Other lymphomas?: Castleman disease and human herpesvirus 8

Abstract

Castleman disease constitutes a heterogeneous group of low-frequency lymphoproliferative disorders. It is classified based on the number of affected nodal areas into different variants: unicentric (UCD) or multicentric (MCD). In turn, it can be idiopathic or associated with infections by the human immunodeficiency virus (HIV) and/or human herpesvirus 8 (HHV-8, also known as Kaposi's sarcoma-associated herpesvirus). The latter has an estimated frequency of 1 in 100,000 people. Castleman disease can exhibit an indolent or aggressive clinical course, with severe cases leading to multi-organ failure. Diagnosis is based on identifying morphological abnormalities in the affected lymph node and immunohistochemistry (IHC) techniques using LANA-1 antigen staining to confirm the presence of HHV-8. Detection of the viral genome in blood samples has been proposed as a biomarker to predict disease recurrence risk, enabling early treatment initiation. We present the clinical case of a 65-year-old male patient, HIV-negative, who in 2018 developed B symptoms along with muscle weakness and generalized lymphadenopathy. The clinical picture rapidly progressed to multiorgan failure. He was diagnosed with HHV-8-associated multicentric Castleman disease, for which he received treatment, achieving complete remission. In 2021, the patient experienced his first relapse, which, after receiving a different treatment, led to a second remission. During follow-up through various biochemical parameters, a sustained increase in HHV-8 viral load was detected between late 2023 and early 2024. Since the patient did not exhibit additional symptoms or new findings on imaging studies, a decision was made to adopt a watchful waiting approach with strict monitoring. Reports suggest that viral reactivation could predict clinical relapse of the disease, with potential early preventive strategies being proposed for this event. However, there is currently no consensus on its systematic application in clinical practice. We believe that monitoring HHV-8 viral load in patients with Castleman disease throughout their treatment could be relevant. However, given the low prevalence of the disease, a larger number of cases needs to be studied to establish this.