Discrimination of Epstein-Barr virus-related posttransplant lymphoproliferations from acute rejection in lung allograft recipients

Organ allograft recipients have a propensity to develop Epstein-Barr virus-associated posttransplant lymphoproliferative disorders (PTLDs). This is especially true of lung allograft recipients, who have an unusually high incidence of 8% and a predilection for developing PTLD in the allograft. Distinction of PTLD from acute cellular rejection by transbronchial biopsy, the standard means of monitoring the status of the lung allograft, may be difficult but is of clinical importance because of the different therapeutic strategies used to treat Epstein-Barr virus-related PTLD and rejection. To discriminate these two entities, we analyzed transbronchial biopsies from 11 cases of acute cellular rejection and one case of PTLD, and open lung biopsies from four cases of PTLD in the allograft of lung transplant recipients. Areas of particular interest were the main tumor mass of the PTLD and the pulmonary parenchyma adjacent to the mass where perivascular mononuclear infiltrates predominated and mimicked acute cellular rejection. The specimens were examined by routine histochemistry and immunohistochemistry for B- and T-cell antigens and Epstein-Barr virus latent membrane protein expression. The main tumor mass in the PTLD cases revealed consolidation of lung parenchyma by a monomorphous lymphocytic infiltrate, which was composed of large lymphoid cells that marked as B lymphocytes. The acute cellular rejection cases and peripheral areas of the PTLD lesions were composed of polymorphous, perivascular lymphocytic infiltrates with similar numbers of B and T cells. All cases of PTLD, both the main mass and the peripheral infiltrates, had lymphocytes that stained positively with antibody to Epstein-Barr virus latent membrane protein. None of the acute cellular rejection cases was positive with this antibody. While a sheetlike monomorphous infiltrate with a mononuclear composition of more than 25% B cells and more than 30% large lymphoid cells favored PTLD over acute cellular rejection, positive immunohistochemical stains for Epstein-Barr virus latent membrane protein are most helpful in separating PTLD from acute rejection when this differential diagnosis arises in small biopsy samples.