Abstract
Background Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder stratified into non-severe and severe categories according to Castleman Disease Collaborative Network (CDCN) criteria. Patients labelled “severe” face substantially higher mortality and are therefore candidates for prompt multi-agent chemotherapy. Pulmonary involvement (PI), most commonly lymphocytic interstitial pneumonitis, has been included as one of the CDCN diagnostic criteria for severe iMCD. However, owing to the rarity of iMCD, most consensus statements to date, including those addressing PI, rest only on expertise or limited observational data. Although PI has already been associated with disease severity, its prognostic weight remains unclear without persuasive evidence. We undertook this study to delineate the baseline characteristics and long-term outcomes of patients with iMCD-PI.
Methods This single-centre, retrospective study utilized the largest single-centre registry of Chinese iMCD patients at Peking Union Medical College Hospital (PUMCH). Patients diagnosed with iMCD in PUMCH according to the Castleman Disease Collaborative Network (CDCN) consensus criteria (January 2010-September 2024) were included. Baseline PI was assessed using the chest CT scan obtained closest to iMCD diagnosis. Patients were stratified into PI and non-PI groups based on CT findings, with PI confirmed through integrated radiologic and clinical evaluation. Among patients with abnormal baseline CT findings, those with alternative explanations for lung disease were excluded.
The PI cohort was subsequently categorized into three subgroups based on CT pattern: 1) the nodule subgroup only manifested nodules without the findings of cysts and consolidation; 2) the cyst subgroup was defined as the presence of a cyst and the of consolidation; 3) the consolidation subgroup was recorded as long as consolidation was present, with or without nodules or cysts. Patients were followed through December 31, 2024, with survival status documented for prognostic analysis.
Results The study included 429 iMCD patients, with PI identified in 102 (23.8%). Among the PI cohort, 54 patients (52.9%) were male, with a median diagnosis age of 41 years (range: 18-68). Disease onset was significantly more insidious in PI patients compared to non-PI counterparts (median time to diagnosis: 26.4 vs. 7.0 months; P<0.001). The plasmacytic variant was the predominant histopathology (84.2%), with clinical subtypes comprising IPL (idiopathic plasmacytic lymphadenopathy; 51.0%) and NOS (not otherwise specified; 49.0%). No TAFRO cases were identified. CRP, haemoglobin and albumin levels were comparable between PI and non-PI groups, whereas serum IgG was significantly higher in PI patients (median 37.2 g/L vs 23.6 g/L; P<0.01).
At presentation, 55/99 (55.6%) PI patients reported respiratory symptoms. Among 69 patients who underwent pulmonary function testing (PFT), 54 (78.3%) exhibited reduced diffusion capacity (DLco), and 16 (23.3%) demonstrated restrictive defects. Radiological classification identified 28 nodule-subtype, 59 cyst-subtype, 11 consolidation-subtype, and 4 unclassifiable cases. PFT revealed significant differences among subtypes: the nodule group had superior DLco compared to cyst and consolidation groups (DLco %pred median: 74.6 [nodule] vs. 67.1 [cyst] vs. 61.1 [consolidation]; P=0.010), while the consolidation group had significantly lower total lung capacity (TLC) than cyst and nodule groups (TLC %pred median: 79.5 [consolidation] vs. 89.0 [cyst] vs. 92.5 [nodule]; P=0.024).
During a median follow-up of 42.5 months, 4 deaths occurred within the PI cohort (1 nodule, 2 cyst, 1 consolidation). The 5-year overall survival for the PI cohort was 94.4% (95% CI 91.1–97.7%). Survival did not differ significantly between PI and non-PI patients (P = 0.232) or across radiologic subgroups (P=0.749).
Conclusions PI occurs exclusively in iMCD-IPL/NOS subtypes and is absent in TAFRO. While CT-defined PI subtypes exhibit distinct pulmonary functional impairments, patients demonstrate favourable survival comparable to non-PI counterparts, without subtype-based survival differences. These findings challenge PI's role as a severity-defining criterion in iMCD, warranting clinical reconsideration.
