A Brain Tumor from a Posttransplant Lymphoproliferative Disorder in a Kidney Transplant Recipient / 대한이식학회지

Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication from organ transplantation. PTLD usually manifests as a mass in the lymph node or an extranodal mass in solid organs, such as the liver, transplanted kidney, tonsil, bone marrow, or spleen. PTLD rarely involves the central nervous system (CNS); however, here we report a case of PTLD that manifested as a brain tumor after kidney transplantation. A 52-year-old man who started peritoneal dialysis due to autosomal dominant polycystic kidney disease, underwent kidney transplantation 4 years ago. After kidney transplantation, he took tacrolimus, mycophenolate mofetil, and steroids. He was admitted to our hospital, complaining of a severe headache. Brain magnetic resonance imaging showed a multifocal, irregular, and round enhancing mass in the left basal ganglia. He underwent a needle biopsy for the enhancing mass and the pathological diagnosis was diffuse large B cell lymphoma. After this mass was confirmed as PTLD by histologic diagnosis, the patient had a reduction in his immunosuppression regimen (including a change from tacrolimus to sirolimus) and was treated with chemotherapy for PTLD. After 20 days, the patient expired from sepsis. PTLD involving the CNS is a rare and serious complication associated with solid organ transplantation. PTLD should be included in the differential diagnosis of brain tumors in recipients of solid organ transplants.

Hematopoietic Stem Cell Transplantation after Posttransplant Lymphoproliferative Disorder

A 16-yr-old girl received liver transplantation for fulminant hepatitis. Aplastic anemia developed, and she received hematopoietic stem cell transplantation (HSCT). Eleven months after liver transplantation, abdominal lymph node enlargement and colon ulcers were observed, and colon biopsy showed posttransplant lymphoproliferative disorder (PTLD). Immunosuppression reduction was attempted, but it produced no therapeutic effect. Fourteen months after liver transplantation, she received a second HSCT due to engraftment failure, and PTLD resolved completely. The second HSCT can serve as cellular therapy for PTLD.

Hodgkin's Lymphoma-like Posttransplantation Lymphoproliferative Disorder after Allogeneic Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation (HSCT) recipients have a risk of post-transplant lymphoproliferative disorder (PTLD), which normally develops in Epstein-Barr virus (EBV) transformed donor B lymphocytes. The incidence of Hodgkin's lymphoma (HL) ranges from 1.8% to 3.4% of PTLD after HSCT. There are no case reports of early onset HL-like PTLD that developed less than one year after HSCT. We encountered a case of early onset PTLD after an unrelated HSCT following reduced-intensity conditioning with cyclophosphamide/fludarabine/thymoglobulin. A 24 year old patient with severe aplastic anemia developed multiple lymphadenopathies at day 95 after HSCT. The excisional biopsy revealed HL-like PTLD, which tested positive to immunohistochemical staining for the EBV. The Ann Arbor stage was IIA. Immunosuppressive agents were discontinued for 2 weeks in order to induce a graft-versus-lymphoma effect without a response. A total 4 cycles of chemotherapy with doxorubicin (adriamycin)/bleomycin/ vinblastine/dacarbazine (ABVD) and radiotherapy (total dosage 3,400 cGy) were then carried out. The response to salvage treatment was complete remission. The patient showed no evidence of the disease at the follow-up performed 32 months after HSCT.

Severe Acute Rejection Developed in Posttransplant Lymphoproliferative Disorder Patient after Discontinuing the Immunosuppression / 대한이식학회지

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. PTLD is the disorder arising from the combined effects of Epstein-Barr virus associated lymphoproliferation with the disruption of the normal immune control of cytotoxic T cells. The only effective treatment of PTLD is often the reduction or elimination of intense immunosuppressive therapy. But we presented here a case of severe acute rejection developed in orthotopic liver transplantation patient after discontinuing the immunosuppression. A 58 year-old male had a liver transplantation for hepatitis B viurs-associated liver cirrhosis and taking cyclosporine postoperatively. He presented two months later with palpable neck mass and abdominal pain. CT scan showed multiple lymphadenopathies in retroperitoneum and more than 3 cm conglomerulated mass in left supraclavicular area. Percutaneous needle biopsy was done in which a this neck mass proved not to be a infectious mononucleosis-like disease or a definite lymphoma. In situ hybridization (ISH) for EBV encoded RNA was positive in a few cell. It suggested a possibility of PTLD, Even though the lymph node is totally necrotic in the given specimen. At that time, the immunosuppression was discontinued, and he was treated with iv gancyclovir. No chemothreapy was administered. Two weeks later, severe acute rejection (RAI=7) followed requiring treatment with steroid pulse. Tacrolimus had replaced cyclosporine and was maintained. Liver function test profile decreased gradually. Serial CT scan showed partial improvement of multiple necrotic lymphadenopathy in the retroperitoneum and supraclavicular area. Two months later, he presented with palpable neck mass and abdominal pain repeatedly. Another incisional biopsy was performed. The results showed B cell lymphoma with CD20 (+), CD3 (-), bcl6 (-), Ki-labelling index 80%, bcl (-), p53 (-). He received 2 courses of cyclophosphamide (600 mg/m2, on day 1 of each course) and prednison (2 mg/kg/day for 5 day). The first 2 courses were given in combination with 4 weekly doses of rituximab (375 mg/m2, i.v). After symptomatic improvement, he was discharged.

NK/T-cell Lymphoma Involving Multiple Organs in Renal Transplant Recipient / 대한신장학회잡지

Posttransplant lymphoproliferative disorders (PTLDs) represent a potentially life-threatening complication following renal transplantation. Their incidence is usually low, in the range of 1-2%. The majority of PTLD is B cell origin and strongly associated with Epstein Barr virus (EBV). PTLD of T cell origin is uncommon and has a poor prognosis. We have experienced a case of NK/T cell lymphoma involving stomach, mesenteric lymph nodes, and heart after renal transplantation. The patient was 34 years old man who received renal transplant in 1999. He was admitted with a complaint of fever and pancytopenia for 2 weeks in 2003. Though antibiotic and antifungal treatment, fever and pancytopenia were continued. On the third hospital day, he present waterly diarrhea. We found multiple hemorrhagic erosions in the stomach by gastrofiberscopy and did biopsy there. Gastric mucosal biopsy showed infiltration by atypical cells between the mucosal glands and submucosal layer. The immunophenotype of these tumor cells were CD3+, UCHL+, and CD56+ and all negative for B cell markers. He was dead because of massive gastrointestinal bleeding after endoscopic biopsy of stomach. The autopsy revealed the widespreading of tumor cells involving heart and mesenteric lymph nodes.

NK/T-cell Lymphoma Involving Multiple Organs in Renal Transplant Recipient / 대한신장학회잡지

Posttransplant lymphoproliferative disorders (PTLDs) represent a potentially life-threatening complication following renal transplantation. Their incidence is usually low, in the range of 1-2%. The majority of PTLD is B cell origin and strongly associated with Epstein Barr virus (EBV). PTLD of T cell origin is uncommon and has a poor prognosis. We have experienced a case of NK/T cell lymphoma involving stomach, mesenteric lymph nodes, and heart after renal transplantation. The patient was 34 years old man who received renal transplant in 1999. He was admitted with a complaint of fever and pancytopenia for 2 weeks in 2003. Though antibiotic and antifungal treatment, fever and pancytopenia were continued. On the third hospital day, he present waterly diarrhea. We found multiple hemorrhagic erosions in the stomach by gastrofiberscopy and did biopsy there. Gastric mucosal biopsy showed infiltration by atypical cells between the mucosal glands and submucosal layer. The immunophenotype of these tumor cells were CD3+, UCHL+, and CD56+ and all negative for B cell markers. He was dead because of massive gastrointestinal bleeding after endoscopic biopsy of stomach. The autopsy revealed the widespreading of tumor cells involving heart and mesenteric lymph nodes.

Outbreak of Posttransplant Lymphoproliferative Disorder (PTLD) in a Single Center / 대한이식학회지

Post transplant lymphoproliferative disorder is a serious complication after renal transplantation. Although the precise etiology is unknown, the Ebstein-Bar virus and immunosuppressive agents appear to be risk factors. The presentation of PTLD is diverse. Many patients develop symptoms in head and neck, which make diagnosis difficult. We experienced 3 cases of PTLD successively one or three months apart during year 2002. Before 2002, PTLD was very rare in our center. The incidence of PTLD in renal transplants in our center is 0.7% (5 out of 752), which is similar to that of other reports. But the incidence is very high during year 2002. This seems to be intensified immunosuppression recently adopted. EBV monitoring is necessary for early detection of PTLD in renal transplants.

A case of posttransplantation lymphoproliferative disease developed in renal transplant recipient and treated with rituximab / 대한내과학회지

Posttransplant lymphoproliferative disorder (PTLD) are among the most serious and potentially fatal complications of chronic immunosuppression in organ transplant recipient and also the most common malignancies, accounting for 21 percent of all malignancies in organ transplants versus 5 percent of malignancies in the general population. PTLD is associated with immunosuppression and Epstein Barr virus (EBV). Treatment modality of PTLD includes antiviral agent, interferon, intensive chemotherapy and monoclonal antibody. Choice of treatment modality depends on clinical presentation of PTLD. We report here a case of PTLD involving liver and renal allograft treated with rituximab.

Posttransplant Lymphoproliferative Disorder in Pediatric Liver Transplantation: Samsung Medical Center Experience / 대한소아소화기영양학회지

PURPOSE: In a retrospective study for the pediatric patients who underwent liver transplantation in the past 6 years at Samsung Medical Center, the clinical features of 5 patients with posttransplant lymphoproliferative disorder (PTLD) were analyzed. METHODS: Between June 1996 and June 2002, 41 pediatric patients underwent liver transplantation. Seven of them died in the postoperative period. Thirty-five including one patient who died of PTLD were finally reviewed. Patients were divided into two groups: high risk group, EBV naive recipients of EBV-positive grafts; low risk group, the patients other than those in high risk group. The authors reviewed age at operation, immunosuppressive agent, postoperative duration until diagnosis, postoperative duration until EBV seroconversion, presence of treatment against rejection, and presenting symptoms of PTLD. RESULTS: Five of 41 patients (12.2%) developed PTLD. All of them belonged to high risk group, and the incidence of PTLD in high risk group was 31.3% (5/16). The mean age at operation was 10.8 months old and the mean duration between operation and diagnosis for PTLD was 9.8 months. Primary EBV infection developed after a median of 6 months after transplantation. One patient was diagnosed as laryngeal and gastrointestinal PTLD and the other four, gastrointestinal PTLD. The following symptoms and signs were seen in the patients: anemia (100%), hypoalbuminemia (100%), fever (80%), diarrhea (80%), gastrointestinal bleeding (80%), and anorexia (60%). CONCLUSION: PTLD is one of the major complications after pediatric liver transplantation, especially in the group of high-risk recipients. Anemia, hypoalbuminemia, fever, diarrhea and gastrointestinal bleeding were features that are characteristic of PTLD. The common features of PTLD development were: (i) EBV-positive donors placed into EBV naive recipients, (ii) primary EBV infection about 6 months after transplantation, (iii) young age, about 1 year old at operation, and (iv) the requirement for intensive posttransplant immunosuppression.

A Case of Posttransplant Lymphoproliferative Disease (PTLD) Following Renal Transplantation in a Child

Posttransplant lymphoproliferative disease (PTLD) represents a diverse lymphoproliferative disorder ranging from nonspecific reactive hyperplasia to malignant immunoblastic sarcoma developed in a setting of immunosuppression following organ or cellular transplantation. It is often associated with Epstein-Barr virus (EBV) infection and high dose immunosuppression. PTLD after renal transplantation was reported at first in adult in Korea in 1997. In children there have been several cases of PTLD after liver transplantation but PTLD after renal transplantation has not been reported. This is a case report of PTLD developed 4 months after renal transplantation in a 9-year-old boy. The major clinical manifestations were fever, multiple lymph nodes enlargement and blood-tinged stool. EBV was detected by in-situ hybridization in the enlarged cervical lymph node and the colonic tissue. Histological examination revealed B-cell lineage. Use of ganciclovir and reduction of the immunosuppression level resulted in complete remission of PTLD. This is the first pediatric case report of PTLD following renal transplantation in Korea.

Mucosa-Associated Lymphoid Tissue Lymphoma Following Kidney Transplantation / 대한혈액학회지

Posttransplant lymphoproliferative disorder (PTLD) is one of the most serious complication occuring after solid organ transplantation. In general, mucosa-associated lymphoid tissue (MALT) lymphoma of stomach has not been considered to be part of this spectrum, because most of the MALT lymphoma are associated with not EBV but H.pylori. Until now, there have been only a few cases of MALT lymphoma after transplantation. We report case of gastric MALT lymphoma following renal transplantation and review the reported cases in the literatures.

Epstein Barr Virus-Associated Angiocentric T Cell Lymphoma in Nasal Cavity of Renal Transplantation Recipient / 대한이비인후과학회지

Posttransplant lymphoproliferative disorder (PTLD)is recognized as a significant and morbid complication of organ transplantation. The majority of PTLD is of B cell origin and strongly associated with Epstein Barr virus (EBV). T cell origin is uncommon and has a poor prognosis. There are only a few cases of PTLD of T cell origin, associated with EBV. We have experienced a case of angiocentric T cell lymphoma in nasal cavity, associated with EBV in a renal transplanted recipient. The patient was 25 years old woman who received transplant from her brother in 1995. Angiocentric T cell lymphoma was developed 33 months after the transplantation. We detected EBV mRNA in the neoplastic cells by in situ hybridization. She was treated by radiotherapy and is in complete remission state at present.

A Clinicopathological Study of Posttransplant Liver Biopsy

Liver biopsies are used routinely in the assessment of graft dysfunction following liver transplantation and generally considered to be the most reliable method for the diagnosis of posttransplant complications with overlapping clinical and laboratory findings. To investigate posttransplant complications causing graft dysfunction and usefulness of liver biopsy, we analysed clinicopathologic features of 65 posttransplant liver biopsies, 2 autopsies and an explanted liver, taken from 20 patients. The frequencies of posttransplant complications were acute cellular rejection in 9 patients (45%), postoperative infection in 11 patients (55%), of which cytomegalovirus (CMV) infection and systemic invasive aspergillosis with candidiasis occured in 10 patients (50%) and 1 patient (5%), respectively. Remainders were hepatic arterial thrombosis in two (10%), primary graft dysfunction due to fatty donor liver in one (5%), and posttransplant lymphoproliferative disorder (PTLD) in two (10%). There were no chronic rejection or recurrent disease. Postoperative mortality was 25%. Histologic grade by Banff schema was well correlated with clinical parameters associated with unfavorable short term prognosis. CMV infection was associated with acute cellular rejection in 6 out of 10 patients (60%). Immunohistochemical staining for CMV was more sensitive method than CMV in situ hybridization or histologic detection of viral inclusion on tissue section. It was unique that one case of PTLD developed under the circumstances of the lowest dosage of immunosuppression and took grave outcome. Based on these results, we concluded that clinicopathologic correlation with integration of all the clinical and laboratory findings is necessary in the interpretation of accurate and early diagnosis of posttransplant liver biopsies. The interrelationship between chronic rejection and CMV infection as well as pathogenetic factors of PTLD remains to be clarified through further ongoing observation.