EBV-associated lymphomas in adults

Roschewski, Mark; Wilson, Wyndham H.

doi:10.1016/j.beha.2012.01.005

Cited by 68 publications

(52 citation statements)

References 90 publications

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“…In a series of lung transplant recipients with cystic fibrosis, 7 of the 8 patients with PTLD were R- [17]. However, in our study, all but 1 recipient were adults and most were EBV+, as are more than 90% of normal adults [18]. A systematic monitoring of EBV DNAemia in the follow-up of lung recipients is not recommended [19].…”

Section: Discussionmentioning

confidence: 96%

“…Seventy-three Hodgkin's lymphomas were identified in a cohort of 283,190 solid organ transplant recipients followed for a mean of 3.7 years [23]. These cases were often (79%) EBV+ [23] as are Hodgkin's lymphomas in immunocompetent hosts [18]. In this study, the risk was not elevated in the first 2 years, but increased monotonically over time especially among heart and/or lung transplant recipients [23].…”

Section: Discussionmentioning

confidence: 99%

“…It may not be feasible since the onset of PTLD may be very late and PTLD may occur in the absence of detectable EBV DNAemia [20]. Otherwise, the presence of EBV in the tumor represents a potential target for virus-directed therapies [18]. …”

Section: Discussionmentioning

confidence: 99%

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Lymphoproliferative Disorders after Lung Transplantation: Clinicopathological Characterization of 16 Cases with Identification of Very-Late-Onset Forms

Montpréville

Pavec²,

Ladurie³

et al. 2015

Respiration

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Background: The incidence of posttransplant lymphoproliferative disorders (PTLD) has recently declined, but late cases are increasingly reported in lung transplant recipients. Objectives: We present our experience with PTLD after lung transplantation, attempting to examine the distinguishing characteristics of early versus late cases. Methods: We have reviewed clinical and pathological data of all cases occurring in our institution between 2001 and 2014. Results: Patients, aged 15-63 years, were mostly (12/16) Epstein-Barr virus (EBV) seropositive at the time of transplantation. Eleven early cases, occurring 9.4 ± 5.2 months after transplantation and mostly (9/11) prior to 2010, had EBV+ diffuse large B-cell lymphomas. Lungs and/or thoracic lymph nodes were often involved (n = 8). Treatments included reduction of immune suppression (n = 11), rituximab (n = 8) and chemotherapy (n = 7). Two patients are in complete remission at 26 and 216 months. Nine patients died 8.0 ± 6.5 months after PTLD diagnosis. Of the 5 cases with late PTLD occurring 4-23 years (mean ± SD: 10.4 ± 7.7) after transplantation (and 3/5 after 2009), 1 had pulmonary lymphomatoid granulomatosis (only endothoracic case), 1 cutaneous large T-cell lymphoma, 2 had anaplastic large cell lymphomas, and 1 Hodgkin's disease. Two of the 5 cases were EBV-, including one followed by a second EBV+ PTLD after 8 years of complete remission. Two patients were alive and well (follow-up: 44 and 151 months), one having suffered from EBV-related cholestatic hepatitis 6 years after the PTLD. Conclusion: Our small experience shows a trend toward (very) late occurrence, associated with more unusual clinicopathologic features, but not with a worse prognosis.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Lymphoproliferative Disorders after Lung Transplantation: Clinicopathological Characterization of 16 Cases with Identification of Very-Late-Onset Forms

Montpréville

Pavec²,

Ladurie³

et al. 2015

Respiration

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“…In this way, it shares many clinical features with related lymphoproliferative disorders such as posttransplantation lymphoproliferative disease (PTLD). 7,8 Clinicians must be aware that even lower-grade cases of LYG can evolve into an aggressive lymphoma in up to 15% of cases 9 and the distinction between high-grade LYG and diffuse large B-cell lymphoma (DLBCL) can be subtle and are treated with similar strategies.…”

mentioning

confidence: 99%

Lymphomatoid Granulomatosis

Roschewski¹,

Wilson²

2012

The Cancer Journal

Self Cite

121

153

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Lymphomatoid granulomatosis (LYG) is a very rare Epstein-Barr virus (EBV)-driven lymphoproliferative disease. The atypical lymphoid cells directly accumulate within affected tissues and clinically present in the form of infiltrative lesions. It is usually a progressive disorder that virtually always involves the lung and characteristically presents as bilateral pulmonary nodules. Other commonly affected organ systems include the skin, central nervous system, and kidneys. The rareness of LYG in conjunction with its nonspecific presentation contributes to delays in diagnosis in many situations. Pathologically, it is characterized by the presence of an angiocentric and angiodestructive accumulation of varying numbers of T cells with varying numbers of atypical clonal EBV-positive B cells in a polymorphous inflammatory background. It can be subclassified using a grading system based on the number of EBV-positive large B-cell malignant cells, which is critical in selecting appropriate management strategies. Lower-grade LYG occasionally undergoes spontaneous remission and is best managed with strategies designed to enhance the host's underlying immune system, whereas high-grade LYG is best managed by combination chemoimmunotherapy but has inferior outcomes. Lymphomatoid granulomatosis can lead to progressive pulmonary failure, central nervous system disease, or progression to overt EBV-positive lymphoma without appropriate recognition and management. Improvements in the modern understanding of the biology of LYG, particularly the precise role of EBV in its pathogenesis, offer promise in the development of improved management strategies.

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“…11 Latency III program, in which all of the latency gene products are expressed, is often detected during acute infectious mononucleosis or in certain immunocompromised individuals. 11,38,39 This latency program, also known as growth program, while highly characteristic of immunosuppressed individuals, is only observed in 46% of our EBV-positive cases. This may be explained in part by the tendency to moderate the immunosuppressant regimens in these patients 40 and to the repression of EBNAs during plasma cell differentiation of latency III infected B cells.…”

Section: Discussionmentioning

confidence: 96%

In vivo intratumoral Epstein–Barr virus replication is associated with XBP1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications

et al. 2014

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Post-transplant lymphoproliferative disorders are life-threatening complications following hematopoietic or solid organ transplantation. They represent a spectrum of mostly EBV-driven lymphoplasmacytic proliferations. While the oncogenic effect of EBV is related to latent infection, lytic infection also has a role in lymphomagenesis. In vitro, EBV replication is linked to plasma cell differentiation and XBP1 activation, although this phenomenon has never been addressed in vivo. We analyzed for the first time latent and lytic intratumoral EBV infection in a series of 35 adult patients with a diagnosis of post-transplant lymphoproliferative disorder (26M/9F, median age 54 years). A complete EBV study was performed including the analysis of the latent EBER, latent membrane protein-11, and EBV nuclear antigens as well as the immediate-early BZLF1/ ZEBRA and early BMRF1/EADE31 lytic genes. XBP1 activation was assessed by nuclear protein expression. EBV infection was observed in 28 (80%) cases being latency II and III the most frequently observed 22 (79%). Intratumoral EBV replication was detected in 17 (60%) cases. Among these, XBP1 activation was observed in 11/12 evaluable cases associated with strong cytoplasmic immunoglobulin expression consistent with plasma cell differentiation. Intriguingly, the combination of latency III infection and EBV replication identified a high-risk subgroup of patients with significantly shorter survival (overall survival at 1 year 18% vs 48%) and early-onset (median of 7 vs 26 months) post-transplant lymphoproliferative disorder. Moreover, these patients appear to be more heavily immunosuppressed, so they exhibit lower rates of rejection and graft vs host disease but higher rates of cytomegalovirus reactivation. In conclusion, EBV replication is associated with plasma cell

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EBV-associated lymphomas in adults

Cited by 68 publications

References 90 publications

Lymphoproliferative Disorders after Lung Transplantation: Clinicopathological Characterization of 16 Cases with Identification of Very-Late-Onset Forms

Lymphoproliferative Disorders after Lung Transplantation: Clinicopathological Characterization of 16 Cases with Identification of Very-Late-Onset Forms

Lymphomatoid Granulomatosis

In vivo intratumoral Epstein–Barr virus replication is associated with XBP1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications

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