Gequelin LC, Riediger IN, Nakatani SM, Biondo AW, Bonfim CM Hodgkin's lymphoma There is a strong association between Hodgkin's lymphoma (HL) and EBV infection, although its role in this disease's pathogenesis is not fully clarified. The virus has been found in around 40% of HL tumors.(18) Cases in children and the elderly are generally associated with EBV, while adults with HL are more frequently EBV-negative.(19) The histological diagnosis differs from that of other lymphomas because it shows mononuclear Hodgkin's cells and their multinuclear variants known as Reed-Sternberg cells.(19) These two cell types are derived, in the majority of cases, from B cells. Plasmatic viral load can be quantified in virtually all EBV-positive HL patients before treatment and the response to therapy is associated to the reduction in viral load.(18) These data suggest that the analysis of plasmatic DNA through real-time PCR is an excellent tool for the prognosis and monitoring of HL patients.(2) Non-Hodgkin lymphoma Although overall non-Hodgkin lymphoma (NHL) rates are high, there is a great variety of types of these lymphomas and a variation of incidence between countries. In general, only 5% of the tumors are EBV-positive. This ratio rises up to 40%, however, in AIDS-related cases.(20) Enlarged cervical, axillary and/or inguinal ganglia, excessive nocturnal sudoresis, fever, itchy skin and weight loss without apparent reason must be investigated by the physician.(21) Burkitt's lymphoma At present, Burkitt's lymphoma (BL) represents a subset of NHL and is a type of tumor composed of small malignant B lymphocytes. It can be classified in two types: endemic and sporadic. In the endemic type, there are three factors that contribute to its development: malaria, EBV, and the expression of the c-myc gene. The disease affects children in Equatorial Africa and New Guinea (malaria endemic zone), and frequently the tumor starts in the jaw. It is known that malaria causes T cell immunodeficiency, reducing the control over the proliferation of EBV-infected B cells. Over 95% of African patients with BL were previously infected by EBV.(19) In the sporadic variant of BL, although histologically similar to the endemic form, only between 20 and 30% of tumor cells carry the EBV genome.(22) It is important to note that, in the AIDS-related sporadic variant, 30-40% of the tumors are EBV-positive.(23) Post-transplant lymphoproliferative disease Post-transplant lymphoproliferative disease (PTLD) occurs due to the iatrogenic suppression of T cell functions(24) and is characterized by an abnormal proliferation of B cells.(5) 384 The main risk factors are post-transplant primary infection, previous splenectomy, second transplant, patient age, acute or chronic graft-versus-host disease (GvHD), co-infection by cytomegalovirus or other viruses, regimen and intensity of immunosuppression therapy (use of anti-thymocyte globulin - ATG), T cell depletion,(25) transplants with HLA disparity(26) and EBV-negative recipient with EBV-positive donor.(7) The use of umbilical cord blood as a source of cells for allogeneic transplants also increases the risk of PTLD. Explanations include the low quality of T cells from cord blood, donor-recipient HLA incompatibility and/or partial compatibility and the use of ATG.(27) PTLD pathogenesis differs between hematopoietic stem cell transplantation (HSCT) and solid-organ transplantation (SOT). As immunosuppression in SOT has to be maintained throughout the patient's life, there is a constant risk of PTLD. The incidence varies according to the transplanted organ. The following rates are reported: intestines and multiple organs - 11 to 13%; lungs - 2 to 9%; heart - 2 to 6%; liver - 1 to 3%; and kidney - 1%.(28,29) One explanation may be related to the type and intensity of the immunosuppressive regime.(7) A multicentric study of 26,901 patients submitted to HSCT suggested a high rate of PTDL in over 50-year-old individuals and also in patients submitted to a second transplant. Other risk factors were also taken into consideration, such as T cell depletion, partial HLA combination, and acute or chronic GvHD. The study in question divided the patients in four groups and calculated the disease rates: individuals without important risk factors, patients with one, two, or more risk factors. The incidences of PTLD were 0.2, 1.1, 3.6 and 8.1%, respectively.(30) The highest frequency of this complication occurs in children and it is often reported during the first year post- transplant with a high incidence during the first six months. It can also happen later, however, as late as ten years after the transplant.(6,25,31) The disease encompasses a great diversity of pathological conditions that often makes the development of a standard classification system difficult.(7) There can be a predominance of monomorphic or polymorphic T and B cells. It can present itself as a self-limited lympho- proliferation or as a fulminant disease, and be localized or of ample dissemination.(32) Despite the variants, the World Health Organization (WHO) recommends its classification in four categories: (a) initial lesions; (b) polymorphic PTLD; (c) monomorphic (lymphomatous) PTLD; (d) classical Hodgkin's lymphoma-type PTLD.(5,7,28) There are several forms of treatment: interventions can be preventive, or start at the moment of identification of a probable or proven EBV-caused disease.(6) Treatment is based on the reduction or removal of the immunosuppressive therapy, the use of anti-CD20 antibody (rituximab), antiviral drugs and, when necessary, conventional antineoplastic therapy.(25) Rev Bras Hematol Hemoter. 2011;33(5):383-8