1. Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses
- Author
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Crowley, Helena M., Georgantzoglou, Natalia, Tse, Julie Y., Williams, Erik A., Mata, Douglas A., Martin, Stuart S., Guitart, Joan, Bridge, Julia A., and Linos, Konstantinos
- Abstract
The histiocytoses comprise a histopathologically and clinically diverse group of disorders bearing recurrent genomic alterations, commonly involving the BRAFgene and mitogen-activated protein kinase pathway. In the current study, a novel CLTC::SYKfusion in 3 cases of a histopathologically distinct histiocytic neoplasm arising as solitary soft tissue lesions in children identified by next-generation sequencing and fluorescence in situ hybridization is described. Morphologically, all 3 neoplasms were composed of sheets of cells with round-oval nuclei and vacuolated eosinophilic cytoplasm but, in contrast to classic juvenile xanthogranuloma (JXG), Touton giant cells were absent. A separate cohort of classic JXG cases subsequently profiled by fluorescence in situ hybridization were negative for the presence of a CLTC::SYKfusion suggesting that CLTC::SYKfusion-positive histiocytoma is genetically and histologically distinct from JXG. We postulate that the CLTC::SYKfusion leads to aberrant activation of the SYK kinase, which is involved in variable pathways, including mitogen-activated protein kinase. The identification of a novel CLTC::SYKfusion may pave the way for the development of targeted therapeutic options for aggressive disease.
- Published
- 2023
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