1/49. Clonal expansion of gammadelta-T lymphocytes in an HTLV-I carrier, associated with chronic neutropenia and rheumatoid arthritis.We report on an HTLV-I carrier showing clonal proliferation of gammadelta-T lymphocytes associated with chronic neutropenia and rheumatoid arthritis (RA). A 75-year-old Japanese woman had a 20-year history of RA and was found to have neutropenia and lymphocytosis by routine examinations. Her white cell count was 5,800/microl with 89% lymphocytes. The proliferating gammadelta-lymphocytes did not show the typical morphology of large granular lymphocytes (LGL) and were positive for CD3, TCRdelta1, and HLA-DR but negative for CD4, CD8, and deltaTCS1. Clonally rearranged TCRgamma-chain (Jgamma) and TCRbeta-chain (Cbeta1) genes were detected by Southern blot analysis. Clonality of these proliferating gammadelta-T cells was confirmed by CDR3 size analysis for the TCRdelta-chain. Anti-HTLV-I antibody was positive and the pX region of HTLV-I proviral dna was detected by PCR analysis, but clonal integration of HTLV-I proviral dna was not detected by Southern blotting analysis. The patient's clinical course has been stable, except for infrequent infectious episodes. The association of HTLV-I/II infection with T-LGL leukemia has been reported by several groups, although most cases exhibit TCRalphabeta type T cells. Analysis of the junctional sequence of TCR on T-LGL leukemia cells may clarify the role of HTLV-I/II infection in clonal T-cell proliferation.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
2/49. Reversible monoclonal lymphadenopathy in autoimmune lymphoproliferative syndrome with functional FAS (CD95/APO-1) deficiency.The FAS (CD95/APO-1) receptor and its ligand play an important role in the initiation of apoptosis under many physiologic conditions. Loss of function mutations of the FAS gene have been described in lpr mice and in humans with autoimmune phenomena, recurrent lymphadenopathies, and hepatosplenomegaly. This syndrome is now called autoimmune lymphoproliferative syndrome type I (ALPS I). Recently, patients with similar clinical symptoms due to a functional FAS deficiency without FAS gene mutations have been distinguished. This disease has been termed autoimmune lymphoproliferative syndrome type II (ALPS II) or autoimmune lymphoproliferative disease (ALD). This report is the first description of the lymph node pathology and immunohistochemistry in a patient with ALPS II. After recurrent bacterial infections, a 4-year-old child developed cervical giant lymphadenopathy suggesting lymphoma. Lymph node histology resembled the findings in Epstein Barr virus-associated posttransplant atypical lymphoproliferations. Confluent sheets of immunoblasts, however, showed a monoclonal expression of IgG/lambda and a monoclonal rearrangement of the JH chain. The same clone was also present in the peripheral blood. Although high-grade lymphoma could not be excluded, the patient's parents insisted on the patient's leaving the hospital with only antibiotic treatment. Surprisingly, the giant lymphadenopathy completely resolved within 7 weeks, and the clone was no longer detectable in the peripheral blood. Twelve months later the patient was still free from lymphoma and was doing well. Retrospectively, transient monoclonal B-cell populations could be identified in an archival frozen blood sample taken when the patient was 3 years old. Increased FAS-independent spontaneous apoptosis was a feature of the patient's lymphocytes and could be the molecular basis for self-elimination of B-cell clones. We conclude that the diagnosis of a FAS-FAS-L deficiency should be considered in children with an otherwise unexplained atypical lymphoproliferation and that a diagnosis of lymphoma in patients with functional FAS deficiency should be made with considerable reservation.- - - - - - - - - - ranking = 11.126989795918keywords = sample (Clic here for more details about this article) |
3/49. light microscopic, immunophenotypic, and molecular genetic study of autoimmune lymphoproliferative syndrome caused by fas mutation.This case provides a complete light microscopic, immunophenotypic, and molecular genetic analysis of autoimmune lymphoproliferative syndrome (ALPS), a rare benign cause of dramatic lymphadenopathy with atypical histology and phenotype that may be mistaken for malignancy. The patient is 3-year-old child who was first clinically evaluated at the age of 16 months because of marked generalized lymphadenopathy and hepatosplenomegaly. Histologic sections of a cervical lymph node demonstrated a marked paracortical proliferation of occasional small and intermediate-sized lymphocytes and numerous large immunoblasts, the majority of which displayed a CD3( ), CD43( ), CD45RO(-) (OPD4, UCHL1) CD4(-), CD8(-) phenotype on paraffin sections, and which had a CD2( ), CD3( ), CD5( ), CD56(-), Tdelta1(-), [CD4(-), CD8(-)] double negative profile on flow cytometric analysis. Southern blot analysis did not identify a clonal T or B cell population, and sequencing of the fas gene identified a mutation that caused a single amino acid substitution in the intracytoplasmic death domain of this protein. An enriched population of CD45RO-negative naive T cells in the paracortex may explain the atypical histologic and immunophenotypic features of this case. Greater awareness of this heritable lymphoproliferative disorder will facilitate its recognition and minimize the possibility of misdiagnosis.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
4/49. Chorioretinal post-transplant lymphoproliferative disorder induced by the Epstein-Barr virus.BACKGROUND: The Epstein-Barr virus (EBV) is responsible for the lymphoproliferative disorders observed in transplanted patients. methods: The case history is described of a 59 year old man with a chorioretinal lesion who had received a single lung transplant and was on immunosuppressive treatment. Immunoglobulin gene rearrangement and EBV detection by polymerase chain reaction (PCR) with semiquantification were used on the vitreous material. RESULTS: A proliferation of B lymphocytes with a monoclonal subpopulation was found by PCR on the vitreous sample. The large amounts of EBV genomes found in the vitreous suggest that EBV was the cause of the lymphoproliferation. Healing of the lesion was achieved by a decrease in immunosuppressive treatment and the use of nucleotide analogues. CONCLUSION: The diagnosis of ocular post-transplant lymphoproliferative disorder (PTLD) can be made by PCR on vitreous material. early diagnosis and treatment can lead to regression of limited monoclonal lesions.- - - - - - - - - - ranking = 11.126989795918keywords = sample (Clic here for more details about this article) |
5/49. Diagnosis of lymphoproliferative disorders: experience of a single institution in the long-term follow-up of discordant cases.OBJECTIVE: To evaluate the usefulness of morphologic diagnosis, immunophenotyping and immunoglobulin (Ig) and T-cell receptor (TcR) gene rearrangement studies in the diagnosis of lymphoproliferative disorder. DESIGN: A retrospective cohort study with clinical follow-up of controversial cases. SETTING: Single institution, tertiary care centre. patients: All 273 patients whose lymphoid tissue samples were sent for molecular analysis by Southern blotting over a 4-year period. INTERVENTIONS: Patient reports were retrieved from the laboratory data system. Repeat assessment and clinical follow-up was done for discordant cases. OUTCOME MEASURES: Correlation between morphologic features and the results of immunophenotype and gene rearrangement studies of the samples. Value of the different tests in discordant cases. RESULTS: The 273 samples included 130 of non-Hodgkin's lymphoma (NHL), 23 of Hodgkin's disease, 80 of benign lymphoid hyperplasia, 16 of atypical lymphoid hyperplasia and other diagnoses. Of the 130 NHL cases diagnosed by morphologic study, 22 (17%) did not show gene rearrangement. Of the 80 morphologically benign samples, 4 (5%) showed gene rearrangement, and malignant disease developed later in those patients. Five (31%) of the 16 cases of atypical lymphoid hyperplasia showed gene rearrangement. Six of the remaining 11 cases had no detectable gene rearrangement, but hematologic malignant disease developed. No gene rearrangement was detected in Hodgkin's disease samples. One carcinoma showed gene rearrangement. Of the NHL group, 86% of the B cells and 50% of the T cells showed gene rearrangement. Seven samples showed both Ig and TcR gene rearrangement. CONCLUSIONS: gene rearrangement analyses correlate highly with conventional morphologic diagnosis and phenotyping. The detection of gene rearrangement in lymphoid tissue has a high specificity (99%) and a reasonable sensitivity (83%) to the development of a lymphoproliferative disorder.- - - - - - - - - - ranking = 66.76193877551keywords = sample (Clic here for more details about this article) |
6/49. Pleural posttransplantation lymphoproliferative disorder following liver transplantation.A case of posttransplantation lymphoproliferative disorder (PTLD) involving the pleura is reported. The patient was a 57-year-old man who underwent liver transplantation 2 years prior to the development of PTLD. The PTLD was pleural-based and was first detected by radiologic studies as a pleural effusion. Transbronchial biopsy and cytologic examination of 2 pleural fluid specimens were nondiagnostic. Subsequent open-wedge biopsy revealed a monomorphic PTLD, composed of large immunoblasts with plasmacytoid differentiation. Immunohistochemical studies demonstrated B-cell lineage with expression of monotypic cytoplasmic immunoglobulin kappa light chain and CD79a, and absence of T-cell antigens. Immunohistochemical and in situ hybridization studies demonstrated Epstein-Barr virus protein and rna, respectively. No evidence of human herpesvirus 8 dna was detected by polymerase chain reaction. We report this case because pleural-based PTLD is rare. The diagnosis of this entity is made more difficult by the fact that PTLD is often underrepresented in pleural fluid cytology samples.- - - - - - - - - - ranking = 11.126989795918keywords = sample (Clic here for more details about this article) |
7/49. Quantitative monitoring of circulating Epstein-Barr virus dna for predicting the development of posttransplantation lymphoproliferative disease.Epstein-Barr virus (EBV)-dna was quantitatively measured to assess posttransplantation virus reactivation by real-time polymerase chain reaction (PCR). In the first retrospective analysis of a 7-year-old boy with lymphoproliferative disease (LPD) after an unrelated cord blood transplantation, serum EBV-dna progressively increased to 4 x 10(5) copies/mL. EBV load was then prospectively monitored in peripheral blood from posttransplantation patients. The second case was an 8 year-old boy with aplastic anemia who received a CD34 cell transplantation. This patient died of LPD with the progression of pulmonary nodules. EBV-dna increased to 4 x 10(4) copies/mL after the control of cytomegalovirus reactivation. On the other hand, EBV-dna was undetectable (<200 copies/mL) in the series of all 58 samples from 10 patients who did not develop LPD after hematopoietic stem cell transplantation. Sequential monitoring of circulating EBV-dna by quantitative PCR may be a useful indicator for predicting the development of posttransplantation LPD.- - - - - - - - - - ranking = 11.126989795918keywords = sample (Clic here for more details about this article) |
8/49. X-chromosome inactivation analysis in a female carrier of FOXP3 mutation.Immune dysregulation, polyendocrinopathy and enteropathy with X-linked inheritance (IPEX) is a serious disease arising from mutations in FOXP3. This gene codifies for a transcription factor whose dysfunction results in hyperactivation of T cells. It is not clear, however, why an intermediate phenotype is not seen in heterozygous females, who are completely healthy. In order to address this question, we investigated X-chromosome inactivation in peripheral blood lymphocytes from a heterozygous female with a child affected by IPEX. No preferential inactivation was shown in freshly sorted CD4 , CD8 , CD19 cells or in IL-2 cultured CD4 and CD8 T cells, indicating that peripheral blood lymphocytes in these women are randomly selected. Moreover, only one single FOXP3 transcript was expressed by CD4 T cell clones analysed by RT-PCR, confirming that this gene is subject to X- inactivation. We hypothesize that hyper-activation of T cell in carriers of FOXP3 mutations is regulated by the presence of normal regulatory T cells.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
9/49. Isolated pleural PTLD after cardiac transplantation.PREAMBLE: Epstein-Barr virus infection (EBV) and immunosuppression promote emergence of posttransplant lymphoproliferative disorders (PTLD) in patients undergoing organ transplantation. OBJECTIVE: We report a case of PTLD confined to the pleura. FINDINGS: The patient was a 62-year-old male who had undergone cardiac transplant in 1993 for ischemic heart disease. Seven years later, he presented with dyspnea and bilateral pleural effusions. The CT scan revealed left sided pleural base thickening. The cytology of the pleural fluid and fine needle aspirate of the pleura was both suggestive of PTLD. However, the tissue submitted for ancillary studies did not contain the diagnostic material. A clinical decision was made to withdraw immunosuppressive therapy and start rituximab. His clinical course was complicated by pneumocystis carinii pneumonia and he died 4 months after the diagnosis of PTLD. autopsy revealed bilateral pleural effusions with pleural nodules involving the visceral and parietal pleura of both lungs. immunohistochemistry demonstrated B cell lineage with kappa/lambda ratio of 1. PCR studies done on the pleural nodules (postmortem specimen) revealed the presence of EBV dna and absence of human herpes virus 8 (HHV8) dna. in situ hybridization revealed positive staining for EBV rna within the neoplasm. CONCLUSION: Pleural-based PTLD is rare. Cytology in conjunction with immunophenotyping and molecular studies can be useful for a definitive diagnosis. In our case, cytology sample was suggestive of PTLD. PCR studies performed on the antemortem specimen confirmed the presence of monoclonal IgH gene rearrangement, while the postmortem specimen revealed oligoclonal IgH gene rearrangement. The change from monoclonal to oligoclonal IgH gene rearrangement suggests reversion of monoclonal to polyclonal PTLD following rituximab and CHOP therapy. We also demonstrated EBV dna and rna in the tumor nodules, supporting EBV-induced PTLD.- - - - - - - - - - ranking = 11.126989795918keywords = sample (Clic here for more details about this article) |
10/49. Serial detection of Epstein-Barr virus dna in sera and peripheral blood leukocyte samples of pediatric renal allograft recipients with persistent mononucleosis-like symptoms defines patients at risk to develop post-transplant lymphoproliferative disease.We tested blood samples of 25 pediatric renal transplant recipients for Epstein-Barr virus (EBV) dna load by quantitative polymerase chain reaction (PCR). Eleven of these transplant recipients showed clinical persistent mononucleosis-like symptoms years after transplantation (Tx). A quantitation of EBV dna by PCR in peripheral blood lymphocyte (PBL) and serum samples revealed variable EBV dna titers. The majority of EBV PCR results in samples of the 14 asymptomatic transplant recipients was repeatedly below detection limit. In contrast, patients with mononucleosis-like symptoms showed persistent EBV genome titers over a period of 6 months, ranging from 75 to 18 750 copies/10 000 PBL and from 680 to 335 000 copies/mL serum, respectively. One child suffering from this mononucleosis-like condition developed an EBV-associated Burkitt-like lymphoma 29 months after Tx. Whereas clinical and histological investigations did not indicate a post-transplant lymphoproliferative disorder (PTLD) until tumor detection, EBV titers in PBL and serum had been high for at least 8 months. We propose that pediatric transplant recipients who show both, recurrent mononucleosis-like symptoms and a sustained high EBV genome load, are at increased risk for severe EBV-related post-transplant complications.- - - - - - - - - - ranking = 77.888928571429keywords = sample (Clic here for more details about this article) |
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