Clinicopathologic Investigation of Early Post-Transplant Lymphoproliferative Disease (EPTLD)
KL Wolniak, MA Proytcheva, BP Nelson. Northwestern University, Feinberg School of Medicine, Chicago, IL; Children's Memorial Hospital, Chicago, IL
Background: PTLD is a potentially lethal complication of organ transplantation. PTLDs fall into 3 main groups: early, polymorphic, and conventional lymphomas. PTLDs grouped as lymphomas often require aggressive therapy, but the clinical behavior of PTLD is unpredictable. Data regarding EPTLDs are limited. Recent studies showed increased mammalian target of rapamycin (mTOR) activation in PTLDs, but clinical correlation was not provided. We investigated the clinical, morphologic, and immunophenotypic features as well as mTOR activation in 16 EPTLD (14 patients) cases.
Design: Sixteen cases of EPTLD were identified. H&E, kappa/lambda, and EBER-ISH stained sections, and clinical data from the medical records were reviewed in all cases. Activation of the mTOR pathway was assessed with immunostain (IS) of formalin fixed, paraffin-embedded tissue with an antibody specific for phosphorylated S6 ribosomal protein (pS6), a downstream effector of activated mTOR; cases were scored using a formula to combine the % positive cells and staining intensity.
Results: Cases included 3 adults and 11 children (2 to 660 months (mo) old). Allografts were 6 livers, 4 hearts, 3 kidneys, 1 pancreas. Immunosuppressive therapy (IM) was cyclosporine 4 cases, tacrolimus 4, mycophenolate mofetil & tacrolimus 6. Median time from transplant to PTLD was 50 mo. (8-135 mo.) in the 12 cases with known data. PTLD sites were tonsil/adenoids 12, lymph node (LN) 3, LN & small bowel 1. Pre-transplant EBV status was available in 5 children: 1+, 4-. All 16 cases were EBER+. PTLD groups were: 11 plasmacytic hyperplasia (PH), 1 infectious mononucleousis, 4 PH & follicular hyperplasia. 13/13 had polytypic plasma cells by IS (12) & flow cytometry (FC;1), 3 had polytypic B-cells by FC. 14/14 cases had increased pS6 staining as compared to normal tonsil (p=.002, F-test). Positive staining was in plasma cells and large and small lymphocytes, in the germinal centers and interfollicular regions. Therapy was known in 10 cases: IM was reduced in 6, 1 received steroids, 3 had surgery only. All 14 patients are alive without PTLD; the pancreas was rejected.
Conclusions: Early PTLD developed a median of 50 mos. after transplant in 14 patients, involved mostly tonsils/adenoids in children, were EBER+, and had good clinical outcome with reduction of IM or surgery. Increased phosphorylation of S6 occured in EPTLD over normal tonsil suggesting investigation of the inhibitor of mTOR, rapamycin, may be of value in EPTLD.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 195, Monday Morning