From Unicentric Castleman Disease to Lymphoma: A Rare Case Highlighting a Diagnostic and Therapeutic Challenge

Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder treated with surgical resection. However, its association with lymphoma, particularly nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), is rare and not well characterized. We report a case highlighting the potential for malignant transformation in an otherwise asymptomatic patient. The patient was a 28-year-old male with a history of UCD (hyaline vascular type) in the mediastinum who presented for routine follow-up of previously enlarged lymph nodes. Surveillance chest CT revealed a new posterior mediastinal lymph node. He was asymptomatic, with an unremarkable examination and laboratory studies except for a shortened activated partial thromboplastin time (aPTT). Histopathology showed lymphocyte-predominant (LP) cells with immunophenotypic positivity for CD20, BCL-6, and epithelial membrane antigen (EMA), consistent with NLPHL. Due to the diagnostic complexity, he was treated as having a non-Hodgkin lymphoma-like entity with R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) Although UCD is typically considered curable with surgical resection, this case demonstrates that, in rare cases, it can progress to lymphoma, specifically NLPHL. The clinical course was asymptomatic, highlighting the variability in presentation and the need for a high index of suspicion in patients with recurrent mediastinal masses. Furthermore, the sequential development of UCD and NLPHL underscores the biological complexity of lymphoproliferative disorders and the potential overlap in immunophenotypic features. This case illustrates that even localized forms of UCD may be associated with subsequent lymphoid malignancy, emphasizing the importance of continuous clinical surveillance and a multidisciplinary approach to management. Histopathological reassessment of new lesions is crucial, and clinicians should consider the possibility of malignant transformation in patients with a history of UCD to ensure accurate diagnosis and timely treatment.