First recognized in 1968, post-transplantation lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoid proliferations that have been described in patients status post lung, heart, bone marrow, and kidney transplantation. The disorder is thought to be due to immunosuppression with loss of normal control over proliferation of Epstein-Barr virus (EBV) immortalized B-cell lymphocytes as a result of loss of T-cell lymphocyte control. Patients who are seronegative for EBV prior to transplantation are more susceptible to developing PTLD early in the post-transplant period, implying newly acquired infection rather than reinfection or reactivation of latent infection. Reversal of the disorder has been documented once immunosuppression has been reduced.

PTLD may present as systemic disease or only involve the transplanted lungs. Most cases occur within the first couple of years post-transplant. Involvement of the lungs can be clinically asymptomatic or patients may present with fever, cough, and respiratory compromise. Single or multiple nodules or diffuse infiltrates are seen radiographically, with lung tissue biopsies showing lymphoid hyperplasias, features of lymphoid interstitial pneumonia, or overt lymphoma. Examination of the tissue is performed to determine cell phenotype and immunoglobulin clonality (immunohistochemistry, flow cytometry) and presence of EBV (immunohistochemistry or in situ hybridization). Classification of PTLD is currently based on the recommended World Health Organization (WHO) classification scheme, which delineates four categories: early lesions (reactive plasmacytic hyperplasia, infectious mononucleosis); polymorphic PTLD; monomorphic PTLD (usually lymphomas—B-cell and T-cell with further subclassification the same as with the lymphoma classification); and other uncommon types of lymphocytic proliferations (plasmacytoma-like or Hodgkin disease-like lesions).