Posttransplantation Lymphoproliferative Disorders

PTLD are frequently difficult to classify based on morphology alone, and frequently expert hematopathologists cannot agree on classification. Therefore, a strict molecular classification would be ideal. Correlation between molecular alterations and outcome appears to exist for lesions occurring in SOT recipients14 but not in those occurring after BMT.13 Assessment of the presence of EBV is an important first step for the diagnosis of PTLD, since this virus is present in approximately 95% of cases, and the pathogenesis and clinical outcome of EBV-negative post-transplant lymphomas appear to be different.15,16 Study of clonality (by IGH rearrangement or EBV terminal repeat analysis) also is important for understanding the nature of the lesions and confirming a diagnosis of PTLD as opposed to reactive hyperplasia or rejection (if the infiltrate involves the allograft). Monoclonal rearrangements are common in both polymorphic and monomorphic PTLD, and their presence is sometimes useful in distinguishing these from PH, which usually shows a polyclonal pattern. Clonality analysis also is useful to determine whether multiple lesions are clonally related by having the same size rearrangement or EBV terminal repeats, which is not always the case in PTLD patients, who frequently have separate tumors that represent independent clonal expansions. The presence of structural alterations in oncogenes (MYC, NRAS) or tumor suppressor genes (TP53), or both, is usually indicative of a high-grade or monomorphic lesion. Analysis for mutations in the BCL6 gene also predicts clinical outcome of PTLD in SOT patients but not in BMT patients. A model of tumor progression in SOT PTLD is shown in Figure 34-1.

Quantitative analysis of peripheral blood or serum EBV in transplant patients is helpful in identifying patients at risk for PTLD.17-20 In addition, several recent studies suggest a correlation between tumor burden and viral loads, so quantitative EBV testing may be useful in monitoring response to therapy once PTLD develops.21-23

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