Renzo Salas

ALK-positive diffuse large B-cell lymphoma: report of four cases and review of the literature

BackgroundAnaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-DLBCL) is a rare lymphoma with several clinicopathological differences from ALK-positive anaplastic large cell lymphoma (ALCL). The latest WHO classification of lymphomas recognizes ALK-DLBCL as a separate entity.MethodsA comprehensive comparison was made between the clinical and pathological features of the 4 cases reported and those found in an extensive literature search using MEDLINE through December 2008.ResultsIn our series, three cases were adults and one was pediatric. Two cases had primary extranodal disease (multifocal bone and right nasal fossa). Stages were I (n = 1), II (n = 1), III (n = 1) and IV (n = 1). Two cases had increased LDH levels and three reported B symptoms. IPI scores were 0 (n = 1), 2 (n = 2) and 3 (n = 1). All cases exhibited plasmablastic morphology. By immunohistochemistry, cases were positive for cytoplasmic ALK, MUM1, CD45, and EMA; they marked negative for CD3, CD30 and CD20. Studies for EBV and HHV-8 were negative. The survival for the patients with stage I, II, III and IV were 13, 62, 72 and 11 months, respectively.ConclusionALK-DLBCL is a distinct variant of DLBCL with plasmacytic differentiation, which is characterized by a bimodal age incidence curve, primarily nodal involvement, plasmablastic morphology, lack of expression of CD20, aggressive behavior and poor response to standard therapies, although some cases can have prolonged survival as the cases reported in this study. ALK-DLBCL does not seem associated to immunosuppression or the presence of EBV or HHV8. Further prospective studies are needed to optimize therapies for this entity.

EBV-positive diffuse large B-cell lymphoma in a human T-lymphotropic virus type 1 carrier

The development of B-cell lymphomas has been seldom described in HTLV-1 carriers. We present the case of an elderly Peruvian HTLV-1 carrier who was diagnosed with EBV-positive diffuse large B-cell lymphoma. Despite an initial good response to therapy, patient died during treatment due to fatal Pneumocystis jirovecci pneumonia. EBV infection is characterized by B-cell lymphotropism and selective immunodeficiency. HTLV-1, on the other hand, induces T-cell dysfunction and B-cell proliferation. Finally, immunosenescence is characterized by T-cell dysregulation, decreased apoptosis and cytokine upregulation. In this elderly patient, the combination of EBV and HTLV-1 coinfection and immunosenescence may have played a role in the development of this aggressive diffuse large B-cell lymphoma. Furthermore, the immunodeficiency caused by the viral infections and chemotherapy may have played a role in developing life-threatening infectious complications.

Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone: report of two cases from South America

Epstein–Barr virus (EBV)-positive diffuse largeB-cell lymphoma (DLBCL) of the elderly is a novelentity included in the World Health Organization(WHO) classification of hematopoietic and lymphoidtumors [1]. EBV-positive DLBCL of the elderly is avery aggressive disease that occurs more frequently inpatients older than 50 years and presents withfrequent extranodal involvement and the presenceof EBV in tumoral cells. The prognosis is poor andthe survival is short [2]. A few studies have reportedlower response rates to conventional anthracycline-based chemotherapy in comparison with responsesseen in EBV-negative patients with DLBCL [2,3],but there are no data on EBV-positive DLBCL of theelderly treated with rituximab in combination withchemotherapy. In this letter, we present two cases ofEBV-positive DLBCL of the elderly with a goodinitial response to the combination of rituximab,cyclophosphamide, doxorubicin, vincristine, andprednisone (R-CHOP).Our first case is a 74-year-old man without asignificant past medical history and an EasternCooperative Oncology Group (ECOG) performancestatus of 1. One week prior to admission, hedeveloped progressive colicky abdominal pain andbloating. He denied B symptoms. An intestinalobstruction was suspected and a 464 cm ilealmass was identified. The patient underwent a partialileal resection. Pathological studies revealed alymphoproliferative process with monomorphic ap-pearance and scattered areas of necrosis. Based onimmunohistochemical studies, the sample was mostconsistent with a CD20-positive diffuse large B-celllymphoma with a non-germinal center (NGC)phenotype (CD10 negative, BCL6 negative, andMUM1 positive). Expression of CD30 and BCL2was negative, and Ki67 expression was 80%. EBV-encoded RNA (EBER) in situ hybridization (ISH)was positive in the tumoral cells (Figure 1). Furtherstaging showed a 2 cm mass in the lower lobe of theright lung. A bone marrow biopsy was negative forlymphomatous involvement, and lactate dehydro-genase (LDH) levels were within normal limits. Thepatient was diagnosed with stage IVA EBV-positiveDLBCL of the elderly. His International PrognosticIndex (IPI) score was 3. The patient received sixcycles of R-CHOP administered every 21 days withgrowth factor support. At the end of treatment, therewas no evidence of disease. Unfortunately, 12months after his initial diagnosis, the patient pre-sented with seizures, and a computed tomography(CT) scan of the brain showed multiple parenchymallesions consistent with relapsed lymphoma. Thepatient underwent brain irradiation with radiological