Domingo Morales

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 of the elderly: A case series from Peru

EBV‐positive diffuse large B‐cell lymphoma (DLBCL) of the elderly is an entity recently included in the WHO classification of lymphoid tumors. We have reviewed our experience and clinical outcomes of this distinct subtype of DLBCL. Between 2002 and 2009, cases of DLBCL were identified from medical records of the Hospital Nacional Edgardo Rebagliati Martins in Lima, Peru, and underwent pathological evaluation including immunohistochemistry for CD20, CD10, bcl‐6, MUM1/IRF4, and EBV‐encoded RNA in situ hybridization. Clinical data were gathered, tabulated, and reported descriptively. Survival analyses were performed using Kaplan‐Meier estimates. Out of 199 cases of DLBCL, 28 cases of EBV‐positive DLBCL of the elderly were identified. The median age was 75 years with male predominance (1.5:1). B‐symptoms were present in 43%, advanced stage in 50% and International Prognostic Index (IPI) score > 2 in 57% of patients; 68% of patients had a nongerminal center (NGC) phenotype. The complete response rates to R‐CHOP and CHOP were 63% and 33%, respectively. The median overall survival (OS) for the group was 5 months. In the univariate analysis, age ≥70 years, lymphocyte count <1.0 × 109/L, and advanced clinical stage were associated with worse OS in patients treated with chemotherapy with and without rituximab. EBV‐positive DLBCL of the elderly is a clinically aggressive entity with a short OS and typically presents with advanced stage, high IPI score, and a NGC phenotype. Further studies are needed to investigate if rituximab‐containing regimens are associated with better response and OS rates in EBV‐positive DLBCL of the elderly. Am. J. Hematol. 86:663–667, 2011.

Epstein-Barr virus as a prognostic factor in de novo nodal diffuse large B-cell lymphoma.

Although the International Prognostic Index (IPI) score is a valuable prognostic tool in diffuse large B-cell lymphoma (DLBCL), other risk-stratifying factors may be of value. The aim of this study was to define the prognostic value of EBV expression in de novo nodal DLBCL. Seventy-four cases were selected between January 2002 and December 2007. Clinical data were reviewed and tissue samples were evaluated for expression of CD20, CD10, bcl-6, MUM1, and EBV-encoded RNA (EBER). Of 74 evaluated cases, 53 cases (72%) were of non-germinal center-like subtype and 11 cases (15%) were positive for EBER. In a univariate analysis of the 57 patients who received chemotherapy, factors associated with survival were EBV status, performance status, LDH level, and IPI score. Using a multivariate analysis, a prognostic model was developed using IPI score and EBV status, which showed statistical significance. Our study supports EBV status as a powerful prognostic factor in de novo nodal DLBCL. Prospective studies should be carried to validate this hypothesis.

EBV-Positive Diffuse Large B-Cell Lymphoma in Young Immunocompetent Individuals

Introduction The 2008 World Health Organization (WHO) classification of lymphoid neoplasms uses morphological, immunophenotypical, genetic, and clinical criteria to define more than 30 types of B-cell leukemia and lymphoma. The most common lymphoid neoplasm orldwide is diffuse large B-cell lymphoma (DLBCL), which acounts for approximately 30% of all lymphomas (including Band /NK-cell neoplasms). The category of DLBCL is heterogeneous nd encompasses a variety of clinicopathologic, immunophenotypic, nd molecular features. The clinical course of patients who have LBCL can be difficult to predict, which led to a search for clinical nd/or pathological factors that can be used to risk-stratify these atients, including the International Prognostic Index (IPI) score, immunophenotype, and a variety of high-throughput methods inluding gene expression, array comparative genomic hybridization, and microRNA profiling.

Lymphopenia as a prognostic factor in patients with peripheral T-cell lymphoma, unspecified

Peripheral T-cell lymphoma, unspecified (PTCLU) is the most common T-cell lymphoma variant. The molecular heterogeneity of PTCLU is reflected by a diverse clinical course. Several prognostic factors have been studied, but further refinement is needed. The aim of our study was to retrospectively evaluate the presence of lymphopenia, defined as a lymphocyte count of <1000 cells/mm3, as a prognostic factor for survival in patients with PTCLU. Sixty-nine cases with a pathological diagnosis of PTCLU were included in our analysis. Lymphopenia was seen in 38% of the patients and was statistically associated with a worse response to chemotherapy. In univariate analysis, lymphopenia, IPI score >2, and Prognostic Index for PTCLU (PIT) score >2 were associated with a worse overall survival. In multivariate analysis, lymphopenia and a PIT score >2 were the only independent poor prognostic factors, implying an important role of the patients immune system in both response to therapy and survival.

Different prognostic factors for survival in acute and lymphomatous adult T-cell leukemia/lymphoma

INTRODUCTION Adult T-cell leukemia/lymphoma (ATLL) is a clinically aggressive and heterogeneous entity; hence it is likely that different variants of ATLL have different prognostic factors. METHODS 95 patients with ATLL seen at our institution between 1987 and 2008 were included. Clinical data were compared, according to ATLL variant, using the Mann-Whitney and the Chi-square tests for continuous and categorical variables, respectively. Kaplan-Meier estimates compared using the log-rank test and Cox proportional-hazard test were used for the univariate and multivariate analysis, respectively. RESULTS Median age was 61 years with male-to-female ratio of 1.07:1. Patients with acute ATLL were more likely to present with bone marrow, liver and spleen involvement, higher β2-microglobulin and lower albumin levels. Poor performance status, high IPI score, presence of B symptoms, high LDH and low albumin levels were associated with a worse survival in lymphomatous ATLL. High LDH, high β2-microglobulin and high PIT score were associated with worse survival in acute ATLL. In the multivariate analysis, low albumin level and presence of B symptoms were independent factors for worse survival in lymphomatous ATLL, and high β2-microglobulin level was independent factor for worse survival in acute ATLL. CONCLUSIONS Aggressive ATLL variants have a distinct, almost mutually exclusive profile of prognostic factors.

The neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with peripheral T-cell lymphoma, unspecified

Peripheral T-cell lymphoma (PTCL) encompasses a group of rare and aggressive lymphomas. PTCL, unspecified (PTCLU) is the most common subtype of PTCL, and carries a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCLU (PIT) scoring systems are powerful risk-stratification tools in patients with PTCL. The aim of this study was to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is a prognostic factor in PTCLU. We retrospectively studied 83 patients with diagnosis of PTCLU. In the univariate analysis, NLR ≥ 4 was associated with worse overall survival (HR 3.96, 95% CI 1.92–8.17; p < 0.001). In the multivariate analysis, NLR ≥ 4 was independently associated with worse overall survival after adjustment for the PIT score (HR 4.30, 95% CI 1.90–9.69; p < 0.001), and for the IPI score (HR 2.60, 95% CI 1. 12–6.04; p = 0.03). Our study suggests the NLR could be helpful in refining the survival prognostication in patients with PTCLU.

Follicular lymphoma with leukemic phase at diagnosis: A series of seven cases and review of the literature

Follicular lymphoma (FL) is a prevalent type of non-Hodgkin lymphoma in the United States and Europe. Although, FL typically presents with nodal involvement, extranodal sites are less common, and leukemic phase at diagnosis is rare. There is mounting evidence that leukemic presentation portends a worse prognosis in patients with FL. We describe 7 patients with a pathological diagnosis of FL who presented with a leukemic phase. We compared our cases with 24 additional cases reported in the literature. Based on our results, patients who present with leukemic FL tend to have higher risk disease. Leukemic FL also seems to be associated with a worse prognosis; however, larger studies are needed to confirm our findings. A discrepancy with previously reported cases of FL in leukemic phase raises the possibility of differences attributable to geographic regions.

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.

Peripheral T-cell lymphoma with a regulatory T-cell phenotype: Report of a nodal and an extranodal case from Peru

T-cell regulatory lymphocytes (T reg) are identified by their reactivity with CD4, CD25, and FOXP3, and are variably present in the background of various neoplasms including hematopoietic tumors, and function modulating the immune response, including control of autoimmunity. Adult T-cell leukemia/lymphoma is an aggressive lymphoma associated with human T-lymphotrophic virus 1 infection characterized by the presence of neoplastic lymphocytes with a T reg phenotype; however, this phenotype is not characteristically found in other lymphomas. Here, we report 2 apparently immunocompetent human T-lymphotrophic virus 1-negative patients with nodal and extranodal peripheral T-cell lymphoma, not otherwise specified with a T reg immunophenotype, based on the strong CD25 and FOXP3 positivity of the neoplastic cells. One patient was a 48-year-old woman with an early stage tumor in the cavum, who despite of chemotherapy subsequently developed systemic disease and died of tumor progression 46 months from diagnosis. The second patient was a 65-year-old male with generalized adenopathy and B symptoms who received chemotherapy achieving a complete remission but had recurrence and died 36 months from diagnosis. The histopathology revealed a diffuse infiltrate with an interfollicular distribution in the second case, with nodal involvement, consisted of large cells with clear cytoplasm associated with vascular proliferation and abundant mitoses. Neoplastic cells of first case showed typical T reg phenotype, whereas the second case had a CD4/CD8 double negative T reg variant. Only a single similar case was found in a review of the literature. We conclude that peripheral T-cell lymphoma, not otherwise specified with a T reg phenotype may represent a distinct category of T-cell lymphoma with an aggressive clinical course and poor prognosis.