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Published on: May 10, 2017
Autopsy pathology of pediatric posttransplant lymphoproliferative disorder
M H Collins1, K T Montone, A M Leahey
1Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. margaret.collins@uc.edu
Insights
Posttransplant lymphoproliferative disorder (PTLD) can rapidly progress in children after organ or bone marrow transplants. Autopsy findings reveal PTLD often disseminates widely, impacting multiple organs and contributing to death, even when EBV serology is inconclusive.
Area of Science:
- Pediatric Pathology
- Transplant Medicine
- Oncology
Background:
- Posttransplant lymphoproliferative disorder (PTLD) is a serious complication following organ and bone marrow transplantation, particularly in children.
- PTLD is associated with Epstein-Barr virus (EBV) infection and can lead to significant morbidity and mortality.
Purpose of the Study:
- To compare antemortem and postmortem PTLD histology in pediatric transplant recipients.
- To assess the extent and associated pathology of PTLD at autopsy.
- To determine the cause of death in children with PTLD.
Main Methods:
- Autopsy examinations were conducted on 7 pediatric patients (3 bone marrow, 4 liver transplant recipients).
- PTLD was histologically classified as hyperplasia or lymphoma.
- In situ hybridization for EBER1 mRNA and EBV serologies were performed.
Main Results:
- PTLD was diagnosed antemortem in 5 patients and at autopsy in 2 patients.
- Postmortem histology largely matched antemortem findings, with lymphoma being the predominant type.
- Autopsies revealed widespread PTLD dissemination in 4 patients, affecting lymph nodes, brain, gastrointestinal tract, and kidneys.
- Other causes of death included organ infection, infarcts, and diffuse alveolar damage.
Conclusions:
- PTLD can manifest rapidly within weeks post-transplant in children.
- The spectrum of PTLD ranges from localized to widely disseminated disease.
- Autopsy is crucial for understanding the true incidence, natural history, and pathology of PTLD in transplant patients.
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.
