{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:11:16Z","timestamp":1788779476168,"version":"build-2803163510"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Numerous case reports regarding adult multisystem Langerhans cell histiocytosis (MS-LCH) have been published, yet the vast majority only describe single-organ involvement. Cases presenting sequential multi-organ lesions, clinical manifestations mimicking idiopathic hypophysitis and refractory gastritis, accompanied by long-term missed diagnosis and delayed definitive confirmation remain extremely rare. This article reports a 44-year-old female patient with delayed-diagnosed multisystem LCH. Her initial symptom was isolated central diabetes insipidus, which was misdiagnosed as infundibulohypophysitis. Subsequently, she developed intractable gastrointestinal discomfort accompanied by unexplained 10\u00a0kg weight loss. The definitive diagnosis was established nearly 10 months after symptom onset until a subcutaneous frontal skull mass emerged. Pathological diagnosis was obtained via surgical resection. The patient received cytarabine induction chemotherapy followed by salvage therapy combining TCD regimen and denosumab, achieving sustained partial remission of systemic lesions. Targeted next-generation sequencing identified a grade II somatic MAP2K1 mutation without the common BRAF V600E hotspot mutation, providing definitive molecular evidence for long-term maintenance targeted therapy with MEK inhibitors. This case is intended to deepen clinicians\u2019 recognition on the diagnostic and therapeutic strategies of adult LCH, facilitate early confirmed diagnosis and timely clinical intervention to reduce related complications, and further explore its underlying pathogenesis as well as individualized management regimens.<\/jats:p>","DOI":"10.3389\/fonc.2026.1885471","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:38:10Z","timestamp":1788777490000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A case report of delayed-diagnosed adult multisystem Langerhans cell histiocytosis with isolated MAP2K1 somatic mutation and systematic literature review"],"prefix":"10.3389","volume":"16","author":[{"given":"Qijian","family":"Zhang","sequence":"first","affiliation":[{"name":"The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"He","sequence":"additional","affiliation":[{"name":"The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Dong","sequence":"additional","affiliation":[{"name":"The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiang","family":"Yang","sequence":"additional","affiliation":[{"name":"The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfei","family":"Shao","sequence":"additional","affiliation":[{"name":"The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Huang","sequence":"additional","affiliation":[{"name":"The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University","place":["Wuxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021014343","article-title":"International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults","volume":"139","author":"Goyal","year":"2022","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41572-021-00307-9","article-title":"Histiocytic disorders","volume":"7","author":"McClain","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1275085","article-title":"Current advances in molecular pathogenesis of Langerhans cell histiocytosis","volume":"71","author":"Guyot-Goubin","year":"2024","journal-title":"Pediatr Blood Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s44228-023-00034","article-title":"Adult-onset Langerhans cell histiocytosis: clinical characteristics and treatment outcomes","volume":"37","author":"Davulcu","year":"2023","journal-title":"J Clin Lab Anal"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22247","article-title":"MAP2K1 and MAP3K1 mutations in Langerhans cell histiocytosis","volume":"54","author":"Nelson","year":"2015","journal-title":"Genes Chromosomes Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010706","article-title":"Long-term outcomes among adults with Langerhans cell histiocytosis: a single-institution retrospective cohort of 219 patients","volume":"7","author":"Yu","year":"2023","journal-title":"Hematol Commun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac381","article-title":"Diagnosis and management of central diabetes insipidus in adults","volume":"107","author":"Tomkins","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.21037\/qims-21-823","article-title":"Role of 18F-FDG PET\/CT in the diagnosis and management of patients with Langerhans cell histiocytosis","volume":"12","author":"Luo","year":"2022","journal-title":"Quantitative Imaging Med Surg"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19951215)76:12<2471::AID-CNCR2820761211>3.0.CO;2-Z","article-title":"Langerhans\u2019 cell histiocytosis (histiocytosis X) of bone. 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