Histologic, Molecular, and Radiologic Characterization of Resolving Cerebral Posttransplant Lymphoproliferative Disorder

Lymphoproliferative disorders (LPDs) are commoner in pediatric versus adult immunosuppressed transplant recipients, and frequently involve the central nervous system. In these circumstances, the justification for biopsy is heavily influenced by the likely diagnostic yield. The present study centers on a 12-y-old renal transplant patient who developed multifocal cerebral LPD and had serial magnetic resonance (MR) examinations during the course of her illness from which she has completely recovered upon reduction of immunosuppression. She underwent stereotaxic biopsy, which was analyzed by both immunocytochemistry and polymerase chain reaction to examine the general question of how to release the maximum amount of information contained within, as well as to obtain a tissue diagnosis in this particular case. We show that a combination of these methods permits identification of the immunophenotype, lineage, clonality, viral involvement, and origin of abnormal cellular infiltrates. The biopsy also showed a novel histologic pattern of LPD, comprising numerous benign T cells obscuring a tiny clone of B cells. The MR examinations documented, for the first time, the differences in signal that accompany clinical resolution at both biopsied and nonbiopsied sites, showing that the latter may be associated with reduction, but not elimination, of MR signal abnormality. We conclude: 1) a combination of conventional and polymerase chain reaction analysis offers the greatest diagnostic yield from stereotaxic biopsies, even when the available tissue is minimal;2) a focal polyclonal T cell infiltrate should prompt further investigation to exclude an underlying B cell lesion.