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Microscopic examination of the enucleation specimen revealed a periapical cyst with large collections of atypical cells with grooved folded nuclei with eosinophils consistent with LCH. Immunohistochemistry (IHC) was performed to confirm the diagnosis.\n                      <jats:italic>BRAF<\/jats:italic>\n                      mutation status was evaluated with the\n                      <jats:italic>BRAF<\/jats:italic>\n                      p. V600E antibody and the automated real-time PCR-based Idylla\u2122 assay, capable of qualitative detection of 5 mutations in codon 600 of the\n                      <jats:italic>BRAF<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The LCH cells were positive for S100, CD1a, and Langerin (CD 207) and negative for\n                      <jats:italic>BRAF<\/jats:italic>\n                      p. V600E mutations. Ki-67 was 45%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The association of LCH with a periapical cyst could be explained by the active surveillance and migration of neoplastic Langerhans-type cells in blood to the site of apical chronic inflammation, in a patient with LCH. Careful attention to morphologic features in conjunction with Langerin IHC, helps exclude other closely-related dendritic tumours.\n                      <jats:italic>BRAF<\/jats:italic>\n                      p. V600E testing, ideally with real-time PCR assays, can help identify patients who may benefit from\n                      <jats:italic>BRAF<\/jats:italic>\n                      inhibitor therapies. New generations of sequencing that cover a large panel of genetic alterations beyond the frequent\n                      <jats:italic>BRAF<\/jats:italic>\n                      p. V600E mutations (e.g. rare in-frame\n                      <jats:italic>BRAF<\/jats:italic>\n                      deletions), could provide valuable information about the extent, prognosis and treatment of LCH patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12105-025-01763-5","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T01:30:58Z","timestamp":1742002258000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["BRAF p.V600E-Negative Langerhans Cell Histiocytosis Associated with a Periapical Cyst: A Case Presentation with Broad Review of the Differential Diagnosis and Disease Pathophysiology"],"prefix":"10.1007","volume":"19","author":[{"given":"Anneze","family":"Odendaal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwin","family":"Kassan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon Janse","family":"van Rensburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir H.","family":"Afrogheh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,15]]},"reference":[{"key":"1763_CR1","unstructured":"Jaffe R (2008) Tumours derived from Langerhans cells. 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