The neuropathology of organ transplantation: comparison and contrast in 500 patients.

The main objective of this report is to compare and contrast the type and frequency of neuropathological findings following liver, heart, lung, heart-lung, kidney and bone marrow transplantation and to provide an overview of the major systemic complications in patients that received allografts. This is a retrospective analysis of the complete autopsy records and clinical histories of 500 adults who underwent organ transplantation at the University of Pittsburgh Medical Center during the interval of March, 1981 through July, 1997. This study is based on the neuropathological and systemic findings among 225 liver, 101 heart, 40 lung, 28 heart-lung, 74 kidney and 32 bone marrow transplants. Clinico-pathological correlations were made. All patients received base-line immunosuppressive therapy with one or more of the following drugs: cyclosporine, corticosteroids and azathioprine. Since August, 1989, the primary immunosuppressive agent is FK-506 (Tacrolimus). Some patients received antilymphocyte globulin (OKT3), when acute rejection was imminent. Light microscopic examination of tissue sections, stained with hematoxylin and eosin and in some cases with special stains were made. Ultrastructural evaluation were also performed in selected cases. All of the studies were carried out at the University of Pittsburgh Medical Center, Department of Pathology, Neuropathology Division. Cerebrovascular complications were the most frequent and were seen in 51% of the liver, 59% of the heart, 58% of the lung, 50% of the heart-lung, 49% of the kidney and 44% of the bone marrow allografts. Aspergillus sp. infection was the most common of all CNS infections followed by viral, bacterial and protozoal. Primary Central Nervous System Lymphoma (PCNSL) was seen in 2% of the liver, and 2% of the heart recipients. Post transplant lymphoproliferative disorder (PTLD) involving the brain was seen in 2% of the liver allografts, 3% of the heart, and 7% of the heart-lung recipients. PTLD systemically was seen in 6% of the liver, 7% of the heart, 5% of the lung, 11% of the heart-lung and 4% of the kidney allografts. Graft-versus-host disease was seen only in 41% of the bone marrow recipients. There was no statistically significant difference between the incidence of the total CNS complications among the different organ transplant groups (p value > 0.10), but there was a statistically significant difference in the systemic complications among the organ transplant groups (p value < 0.001). In conclusion that immunocompromised patients with impaired cellular and humoral immunity are at risk for the development of opportunistic infections and hematologic abnormalities. PTLD appears to be different in its pathogenesis from that of PCNSL which occurs anew in the brain of these patients. The neurological complications may be reduced by earlier recognition and better understanding of their etiopathogenesis.