Epstein- Barr Virus Related Malignant and Non-Malignant Transformation in Two Paediatric Liver Transplant Patients

Abstract

Listen

Translate article

Introduction: Epstein-Barr virus (EBV)-associated smooth muscle tumors (EBV-SMT) are a distinctive group of mesenchymal tumors that develop exclusively in patients with clinical immunosuppression, predominantly in HIV and recipients of solid organ transplantation, particularly paediatric patients. The incidence of developing neoplastic disorders after solid organ transplantation is highly dependent on the intensity of the prophylactic anti-viral regimen, the induction therapy, as well as high levels of calcineurin inhibitors. Recently 2 of our liver transplant patients have been diagnosed with both benign and malignant EBV- related smooth muscle tumours presenting as significant gastrointestinal bleeds. Since the 1970‘s, there have been a small number of cases of leiomyomas in immunosuppressed patients post transplant. Case Presentation: Patient ZH underwent a liver transplant for missed biliary atresia at one year five months of age. Her course was complicated by portal vein thrombosis and a failed Meso-Rex shunt two months post transplant. Despite this, her liver remained well perfused on hepatic arterial blood supply with no problems with rejection. A meso-caval shunt was done at six years of age when she continued having significant gastrointestinal bleeds. A mesenteric lymph node removed incidentally during surgery was consistent with leiomyosarcoma on histology. Further imaging showed lung metastatic lesions and at a subsequent laparotomy a primary ileal lesion was resected. She completed chemotherapy and six weeks later had another gastrointestinal bleed which revealed a leiomyoma on histology from a rectal biopsy. She was commenced on IVI gancyclovir and tacrolimus was changed to sirolimus. Despite the above management, a repeat colonic biopsy following another gastrointestinal bleed confirmed the presence of a leiomyoma. Patient AJG underwent a liver transplant at four years of age for biliary atresia. He had an uncomplicated course post transplant except for raised EBV levels initially treated with three months of intravenous gancyclovir and then oral valgancyclovir. He had a massive gastrointestinal bleed two years later which revealed features consistent with post transplant lymphoproliferative disorder of terminal ileum and leiomyoma in the sigmoid colon. Discussion: Smooth muscle EBV induced tumours after organ transplantation are rare, occurring more often in the paediatric population. These tumours are generally insidious and their prognosis depends on the size, site and surgical options. There is no standard treatment. Although the benign variant carries a good prognosis, leiomyosarcoma carries a poor prognosis. We are highlighting these two cases to emphasise the need for ongoing vigilance to detect EBV-associated malignancies with regular EBV PCR monitoring and adjustment of immunosuppression if EBV PCR titres rise. Management involves an interdisciplinary approach with input from transplant physicians, surgeons and oncologists. Management involves surgical resection of all lesions if possible, reduction of immunosuppression and possibly changing from a calcineurin inhibitor to a MTOR inhibitor. Once malignant transformation has occurred, the prognosis is poor.