Background: Castleman disease (CD) is an extremely rare lymphoproliferative disease presenting with abnormal lymph node enlargement. Determination of the number and location of lymph nodes involved further subdivides CD into unicentric castleman disease (UCD) and multicentric castleman disease (MCD). UCD tends to have a milder clinical course and can be treated with one time resection, whereas MCD may involve multiple lymph node regions and cause systemic symptoms. While UCD is typically idiopathic, MCD may be idiopathic or present as a sequelae of human herpesvirus 8 (HHV8) and human immunodeficiency virus (HIV) infection. Due to the rarity of CD, research on this disease is sparse. The goal of this study is to investigate the clinical presentation and features of patients with CD and their treatment, complications, and outcomes.

Methods: This retrospective study utilized ICD code retrieval and key word identification to obtain a list of all patients with diagnosis of Castleman Disease in a single institution's electronic medical record. Patient demographic data was obtained including date of birth, race, sex, and age. Through manual chart review, clinical records were reviewed including surgical and pathology reports, labs, imaging, and oncology treatment records. Data was aggregated and descriptive statistical analysis was performed.

Outcomes: A total of 81 patients were initially identified. Of these, 30 were determined to have UCD (37.0%), 14 had MCD (17.3%), 3 lacked definitive diagnosis (3.7%), 15 had CD but lacked sufficient clinical or pathological data for inclusion (18.5%), and 19 were incorrectly identified (23.5%). Analyses were restricted to the 44 patients with confirmed and classifiable disease (UCD or MCD).

Among the 30 UCD patients, the average age of diagnosis was 31.1 and ranged from 7 to 51. The most common sites of lymphadenopathy were cervical (30.0%), axillary (16.7%), retroperitoneal (13.3%), and mediastinal (10.0%). Of the 19 UCD patients with histopathologic subtyping information available, 100% were subtyped as hyaline vascular variant. Of the 30 UCD patients, all underwent excisional biopsy or resection; no recurrences were noted.

Of the 14 MCD patients, the average age of diagnosis was 47.2, ranging from 27 to 81. A histopathologic subtyping was available in 7 cases, with hyaline vascular variant in 4 (57.1%), plasmacytic in 1 (14.3%), and mixed plasmacytic/hyaline vascular in 2 (28.6%). Two patients' MCD was associated with HIV and HHV8 infection. Of these two, one had Kaposi sarcoma. TAFRO syndrome was identified in 2 patients and POEMS syndrome in 1 patient. Treatment varied in this group including rituximab, siltuximab, and tocilizumab. Of the patients with treatment follow up information, 16.7% had resolution of symptoms without recurrence after completing cycle of treatment, 50% had recurrence of symptoms requiring ongoing treatment, and 33% had progression of symptoms despite treatment.

Discussion: This study represents a retrospective analysis of Castleman Disease (CD) at a single institution and offers insight into the clinical characteristics, histopathologic subtypes, and associated complications of both UCD and MCD. UCD was more common than MCD and presented at a younger age, with the majority of patients showing involvement of cervical or axillary lymph nodes. All subtyped UCD cases demonstrated the hyaline vascular variant, consistent with prior literature and supporting its localized and typically benign clinical course.

In contrast, MCD patients had a broader age range and more varied histologic subtypes, with a notable presence of plasmacytic and mixed variants. Although HIV/HHV8-associated MCD was observed in a minority of cases, these patients represented the most clinically complex, with additional diagnoses Kaposi Sarcoma and DLBCL. Furthermore, the identification of syndromic variants such as TAFRO underscores the heterogeneity of MCD.

This investigation highlights the importance of accurate classification and comprehensive diagnostic evaluation in CD. While limited by sample size and single-institution design, this study contributes to the growing body of literature on this rare disease and emphasizes the need for ongoing research into its pathophysiology, optimal management, and long-term outcomes.

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2025
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