Epstein-Barr Virus Status and Latency State of Lymphoproliferative Disorders in Inflammatory Bowel Disease Patients Treated with Immunomodulators
Megan O Nakashima, Aaron M Gruver, Ashish Atreja, Eric D Hsi. Cleveland Clinic, Cleveland, OH
Background: Inflammatory bowel disease (IBD) is often treated with immune-modulating drugs such as thiopurines (6-MP) and anti-tumor necrosis factor antibodies (aTNFs) which may increase risk of lymphoproliferative disorders (LPD). Epstein-Barr virus (EBV) is often implicated in LPDs of immunosuppressed patients (pts). Here we characterize LPD occurring in IBD pts including EBV status and latency state.
Design: Cases were identified by cross-referencing IBD pts with all LPDs diagnosed at our institution (1996-2011). LPD morphology was reviewed; cases were fully immunophenotyped. In situ hybridization (EBER) and immunohistochemical stains (LMP1, EBNA2) were performed on paraffin-embedded tissue. Treatment (tx) histories were obtained via medical record.
Results: 15 patients developed LPDs after tx for IBD; ten with Crohns disease (CD) and five with ulcerative colitis (UC). Details of IBD tx, LPD type, EBV status and latency type, LPD tx, and pt status are shown in Table 1. All EBER+ LPD pts were treated with aTNFs, four also with 6-MP. The latency III diffuse large B-cell lymphomas (DLBCLs) and plasmablastic lymphoma (PBL) showed both Hodgkin-like (HRS) cells and geographic necrosis, a combination not seen in EBV-cases. LPDs in pts who received neither drug were EBV-. Fisher's exact test showed associations between EBV positivity and tx with aTNFs (p=0.031) and with aTNF+6-MP (p=0.005).
|Histology||EBV (Latency)||aTNF||6-MP||HRS/necr||LPD Tx||Outcome||F/U (mo)|
|ngcDLBCL||+ (III)||Y||Y||Y/Y||Surgery, ?||Death||?|
|ngcDLBCL||+ (III)||Y||Y||Y/Y||Surgery, d/c aTNF||Remission||9|
|PBL||+ (I)||Y||Y||Y/Y||Surgery, chemo||Remission||46|
|cHL||+ (II)||Y||Y||Y/Y||Chemo, radtx||Remission||46|
|gcbDLBCL||+ (II)||Y||N||N/N||Chemo||Death (cirrhosis)||4|