Follicular dendritic cell sarcoma in association with Castleman disease complicated by paraneoplastic pemphigus: a retrospective analysis of six cases

Abstract Background Follicular dendritic cell sarcoma (FDCS) arising from Castleman disease(CD) is an extremely rare entity. This study aimed to evaluate the detailed clinicopathological characterization, including histomorphology, immunohistochemical profiles, clinical presentations, and follow-up data in patients with FDCS arising from CD. Methods In this study, we retrospectively analyzed 6 cases of FDCS arising in the context of CD, with comprehensive evaluation of their clinical presentations, histopathological characteristics, and immunophenotypic profiles. Results The cohort comprised 3 male and 3 female patients, aged 31 to 79 years. All cases originate within lymph nodes, with localizations in the mediastinum ( n = 2), axilla ( n = 1), retroperitoneum ( n = 2), and pelvic cavity ( n = 1). Notably, paraneoplastic pemphigus (PNP) was observed in 5 cases. Histopathological examination revealed characteristic fascicular, whorled, or diffuse proliferation of spindle to oval cells forming nodular structures within markedly enlarged lymph nodes. Residual CD features, including atrophic lymphoid follicles and hyalinized vascular proliferation, were identified adjacent to FDCS lesions. One case demonstrated extensive plasma cell infiltration in interfollicular regions. Immunohistochemical analysis showed variable expression of CD21, CD23, and CD35 in neoplastic cells. EGFR was strongly positive in 5(5/5) cases, while showed variable expression of PD-ligand 1 (PD-L1), the Combined Positive Score (CPS) range from 0 to 70. Five cases were classified as hyaline-vascular CD(HVCD) with concurrent FDCS, including one case that recurred as FDCS 31 months postoperatively. One case initially diagnosed with multicentric plasma cell type CD complicated by FDCS exhibited recurrence of plasma cell type CD 7 months postoperatively. The study identified 5 cases with associated PNP. Clinical outcomes revealed four cases died within five years, one case lost to follow-up, and one is alive without disease. Conclusions In our cohort, FDCS arising from CD was frequently associated with PNP and demonstrated poor clinical outcomes. While these observations are limited by the small sample size and require external validation, they strongly suggest that this subset represents a high-risk population. Enhancing pathologists' awareness of this distinctive association remains an essential step toward early diagnosis and optimized patient care.