Brady Beltran

Breast Implant–Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients

PURPOSE Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. PATIENTS AND METHODS We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. RESULTS The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). CONCLUSION Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.

Human immunodeficiency virus-associated plasmablastic lymphoma: Poor prognosis in the era of highly active antiretroviral therapy

Plasmablastic lymphoma (PBL) is a rare and aggressive B‐cell lymphoma strongly associated with human immunodeficiency virus (HIV) infection. The authors conducted a multi‐institutional, retrospective study to describe characteristics and determine prognostic factors in HIV‐associated PBL.

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.

The Hans algorithm is not prognostic in patients with diffuse large B-cell lymphoma treated with R-CHOP.

Our objective was to evaluate the non-germinal center (GC) profile as a marker for response and survival in DLBCL and to compare the characteristics of patients with GC and non-GC DLBCL treated with rituximab-containing regimens. In this patient-level meta-analysis, retrospective data from 712 newly diagnosed DLBCL patients treated with chemoimmunotherapy from 7 centers were analyzed. GC and non-GC profiles were defined according to the Hans algorithm. Although the non-GC profile showed a trend towards worse overall survival (HR 1.24, 95% CI 0.92-1.66; p=0.15) and progression-free survival (HR 1.29, 95% CI 0.96-1.73; p=0.09), it did not retain its value in the multivariate survival analysis. Additionally, the non-GC profile was independently associated with worse complete response rates (OR 0.55, 95% CI 0.37-0.83; p<0.01) in the multivariate logistic regression analysis. Interestingly, Asian patients had higher proportion of GC DLBCL (p=0.01).

EBV-positive diffuse large B-cell lymphoma of the elderly: 2016 update on diagnosis, risk-stratification, and management

Epstein–Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid neoplasms. It is a disease typically seen in the elderly and thought to be associated with chronic EBV infection and severe immunosuppression with a component of immunosenescence. Recent research, however, has suggested that EBV‐positive DLBCL can be seen in younger, immunocompetent patients.

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.