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

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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.

Acknowledgements

We would like to thank all members of the intestinal transplant team of the University Medical Center Groningen for their joint efforts to care for children with intestinal failure.

Endoscopy_UCTN_Code_CCL_1AD_2AJ

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