A 50-year-old male presented to the hospital with fevers, night sweats, and painful lymphadenopathy for one week. Abdominal computed tomography (CT) revealed marked splenomegaly and iliac lymphadenopathy. Labs showed platelets 67, hemoglobin 11.1, 3% atypical lymphocytes, 26% monocytes, AST 50, ALT 39, negative acute hepatitis panel, negative HIV, negative heterophile antibody, CMV IgG 3.7, CMV IgM <8, negative blood cultures. His symptoms resolved and he was discharged with presumed Epstein-Barr virus (EBV) mononucleosis and told to follow up with outpatient hematology and infectious disease. After discharge, EBV titers resulted, showing previous EBV infection. Over the next 3 months, he experienced intermittent fevers to 106 °F, worsening cough, painful lymphadenopathy and night sweats. He returned to the hospital 3 months after his initial presentation, where he was found to be tachypnic, tachycardic and febrile to 104 °F. He was pancultured, started on broad spectrum antibiotics, given fluids and admitted for sepsis. On exam, he had splenomegaly and painful inguinal lymphadenopathy. Labs showed platelets 57, hemoglobin 11.7, 2% atypical lymphocytes, 27% monocytes, AST 61, ALT 81, negative heterophile antibody, negative HIV, negative CMV, negative TB quantiferon gold, negative blood cultures, and EBV titers again showing past infection. Repeat CT chest/abdomen/pelvis had increased number of mildly enlarged bilateral axillary and subpectoral lymph nodes, stable splenomegaly, and larger retroperitoneal iliac chain lymphadenopathy. Given his second presentation with persistence of symptoms including fevers, tachycardia, and tachypnea and after a second repeat negative infectious workup, the patient underwent excisional axillary lymph node biopsy and was subsequently discharged. The biopsy revealed angiofollicular lymph node hyperplasia and a diagnosis of multicentric Castleman’s disease (CD) hyaline-vascular type was made. The patient was contacted and told to follow up with hematology to start treatment as an outpatient.
Discussion:
CD is a lymphoproliferative disorder typically associated with HIV and human herpes virus-8. It is classified as unicentric or multicentric and can be associated with Kaposi sarcoma, Hodgkin lymphoma, non-Hodgkin lymphoma, and POEMS syndrome. Multicentric CD disease presents with generalized lymphadenopathy, hepatosplenomegaly, pulmonary symptoms, edema, fevers, and night sweats. The pathogenesis is not well understood but is thought to be due to lymph node hyperplasia from excess IL-6. Diagnosis is confirmed with lymph node biopsy. Treatment for CD depends on histological type and other co-morbidities. Multicentric disease is generally treated with steroids, chemotherapy, or a combination of both.
Conclusions:
Castleman’s disease is a rare lymphoproliferative disorder that presents with non-specific symptoms, many of which overlap with many other disease entities. When initial routine workup for such patients returns negative, it is important to pursue different avenues to make a diagnosis.