Virus-positive Diffuse Large B-cell Lymphoma Research Articles

Aggressive Posttransplant Lymphoproliferative Disease in a Renal Transplant Patient Treated With Alemtuzumab

Post transplant lymphoproliferative disease (PTLD) is a rare but potentially fatal complication after solid organ transplantation. The risk of PTLD varies with type of organ transplant, Epstein-Barr virus serostatus of the donor and recipient, age, and intensity of immunosuppression. We report a case of a 45-year-old man who developed aggressive PTLD 7 months after receiving a cadaveric renal transplant. He received 30 mg alemtuzumab intravenously intraoperatively as induction immunosuppression followed by maintenance immunosuppression with tacrolimus and mycophenolate mofetil. The patient presented with intestinal perforation and gastrointestinal bleeding. Histopathology revealed Epstein-Barr virus-positive diffuse large B-cell lymphoma with a high mitotic index involving multiple segments of small and large intestines and leading to perforation of the ileum, jejunum, and cecum. The patient had Stage IV disease and treatment consisted of immunosuppression reduction and 375 mg/m rituximab weekly for four doses. Unfortunately, the patient had recurrent intestinal perforation followed by fatal gastrointestinal bleeding. There have been very few case reports of PTLD after alemtuzumab induction in renal transplant and the case discussed had simultaneous multiple perforations in the small intestine and colon.

Epstein-Barr virus-positive diffuse large B-cell lymphoma following peripheral T-cell lymphoma, not otherwise specified: report of a case

患者女,70岁.因自觉右耳后肿块3个月、持续低热1个多月于2008年7月入院.起病以来,患者纳差、乏力,体重明显减轻.体检:全身浅表淋巴结肿大.CT示双侧颈部、耳后、腋下、纵隔、腹股沟可触及多发肿大的淋巴结.实验室检查:红细胞3.38×1012/L,血小板计数96×109/L.骨髓涂片:骨髓增生活跃,粒系增生活跃,嗜酸细胞比例增高.取右腋下淋巴结活检。

Clinicopathological differences between EBV-positive and EBV-negative diffuse large B-cell lymphoma.

8083 Background: Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV-positive DLBCL) of the elderly is a new entity considered in the new WHO classification of lymphoid malignancies. EBV-positive DLBCL is a very aggressive entity with a short survival. Few data comparing the clinicopathological features between EBV-positive and EBV-negative DLBCL are available. Our study attempts to compare these characteristics and also identify prognostic factors. Methods: Between January 2002 and December 2009, 102 patients diagnosed with DLBCL were included in the analysis; 21 cases were EBV-positive and 81 cases were EBV-negative. Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the immunohistochemical expression of bcl-6, CD10, CD30 and MUM-1. Samples from patients were also analyzed for the presence of EBV-encoded RNA (EBER). Descriptive statistics were used to assess categorical and continuous variables. Survival curves for OS were estimated using the Kaplan-Meier method and compared using the log-rank test. For the multivariate analysis, the Cox proportional-hazard regression test was used. Results: Mean age for EBV-positive and EBV-negative patients was 73 and 65years, respectively (p=0.043). Sex, LDH levels, performance status, clinical stage, response to initial treatment and extranodal involvement were not significantly different between groups. The EBV status demonstrated a substantially poorer overall survival 3 months (95% CI, 0.0–2.6 months) and 15.5 months (1.0–43.0 months) in EBV-positive and EBV-negative, respectively (p=0.022). At the multivariate level, EBV status was an independent factor compared with the International Prognostic Index (IPI) score (p=0.001) with a 2.4-fold (95% CI, 1.2–4.8) risk for death for EBV-positive cases. In the EBV-positive group, a non-germinal center profile, the Oyama score and the IPI score were associated with survival. In the multivariate analysis only IPI score was significant (p=0.0045). Conclusions: EBV- positive DLBCL correlated with advanced age and a poor survival in comparison with EBV-negative DLBCL. The IPI score was a better prognostic tool than the Oyama score in EBV-positive patients. No significant financial relationships to disclose.

Ocular Involvement by Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma of the Elderly: A New Disease Entity in the World Health Organization Classification

Ocular Involvement by Epstein-Barr Virus–Positive Diffuse Large B-Cell Lymphoma of the Elderly: A New Disease Entity in the World Health Organization Classification

Epstein-Barr virus–positive diffuse large B-cell lymphoma in elderly patients is rare in Western populations

In the currently published World Health Organization-Classification, the new entity of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly was introduced largely based on findings from East-Asian populations. Little is known about its frequency or characteristics in the West, especially in European populations. Using a tissue microarray approach, we identified 8 out of 258 diffuse large B-cell lymphoma cases fulfilling the World Health Organization criteria of an Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly, suggesting an incidence of 3.1% in a European population. The median patient age was 65 years. The highest diagnostic sensitivity was only achieved by EBER in situ hybridization. No correlation between Epstein-Barr virus status and outcome was noted except in latency type 3 lymphomas, which had a very poor survival. Sixty-seven percent of Epstein-Barr virus-positive cases showed the presence of necrosis and 50% expressed the activation marker CD30. However, no morphological or immunohistochemical features reliably distinguished all Epstein-Barr virus-positive diffuse large B-cell lymphoma cases. Thus, to identify these Epstein-Barr virus-positive diffuse large B-cell lymphoma in the elderly, EBER in situ hybridization of all de novo diffuse large B-cell lymphoma cases of patients older than 50 years should be considered. In summary, Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly is rare in Europeans older than 50 years. It can only be diagnosed by EBER-ISH, and its precise prognostic role is unclear. Whether routine testing of all diffuse large B-cell lymphoma patients older than 50 years can be recommended depends essentially on its clinical relevance. Future studies are needed to address this question.

Primary central nervous system lymphoma after liver transplantation treated by radiosurgery combined with fractionated radiotherapy

Post-transplant primary central nervous system lymphoma is a rare malignant tumor. A 65-year-old man underwent orthotopic liver transplantation for liver carcinoma. Nine months later, he presented with left-sided motor weakness and MRI of the brain showed a rim-enhancing mass in the right paracentral area. The diagnosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma was confirmed through stereotactic biopsy. The authors report a case of post-transplant primary central nervous system lymphoma after liver transplantation that was treated successfully by gamma knife radiosurgery combined with fractionated whole brain radiotherapy.

Clinical characteristics and outcome for hepatitis C virus-positive diffuse large B-cell lymphoma

Several previous studies have addressed the association between hepatitis C virus (HCV) infection and non-Hodgkin lymphoma (NHL), but there are few studies on HCV-related diffuse large B-cell lymphoma (DLBL). We conducted this retrospective study to investigate the distinctive clinical characteristics and outcome for HCV-positive DLBL. We compared the clinical characteristics and outcomes of 32 HCV-positive DLBL cases from nine Korean institutions with those of 371 HCV-negative DLBL cases. A higher percentage of HCV-positive DLBL cases were associated with old age (≥60) than HCV-negative DLBL cases at diagnosis (59.4% vs. 36.1%, respectively, P = 0.009) and HCV-positive cases were less likely than HCV-negative cases to have extranodal involvement (53.1% vs. 71.1%, respectively, P = 0.044). The nodal presentation was the only independent factor favorably influencing the event free survival (EFS) in HCV-positive DLBL (HR = 0.11, 95% CI; 0.01 – 0.95, P = 0.012). In comparison to patients with HCV-negative DLBL, HCV-positive DLBL patients had a superior complete response rate (P = 0.023) and EFS (P = 0.02). In Korean patients, HCV-positive DLBL is more common with old age and has less extranodal involvement than does HCV-negative DLBL. The superior survival outcome for HCV-positive DLBL should be verified by further investigation, especially with respect to its correlation with transformed low-grade NHL.

Case 38: Central nervous system lymphoma in a patient previously treated for Wegener's granulomatosis

A 72-year-old woman with a past history of Wegener's granulomatosis presented with a primary central nervous system lymphoma; this was found to be an Epstein–Barr virus-positive diffuse large B-cell lymphoma.