Cutaneous Langerhans Cell Sarcoma Harboring BRAF V600E Mutation Followed by Chronic Myelomonocytic Leukemia and...

Langerhans cell sarcoma (LCS) is an extremely rare and aggressive neoplasm of histiocytic and dendritic cell lineage. We report a case of cutaneous LCS in a 74-year-old woman, harboring a BRAF V600E mutation and demonstrating an aggressive clinical course, including multiple metastatic lesions. During follow-up, the patient was diagnosed with chronic myelomonocytic leukemia and subsequently developed Epstein-Barr virus-positive diffuse large B-cell lymphoma. Additional molecular analyses demonstrated BRAF V600E in the primary LCS but not in the CMML bone marrow or the EBV-positive DLBCL, arguing against a common BRAF-driven clonal origin. Although an earlier shared founder alteration between LCS and CMML cannot be excluded, the subsequent EBV-positive DLBCL most likely developed independently in the setting of CMML-associated immune dysregulation. This case highlights the complexity of multiple hematologic neoplasms and emphasizes the importance of integrated clinicopathologic and molecular evaluation in rare histiocytic neoplasms.