A80-4-40 When Right Becomes Left: A Novel Presentation of Untreated Primary Effusion Lymphoma

Introduction Primary effusion lymphoma (PEL) is characterized by effusions that demonstrate monoclonal B lymphocytes positive for latency-associated nuclear antigen, associated with human herpesvirus 8 (HHV-8). It is rare, representing about 3% of AIDS-related lymphomas, and occurs most commonly in individuals living with HIV who are concurrently infected with HHV-8. The typical presentation of PEL is with an effusion but without concurrent lymphadenopathy, organomegaly, or a mass. PEL is an aggressive cancer whose estimated mean survival is nine months and whose natural history can include progression to extracavitary sites. However, study of this disease is limited by its rarity. We present a novel instance of a patient with right-sided PEL who had spontaneous resolution of her effusion but a new left-sided PEL. Case description A 65-year-old woman with a history of HIV (viral load 1680, CD4 count less than 200), complicated by Kaposi’s sarcoma (in remission after chemotherapy greater than 20 years ago), end-stage kidney disease (ESKD) on hemodialysis, MRSA endocarditis (status post mitral valve replacement), recurrent deep venous thromboses, and chronic lymphedema who presented initially in March 2024 with a right-sided pleural effusion. Pleural fluid cytology was notable for HHV-8-positive malignant cells. A PET scan performed one month later demonstrated an FDG-avid right pleural effusion and no other lesions. Although the patient was planned for initiation of chemotherapy, chronic deep venous thromboses and a tunneled dialysis catheter prohibited vascular access, and several missed appointments delayed management. Nonetheless, her HHV-8 viral load progressively decreased on ganciclovir therapy, and repeat CT scans in May, June, and August 2025 demonstrated progressive resolution of the right-sided effusion. However, also evident was the development of a new small left pleural effusion, managed with increased ultrafiltration. In October 2025, the patient was hospitalized with shortness of breath, and an enlarging left pleural effusion was found. Pleural fluid cytology demonstrated HHV-8-positive malignant cells. Discussion The pulmonary physician is uniquely positioned as a catalyst of the diagnosis and management of thoracic malignancies and diseases of the pleural space. Therefore, recognizing all pathologies is of utmost importance. The differential diagnosis of a new left-sided pleural effusion in this patient with PEL, HIV, and ESKD was broad and included a transudative effusion, uremic pleuritis, and an alternative malignancy. Consideration of a rare entity--spontaneous resolution of a PEL-associated right pleural effusion, with extension of disease into the contralateral pleural cavity--was paramount in this case to secure the correct diagnosis.