Department of Pathology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, Fujian, China.
Department of Pathology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001, Fujian, China.
Hum Pathol. 2024 Nov;153:105668. doi: 10.1016/j.humpath.2024.105668. Epub 2024 Oct 5.
Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell (FDC) sarcoma (EBV + IFDCS) is a rare entity, and its histopathological characteristics have not been fully described. This study aimed to investigate the clinical characteristics, pathological features, and molecular genetic profiles of EBV + IFDCS to improve our understanding of these lesions. A total of 12 EBV + IFDCS specimens were obtained from patients in our pathology diagnostic center. The clinical data, morphology, immunohistochemistry, in situ hybridization, and high-throughput DNA-targeted sequencing data were collected, and follow-up data were analyzed. These data were compared with those of 6 patients with traditional FDCS. The patients with EBV + IFDCS ranged from 21 to 84 years old, with a mean age of 52.3 years and a male-to-female ratio of 1:5. At the last follow-up, all patients were alive, with 2 experiencing recurrence and metastasis. In these cases, four were classified as the classical subtype, four as the angiomatoid/sclerosing subtype, and four as the lymphoma-like subtype, with two cases also exhibiting epithelioid granulomas. All patients exhibited heterogeneous expression of follicular dendritic cell markers (CD21, CD23, CD35, and CXCL13) alongside the fibroblast marker SMA, with significantly higher expressions of IgG4, EBER, and SMA in EBV + IFDCS patients compared to FDCS patients (P < 0.05). Conversely, SSTR2, EGFR, and STAT3 expression were significantly lower in the EBV + IFDCS group (P < 0.05). The average value of EBER was significantly higher in the classical subtype group (P = 0.022). Among the four cases of EBV + IFDCS analyzed for molecular genetic features, one patient exhibited germline mutations in the CDKN1C, PDGFRA, MSH2, FANCG, MLH1, ALK, and RUNX1 genes; three exhibited simultaneous SNP variations in the MTHFR gene; and two exhibited simultaneous SNP variations in the NQO1 gene. We conducted KEGG pathway analysis on the mutant genes, revealing significant enrichment in the cAMP signaling pathway, which plays a crucial role in tumor development. Survival analysis demonstrated that the median PFS rates were not reached (NR) for EBV + IFDCS patients, compared to 5 months (HR = 7.76) for FDCS patients. The 3-year PFS rates were 66.67% and 16.67%, respectively. Compared with the FDCS group, EBV + IFDCS patients had a significantly longer median PFS time (p < 0.05). In conclusion, EBV + IFDCS represents a group of tumors with unique clinical, morphological, immunological, prognostic, and molecular cytogenetic characteristics.
EB 病毒阳性炎症滤泡树突状细胞肉瘤（EBV+IFDCS）是一种罕见的实体瘤，其组织病理学特征尚未完全描述。本研究旨在探讨 EBV+IFDCS 的临床特征、病理特征和分子遗传学特征，以提高对这些病变的认识。共从我院病理诊断中心的患者中获得了 12 例 EBV+IFDCS 标本。收集了临床资料、形态学、免疫组化、原位杂交和高通量靶向 DNA 测序数据，并进行了随访分析。将这些数据与 6 例传统 FDCS 患者进行了比较。EBV+IFDCS 患者年龄为 21~84 岁，平均年龄为 52.3 岁，男女比例为 1:5。末次随访时，所有患者均存活，2 例复发转移。在这些病例中，4 例为经典型，4 例为血管外皮瘤样/硬化型，4 例为淋巴瘤样型，其中 2 例还表现为上皮样肉芽肿。所有患者均表现为滤泡树突状细胞标志物（CD21、CD23、CD35 和 CXCL13）和纤维母细胞标志物 SMA 的异质性表达，与 FDCS 患者相比，EBV+IFDCS 患者 IgG4、EBER 和 SMA 的表达显著升高（P<0.05）。相反，EBV+IFDCS 组 SSTR2、EGFR 和 STAT3 的表达明显降低（P<0.05）。经典型组 EBER 的平均数值明显升高（P=0.022）。对 4 例 EBV+IFDCS 进行分子遗传学特征分析，其中 1 例患者存在 CDKN1C、PDGFRA、MSH2、FANCG、MLH1、ALK 和 RUNX1 基因突变，3 例同时存在 MTHFR 基因 SNP 变异，2 例同时存在 NQO1 基因 SNP 变异。对突变基因进行 KEGG 通路分析，结果显示 cAMP 信号通路显著富集，该通路在肿瘤发生发展中发挥着重要作用。生存分析表明，EBV+IFDCS 患者的中位 PFS 率未达到（NR），而 FDCS 患者为 5 个月（HR=7.76）。3 年 PFS 率分别为 66.67%和 16.67%。与 FDCS 组相比，EBV+IFDCS 患者的中位 PFS 时间明显延长（p<0.05）。综上所述，EBV+IFDCS 是一组具有独特的临床、形态、免疫、预后和分子细胞遗传学特征的肿瘤。
