Full Papers
IgG4-related Castleman disease: clinical-pathological features and therapeutic implications
J. Mahajne1, L. Bongiovanni2, A. Gonzalez Garcia3, M.P. Iranzo Alcolea4, M. Lanzillotta5, T. Calimeri6, F. Erbella7, A.J. Ferreri8, L. Dagna9, M. Ponzoni10, E. Della-Torre11
- Università Vita-Salute San Raffaele, Milan; and Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan; and Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
- Systemic Autoimmune Diseases Unit, Department of Internal Medicine, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Strategic Program on Lymphomas, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
- Strategic Program on Lymphomas, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan; and Strategic Program on Lymphomas, IRCCS, San Raffaele Scientific Institute, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan; and Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan; and Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Università Vita-Salute San Raffaele, Milan; and Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy. dellatorre.emanuel@hsr.it
CER19834
Full Papers
PMID: 43006875 [PubMed]
Received: 23/02/2026
Accepted : 13/07/2026
In Press: 10/11/2026
Abstract
OBJECTIVES:
IgG4-related disease (IgG4-RD) and idiopathic multicentric Castleman disease (iMCD) are considered mutually exclusive. A clinical entity with features of IgG4-RD and iMCD has been named IgG4-related Castleman disease (IgG4-CD) but remains poorly characterised. We here describe demographic, clinical, histological characteristics of IgG4-CD, its prognosis and response to immunosuppressive treatment.
METHODS:
This retrospective study included patients with IgG4-RD and iMCD referred to San Raffaele Hospital (Milan, Italy) and Ramón y Cajal Hospital (Madrid, Spain). IgG4-CD was defined based on fulfillment of international diagnostic criteria for CD and IgG4-RD. Demographics, epidemiological, clinical, serological data, pathological findings and treatment outcomes were recorded. Results were compared with IgG4-RD and iMCD patients.
RESULTS:
Eight patients with a median age of 63 years (range 49–71) at the time of IgG4-CD diagnosis were included. All presented with constitutional symptoms. All lymph node biopsies showed high-grade plasmocytosis and features of CD. IgG4-CD extranodal involvement included salivary and lacrimal glands, pancreas, and bile ducts. Lymph nodes were more frequently involved in IgG4-CD than in IgG4-RD, serum IgG4 were higher in IgG4-CD than in IgG4-RD and iMCD, C-reactive protein in IgG4-CD was lower than in iMCD (p<0.0001). Erythrocyte sedimentation rate (ESR) was higher in IgG4-CD than in IgG4-RD (p=0.0334). All patients responded to glucocorticoids or second-line therapy with rituximab with a favourable outcome at the longest available follow-up.
CONCLUSIONS:
IgG4-CD is characterised by constitutional symptoms, elevated ESR and IgG4 levels, and high-grade lymph node plasmacytosis. Good response to anti-CD20 therapy and a favourable prognosis mark a difference with iMCD.
