Posttransplant lymphoproliferative disorders in heart-lung transplant recipients: primary presentation in the allograft

Heart-lung transplant recipients are predisposed to acute rejection episodes, bronchiolitis obliterans, and opportunistic infections. In 9.4% of recipients at the University of Pittsburgh, a posttransplant lymphoproliferative disorder (PTLD) developed, and in 60% of cases, it presented in the allografted lungs and was associated with primary infection by Epstein-Barr virus (EBV). The PTLD is histologically indistinguishable from a primary pulmonary lymphoma and consists of a mixed population of large lymphoid cells, immunoblasts, and plasma cells. Two cases of PTLD were monoclonal with immunohistochemical and Southern blot analysis. Despite this, there was clinical recovery with reduced immunosuppression and acyclovir. We discuss the role of EBV in the development of PTLD and the pathogenesis of primary presentation in the allograft.     

Posttransplant lymphoproliferative disorders: A fine-needle aspiration biopsy study

Fine-needle aspiration biopsy (FNAB) has been used with high sensitivity and specificity in the diagnosis of both Hodgkin's and non-Hodgkin's lymphoma. However, studies of FNAB of posttransplant lymphoproliferative disorders (PTLDs) are rare. The clinical course of 593 allograft recipients (cardiac, 288; renal, 250; lung, 50; and heart/lung, 5) was reviewed. Twenty-six patients developed PTLD with an overall incidence of 4.4%. Of these patients, 12 underwent FNAB. Their age ranged from 33–67 yr (mean, 55 yr). The interval between transplantation and FNAB ranged between 2–14 mo (average, 8.4 mo). The lungs were the most common site aspirated (7 cases), followed by lymph nodes (3 cases) and other extranodal sites (2 cases, liver and paraspinal mass). The cytologic features of these aspirates could be classified into two categories: a polymorphous smear composed of a spectrum of mature and immature lymphocytes with scattered plasma cells and histiocytes; and a monotonous population of large lymphoid cells consistent with malignant lymphoma, large-cell type. Surgical biopsies were available in 10 (83.3%) cases and confirmed the FNAB diagnosis. In summary, FNAB appears to be a highly sensitive and specific diagnostic tool in patients with PTLD. Diagn. Cytopathol. 16:392–395, 1997. © 1997 Wiley-Liss, Inc.     

Regional referral system for patients with acute mechanical support: experience at the Cleveland Clinic Foundation

Regional referral networks ("hub and spoke") have been created to facilitate the transfer of patients on mechanical circulatory support. Although individual centers report good success, overall outcomes have remained poor. We investigated whether preoperative variables influenced survival and could be used to help select patients best served by referral. A retrospective chart review was conducted on all patients transferred to our institution supported on cardiac assist devices. Between January 1995 and September 2003, 39 patients were received in transfer for continued care after the implantation of a cardiac assist device. Eighty-five percent of patients had the ABIOMED BVS 5000 implanted. The most common indication was postcardiotomy shock. Sixty-four percent of patients were not candidates for heart transplantation due to medical or social contraindications. The 30-day mortality of this group was 62%. Survivors had less comorbidity and were less likely to have complex surgeries, neurologic impairment, and multisystem organ failure when presenting to our center. Devices were weaned in 30% of cases. Only six patients (15%) were successfully transplanted, and five of these patients have done well at follow-up. Based on our experience, we believe that cardiogenic shock patients benefit from a regional referral system if they have not had complex cardiac surgical procedures or developed multisystem organ failure. Furthermore, there is a survival advantage when using long-term devices because this allows possible recovery or transplantation.     

B-cell lymphoproliferative disorders in solid-organ transplant patients: detection of Epstein-Barr virus by in situ hybridization.

B-cell lymphoproliferative disorders (BLPDs) occur in approximately 2% of transplant recipients and are frequently fatal. Indirect serologic evidence has implicated Epstein-Barr virus (EBV) as an etiologic factor in these lesions. Direct evidence of the presence of EBV in these lesions has been obtained in relatively few cases. We used in situ hybridization (ISH) with a probe for the BamHI-W region of the EBV genome to study 52 tissue specimens from 28 solid-organ transplant patients who had BLPD. Epstein-Barr virus-infected lymphoid cells were identified in 26 of these 28 patients. The two patients without ISH evidence of EBV infection showed no distinctive clinical, morphologic, or serologic features. Previous filter-hybridization studies of these two patients had demonstrated evidence of EBV infection. Seven additional transplant patients without evidence of BLPD were studied as controls and showed no evidence of EBV in their lymphoid cells by ISH. These data provide further support for the etiologic role of EBV in the pathogenesis of posttransplantation lymphoproliferative disorders.     

Prevalence and spectrum of T-cell lymphoproliferative disorders in patients with Hypereosinophilia: A reference laboratory experience

Hypereosinophilia (HE) is defined as persistently elevated absolute eosinophil count (AEC) ≥ 1.5 × 10⁹/L, which can be due to a variety of underlying causes. In this study, we investigated the prevalence and spectrum of T-cell lymphoproliferative disorders in 124 consecutive patients with HE by flow cytometric immunophenotyping. Available medical records, pathology reports and T-cell receptor (TCR) gene rearrangement were reviewed. Fifteen patients (12%) with HE had abnormal T-cell populations that were initially detected by flow cytometry. The presence of immunophenotypically abnormal T cells was not associated with higher AEC or higher absolute lymphocyte count levels, in comparison to those without abnormal T cells. Molecular studies concordantly identified a clonal TCR gene rearrangement in 8 of 10 cases tested. Based on the combination of clinical presentation, morphologic findings and laboratory studies, seven patients were diagnosed with the lymphocytic variant of hypereosinophilic syndrome and five with overt T-cell lymphoma (4 peripheral T-cell lymphoma NOS, 1 primary cutaneous T-cell lymphoma). The remaining three had an unknown diagnosis due to lack of information and additional workup would be warranted. These findings underscore the importance of flow cytometry as a screening tool to identify T-cell lymphoproliferative disorders in patients with HE.     

Immunodeficiency-associated lymphoproliferative disorders.

The incidence of lymphoproliferative disease is significantly higher in individuals who have congenital, acquired, or iatrogenically induced immunodeficiency. The immunodeficiency-associated lymphoproliferative disorders are clinically and pathologically heterogeneous, are of variable clonal composition, and vary according to the immunodeficiency syndrome. Nonetheless, they share several features, including frequent origination in or involvement of extranodal sites, diffuse aggressive histology, B-cell lineage derivation, association with the Epstein-Barr virus (EBV), and, often, rapid clinical progression. Reactive and atypical lymphoid hyperplasias and malignant lymphomas occur in association with congenital (primary) immunodeficiency. Post-transplantation lymphoproliferative disorders are often comprised of a polymorphic cell population, making it difficult to identify their benign or malignant nature by histopathologic criteria alone. Recent studies suggest that they are divisible into plasmacytic hyperplasias, polymorphic lymphoproliferative disorders, and malignant lymphomas. The plasmacytic hyperplasias are polyclonal and generally regress spontaneously following withdrawal of immunosuppression. The malignant lymphomas are monoclonal, possess a variety of genetic alterations, and generally progress despite aggressive therapy. The polymorphic lymphoproliferative disorders are also monoclonal but display variable clinical behavior, their progression apparently correlating with bcl-6 gene mutation. Non-Hodgkin's lymphoma (NHL) is the second most common AIDS-related neoplasm and an AIDS-defining illness. AIDS-related NHLs are divisible by anatomic site of origin into systemic (nodal/extra nodal), primary central nervous system, and body cavity-based (primary effusion) lymphomas; and by histopathology into Burkitt's and Burkitt's-like lymphoma, large cell lymphoma, and large cell immunoblastic (plasmacytoid) lymphoma More than 90% are monoclonal B-cell neoplasms. The primary effusion lymphomas contain the Kaposi's sarcoma-associated herpesvirus. Multiple molecular pathways appear to operate in AIDS lymphomagenesis and some may be preferentially associated with specific histopathologic categories or anatomic sites of origin. In conclusion, the immunodeficiency-associated lymphoproliferative disorders often represent a significant diagnostic problem requiring correlative analysis of the clinical behavior of the patient with the histopathology, immunophenotype, clonal composition, viral content, and genetic alterations of the lymphoproliferative disorder. They also represent an important biological model for studying the development and progression of lymphoid neoplasia     

T-lymphocyte colonies in the lymphoproliferative disorders.

Human lymphocytes from peripheral blood, bone marrow spleen and lymph nodes were cultured. Continuous phytoheamagglutinin (PHA) stimulation was used, first during a 24 h liquid preincubation, then during a 5 day culture in methylcellulose. In normal donors a rapid colony formation took place, with a mean of 124+/-82 colonies per 1 times 10(5) preincubated lymphocytes. Cells from such colonies were studied by cytology, scanning electron microscopy and rosette formation techniques; arguments favour the hypothesis that these could be T lymphocytes. Neither granulocytes nor macrophages could be grown, and no lymphoid colony formation occurred without PHA stimulation. The same technique was applied to patients with various lymphoproliferative disorders. Significant colony suppression was observed in nearly every case of chronic lymphatic leukaemia; the number of colonies was reduced in some patients with acute lymphatic leukaemia, lymphosarcoma, dysglobulinaemia and Hodgkin's disease. This lymphoid culture method should be applied to a larger number of patients to determine whether it has a classification value and/or prognostic significance. When colonies were grown in pathological states, rosette formation was identical to that of normal donors; colony formation could be due to persisting normal lymphocytes.     

Cytogenetic abnormalities in chronic B-cell lymphoproliferative disorders in Chinese patients.

We analyzed the cytogenetic findings of 59 Chinese patients with chronic B-cell lymphoproliferative disorders. More than half of the patients (n = 36, 61%) had chronic lymphocytic leukemia. Cytogenetic abnormalities were demonstrated in 44.1% (26/59) of the patients. Trisomy 12 was the most frequent abnormality in chronic lymphocytic leukemia and was found in 27.8% (10/36) of the patients, indicating that the incidence of trisomy 12 in chronic lymphocytic leukemia in Chinese patients might not be low compared with the West as previously suggested. Structural abnormalities involving chromosomes 13 at band q14 were the next most common abnormalities in patients with chronic lymphocytic leukemia. Among the 11 patients with mantle cell lymphoma in leukemic phase, t(11;14) was seen in only 2 patients (18.2%). Several unusual cytogenetic abnormalities also were found.     

Coexistence of acute cellular rejection and lymphoproliferative disorder in a lung transplant patient.

We report the case of a 37-year-old man who underwent bilateral lung transplantation for end-stage cystic fibrosis. Two months after his operation, a computed tomographic scan showed multifocal nodules throughout both lungs. Endobronchial biopsies revealed an Epstein-Barr virus-associated B-cell lymphoproliferation. Transbronchial biopsies revealed perivascular lymphoid infiltrates composed of predominantly small T lymphocytes. These perivascular infiltrates were retrospectively considered to be an acute cellular rejection rather than the periphery of the lymphoproliferative disorder. This opinion was based on several arguments: (a) a decrease in dosage of maintenance immunosuppression led to total regression of the lymphoproliferation but did not affect the perivascular lymphoid infiltrates; (b) the treatment of the acute cellular rejection temporarily induced the disappearance of the perivascular infiltrates; (c) the expression of Epstein-Barr virus was not detected in the perivascular infiltrates; and (d) on autopsy, performed 1 year later, severe obliterative bronchiolitis lesions were discovered, for which acute cellular rejection is the main risk factor. These observations point to the possibility that acute cellular rejection and an Epstein-Barr virus-associated lymphoproliferative disorder may coexist.     

Post-transplantation lymphoproliferative disorders arising in solid organ transplant recipients are usually of recipient origin.

Recent clinical, pathological, and molecular studies have increased our understanding of posttransplantation lymphoproliferative disorders (PT-LPDs). Studies have shown that the majority of PT-LPDs arising in bone marrow transplant recipients are of donor origin; however, the source (host or donor) of the lymphoid cells that make up PT-LPDs arising in solid organ transplant recipients has not been systemically investigated. In this study, 18 PT-LPDs occurring in 16 organ transplant recipients (13 heart, 2 kidney, 1 lung), 9 donor tissues (for 10 recipients), and 14 uninvolved recipient tissues (from 12 patients) were examined employing restriction fragment length polymorphism analysis to determine their host or donor origin. The PstI-digested DNAs were analyzed by Southern blot hybridization using two highly informative polymorphic probes that map to chromosome 21 (CRI-PAT-pL427-4) and chromosome 7 (CRI-PAT-pS194). All solid organ PT-LPDs with corresponding uninvolved recipient DNA showed identical hybridization patterns; none of the PT-LPDs exhibited a hybridization pattern that matched donor DNA. These findings suggest that the vast majority of PT-LPDs arising in solid organ transplant recipients, in contrast to those arising in bone marrow transplant recipients, are of recipient origin.     

Epstein-Barr virus-associated lymphoproliferative disorders.

Herein we have provided a panorama of the clinical, histopathologic, and molecular biologic mechanisms of EBV-induced LPD particularly in immunosuppressed individuals. A listing of EBV-related diseases is shown in Table 4. We have stressed the frequent need to use multiple diagnostic methods for detecting EBV genome, particularly in immunodeficient patients who may fail to mount antibody responses to EBV. Given that we now recognize some of the immunocompromised patient populations at high risk for EBV-induced LPD, and have developed techniques for detecting EBV genome and early LPD, we may eventually prevent the occurrence of some of these life-threatening diseases. For example, we have learned to recognize and distinguish hepatic allograft rejection from EBV-induced LPD in hepatic biopsies (154). A periportal and sinusoidal infiltrate of small and large lymphoid cells, immunoblasts, and plasma cells, alert us to stain frozen liver sections for EBNA. Finding EBV guides the clinicians to reducing immunosuppression which then allows the restoration of immunosurveillance against the EBV-infected B cells. Whether an EBV vaccine can be successful in immunosuppressed individuals remains to be seen. As for other vaccines, many logistical problems prevail, such as the early occurrence of EBV infection during infancy in regions where BL is endemic. Surely, with the menacing threat that approximately 10% of patients with AIDS will develop NHL, new anti-viral therapy against EBV and the causative agent of AIDS and HIV, will be developed. The pathologist and virologist play essential roles in the recognition of EBV infection by performing clinical laboratory determinations. The characteristic histopathologic features of EBV-induced LPD are now recognized and when confirmed with molecular hybridization and immunofluorescent techniques will provide a solid diagnostic approach and, thus, a foundation for developing a sound therapeutic strategy.     

Gene mutations in lymphoproliferative disorders of T and NK/T cell phenotypes developing in renal transplant patients

Post-transplantation lymphoproliferative disorder (PT-LPD) is characterized by lymphoid proliferation after organ or bone marrow transplantation. In Western countries, most cases of PT-LPD are B-cell-derived and Epstein-Barr virus-associated, in which alterations of c-myc, p53, and N-ras genes might play a role in disease progression. In Japan, PT-LPD of T- and NK/T-cell types are not uncommon in renal transplant patients. Mutations of p53 (exons 4 through 8), K-ras (exons 1 and 2), c-kit (exons 11 and 17), and beta-catenin genes (exon 3) in 12 cases of these diseases were analyzed by PCR single strand conformation polymorphism and then by direct sequencing. p53 gene mutations were detected in 5 of 5 cases of peripheral T-cell lymphoma, 3 (60%) of 5 cases of adult T-cell leukemia/lymphoma, and 1 of 2 cases of NK/T cell lymphoma. Twenty-five percent of T and NK/T cell lymphomas showed K-ras mutations. Mutations of c-kit and beta-catenin genes were found in 33% of cases. Among a total of 42 substitution mutations, 40 were transitions with involvement of CpG sites in 20 to 30% of cases. Most cases had at least one mutation that changed an amino acid, which might have provided the selection pressure for expansion. These findings suggested that p53 gene mutations might play a central role in development of peripheral T-cell lymphoma including adult T-cell leukemia/lymphoma in renal transplant patients.     

Use of quantitative competitive PCR to measure Epstein-Barr virus genome load in the peripheral blood of pediatric transplant patients with lymphoproliferative disorders.

A quantitative competitive PCR (QC-PCR) assay for Epstein-Barr virus (EBV) has been developed to provide accurate measurement of EBV genome load in pediatric transplant recipients at risk for developing posttransplant lymphoproliferative disorder (PTLD). The assay quantifies between 8 and 5,000 copies of the EBV genome in 10(5) lymphocytes after a 30-cycle amplification reaction. For 14 pediatric patients diagnosed with PTLD, the median EBV genome load was 4,000, and 13 of the 14 patients had values of >500 copies per 10(5) lymphocytes. Only 3 of 12 control transplant recipients not diagnosed with PTLD had detectable viral genome loads (median value, 40). This median was calculated by using the highest value obtained by PCR testing on each of these patients posttransplantation. PCR values of >500 copies per 10(5) lymphocytes appear to correlate with a diagnosis of PTLD. By a modified protocol, the EBV genome copy number in latently infected adults was estimated to be <0.1 copy per 10(5) lymphocytes.     

Molecular characterization of post‐transplant lymphoproliferative disorders of donor origin occurring in liver transplant recipients

Post‐transplant lymphoproliferative disorders (PTLDs) represent a frequent complication of solid organ transplantation. Although most PTLDs arise from recipient lymphoid cells, a considerable fraction of cases may arise from donor B‐cells. In an attempt to clarify the histogenesis and pathogenesis of PTLDs derived from donor B‐cells, monoclonal PTLDs occurring in liver transplant recipients were chosen as a model to compare donor (D‐PTLDs) versus recipient PTLDs (R‐PTLDs). The tumour panel included nine D‐PTLDs and six R‐PTLDs. D‐PTLDs were early‐onset, EBV‐infected lymphoproliferations classified as polymorphic PTLD (P‐PTLD; n = 7) or diffuse large B‐cell lymphoma (DLBCL; n = 2) with tumour localization confined to the hepatic hilum. All R‐PTLDs were late‐onset DLBCLs and showed extrahepatic localization. A BCL‐6^?/MUM1⁺/CD138^+/? phenotype, consistent with a post‐germinal centre (GC) stage of pre‐terminal B‐cell differentiation, was observed in all D‐PTLDs and in 2/6 R‐PTLDs, whereas a BCL6⁺/MUM1^?/CD138^? profile, reminiscent of GC B‐cells, was detected in 4/6 R‐PTLDs. The presence of somatic IGHV hypermutation was observed in 6/9 D‐PTLDs and in 4/6 R‐PTLDs, suggesting derivation from antigen‐experienced B‐cells. IGHV4‐39 was the IGHV gene most frequently encountered, being rearranged in 3/9 D‐PTLDs. Among IGHV‐mutated PTLDs, a mutational profile suggesting antigen stimulation and/or selection was observed in 4/6 D‐s and in 2/4 R‐PTLDs. The presence of ongoing IGHV mutations was detected in 2/4 D‐PTLDs. Aberrant SHM was detected in 10/15 (66.7%) PTLDs, including 6/9 D‐PTLDs and 4/6 R‐PTLDs. Our findings suggest that (i) D‐PTLDs show a clinical presentation distinct from R‐PTLDs; (ii) immunophenotypic and genetic features of D‐PTLDs are consistent with mature, GC‐experienced B‐cells; (iii) transformed donor‐derived B‐cells may experience antigen‐driven stimulation and selection, and may acquire genetic lesions during neoplastic expansion in the recipient environment; and (iv) EBV infection and expression of viral oncoproteins may be relevant in the pathogenesis of D‐PTLDs. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Detection of Epstein-Barr virus DNA in sera from transplant recipients with lymphoproliferative disorders

Early diagnosis of Epstein-Barr Virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD) is important because many patients respond to reduction in immunosuppression, especially if PTLD is detected at an early stage. Previous studies have found elevated EBV DNA levels in blood from patients with PTLD, but these assays required isolation of cellular blood fractions and quantitation. We evaluated the presence of cell-free EBV DNA in serum from solid-organ transplant recipients as a marker for PTLD. Five of 6 transplant recipients with histopathologically documented PTLD had EBV DNA detected in serum at the time of diagnosis (sensitivity = 83%), compared with 0 of 16 matched transplant recipients without PTLD (specificity = 100%) (P < 0.001 [Fisher's exact test]). Furthermore, EBV DNA was detected in serum 8 and 52 months prior to the diagnosis of PTLD in two of three patients for whom stored sera were analyzed. Detection of EBV DNA in serum appears to be a useful marker for the early detection of PTLD in solid-organ transplant recipients. Further studies to define the role of such assays in evaluating solid-organ transplant patients at risk for PTLD are warranted.     

Low incidence of Epstein-Barr virus-associated posttransplantation lymphoproliferative disorders in 272 unrelated-donor umbilical cord blood transplant recipients.

Umbilical cord blood (UCB) is being increasingly used for transplantation, but the ability of neonatal T cells to regulate Epstein-Barr virus (EBV)-associated lymphoproliferation is unknown. Because UCB transplantation (UCBT) is associated with a relatively low infused dose of donor T cells, frequent donor-recipient HLA disparity, and use of antithymocyte globulin during conditioning, we hypothesized that the risk of EBV-associated posttransplantation lymphoproliferative disorders (EVB-PTLD) after UCBT may be increased. To investigate the incidence of EBV-PTLD after UCBT, we analyzed 272 unrelated-donor UCBTs performed from August 1993 to December 1999 at Duke University Medical Center and the University of Minnesota. Five cases of EBV-PTLD were identified, with a cumulative incidence of 2% (95% confidence interval, 0.3%-3.7%) at 2 years. EBV-PTLD affected UCB recipients aged 1 to 49 years (median, 8 years), with 4 patients undergoing transplantation for leukemia and 1 for immunodeficiency. Patients received UCB grafts that were HLA matched (n = 1) or mismatched at 1 (n = 1) or 2 (n = 3) HLA loci. Diagnoses occurred at 4 to 14 months (median, 6 months) after UCBT, with 4 of 5 patients having preceding grade II to IV acute graft-versus-host disease and 1 being diagnosed at autopsy. Treatment of 4 patients consisted of withdrawal of immunosuppressive treatment and administration of rituximab, with 2 of 4 patients responding. Thus, the incidence of EBV-PTLD after unrelated-donor UCBT appears similar to that observed after transplantation using unrelated bone marrow (BM) and compares favorably with unrelated-donor T-cell-depleted BM transplantation. Because adoptive immunotherapy with donor lymphocytes is not an available option for recipients of unrelated-donor UCBT, new therapeutic strategies are needed, and rituximab appears promising.     

A psychiatry outpatient consultation-liaison clinic. Experience at the Cleveland Clinic Foundation

This report describes the patients seen during the first 3 months of operation of a psychiatry outpatient consultation-liaison (C-L) clinic. A total of 113 patients were seen. For 8% of the appointments made, patients did not show up; the cancellation rate was 3.8%. Depression, anxiety, stress, and somatic symptoms were the most common reasons for referral, while the most common diagnoses made were major depression, adjustment disorder, and panic disorder. Practitioners in the fields of internal medicine, primary care, and psychology made the majority of the referrals. Patient satisfaction as expressed in a written survey was high. The results showed that an outpatient C-L clinic can be an effective way to access and treat medicine, surgery, and psychology outpatients in a big hospital setting.     

Posttransplantation lymphoproliferative disorders in pediatric patients undergoing liver transplantation

OBJECTIVES: To study the clinicopathologic and molecular genetic findings in posttransplantation lymphoproliferative disorders (PTLDs) following pediatric liver transplantation and to determine the applicability of a recently proposed consensus classification system. DESIGN: The clinical, pathologic, and molecular genetic findings of 11 PTLDs that occurred in 10 patients are presented. These 10 patients were derived from a group of 121 pediatric patients who underwent liver transplantation at the University of California, San Francisco. The PTLDs were classified using the proposed Society for Hematopathology scheme. Clonality was determined by immunohistochemical detection of monotypic immunoglobulin or by using polymerase chain reaction-based methods to detect monoclonal immunoglobulin heavy-chain gene rearrangements. Epstein-Barr virus (EBV) was detected by immunohistochemistry, in situ hybridization, or polymerase chain reaction. Epstein-Barr virus typing and the presence of LMP1 gene deletions were also analyzed by polymerase chain reaction. RESULTS: There were 3 early lesions, 4 polymorphic PTLDs, and 4 monomorphic PTLDs. Monoclonality was demonstrated in 8 of 9 cases assessed. Epstein-Barr virus was present in all cases; of 9 cases assessed by polymerase chain reaction, the virus was type A in 8 and type B in 1. No EBV LMP1 gene deletions were identified. The corresponding liver explants were negative for EBV in 8 cases and positive in 1 case. Greater than 3 foci of disease and monomorphic PTLD were associated with decreased actuarial survival (P <.05). CONCLUSIONS: The prognosis of pediatric patients with PTLD is favorable for early lesions and polymorphous PTLD, particularly in patients with localized disease. Multifocal disease and monomorphic PTLD are associated with an unfavorable prognosis.     

Heart transplant pathology: the British experience.

An account of human heart transplantation as seen by the histopathologists involved at the two UK transplant centres is presented. Between January 1979 and July 1984 179 patients received 186 hearts and 124 are still alive up to four years after operation. Cyclosporin A based immunosuppression has been used in the last 120 patients. Four patients developed neoplastic lesions. The commonest reason for transplantation was ischaemic heart disease (63%), followed by congestive cardiomyopathy (35%). The seven retransplants were for acute or chronic rejection. The monitoring of rejection by endomyocardial biopsies is described, and the causes of death and necropsy findings are presented.