The ambiguous boundary between EBV-related hemophagocytic lymphohistiocytosis and systemic EBV-driven T cell lymphoproliferative disorder

• Published in: International journal of clinical and experimental pathology Vol. 7; no. 9; pp. 5738 - 5749
• Main Authors: Smith, Megan C, Cohen, Daniel N, Greig, Bruce, Yenamandra, Ashwini, Vnencak-Jones, Cindy, Thompson, Mary Ann, Kim, Annette S
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2014
• Subjects: Biopsy; Diagnosis, Differential; Epstein-Barr Virus Infections - diagnosis; Epstein-Barr Virus Infections - genetics; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - pathology; Epstein-Barr Virus Infections - virology; Female; Flow Cytometry; Herpesvirus 4, Human - isolation & purification; Humans; Immunohistochemistry; Karyotyping; Lymphohistiocytosis, Hemophagocytic - diagnosis; Lymphohistiocytosis, Hemophagocytic - genetics; Lymphohistiocytosis, Hemophagocytic - immunology; Lymphohistiocytosis, Hemophagocytic - pathology; Lymphohistiocytosis, Hemophagocytic - virology; Lymphoma, T-Cell - diagnosis; Lymphoma, T-Cell - genetics; Lymphoma, T-Cell - immunology; Lymphoma, T-Cell - pathology; Lymphoma, T-Cell - surgery; Lymphoma, T-Cell - virology; Original; Peripheral Blood Stem Cell Transplantation; Predictive Value of Tests; T-Lymphocytes - immunology; T-Lymphocytes - virology; Treatment Outcome; Young Adult; EBV-related T cell lymphoma; EBV-related HLH; clonal EBV-related HLH; Systemic EBV-positive lymphoproliferative disease of childhood; atypical T cell population
• ISSN: 1936-2625

Epstein Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (EBV-HLH) is a form of acquired, infection-related HLH which typically represents a fulminant presentation of an acute EBV infection of CD8+ T cells with 30-50% mortality rate. Systemic EBV-positive lymphoproliferative disease of childhood (SE-LPD) is a rare T cell lymphoproliferative disorder predominantly arising in the setting of acute EBV infection, often presenting with HLH. Since both entities have been associated with clonal T cell populations, the discrimination between these diseases is often ambiguous. We report a unique case of a 21 years old female who presented with clinical and laboratory findings of florid HLH in the setting of markedly elevated EBV titers (>1 million) and an aberrant T cell population shown to be clonal by flow cytometry, karyotype, and molecular studies. This case raises the differential of EBV-HLH versus SE-LPD. Review of the literature identified 74 cases of reported EBV-HLH and 21 cases of SE-LPD with associated HLH in 25 studies. Of those cases with available outcome data, 62 of 92 cases (67%) were fatal. Of 60 cases in which molecular clonality was demonstrated, 37 (62%) were fatal, while all 14 cases (100%) demonstrating karyotypic abnormalities were fatal. Given the karyotypic findings in this sentinel case, a diagnosis of SE-LPD was rendered. The overlapping clinical and pathologic findings suggest that EBV-HLH and SE-LPD are a biologic continuum, rather than discrete entities. The most clinically useful marker of mortality was an abnormal karyotype rather than other standards of clonality assessment.