Clinicopathologic features and outcomes of follicular dendritic cell sarcoma with or without Castleman disease: A large retrospective cohort analysis.

Abstract

11549 Background: Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a subset associated with unicentric Castleman disease (UCD). However, the impact of CD association on clinicopathologic features and survival outcomes remains unclear. This study aims to elucidate differences in disease characteristics and outcomes in FDCS with and without CD to guide future research and clinical practice. Methods: We retrospectively analyzed 41 FDCS patients seen at Mayo Clinic between January 2000 and December 2024. Patients were categorized into CD-related (n = 9) and FDCS-only (n = 32) groups. Demographic, clinical, pathological, and survival data were compared. Kaplan-Meier survival analyses were used to evaluate overall survival (OS) and progression-free survival (PFS). Epstein-Barr virus-associated inflammatory FDCS were excluded. Results: The CD-related group was younger at diagnosis (46.0 vs. 58.0 years, p = 0.041). Among those with CD-related FDCS, FDCS was diagnosed concurrently as CD in 6/9 (66.7%) and after the diagnosis of CD in 3/9 (33.3%). The FDCS-only patients were more likely to have extranodal disease (71.9% vs. 22.2%) and to have metastasis (62.5% vs 22.2%). One CD-related FDCS patient had paraneoplastic pemphigus. Among 11 patients with next-generation sequencing (NGS) results, 9 had pathogenic mutations. The most common pathogenic mutations included CDKN2A, CDKN2B, and TRAF3 copy number losses. Surgery was the preferred first-line intervention in FDCS-only and CD-related FDCS groups (19/32, 59.4% vs. 6/9, 66.7%). Eight out of 32 (25.0%) of the FDCS-only group received chemotherapy at first-line, most commonly Gemcitabine/Docetaxel or Adriamycin/Ifosphamide. While Gemcitabine/Docetaxel was the most preferred in the second line, different regimens were pursued in the third and later lines of therapy, including Pembrolizumab, Pazopanib, and stem cell transplant. Five out of 6 patients in the CD-related FDCS group received either adjuvant radiation or chemotherapy, which led to complete remission during the follow-up periods. The median follow-up was 22.4 months for the whole population. There was a trend for better OS and PFS among CD-related FDCS patients. The respective 2-year OS rates were 100% and 66.7%, and 2-year PFS rates were 57.1% and 43.1% for CD-related FDCS and FDCS-only patients, respectively. Conclusions: This study provides novel insights into clinicopathologic differences and survival trends for FDCS. Our data would suggest a less aggressive disease course among CD-related FDCS, which implies the need for different treatment strategies for CD and non-CD-related FDCS. Further research is warranted to elucidate these mechanisms, such as multi-omic analysis on benign FDC proliferation in the microdissected UCD areas and the adjacent FDCS cells to determine factors associated with progression to sarcoma.