Tabanelli et al. Journal of Medical Case Reports 2011, 5:218 http://www.jmedicalcasereports.com/content/5/1/218 Page 3 of 5 Figure 2 Pathological findings on lymph node biopsy. CD3, CD8, CD56, TIA1 immunostains and Epstein-Barr encoded RNA (EBER) in situ hybridization are shown. A second bone marrow biopsy was performed, reveal- ing (hypo)aplasia with a minimum percentage of CD79a- , CD3+, CD4-, CD8+, EBER- small lymphocytes and absence of the previously observed CD8+ large cells. VP16 was then replaced with cyclosporine, obtaining a white blood cell count increase and a further decline of splenomegaly, but with no improvement in thrombocy- topenia. A third bone marrow biopsy showed an increased cellularity with reappearance of numerous CD8+ lymphocytes and evident hemophagocytosis. Our patient then developed rectal hemorrhages only treatable with surgery, which turned out to be sustained by microvascular thrombosis on histological examina- tion. Finally, after a short period of relative good health, our patient had a relapse of rectal bleeding and died soon after with cerebral manifestations. Discussion Systemic EBV+ T cell LPD of childhood is a rare disor- der characterized by an aggressive disease course and dismal prognosis [5]. As death unfortunately often occurs within a few weeks, and at present there is no specific treatment, a prompt diagnosis is necessary. Our case report highlights the fact that, though rare, such a disease can occur also in Europe. On reviewing the literature, we found only 14 cases reported in Western countries [6,11-14], specifically cases recorded in Europe and the USA (Table 1). Inter- estingly, the majority of cases have been reported in eastern Asia [5], specifically in Japan and Taiwan. The geographical distribution has been suggested to indicate possible genetically determined defects in T cell responses to EBV in certain populations. Our review of Western cases showed that four of those 14 patients developed a T cell LPD after CAEBV infection [6,11], and 10 presented a fulminant EBV T cell LPD following acute EBV infection. In the former group, ethnic origin was specified only in one case (white); in the latter group, one patient was of Cauca- sian descent, four were Asian or Native American, while in five cases the ethnic group was not specified. Mean age at onset was 17 years and the male/female ratio was 2.3:1. Common symptoms were fever, hepatosplenome- galy and hematophagocytic syndrome; the clinical courses were fulminant in patients with T cell LPD after acute IM. In particular, in the acute IM group three cases had a CD8+ phenotype, two a CD4+ phenotype and one showed double positivity for CD8 and CD4; in one case phenotype was not interpretable and in three cases it was not reported. TCRa presented with clonal rearrangements in nine out of 10 patients and EBV gen- ome was clonal in all but one case. In contrast, among patients with T cell LPD after CAEBV infection two were CD4+, one was CD45RO+ and one presented with an admixture of CD8+ and CD4+ lymphocytes; three cases presented with monoclonal patterns with regard to rearrangement of both TCRa genes and EBV genome. In the remaining case, only the EBV positivity was assessed. In all described cases, an accurate diagnostic investiga- tion including clinical, morphological, immunohisto- chemical, and molecular analyses was necessary in order to formulate a correct diagnosis. In particular, the differ- ential diagnosis with aggressive NK cell leukemia was based on surface sCD3 and CD8 positivity, CD56 nega- tivity, and evidence of TCRa rearrangement in systemic EBV+ T cell LPDs, and also sCD3/CD8 negativity, CD56 positivity and germline TCRa patterns in aggressive NK cell leukemia cases. Conclusion In conclusion, our case report underlines the impor- tance of a comprehensive diagnostic approach in the management of atypical EBV+ LPDs. In fact, though, at present, specific therapies are not available, the correct