EBV-positive follicular dendritic cell sarcoma has unique clinicopathological and molecular characteristics
YANG Yanru
MA Jing
WANG Yingmei
FAN Linni
WANG Zhe
Abstract：Objective To investigate the clinicopathological and molecular genetic characteristics of a novel subtype of follicular dendritic cell sarcoma(FDCS)—EBV-positive follicular dendritic cell sarcoma(EBV+FDCS),and distinguish its differences from conventional FDCS and EBV-positive inflammatory follicular dendritic cell sarcoma(EBV+IFDCS).Methods A retrospective analysis was conducted on the clinicopathological features,immunophenotype,and follow-up outcomes of 4 cases of EBV+FDCS.Whole-exome sequencing(WES)and RNA-Seq were performed to analyze its unique genetic profile.Existing sequencing data on FDCS from PubMed,Scopus,GEO,and COSMIC databases were retrieved for comparative analysis.Results The 4 EBV+FDCS patients were aged 32-64(mean 51.75)years.Two cases occurred in cervical lymph nodes,while the other two occurred outside lymph nodes,located in the maxillary sinus and nasopharynx.Under low magnification,tumor cells exhibited diverse arrangement patterns,including diffuse or nodular arrangements,with focal perivascular geographic necrosis.Under high magnification,tumor cells displayed epithelioid morphology,with abundant cytoplasm and eosinophilic granular changes,high-grade nuclei(enlarged,hyperchromatic,with small nucleoli),and frequent mitotic activity[(10-40)/10 HPF)].Immunophenotypically,tumor cells expressed multiple FDC markers,including CD21,CD23,CD35,CXCL13,Fascin,and Clusterin,with diffuse positivity for EBER in situ hybridization.WES revealed gene mutations in BCLAF1,KMT2C,and PPP6C,differing from previously reported mutational characteristics in EBV+IFDCS and FDCS.RNA-Seq showed that the expression levels of TOP20 genes in EBV+FDCS were significantly different from those in classical FDCS.Cluster analysis showed that EBV+FDCS was an independent group distinct from FDCS,EBV+IFDCS and nasopharyngeal carcinoma.Follow-up data showed that among the 4 patients,2 patients died of the disease 2 months and 5 months after the initial diagnosis,respectively,1 patient was lost to follow-up,and 1 patient remained progression-free survival by the end of the follow-up.Conclusion EBV+FDCS with high-grade morphology and aggressive behavior,has unique clinicopathological and molecular characteristics that differs from EBV+IFDCS and conventional FDCS.It may represent a novel mesenchymal dendritic cell-derived tumor subtype.
Keywords：dendritic cell sarcomafollicularEpstein-Barr virus infectionstumor gradingimmunophenotypingmolecular probe techniqueswhole-exome sequencinggene expression profilingnasopharyngeal carcinoma
Publication Date：2025-07-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 862-868 )