Expanding Our Knowledge of Molecular Pathogenesis in Histiocytoses: Solitary Soft Tissue Histiocytomas in Children With a Novel CLTC::SYK Fusion.

Abstract

The histiocytoses comprise a histopathologically and clinically diverse group of disorders bearing recurrent genomic alterations, commonly involving the BRAF gene and mitogen-activated protein kinase pathway. In the current study, a novel CLTC :: SYK fusion 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::SYK fusion suggesting that CLTC::SYK fusion-positive histiocytoma is genetically and histologically distinct from JXG. We postulate that the CLTC::SYK fusion 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::SYK fusion may pave the way for the development of targeted therapeutic options for aggressive disease.

• Authors: Helena M Crowley, Natalia Georgantzoglou, Julie Y Tse, Erik A Williams, Douglas A Mata, Stuart S Martin, Joan Guitart, Julia A Bridge, Konstantinos Linos
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 47 Issue 10 Pg. 1108-1115 (10 01 2023) ISSN: 1532-0979 [Electronic] United States
• PMID: 37522373 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Mitogen-Activated Protein Kinases
• SYK protein, human
• Syk Kinase
• CLTC protein, human
• Clathrin Heavy Chains

Topics

• Child
• Humans
• In Situ Hybridization, Fluorescence
• Xanthogranuloma, Juvenile (genetics, metabolism, pathology)
• Histiocytoma
• Mitogen-Activated Protein Kinases (genetics)
• Syk Kinase (genetics)
• Clathrin Heavy Chains (genetics)