Objectives: Langerhans cell sarcoma (LCS) is a very rare, highly malignant tumor that originates from Langerhans cells. The differential diagnosis of LCS and Langerhans cell histiocytosis (LCH) still faces limitations, and the molecular changes involved in LCS are unclear. Molecular biomarkers and immunophenotypes may help distinguish between LCS and LCH. In this manuscript, the pathological and molecular markers in LCS are explored. Methods: The expression patterns of ASPP1, ASPP2, and inhibitor of apoptosis-stimulating p53 protein (iASPP) were examined using the immunohistochemical method and immunofluorescence staining. Then, genetic features, such as B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E, K-ras, and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), were assayed using the amplification refractory mutation system (ARMS) method. Finally, whole-exon sequencing of LCS was performed. Results: Immunohistochemically, in all samples of LCS, ASPP2 was detected in ovoid and elliptic tumor cells. In the case of LCH, ASPP2 was expressed not only in ovoid and elliptic cells but also in histiocytic cells. The expression of iASPP was observed in five cases LCS (5/6), and no positive reaction was observed in the case of LCH. No ASPP1 expression was observed in LCH and LCS. During triple-color immunofluorescence analysis, ASPP2 and iASPP were co-expressed on Langerin+ LCS tumor cells. No mutations of BRAF V600E, K-ras, or ROS1 were detected in LCH and LCS. No gene mutation or rearrangement was detected in LCS except for the MAP2K1 gene. The mutation site was nonsynonymous in 607 bp of MAP2K1, resulting in a change from base G to A; thus, the amino acid E changed to K at the 203 site (4/6, 66.67%). Conclusions: Combined detection of ASPP2 and iASPP in tissue samples may provide valuable markers to differentiate between LCH and LCS. The MAP2K1 variants c.607G > A is the first potential marker to be reported in LCS.
Wang et al. (Thu,) studied this question.