Autopsy Pathology of Pediatric Posttransplant Lymphoproliferative Disorder

Abstract

ABSTRACT. Objectives. Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality, is related to Epstein-Barr virus (EBV) infection, 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 marrow (n ‫؍‬ 3) or liver (n ‫؍‬ 4) transplant. PTLD was classified histologically as hyperplasia or lymphoma. In situ hybridization for EBER1 messenger RNA was performed on tissue samples from all cases. EBV serologies were used to categorize infections as negative, primary, or reactive.Results. PTLD was diagnosed in 5 children 12 to 35 (mean: 22) days before death, 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 histology resembled antemortem histology; 5 PTLDs were lymphoma, 1 was hyperplasia, and 1 contained both lymphoma and hyperplasia. EBER1 messenger RNA was detected in 6 B-cell PTLDs, including lesions from patients who did not have EBV serology that indicated active infection. Complete autopsy of 4 patients 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 dysfunction (renal failure, gastrointestinal hemorrhage) was caused by massive PTLD infiltration in 2 patients. The conditions other than PTLD that contributed to morbidity and death were organ infection (5 cases), infarcts (4 cases), 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 widely disseminated and symptomatic. PTLD may cause demise quickly after the onset of signs and symptoms, through massive organ infiltration or associated conditions, such as diffuse alveolar damage. EBV serology may not accurately reflect the presence or extent of PTLD. Autopsy studies of transplant patients are necessary to identify the true incidence, natural history, and response to treatment of PTLD. Pediatrics 2001;107(6). URL: http:// www.pediatrics.org/cgi/content/full/107/6/e89; posttransplant lymphoproliferative disorder, autopsy, pediatric pathology, Epstein-Barr virus, lymphoma, mortality.ABBREVIATIONS. PTLD, posttransplant lymphoproliferative disorder; EBV, Epstein-Barr virus; CHOP, Children's Hospital of Philadelphia; LMP, latent membrane protein; Ig, immunoglobulin; VCA, viral capsid antigen; GI, gastrointestinal; PCR, polymerase chain reaction. P osttransplant lymphoproliferative disorder (PTLD) is related to Epstein-Barr virus (EBV)infecti...

The post-transplant lymphoproliferative disorder?a literature review

“…Infectious mononucleosis or benign hyperplasia-the mildest form manifesting clinically with fever, tonsillar and/or adenoidal hypertrophy, and cervical lymphadenopathy. On histology the nodal architecture is maintained [47]. The first two stages are relatively benign [16,48] and depend on continued viral replication.…”

Composite B-cell and T-cell Lineage Post-transplant Lymphoproliferative Disorder of the Lung with Unusual Cutaneous Manifestations of Mycosis Fungoides

“…1,4 In one study examining T-cell PTLD in a pediatric population, 78.5% of the patients died from their disease 5 in contrast to the 45% mortality cited in one report examining cases of pediatric B-cell PTLD. 6 Our patient died in early September 2010, approximately 9 months after the diagnostic skin biopsy was taken.…”

“…This time interval would be more consistent with that of a T-cell PTLD rather than that of a Bcell PTLD, in which the mean and median time from transplant to development of disease has been found to be only 16.5 and 7 months, respectively. 6 Despite this, because the definitive histopathologic diagnoses of the skin and lung lesions were made only weeks apart, we cannot determine with certainty which neoplastic cell line arose first nor are we able to definitively determine whether the lung involvement or the skin involvement by this patient's PTLDs occurred first.…”

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