{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T01:59:07Z","timestamp":1783216747903,"version":"3.54.6"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Erdheim\u2013Chester disease (ECD) is a rare form of non\u2010Langerhans cell histiocytosis with diverse clinical manifestations, often associated with mutations in the mitogen\u2010activated protein kinase\/extracellular signal\u2010regulated kinase (MAPK\/ERK) pathway. <jats:italic>BRAF<\/jats:italic> and <jats:italic>KRAS<\/jats:italic> mutations, which are driver mutations of oncogenes, participate in the same signaling pathway (MAPK\/ERK pathway) and are usually mutually exclusive. We report a case of ECD with concurrent <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> and <jats:italic>KRAS<\/jats:italic><jats:sup>G12R<\/jats:sup> mutations treated using BRAF and MEK inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case<\/jats:title><jats:p>A 70\u2010year\u2010old man was referred to our hospital with a mesenteric nodal lesion on computed tomography scan. The patient experienced symptoms consistent with ECD, including central diabetes insipidus. Biopsy revealed histiocytes positive for CD68 and CD163, negative for S100, CD1a, and CD21. Liquid\u2010based comprehensive genomic profiling and tissue\u2010based cancer gene panel test identified <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> and <jats:italic>KRAS<\/jats:italic><jats:sup>G12R<\/jats:sup> mutations with different variant allele fraction. Additional immunohistochemistry with an antibody specific to mutant <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> protein stained some proliferating histiocytes, consistent with ECD. Based on the genomic profiling results, we hypothesized that there was a coexistence of a clone harboring <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> and another clone harboring <jats:italic>KRAS<\/jats:italic><jats:sup>G12R<\/jats:sup>, and planned a combination therapy with BRAF and MEK inhibitors targeting each clone, respectively. The patient received oral encorafenib at 100\u2009mg once daily and oral binimetinib at 15\u2009mg twice daily. The combination therapy resulted in rapid resolution of symptoms and significant improvement in imaging findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case represents a unique presentation of ECD with concurrent <jats:italic>BRAF<\/jats:italic><jats:sup>V600E<\/jats:sup> and <jats:italic>KRAS<\/jats:italic><jats:sup>G12R<\/jats:sup> mutations. Combination therapy with encorafenib and binimetinib targeting each clone resulted in a remarkable therapeutic effect and was well\u2010tolerated. This is the first reported case of ECD treated with encorafenib and binimetinib. The combination therapy with BRAF and MEK inhibitors is one of the rational treatment options for cases of ECD with a suspicion of multiple clones.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.70093","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T15:18:42Z","timestamp":1735226322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of Combined Encorafenib and Binimetinib Treatment for Erdheim\u2013Chester Disease Harboring Concurrent <i>BRAF<\/i><scp><sup>V600E<\/sup><\/scp> and <i>KRAS<\/i><scp><sup>G12R<\/sup><\/scp> Mutations: A Case Report"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3210-9491","authenticated-orcid":false,"given":"Yuto","family":"Hibino","sequence":"first","affiliation":[{"name":"Department of Hematology and Medical Oncology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-9063","authenticated-orcid":false,"given":"Hiroyuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuki","family":"Hirose","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Tokunaga","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6353-776X","authenticated-orcid":false,"given":"Kota","family":"Washimi","sequence":"additional","affiliation":[{"name":"Department of Pathology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Yokose","sequence":"additional","affiliation":[{"name":"Department of Pathology Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Kasajima","sequence":"additional","affiliation":[{"name":"Center for Cancer Genome Medicine Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiko","family":"Hiroshima","sequence":"additional","affiliation":[{"name":"Center for Cancer Genome Medicine Kanagawa Cancer Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Miyagi","sequence":"additional","affiliation":[{"name":"Kanagawa Cancer Center Research Institute  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Hematology and Clinical Immunology Yokohama City University Graduate School of Medicine  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019003507"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01613-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature00766"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0171-x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.37.24052"},{"key":"e_1_2_11_7_1","first-page":"20971","article-title":"Nucleotide Binding Site Specificity of the Ras\u2010Related GTPases p21ras and Rap1B Analyzed by Site\u2010Directed Mutagenesis","volume":"266","author":"Smith M. J.","year":"1991","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.5029"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/21541248.2016.1212689"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/418934a"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-26439-0_11"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-740217"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-03-771873"},{"key":"e_1_2_11_14_1","first-page":"257","article-title":"Phase 2 Trial of Single\u2010Agent Cobimetinib for Adults With BRAF V600\u2010Mutant and Wild\u2010Type Histiocytic Disorders","volume":"130","author":"Diamond E. L.","year":"2017","journal-title":"Blood"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocpiqo.2018.05.001"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0606"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30142-6"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26232"}],"container-title":["Cancer Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.70093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T06:44:46Z","timestamp":1735541086000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cnr2.70093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":17,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/cnr2.70093"],"URL":"https:\/\/doi.org\/10.1002\/cnr2.70093","archive":["Portico"],"relation":{},"ISSN":["2573-8348","2573-8348"],"issn-type":[{"value":"2573-8348","type":"print"},{"value":"2573-8348","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70093"}}