Epstein–Barr virus–associated leiomyosarcomas in liver transplantation recipients. Origin from either donor or recipient tissue

Abstract

Background. Leiomyosarcoma, a mesenchymal malignancy with smooth muscle differentiation, is extremely rare in children. Immunosuppression, due to either antirejection medication in organ transplantation recipients or human immunodeficiency virus infection (HIV), appears to constitute a predisposition. Methods. Two cases of leiomyosarcoma in pediatric liver transplantation recipients were investigated and compared clinically with respect to site of origin and course of the disease and pathologically by routine histology and electron microscopy, by forensic DNA methodology for origin from donor or recipient tissue, and by EBER‐1 in situ hybridization for evidence of latent Epstein‐Barr virus (EBV) infection. Results. A 9‐year‐old male developed a high grade, poorly differentiated leiomyosarcoma in his allografted liver 2 years after transplantation, and despite antineoplastic chemotherapy, he died of metastatic disease. The genotype of his tumor indicated an origin from allografted tissue. A 12‐year‐old female had a low grade retroperitoneal leiomyosarcoma involving the superior mesenteric vein. After resection, she remained disease free without chemotherapy. The genotype of her tumor indicated an origin from native tissue. In both tumors, latent EBV infection was documented. Conclusions. Neoplastic smooth muscle proliferation in immunosuppressed liver transplantation recipients is analogous to the more common posttransplantation lymphoproliferative disorder in involving transformation of either engrafted donor tissue or recipient tissue elsewhere in the body, in displaying a wide spectrum of histologic differentiation, grade and clinical behavior, and in exhibiting evidence of latent EBV infection.

Unresectable Squamous Cell Carcinoma of Donor Origin Treated With Immunosuppression Withdrawal and Liver Retransplantation

“…There have been very few documented cases of nonlymphoid solid organ tumors of donor origin reported following liver transplantation (11)(12)(13)(14)(15)(16)(17)(18)(24)(25)(26)(27)(28). These cases have included donor transmitted neuroendocrine carcinoma (13), Kaposi's sarcoma (17), leiomyosarcoma (16), melanoma (11), adenocarcinomas (18,26), glioblastomas (15,27,28), and choriocarcinomas (12,14,24,25) Our case represents such a case and, to our knowledge, is the only reported case of donor-transmitted SCC occurring in a transplanted liver.…”

“…Discovery of a donor-derived malignancy in an allograft is a very unusual occurrence following solid organ transplantation. Many of these tumors are lymphoproliferative, however, cases of various nonlymphoid donor-derived malignancies developing in solid organ recipients have also been described (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Establishing the origin of malignancy can be very difficult yet has significant implications for successful treatment.…”

Smooth muscle tumors of soft tissue and non-uterine viscera: biology and prognosis

“…The smooth muscle tumors can occur in peripheral soft tissue, intracranial space, or visceral sites, and tumor multiplicity is common. [76][77][78][79][80][81][82][83][84][85] Molecular genetic analysis has shown that multiple tumor represent independent clones rather than dissemination of a single neoplastic clone. 85 In multiple tumor cases, tumors arising in the transplant are of donor cell origin, whereas those at the other sites arise from recipient cells, which also points to polyclonal origin of multiple tumors.…”

“…85 In multiple tumor cases, tumors arising in the transplant are of donor cell origin, whereas those at the other sites arise from recipient cells, which also points to polyclonal origin of multiple tumors. 82 Although these tumors were originally divided into EBV-associated leiomyomas and leiomyosarcomas, current classification holds them all collectively as smooth muscle tumors as they are usually indolent although somewhat unpredictable in behavior. True metastatic behavior is rare, and was observed only in 4 of 51 AIDS-associated (8%) 77 and 1 of 19 cases (5%) in a mixed AIDS and transplantation-associated series.…”

EBV-associated hepatic smooth muscle tumor of uncertain biologic behavior after heart transplantation in a pediatric patient: case report

“…Their multifocal nature is thought to be the result of multiple independent infections, rather than metastasis (6). Despite the multifocal nature of the disease, EBV-SMTs mostly appear to be indolent and discovered by means of surveillance imaging studies, especially in the absence of intracranial involvement (8,21). However, fever, abdominal pain, anorexia, weight loss, graft dysfunction, neurologic symptoms and pulmonary symptoms has been reported (8,(22)(23)(24).…”