Autopsy pathology of pediatric posttransplant lymphoproliferative disorder

Objectives. Posttransplant lymphoproliferative disorder (PTLD) causes signi ficant morbidity and mortality, is related to Epstein-Barr virus (EBV) infe ction, and is more common in children than in adults. We reviewed autopsies of children who died with PTLD to compare postmortem with antemortem PTLD histology, to assess the extent of PTLD, to document associated pathology, and to identify cause of death. Methods. Postmortem examinations were performed on 7 patients after bone ma rrow (n = 3) or liver (n = 4) transplant. PTLD was classified histologicall y as hyperplasia or lymphoma. In situ hybridization for EBER1 messenger RNA was performed on tissue samples from all cases. EBV serologies were used t o categorize infections as negative, primary, or reactive. Results. PTLD was diagnosed in 5 children 12 to 35 (mean: 22) days before d eath, and 1.5 to 4 (mean: 3) months after transplant; PTLD was diagnosed in 2 cases at autopsy 2.5 and 4 months after transplant. Postmortem PTLD hist ology resembled antemortem histology; 5 PTLDs were lymphoma, 1 was hyperpla sia, and 1 contained both lymphoma and hyperplasia. EBER1 messenger RNA was detected in 6 B-cell PTLDs, including lesions from patients who did not ha ve EBV serology that indicated active infection. Complete autopsy of 4 pati ents who died with biopsy-proven PTLD revealed widely disseminated disease, and lymph node, brain, gastrointestinal tract, and kidney were involved in all 4 patients. Cases diagnosed at autopsy were 1 widely disseminated PTLD that had been suspected but not proven antemortem, and 1 PTLD confined to abdominal lymph nodes that was not suspected antemortem. Severe organ dysfu nction (renal failure, gastrointestinal hemorrhage) was caused by massive P TLD infiltration in 2 patients. The conditions other than PTLD that contrib uted to morbidity and death were organ infection (5 cases), infarcts (4 cas es), and diffuse alveolar damage (3 cases). Conclusions. PTLD may occur within weeks after transplant in children. The distribution of PTLD comprises a spectrum from localized and subclinical to demise quickly after the onset of signs and symptoms, through massive orga n infiltration or associated conditions, such as diffuse alveolar damage. E BV serology may not accurately reflect the presence or extent of PTLD. Auto psy studies of transplant patients are necessary to identify the true incid ence, natural history, and response to treatment of PTLD.