1/8. Primary juxtaarticular soft tissue lymphoma arising in the vicinity of inflamed joints in patients with rheumatoid arthritis.AIMS: Primary soft tissue lymphoma is uncommon and little is known regarding its aetiology and pathogenesis. In a review of 37 soft tissue lymphomas we uncovered three cases associated with rheumatoid arthritis which we report herein. methods AND RESULTS: The clinical records and pathology of the cases are described together with the results of in situ hybridization studies with oligonucleotide probes to Epstein-Barr virus (EBV) encoded rna (EBER). All three patients were females with a long-standing history of rheumatoid arthritis ranging from 9 to 17 years. Each presented with a soft tissue mass in the vicinity of a joint affected by rheumatoid disease. All had received prior treatment with nonsteroidal anti-inflammatory drugs and one also received gold, penicillamine and intra-articular steroids to affected joints. None had received methotrexate. Histologically, the juxtaarticular soft tissue masses were all B-cell lymphomas. None were associated with EBV as determined by in situ hybridization. CONCLUSIONS: These cases document an association between rheumatoid arthritis and soft tissue lymphoma of B-cell type, arising in the vicinity of an affected joint. Chronic local immune stimulation may have played a significant role in the genesis of these lymphomas, unlike the frequently reversible and EBV-positive lymphomas that occur in rheumatoid patients on immunosuppressive therapy.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/8. Epstein-Barr virus-associated B-cell type non-Hodgkin's lymphoma with concurrent p53 protein expression in a rheumatoid arthritis patient treated with methotrexate.A Japanese male patient received various medications for his long-standing rheumatoid arthritis (stage IV, class II). He developed a mass on the right anterior chest wall after being treated with methotrexate (MTX) for 4 months. A biopsy of the mass showed it to be Epstein Barr virus (EBV)-associated lymphoma of B-cell phenotype stage IE (bulky mass), with positive EBV-encoded small RNAs (EBERs) in situ hybridization, EBV latent membrane protein-1 (LMP-1) negative, EB nuclear antigen-2 (ERNA-2) negative, CD20/L26 ( ), CD45RO/UCHL-1 (-). A single band of the joined termini of the EBV genome was demonstrated in dna extracted from the mass, suggesting a clonal disorder of the mass. Immunostaining of the mass with p53 antibody was also positive. With discontinuation of MTX and administration of chemotherapy, the tumor disappeared but recurred after 3 months. This case suggests that concordant p53 expression and latent EBV infection may play an important role in the pathogenesis of lymphomas arising in patients with rheumatoid arthritis who are immunosuppressed with MTX.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
3/8. methotrexate-induced pulmonary lymphoma.methotrexate has proven to be effective in treating rheumatoid arthritis (RA), and is believed to be nononcogenic in the low weekly dose typically employed in the patients with RA. We report, however, a patient with RA in whom a rapidly enlarging diffuse large B-cell lymphoma developed in the left upper lung after weekly treatment with methotrexate for 5 years. The patient had a positive serum IgG for Epstein-Barr virus but a negative in situ hybridization of the resected specimen. methotrexate therapy was discontinued, and the patient elected for clinical observation instead of chemotherapy or radiation therapy. There has been no clinically detectable recurrence of the lymphoproliferative disorder for 2 years. We believe that methotrexate has an oncogenic potential even in low weekly dosing in a subset of patients with RA and latent Epstein-Barr virus infection. The strongest causal link is demonstrated by the persistent tumor remission after stopping treatment with methotrexate.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
4/8. Atypical lymphoplasmacytic and immunoblastic proliferation from rheumatoid arthritis: a case report.A case of atypical lymphoplasmacytic and immunoblastic proliferation (ALPIBP) in the lymph nodes associated with well-documented rheumatoid arthritis (RA) is presented. A 68-year-old Japanese female with a 6-year history of RA presented with right neck lymphadenopathy of 3 months duration. A biopsy specimen showed paracortical hyperplasia and numerous lymphoid follicles. On high-power field, the paracortical area was diffusely infiltrated by a polymorphous population consisting of numerous mature plasma cells, plasmacytoid cells, immunoblasts, including Hodgkin-like cells, small- to medium-sized lymphocytes, and histiocytes. Immunohistochemical study demonstrated that immunoblasts usually were CD20 , and a portion of them was CD30 . The histomorphological findings of the present case are similar to those of methotrexate (MTX)-induced atypical lymphoproliferative disorders (LPDs) in some aspects. However, Epstein-Barr virus-encoded small rna-positive cells were not identified by in situ hybridization. The polytypic nature of B lymphocytes also was demonstrated by immunohistochemistry and polymerase chain reaction. Moreover, there was no history of MTX therapy in the present case, indicating that MTX-induced, LPD-like ALPIB may occur even in the RA patients not treated with MTX therapy.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
5/8. Epstein-Barr virus clonality in lymphomas occurring in patients with rheumatoid arthritis.OBJECTIVE: A causative role for Epstein-Barr virus (EBV) in the development of lymphoma in patients with rheumatoid arthritis (RA) has been proposed. We investigated the molecular features of EBV-positive diffuse large cell lymphomas in 2 patients with RA. methods: Southern blot analysis for immunoglobulin gene rearrangements, terminal repeat analysis for clonality of the EBV genome, and double-labeling of the lymphoma cells by in situ hybridization and immunoperoxidase staining were performed. RESULTS: In both cases, double-labeling studies localized the EBV genome to the malignant B cells. Both neoplasms contained clonal immunoglobulin gene rearrangements and clonal EBV genomes. CONCLUSION: Our data indicate that EBV infection was an early step in the development of these neoplasms. The findings further extend knowledge on the similarity of this subset of lymphomas to posttransplantation lymphomas and emphasize the role of immunosuppression in their genesis.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
6/8. Epstein-Barr virus and lymphoproliferation in methotrexate-treated rheumatoid arthritis.Generalized lymphadenopathy developed in a 60-year-old female receiving methotrexate and prednisone for treatment of rheumatoid arthritis. Histologic examination of an enlarged right axillary lymph node revealed effacement of normal architecture by a polymorphic population of lymphocytes. The recognition that the patient was medically immunosuppressed and the similarity of lymph node histology to that of a polymorphic post-transplantation lymphoid proliferation led to suspicion that the adenopathy might represent an immunosuppression-related lymphoid proliferation. This possibility was supported by regression of the adenopathy on discontinuation of methotrexate, despite continued corticosteroid therapy, which is an outcome reminiscent of the remissions observed with reduction of immunosuppressive therapy in post-transplantation lymphoproliferative disorders. Subsequent ancillary laboratory studies of lymph node tissue included genetic probe analysis, which revealed a monoclonal population of b-lymphocytes containing clonal Epstein-Barr virus dna. in situ hybridization studies performed on lymph node tissue revealed expression of Epstein-Barr virus-encoded rna 1 transcripts, and immunohistochemical studies revealed expression of Epstein-Barr virus latent membrane protein 1. These ancillary studies confirmed the similarity to post-transplantation lymphoproliferative disorder. Although immunosuppression-related lymphoproliferative disorders share features with malignant lymphoma, the possibility of resolution in situations in which immunosuppression can be reversed provides a distinction from true malignancy and is of profound importance in therapeutic decision making.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
7/8. methotrexate-associated lymphoma in patients with rheumatoid arthritis: report of two cases.This report describes 2 patients with longstanding seropositive rheumatoid arthritis (RA) treated with oral methotrexate (MTX) who developed large cell lymphoma of B cell phenotype. in situ hybridization studies showed nuclear staining for Epstein-Barr virus (EBV) within the malignant lymphoid cells. In both cases, the lymphoma was undetectable several weeks after diagnostic biopsy followed by discontinuation of MTX. These observations suggest that, in patients with RA who develop an EBV-associated lymphoproliferative disorder, a trial of discontinuation of immunosuppressive agents may be warranted before chemotherapy is considered. In addition, there is a need for a heightened awareness of the development of lymphoma in this patient population.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
8/8. Acute myeloid leukemia after azathioprine treatment for autoimmune diseases: association with -7/7q-.azathioprine is used as an immunosuppressant in a variety of clinical situations, and its prolonged use is associated with an increased risk of solid malignancies. Three patients (one with rheumatoid arthritis and two with systemic lupus erythematosus) treated with azathioprine for 3 to 7 years developed acute myeloid leukemia (AML). The total cumulative doses of azathioprine varied from 89-260 g. An antecedent prolonged pancytopenic phase suggestive of myelodysplasia developed in all the cases. Morphological analysis showed AML with trilineage myelodysplastic features in residual marrow cells in all the cases. Karyotypic analysis showed deletion of the long arm of chromosome 7 (7q-) in one case and monosomy 7 (-7) in two cases. These were chromosomal aberrations typically associated with mutagen- or therapy-related AML. fluorescence in situ hybridization with a chromosome-7-specific dna probe was used to investigate the distribution of the monosomy 7 clone in two cases. monosomy 7 was demonstrated in both the leukemic blasts and the residual myeloid cells of various stages of differentiation. This finding indicated that the leukemia had evolved from a mutated clone that was capable of terminal differentiation, which was consistent with the biological characteristics of the myelodysplastic syndromes. These cases represented therapy-related AML, as evidenced by clincopathological features, karyotypic aberrations of 7q-/-7, and demonstration of leukemic evolution from an underlying clonal myeloid disorder. The data support the hypothesis that azathioprine might be directly mutagenic.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |