Endoscopic detection of an early manifestation of EBV-related post-transplant lymphoproliferative disorder in a transplanted colon

Intestinal transplantation in children requires close follow-up, including endoscopic monitoring of the transplanted organ via the temporary stoma and/or anus with biopsies taken and reviewed. We present a case of post-transplant lymphoproliferative disorder (PTLD) diagnosed less than 1 month after transplantation. PTLD is a common life-threatening complication after intestinal transplantation, occurring in 13.5 % of pediatric cases, and is mostly related to Epstein-Barr virus (EBV) [1] [2].

A 5-year-old boy presented with intestinal failure secondary to microvillus inclusion disease. He received an isolated intestinal allograft combined with a proximal colonic allograft. To monitor for rejection and inflammation, colonoscopy and endoscopic review through the stoma were performed twice a week in the first 2 weeks and once a week after that.

Lesions were detected 26 days after transplantation ([Fig. 1 a]).

Fig. 1 a Colonoscopic view of transplanted colon 26 days after transplantation, showing erythema and easily bleeding epithelia.

b Biopsy specimen of donor colon, showing a polymorphous lymphocytic infiltrate in the lamina propria, non-tumor-forming (H&E, × 100).

c In situ hybridization for EBV-related small RNAs (EBERs) showing positive B cells surrounding negative crypts containing T cells.

Microscopy of the transplanted colon and the host colon revealed a polymorphous lymphocytic infiltrate in the lamina propria, non-tumor-forming ([Fig. 1 b]). This PTLD consisted of CD20- and CD79a-positive B cells that harbored EBV-related small RNAs (EBERs) as determined by in situ hybridization ([Fig. 1 c]).

The tacrolimus dose was lowered. However, 6 days later endoscopic review showed that the lesions had grown and were also present in the donor proximal ileum ([Fig. 2 a]).

Fig. 2 a Colonoscopic view of transplanted colon 32 days after transplantation, showing tumor forming and white ulceration.

b Biopsy specimen of donor colon, showing ulceration of the colon epithelia with destruction of the crypts (H&E, × 100).

c In situ hybridization for EBERs showing positive B cells in the lamina propria, tumor forming.

Reduction of immunosuppressive therapy and administration of a monoclonal antibody directed against the B-cell receptor CD20 (rituximab) [3] [4] induced immediate regression of the lymphomas and complete remission of the disorder within 3 months after the first dose.

Six months after transplantation there was an acute episode of therapy-resistant rejection, which needed graft exploration and excision. The patient has been relisted for combined intestinal and liver transplantation. He is awaiting the retransplantation at home in a clinically stable condition. This case represents the earliest presentation of intestinal PTLD found during routine endoscopic surveillance.

References

• 1 Intestinal Transplant Registry May 31, 2003. http://www.intestinaltransplant.org/ Publication date: 2003
• 2 Tanner J E, Alfeiri C. The Epstein-Barr virus and post transplant lymphoproliferative disease: interplay of immunosuppression, EBV, and the immune system in disease pathogenesis.  Transpl Infect Dis. 2001;  3 20-69
• 3 Choquet S, Leblond V, Herbrecht R. et al . Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study.  Blood. 2006;  107 3053-3057
• 4 Svoboda J, Kotloff R, Tsai D E. Management of patients with post-transplant lymphoproliferative disorder: the role of rituximab.  Transpl Int. 2006;  19 259-269