PRIMARY EFFUSION LYMPHOMA IN A HIV NEGATIVE AND HUMAN HERPESVIRUS 8 POSITIVE POST-CARDIAC TRANSPLANT PATIENT

Case Presentation: A 63 year-old gentleman had a history of ischemic cardiomyopathy treated with Orthotopic Heart Transplant (OHT), on tacrolimus & prednisone; cutaneous Kaposi Sarcoma (KS); & negative pre-transplant Human Herpesvirus 8 (HHV8) serology. He presented 5 months after OHT with progressive dyspnea on exertion, orthopnea & bilateral lower extremities swelling since 1 week. On examination, he was alert, hypoxemic & afebrile. Chest exam revealed bilateral crackles & decreased breath sounds on the left. Chest X-ray & CT scan showed left sided pleural effusion & patchy infiltrates.
He underwent ultrasound guided chest tube insertion & was started on aggressive diuresis. The pulmonary infiltrates improved, but the pleural effusion persisted. Pleural fluid studies showed non-hemorrhagic exudative fluid. Cytopathology exam showed malignant lymphocytes with increased nuclear size & contour abnormalities. Immunohistochemical stains were positive for CD45, CD30, HHV8, CD138 & MUM1, consistent with a diagnosis of Primary Effusion Lymphoma (PEL). He was also noted to have HHV8 viremia & bone marrow involvement with PEL.

He received 1 cycle of chemotherapy with cyclophosphamide, vincristine, prednisone & anti-CD30 monoclonal antibody Brentixumab. The immunosuppressive regimen was changed from tacrolimus to sirolimus, to decrease his level of immune suppression. He responded favorably & was discharged home, with plans for outpatient chemotherapy.

Discussion: PEL is a rare mature B-cell Non-Hodgkin’s lymphoma (NHL) presenting primarily as body cavity effusions (pleural, pericardial or peritoneal). HIV & HHV8 infections have been implicated in its pathogenesis, with patients exhibiting other HHV8 related diseases such as KS & multicentric Castleman’s Disease. The incidence of PEL in HIV & HHV8 negative patients is rare, with less than 60 documented cases.

HHV8 encoded proteins have been found responsible for the neoplastic transformation in PEL. PEL was originally reported in young-to-middle aged HIV-infected patients, accounting for approximately 4% of all NHL cases in this group. They are usually treated with standard NHL chemotherapy regimens & have a poor prognosis despite treatment. PEL is now being diagnosed in other immune-compromised patients such as those with HCV, HBV, EBV infections; alcoholism; cirrhosis & cancer. HIV-negative PEL patients have a variable clinical course & better treatment outcomes.

Our case was a unique presentation of PEL in an HHV8 and HIV-negative OHT recipient, who had HHV8 seropositivity post-transplant. Also, interestingly, PEL in our patient appeared soon after OHT. He had a remote history of KS with negative HHV8 serology & was not from an HHV8 endemic region.

Conclusions: PEL is a rare NHL occurring as body cavity effusions & with poor prognosis despite treatment. Clinicians should keep PEL as a differential diagnosis of isolated pleural effusion in solid organ transplant recipients, even if the patient is HIV negative & with no apparent risk factors for HHV8.