Journal Article

168 A Case of Epstein-Barr Virus-Related Hemophagocytic Lymphohistiocytosis in Association With Pembrolizumab Therapy

Krishna Shah and Melissa Kesler

in American Journal of Clinical Pathology

Published on behalf of American Society for Clinical Pathology

Volume 149, issue suppl_1, pages S71-S72
Published in print January 2018 | ISSN: 0002-9173
Published online January 2018 | e-ISSN: 1943-7722 | DOI:
168 A Case of Epstein-Barr Virus-Related Hemophagocytic Lymphohistiocytosis in Association With Pembrolizumab Therapy

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A 75-year-old man with history of metastatic bladder cancer (4/2015) status post chemotherapy and thymoma (9/2015) status post resection, currently undergoing treatment with pembrolizumab, presented with fever, fatigue, and acute onset pancytopenia. Work-up revealed elevated ferritin, low fibrinogen, splenomegaly, elevated soluble CD25, and decreased natural killer cell activity. Bone marrow biopsy was performed to evaluate for hemophagocytic lymphohistiocytosis (HLH). Biopsy showed a normocellular bone marrow with histiocytic hyperplasia and hemophagocytosis confirming the presumed diagnosis of HLH. He was started on treatment accordingly. It was later found that the patient had coexistent Epstein-Barr virus (EBV) reactivation. Pembrolizumab is a monoclonal antibody used as first-line treatment for patients with certain tumors shown to have high PD-L1 expression on neoplastic cells. It is a second-line treatment for patients that have evidence of disease progression on or after platinum containing chemotherapy. This antibody specifically binds to PD-L1 receptors on T-cells (an inhibitory immune checkpoint molecule) effectively blocking tumor cells with PD-L1 ligands from inactivating T-cells. Adverse side effects of pembrolizumab include immune-mediated infections along with thyroid dysfunction, colitis, and type 1 diabetes mellitus; however, there has been no report of its association with HLH. HLH is characterized by impaired T-cell and NK response during episodes of persistent and excessive activation of macrophages. The pathogenesis of HLH is related to defects in the regulatory pathways responsible for normal termination of the inflammatory response. The clinical signs and symptoms result from production of proinflammatory cytokines, mediated by uncontrolled activation of T-cells and antigen-presenting cells. The most common infectious trigger for HLH is viral infection. In this case, EBV was likely the primary cause, but the effects of concurrent PD-L1 inhibitor may have perpetuated the inappropriately prolonged T-cell activation, thereby facilitating the development of HLH.

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Subjects: Medical Skills ; Pathology

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