Cutaneous Langerhans Cell Sarcoma Harboring BRAF V600E Mutation Followed by Chronic Myelomonocytic Leukemia and EBV-Positive Diffuse Large B-Cell Lymphoma.

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.

Abstract from PubMed