Pathological features of multicentric plasmacytic variant Castleman disease with IgG4 elevation

MA Xuening; MENG Ping; LI Yiying; LI Ping; SUN Ping

doi:10.3969/j.issn.1007-8096.2025.11.1461

Abstract：Objective To explore the clinical and pathological features,immunophenotype,and differential diagnosis of multicentric plasma cell type Castleman disease(PC-MCD)with elevated IgG4,aiming to enhance the understanding of the disease.Methods The clinical data of one patient diagnosed with PC-MCD were retrospectively analyzed,the tissue structure and cell morphology of lymph nodes were analyzed by routine hematoxylin-eosin(HE)staining,the immunophenotype and Epstein-Barr virus(EBV)infection status were analyzed by immunohistochemical staining and in situ hybridization,and the differential diagnosis of Epstein-Barr virus(EBV)infection status was discussed in combination with literature analysis.Results The patient was an 18-year-old male who presented with a two-year history of multiple lymphadenopathies in the cervical region.Laboratory serological tests showed elevated IL-6(265.8 pg/mL),IgG and IgA levels,significantly elevated serum IgG4(30.100 g/L).Free light chain kappa and free light chain lambda were also abnormally elevated.Histopathological examination demonstrated the disappearance of the subcapsular sinus in the lymph nodes,along with follicular hyperplasia of varying sizes.Some germinal centers exhibited atrophy with eosinophilic deposition,while the follicular mantle zone was expanded.A small number of peripherally arranged lymphocytes exhibited a concentric pattern,forming an"onion skin"appearance.The interfollicular and paracortical areas showed diffuse infiltration of plasma cells,small blood vessel proliferation,occasional intrafollicular invasion,and hyalinization.Immunohistochemical staining revealed that the majority of follicular cells were positive for CD20 and CD79a.Germinal center cells were positive for CD10 and Bcl-6 but negative for Bcl-2,with a high Ki-67 proliferation index(90%+).Marginal zone cells were positive for MNDA and negative for cyclin D1.Interfollicular cells were positive for CD3 and Bcl-2,with plasma cells showing positivity for MUM1.Kappa and lambda light chains were partially expressed in plasma cells,exhibiting a polyclonal pattern without light chain restriction.IgG4-positive plasma cells were observed,but the IgG4+/IgG+ratio was<40%.Ki-67 staining indicated high proliferative activity in the germinal centers and approximately 10%positivity in the interfollicular areas.Follicular dendritic cells were positive for CD21 and CD23.EBER in situ hybridization was negative.No clonal rearrangements were detected in IGH,IGK,or IGL gene analyses.Conclusion PC-MCD with elevated IgG4 exhibits the histopathological features similar to those of IgG4-related disease.Differentiation based solely on histological and immunophenotypic findings is challenging.Accurate diagnosis requires a comprehensive assessment incorporating the diagnostic criteria and exclusion criteria for IgG4-related disease,along with clinical manifestations and laboratory findings.