Case study
Idiopathic multicentric Castleman disease presenting as generalized lymphadenopathy: A case report
Monapriya Bindi1, Shiva Prasad B N1, Vijay H V2, Narendra K L2
Author Affiliations
1Department of Clinical Immunology and Rheumatology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India.
2Apollo BGS Hospital, Mysuru, Karnataka, India
Correspondence: Dr. Shiva Prasad BN
IJRCI. 2026,14(1):CS2.
Submitted: 29 May 2026; Accepted: 12 August 2026; Published: 24 August 2026
DOI: 10.15305/ijrci/v14i1/357
© IJRCI
Abstract
A 48-year-old male presented with easy fatigability, and on evaluation, he was found to have generalized lymphadenopathy and elevated erythrocyte sedimentation rate (ESR-70 mm/hr). Neck ultrasound revealed enlarged left paratracheal lymph nodes. He had positive Mantoux test, a diagnosis of tuberculous lymphadenopathy was made and started on antitubercular medication. However, the patient’s condition deteriorated over the next month with new onset of dyspnea on exertion, dysphagia, generalized pruritus, and progressive persistent lymphadenopathy. Laboratory results indicated elevated ESR (72 mm/hr), gamma-glutamyl transpeptidase (GGTP 370 U/L), and AST (95 U/L) levels, although alkaline phosphatase levels were normal. The hemogram and liver, renal, and thyroid function test results were normal. CRP, autoantibody tests, and serum protein electrophoresis results were also negative. CT thorax revealed cervical, axillary, hilar and mediastinal lymphadenopathy. The left axillary lymph node biopsy was negative for tuberculosis (AFB and PCR) but exhibited histological characteristics indicative of Castleman disease. His viral serology was negative for VDRL, HIV, HBSAG, and HCV. Immunohistochemistry (IHC) on lymph node biopsy was negative for the lymphoma panel and HHV 8. The diagnosis of idiopathic multicentric Castleman disease (iMCD) was confirmed using clinical, laboratory, and histological evaluations after the elimination of viral and neoplastic etiologies. He was initially treated with intravenous steroids, followed by oral steroids and immunosuppressive drugs.
Keywords: Idiopathic multicentric Castleman disease; Generalized lymphadenopathy; Lymph node histopathology; HHV-8-negative; Systemic inflammation; Tuberculous lymphadenitis
Introduction
Idiopathic multicentric Castleman disease (iMCD) is a rare, life-threatening systemic disorder characterized by generalized lymphadenopathy, pronounced systemic inflammation, and the potential for multi-organ dysfunction. Unlike unicentric Castleman disease, which affects a single lymph node region, iMCD involves multiple lymph node regions and is characterized by a hyperinflammatory state driven by dysregulated cytokine activity, most notably interleukin-6 (IL-6). The etiology of iMCD remains unknown, distinguishing it from HHV-8-associated multicentric Castleman disease, which accounts for one-third to one-half of all multicentric Castleman disease cases.¹˒² iMCD presents a diagnostic challenge because of its nonspecific symptoms, such as fever, fatigue, weight loss, and generalized lymphadenopathy, which overlap with a broad spectrum of neoplastic, infectious, and autoimmune disorders.
Laboratory investigations often reveal polyclonal lymphocyte proliferation, cytopenia, and biochemical evidence of systemic inflammation. The disease can progress rapidly, with severe cases characterized by cytokine storms and life-threatening organ dysfunction.³ Given its rarity and the complexity of its presentation, prompt recognition and diagnosis of iMCD are crucial for initiating potentially life-saving therapies. This case highlights the diagnostic journey of a patient with idiopathic multicentric Castleman disease presenting with generalized lymphadenopathy, underscoring the importance of a high index of suspicion and a multidisciplinary approach to the evaluation of unexplained lymphadenopathy.
Case report
A 48-year-old male medical professional noticed easy fatigability for over two weeks. He evaluated himself for the same and was diagnosed with asymptomatic cervical lymphadenopathy and an elevated erythrocyte sedimentation rate (ESR) of 70 mm/h. Ultrasonography of the neck identified enlarged left paratracheal lymph nodes. He had a positive Mantoux test. On this basis, he diagnosed himself with TB lymphadenitis (FNAC/biopsy was not performed at this time). He was started on antitubercular therapy. Despite one month of ATT, his symptoms worsened, and he developed grade II–III dyspnea on exertion according to the NYHA classification, dysphagia, generalized itching, and progressive lymphadenopathy. There was no cough, chest pain, abdominal symptoms, skin lesions, muscle weakness, or arthritis. The patient was referred to the current setting for further evaluation. His general examination was normal, except for generalized lymphadenopathy in the cervical and axillary regions. The systemic examination findings were normal.
Laboratory investigations revealed an elevated ESR of 72 mm/h, while the C-reactive protein level was normal. The hemogram, liver function tests, thyroid function tests, and renal function tests were normal, except for AST: 95 (40 IU/L) and GGT: 350 (55 IU/L). His serum alkaline phosphatase and serum CPK levels were also normal. He was non-diabetic, and his ABGA was normal. Chest radiography and abdominal USG were normal. HIV, HBsAg, HCV, and VDRL were negative. The results for RF, anti-CCP antibodies, ANA (IF), ANCA (IF), and the APLA panel were negative. C3 and C4 were within normal limits. Serum protein electrophoresis with immunofixation did not reveal any M bands or monoclonal proliferation. Contrast-enhanced CT of the thorax revealed prominent mediastinal and hilar lymphadenopathy, as well as bilateral axillary, supraclavicular, and cervical lymphadenopathy, consistent with generalized lymphadenopathy (Fig. 1).
Fig. 1: CT findings demonstrating generalized lymphadenopathy in idiopathic multicentric Castleman disease
FNAC smears revealed lymphocytes, histiocytes, and epithelioid cells in clusters and singly, with thin fibrin strands and RBCs in the background, suggesting granulomatous lymphadenitis. A left axillary lymph node biopsy revealed a partially effaced lymph node with a few active germinal centers, with plasmacytosis in the paracortical and interfollicular regions, including cells with plasmablastic morphology. Areas of regressed follicles with mantle cell expansion, onion-skinning of mantle cells around germinal centers, and proliferating hyalinized blood vessels penetrating the follicles were noted (Fig. 2). Prominent sinus histiocytosis was observed. These findings were suggestive of Castleman syndrome. The biopsy TB PCR was negative. HIV serology by ELISA and Western blot was also negative. IHC did not reveal any lymphoma and was negative for HHV-8. Based on the clinical, radiological, and pathological features, a diagnosis of iMCD was made.
Fig. 2: Histopathological features of lymph node involvement in idiopathic multicentric Castleman disease
The patient was started on intravenous methylprednisolone pulse therapy for three days, followed by 1 mg/kg of prednisolone. The patient responded well to the treatment. He was started on azathioprine and counseled regarding biological agents (tocilizumab and rituximab). After one year of treatment, the patient developed COVID-19 infection complicated by sepsis and succumbed to it.
Discussion
This case highlights the diagnostic complexity of iMCD, particularly when infectious mimics such as tuberculosis and COVID-19 are prevalent in India. This case highlights the importance of early lymph node biopsy in unexplained lymphadenopathy with systemic inflammation. In the present case, testing for human herpesvirus 8 (HHV-8) was negative, thereby excluding HHV-8-associated MCD and supporting the diagnosis of idiopathic MCD. This finding is crucial because it differentiates iMCD from other subtypes and guides appropriate management.
iMCD is an uncommon polyclonal lymphoproliferative disorder. It is a considerable diagnostic challenge owing to its nonspecific clinical symptoms and the necessity of ruling out a wide array of similar disorders. In contrast to unicentric Castleman disease, which is confined and typically indolent, iMCD is characterized by extensive lymphadenopathy, systemic inflammation, and the possibility of multi-organ failure. The pathogenesis of iMCD is unidentified; nevertheless, it is differentiated from other variants of multicentric Castleman disease by the lack of human herpesvirus-8 (HHV-8) infection, a vital diagnostic criterion that informs both assessment and treatment.4,5
The clinical manifestations of iMCD are markedly varied and frequently intersect with autoimmune, autoinflammatory, viral, and neoplastic disorders. Patients frequently exhibit persistent, generalized lymphadenopathy in many anatomical regions with systemic symptoms, including fever, night sweats, fatigue, and weight loss. Laboratory results often reveal anemia, increased acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, and polyclonal hypergammaglobulinemia, indicating a condition of chronic immunological activation. Hypoalbuminemia, increased interleukin-6 (IL-6) concentrations, and organomegaly (hepatomegaly or splenomegaly) are frequently noted.6 iMCD may present with or be linked to other autoimmune phenomena, including the presence of autoantibodies or coexisting autoimmune disorders, such as psoriasis or myasthenia gravis. This overlap might further confound the diagnostic procedure, as numerous autoimmune and autoinflammatory illnesses may exhibit analogous clinical and histological characteristics.7,8
The diagnosis of iMCD is based on a combination of clinical, laboratory, imaging, and, most importantly, histopathological findings of the disease. The international consensus criteria for iMCD require:6,8
· Multicentric lymphadenopathy (enlarged nodes in at least two regions)
· Characteristic lymph node histopathology, such as regressed germinal centers, expanded mantle zones, increased vascularity, and plasmacytosis
· At least two minor criteria, including laboratory abnormalities (anemia, elevated ESR/CRP, polyclonal hypergammaglobulinemia, hypoalbuminemia) and clinical features (organomegaly, edema, constitutional symptoms)
· Exclusion of infectious (notably HHV-8 and HIV), malignant (such as lymphoma), and autoimmune causes.
The omission of HHV-8 is notably important, as HHV-8–related multicentric Castleman disease generally manifests in immunocompromised patients and has a more severe clinical trajectory.9,10
Conclusion
iMCD is an uncommon yet significant condition that necessitates heightened clinical vigilance and comprehensive systematic assessment. The amalgamation of clinical, laboratory, and histopathological data, together with the stringent exclusion of mimics, particularly HHV-8 infection, is crucial for precise diagnosis and appropriate patient management.
Competing interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Citation: Bindi KM, Prasad B N S, Vijay H V, Narendra K L. Idiopathic multicentric Castleman disease presenting as generalized lymphadenopathy: A case report. IJRCI. 2026,14(1):CS2. DOI: 10.15305/ijrci/v14i1/357
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