutations or protein overexpression in benign and malignant pheochromocytomas","volume":"21","author":"Petri","year":"2008","journal-title":"Mod Pathol"},{"issue":"1","key":"2025081304271083300_luaf166-B20","doi-asserted-by":"crossref","first-page":"6044","DOI":"10.1038\/ncomms7044","article-title":"Multi-omics analysis defines core genomic alterations in pheochromocytomas and paragangliomas","volume":"6","author":"Castro-Vega","year":"2015","journal-title":"Nat 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