Altaf et al. Journal of Medical Case Reports 2012, 6:141 http://www.jmedicalcasereports.com/content/6/1/141 C A S E R E P O R T JOURNAL OF MEDICAL CASE REPORTS Open Access Diffuse large B-cell lymphoma in an adolescent female presenting with Epstein-Barr virus-driven hemophagocytic lymphohistiocytosis: a case report Sadaf Altaf1, Grace M Atreaga2, Avni Y Joshi3 and Vilmarie Rodriguez1* Abstract Introduction: Hemophagocytic lymphohistiocytosis is characterized by multisystem inflammation, resulting from prolonged and intense activation of macrophages, histiocytes and CD8+ T-cells. Due to its variable presentation and non-specific findings, timely diagnosis can be challenging. This condition has been associated with malignancies, most commonly with lymphomas and leukemias of T-cell lineage. This case report represents the less commonly associated B-cell lymphomas. We also highlight the difficulties in managing hemophagocytosis with an evolving malignancy. This case report will add to the increasing literature on the diagnosis, complications and management of this complex disorder. Case presentation: A 15-year-old Caucasian girl, previously diagnosed with Crohn’s disease and treated with 6- mercaptopurine, developed Epstein-Barr virus infection-driven hemophagocytic lymphohistiocytosis. The diagnosis was challenging due to her critical illness and the lack of enough features to fulfill diagnostic criteria at presentation (moderately elevated ferritin, normal coagulation profiles and normal triglycerides). While receiving therapy for hemophagocytic lymphohistiocytosis, she developed bulky cervical lymphadenopathy and was diagnosed with diffuse large B-cell lymphoma. Therapy for lymphoma was initiated and she tolerated the therapy well. Conclusion: Hemophagocytic lymphohistiocytosis is a rare disorder, but potentially lethal if not diagnosed and treated in a timely manner. Our case highlights the importance of considering this diagnosis in critically ill patients who may not initially fulfill formal diagnostic criteria. In patients diagnosed with hemophagocytic lymphohistiocytosis, occult malignancies should be aggressively ruled out as they can manifest prior to the hemophagocytic lymphohistiocytosis diagnosis or appear during the treatment phase. An accurate diagnosis is also important because management of Epstein-Barr virus-driven hemophagocytic lymphohistiocytosis and Epstein-Barr virus-driven lymphoma differs due to the difference in pathophysiology and the involvement of different immune cell lines. Introduction Hemophagocytic lymphohistiocytosis (HLH) is charac- terized by multisystem inflammation, resulting from pro- longed and intense activation of macrophages, histiocytes and CD8+ T-cells. Minimal clinicopathologic criteria for the diagnosis of HLH, established by the Histiocyte * Correspondence: rodriguez.vilmarie@mayo.edu 1Division of Pediatric Hematology/Oncology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st Street SW, Rochester MN 55905, USA Full list of author information is available at the end of the article Society [1], include demonstration of a genetic alteration consistent with HLH or demonstration of at least five of the following eight criteria: fever, splenomegaly, cytopenia (affecting two or more cell lines), hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis, low or absent natural killer (NK) cell cytotoxicity, an increased ferritin level and an increased level of soluble interleukin-2 recep- tor (sCD25) [1]. Two forms of HLH are classically described; primary and secondary. Primary or inherited HLH is an autosomal recessive disorder. Rarely, it can be seen as an X-linked © 2012 Altaf et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.