EBV+ B Lymphoma Cell Lines from Patients with Post-Transplant Lymphoproliferative Disease Are Resistant to TRAIL-Induced Apoptosis

Lymphomas associated with post-transplant lymphoproliferative disease (PTLD) represent a significant complication of immunosuppression in transplant recipients. In immunocompetent individuals, EBV-specific cytotoxic T lymphocytes (CTL) prevent the outgrowth of activated B lymphoblasts through apoptosis induction. Soluble versions of TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL) can induce apoptosis in numerous tumor cell types. Given the therapeutic potential of TRAIL, we examined the sensitivity of EBV⁺ spontaneous lymphoblastoid cell lines (SLCL) derived from patients with PTLD to treatment with soluble TRAIL. Despite abundant expression of TRAIL receptors (TRAIL-R), resistance to TRAIL-induced apoptosis was observed in all SLCL examined. This resistance could not be overcome by concomitant treatment with several pharmacological agents. Unlike BJAB positive control cells, for each SLCL tested, cleavage and activation of caspase 8 was inhibited due to failed recruitment of FADD and caspase 8 to TRAIL receptors upon stimulation. Further indicative of a proximal defect, TRAIL receptor aggregation could not be detected on the cell surface of SLCL following ligand engagement. These results suggest that the use of TRAIL for eliminating PTLD-associated tumors may be of limited clinical utility, and illustrate another mechanism by which EBV⁺ B lymphoma cells can evade tumor surveillance at the level of death receptor signaling.     

Pathological variables determining the prognosis of non-Hodgkin''s lymphomas

The aim of the study was to assess the role of pathological grade, cell proliferation, ploidy, immunophenotype and site in determining the prognosis of non-Hodgkin's lymphomas. Of particular interest was the relative value of grades derived from the Kiel classification as opposed to the National Cancer Institute (NCI) working formulation. The study consisted of 181 cases, treated in a relatively uniform way over an 18-month period spanning 1986. Using life table analysis, both NCI working formulation grade and Kiel grade correlated strongly with survival. However, the differences between grades were entirely due to an excess of early deaths in the high-grade and intermediate-grade categories. In patients surviving greater than 0.1 years (37 days), phenotype, site, ploidy and cell proliferation had no effect on survival. There was no evidence that intermediate-grade tumours, when subdivided into Kiel low- and high-grade types, differed in survival from tumours graded as low- or high-grade by both methods. However, NCI working, formulation high-grade tumours, especially those with a high proliferation rate, formed a group with a very high likelihood of death within 0.1 years.     

Nasopharyngeal and nasal malignant lymphoma: a clinicopathological study of 54 cases

Forty-one cases of nasopharyngeal and 13 cases of nasal malignant lymphoma have been examined histologically and immunohistochemically. All of the cases were non-Hodgkin's lymphoma; one case was of follicular type and the remaining 53 were of diffuse type. Large cell lymphoma comprised 48% of cases and most of the immunoblastic lymphomas showing pleomorphism occurred in the nose. Twenty-seven cases were of T-cell and 21 of B-cell phenotype. The predominance of T-cell lymphoma was due to an increased incidence of these in the nose, the T:B ratio of 3.33:1 contrasting with a 1:1.05 ratio in the nasopharynx. Nasopharyngeal lymphomas seem to show an intermediate incidence between the T-cell predominance in the nose and a B-cell predominance in the oropharynx. Since the large cell type of lymphoma was predominant, the differential diagnosis from undifferentiated carcinoma is important and is facilitated by the use of immunostaining methods.     

Malignant lymphoma. Pathology, diagnosis, therapy

Summary Malignant lymphomas can be subdivided into Hodgkin's disease and low- or high-grade non-Hodgkin's lymphoma (NHL). The principal therapeutic options are polychemotherapy and radiotherapy. Besides the histological classification, staging of the disease with particular regard to risk factors is an essential prerequisite for the therapeutic decision. Diagnostic imaging modalities such as computer tomography, magnetic resonance imaging, and ultrasonography have improved the accuracy of clinical staging such that invasive pathological staging is only necessary in exceptional cases. A novel therapeutic approach is high-dose chemotherapy with autologous haematopoietic stem-cell support. This treatment improves the survival of patients with relapsed high-grade NHL. The place of high-dose therapy as the primary therapeutic option in malignant lymphoma is now being assessed in prospective studies following encouraging results from single-centre studies, including those involving the treatment of low-grade lymphoma. The effects of antibodies directed against lymphatic cells are currently being examined in experimental treatments. An assessment of the viability and rate of proliferation of lymphoma tissue on completion of therapy using sensitive radiological and nuclear medical methods is an important aim for the future. Eingegangen am 5. November 1996 Angenommen am 12. November 1996     

Primary gastrointestinal lymphomas in Turkey: a retrospective analysis of clinical features and results of treatment.

Thirty-three patients with primary gastrointestinal lymphoma (GIL) followed at Ankara University Medical School have been evaluated. The most frequent locations of the disease are the small intestine (48.4%) and the stomach (39.3%). The intermediate and high grade lymphomas constitute 84.8% of the cases. The mean age of the patients with small intestinal lymphoma is 28.7 years and 47.1 years for those with gastric lymphoma. The patients treated with surgery and chemotherapy (S+CT) have a longer survival than those treated with chemotherapy (CT) alone. In conclusion: 1) Small intestinal lymphoma occurs more frequently than gastric lymphoma in our study. 2) The median age of the Turkish patients with primary GIL is approximately 10 years less than those in the Western countries. 3) The therapeutic results of S+CT are superior to those of CT in the early stages of the disease.     

Distribution of extracellular matrix components and their receptors in human lymphoid tissue and B-cell non-Hodgkin lymphomas

In this study the distribution patterns of various extracellular matrix components and their receptors (i.e. β1 integrins) in B-cell non-Hodgkin lymphomas were examined and compared to those in reactive lymphoid tissue. Neoplastic follicles within follicular lymphomas showed similar patterns to that observed in reactive follicles, which appeared to be strongly associated with the presence of follicular dendritic cells. Diffuse lymphomas of low and intermediate malignancy grade revealed features comparable to those of interfollicular areas of reactive lymphoid tissue, irrespective to which compartment the tumour cells were related. Highly malignant lymphomas, however, displayed unique extracellular matrix configurations, resulting from active matrix degradation by macrophages; this may support rapid tumour growth. Extranodal lymphomas showed virtually the same matrix patterns as their nodal counterparts, suggesting that (malignant) lymphoid cells generate (at least partly) their own specific microenvironment. In reactive lymphoid tissue β1 integrins were mainly found on resident cells and except for α4, α5 (and β1) the lymphoid cells expressed very little, if any, β1 integrins. In comparison, expression of these integrins on lymphoma cells was reduced (follicular lymphomas) or could not be detected at all (diffusely growing lymphomas); this might contribute to the growth pattern and metastatic properties of the tumours.     

Primary lymphoma of the mandible with diffuse widening of the mandibular canal: report of a case

A case of primary non-Hodgkin's lymphoma (NHL) of the mandible with unusual radiographic presentation is reported. The panoramic radiography revealed diffuse widening of the right mandibular canal with ill-defined margins and absence of edge sclerosis. Computed tomography showed infiltration of the superior portion of the canal with involvement of the vestibular cortex of the bone and of the alveolar ridge. Correspondence to: M. Bertolotto     

Leukemia,lymphoma, and multiple myeloma following selected medical conditions

The role of selected prior medical conditions in the etiology of hematopoietic malignancies was examined in a case-control study of members of two regional branches of the Kaiser Permanente Medical Care Program (USA). Past history of chronic infectious, autoimmune, allergic, and musculoskeletal disorders was abstracted from medical records for leukemia (n = 299), non-Hodgkin's lymphoma (NHL, n = 100), and multiple myeloma (n = 175) cases and matched controls (n = 787). Little difference was found between cases and controls for most of the chronic conditions evaluated, including sinusitis, carbuncles, urinary tract infections, pelvic infections, herpes zoster, asthma, rheumatoid arthritis, psoriasis, bursitis, and gout. Only three statistically significant elevated risks were found, i.e., with combined disc disease myeloma among patients with prior eczema and disk and other musculoskeletal conditions, and NHL following tuberculosis. Only two of these associations showed consistent patterns by sex and geographic region (myeloma with eczema and with musculoskeletal conditions). While prior history of eczema and musculoskeletal conditions may slightly increase risk of myeloma, this study provided little if any support for an association of chronic infectious, autoimmune, allergic, and musculoskeletal conditions with subsequent occurrence of the leukemias or NHL. Additionally, these data did not support a role for chronic antigenic stimulation, as defined in previous epidemiologic studies, in the etiology of hematopoietic malignancies.Ms Doody and Drs Linet, Pottern, Boice, and Fraumeni are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Glass is with the Kaiser Permanente Medical Care Program, Northwest Region, Portland, Oregon, USA. Dr Friedman is with the Kaiser Permanente Medical Care Program, Northern California Region, Oakland, California, USA. Address correspondence to Ms Doody, Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 408, Bethesda, MD 20892, USA. This research was supported in part by National Cancer Institute contracts NO1-CP-01047, NO1-CP-01054, NO1-CP-11009, NO1-CP-11037, NO1-CP-31035, and NO1-CP-61006.     

High-grade T-cell lymphoma following treatment with cyclosporin A

A 47-year-old man with persistent severe oropharyngeal ulceration developed a high-grade T-cell lymphoma soon after commencing treatment with cyclosporin A. Using Southern blotting to identify T-cell beta-chain gene rearrangements, evidence of clonal restriction was found both in blood and lymph node DNA samples. Two BamH1 rearranged bands were demonstrated in both samples. In the blood a 16 Kb band predominated, with a weaker 28 kb band. In the lymph node sample this pattern was reversed. The findings suggest that a bi-clonal population of T-lymphocytes or clonal evolution of an existing T-cell monoclone had developed, and that cyclosporin contributed to the emergence of a high-grade T-cell lymphoma.