{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:26Z","timestamp":1784557046089,"version":"3.55.0"},"reference-count":14,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>\n                      <jats:italic>RET<\/jats:italic>\n                      mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented efficacy compared to previous multi-kinase treatments. Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm usually driven by somatic\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutations, resulting in dysregulated MAPK signalling. We describe a 22-year-old woman with metastatic MTC to regional lymph nodes, lung and liver. Tumour tissue harboured a somatic pathogenic\n                      <jats:italic>RET<\/jats:italic>\n                      variant\n                      <jats:italic>p.(M918T)<\/jats:italic>\n                      and selpercatinib was commenced. She experienced sustained clinical, biochemical and radiological responses. Two years later, she developed rapidly progressive apical lung nodules, prompting biopsy. Histopathology demonstrated LCH with a rare\n                      <jats:italic>BRAF<\/jats:italic>\n                      variant\n                      <jats:italic>p.(V600_K601&gt;D)<\/jats:italic>\n                      . The lung nodules improved with inhaled corticosteroids. We hypothesize that selective pressure from RET blockade may have activated a downstream somatic\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutation, resulting in pulmonary LCH. We recommend continued vigilance for neoplasms driven by dysregulated downstream MAPK signalling in patients undergoing selective RET inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Learning points<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>\n                          Patients with\n                          <jats:italic>RET<\/jats:italic>\n                          -altered MTC can experience rapid disease improvement and sustained disease stability with selective RET blockade (selpercatinib).\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          LCH is a clonal neoplasm driven by MAPK activation, for which the most common mechanism is\n                          <jats:italic>BRAF<\/jats:italic>\n                          mutation.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Both MTC and pulmonary LCH are driven by dysregulated MAPK signalling pathway activation.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>We hypothesise that the RET-specific inhibitor selpercatinib may have caused the activation of dormant LCH secondary to selective pressure and clonal proliferation.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>","DOI":"10.1530\/edm-23-0079","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T08:52:20Z","timestamp":1716886340000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":0,"title":["Pulmonary BRAF-driven Langerhans cell histiocytosis following selpercatinib use in metastatic medullary thyroid cancer"],"prefix":"10.1530","volume":"2024","author":[{"given":"Katherine","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1242-2476","authenticated-orcid":true,"given":"Shejil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Radiology, Royal North Shore Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Kerridge","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal North Shore Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Ru","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, SydPath, St Vincent\u2019s Hospital, Sydney, Australia"},{"name":"St Vincent\u2019s Clinical School, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda","family":"Siddall","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick","family":"Clifton-Bligh","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, Australia"},{"name":"Cancer Genetics Unit, Kolling Institute of Medical Research, Sydney, Australia"},{"name":"Northern Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Gill","sequence":"additional","affiliation":[{"name":"Northern Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, Australia"},{"name":"Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, Australia"},{"name":"Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6670-2254","authenticated-orcid":true,"given":"Matti L","family":"Gild","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, Australia"},{"name":"Cancer Genetics Unit, Kolling Institute of Medical Research, Sydney, Australia"},{"name":"Northern Clinical School, University of Sydney Faculty of Medicine and Health, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Frontiers in Endocrinology","first-page":"102","article-title":"Update on fundamental mechanisms of thyroid cancer","volume":"11","author":"Prete","year":"2020","unstructured":"Prete Ade Souza PBCensi SMuzza MNucci N & Sponziello M. 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