Revealing Homologous Clonality By Synchronous Trisomy 8 in Langerhans CELL Histiocytosis and ACUTE Myeloid Leukemia

Purpose Langerhans cell histiocytosis (LCH) is a disorder in which excess immature Langerhans cells build up in the body. Increasing reports have revealed LCH may share a common origin with myeloid-derived malignancies. Here we report a case of a 45-year-old male, diagnosed as synchronous LCH and acute myeloid leukemia (AML). Relevant tests have been performed to investigate the clonal relationship between LCH and AML. Methods The diagnosis of LCH and AML were based on skin and bone marrow biopsy respectively in Beijing Friendship Hospital, Capital Medical University. No cytotoxic drugs were used before the two diseases were diagnosed. Immunophenotyping was run by immunochemistry or flow cytometry. Karyotype analysis was carried out with G-banding, and the findings were confirmed by fluorescence in situ hybridization (FISH). Mutational analysis of BRAF, KRAS and NRAS genes were performed by ARMS-PCR. Additional gene screening was detected by next-generation sequencing (NGS). Results The case expressed CD1a, S-100, Langerin on the Langerhans cells and CD13, CD34, CD38, CD117, MPO on the leukemic blasts. No other intermingling markers was found on the LCH and AML except CD33 and CD68. Cytogenetic studies showed a karyotype with 47, XY, +8[10], and a confirmatory test revealed the existence of trisomy 8 in both skin and bone marrow lesions by FISH. Cell rate of trisomy 8 on skin, bone marrow and oral mucosa were 9%, 49% and 1%. Mutation analysis revealed KRAS c.436G>A:p.A146T (exon4) in AML and LCH cells, but BRAF c.1799T>A:p.V600E (exon15) only in LCH. Conclusion These findings suggest that LCH cells are derived from myeloid precursors in this case, and BRAF mutation may play an important role in pathogenesis of LCH.