Helicobacter pylori and malignant lymphoma in Spain.

UNLABELLED: Helicobacter pylori has been associated with gastric adenocarcinoma and gastric lymphoma. We report on the systematic evaluation of serologic detection of H. pylori in a lymphoma case-control study. METHODS: Cases (N = 536) were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002 in four centers in Spain. Lymphomas were diagnosed and classified using the WHO Classification. Controls (N = 603) were hospitalized patients frequency-matched to the cases by 5-year age group, sex, and study center. Severe immunocompromised patients were excluded as controls. Patients underwent a personal interview and blood sampling. H. pylori infection was evaluated by the presence of IgG antibodies using the Premier enzyme immunoassay kit (Meridian Diagnostics Inc., Cincinnati, OH). Logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals (OR, 95% CI) for lymphoma categories. RESULTS: Anti-H. pylori antibodies were detected in 68.5% of the cases and 71.3% of the controls (P = 0.29) H. pylori was associated with a 3-fold excess risk of splenic marginal B-cell lymphoma (OR = 3.97, 95% CI = 0.92-17.16). H. pylori was not associated with an overall increased risk of extranodal lymphomas (OR = 0.73, 95% CI = 0.44-1.22) but when specific sites were explored, the four mucosa-associated lymphoid tissue and the six diffuse large B-cell lymphomas primary localized in the stomach were all H. pylori seropositive. CONCLUSION: Persistent infection with H. pylori may be implicated in the development of lymphomas of the gastric mucosa and of the spleen. These results could have clinical implications in the management of splenic marginal zone lymphomas.

Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities.

Plasmablastic lymphoma was initially described as a variant of diffuse large B-cell lymphoma (DLBCL) involving the oral cavity of HIV+ patients and characterized by immunoblastic morphology and a plasma cell phenotype. However, other lymphomas may exhibit similar morphologic and immunophenotypic features. To determine the significance of plasmablastic differentiation in DLBCL and examine the heterogeneity of lymphomas with these characteristics, we examined 50 DLBCLs with low/absent CD20/CD79a and an immunophenotype indicative of terminal B-cell differentiation (MUM1/CD38/CD138/EMA-positive). We were able to define several distinct subgroups. Twenty-three tumors were classified as plasmablastic lymphoma of the oral mucosa type and showed a monomorphic population of immunoblasts with no or minimal plasmacytic differentiation. Most patients were HIV+ and EBV was positive in 74%. Eleven (48%) cases presented in the oral mucosa, but the remaining presented in other extranodal (39%) or nodal (13%) sites. Sixteen cases were classified as plasmablastic lymphoma with plasmacytic differentiation. These were composed predominantly of immunoblasts and plasmablasts, but in addition exhibited more differentiation to mature plasma cells. Only 33% were HIV+, EBV was detected in 62%, and 44% had nodal presentation. Nine cases, morphologically indistinguishable from the previous group, were secondary extramedullary plasmablastic tumors occurring in patients with prior or synchronous plasma cell neoplasms, classified as multiple myeloma in 7 of the 9. Two additional neoplasms were an HHV-8+ extracavitary variant of primary effusion lymphoma and an ALK+ DLBCL. HHV-8 was examined in 39 additional cases, and was negative in all. In conclusion, DLBCLs with plasmablastic differentiation are a heterogeneous group of neoplasms with different clinicopathological characteristics that may correspond to different entities.

Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classic Hodgkin lymphoma.

Around 20% to 30% of patients with Hodgkin lymphoma (HL) do not benefit from standard therapies and finally succumb to their disease. The factors that influence the outcome of HL have not been elucidated, underscoring the demand for the identification of biologic risk factors and new therapeutic targets. We analyzed the gene expression profiles of samples from 29 patients with advanced classic HL treated with standard therapy and compared the expression profiles of patients with favorable and unfavorable clinical outcome. Using supervised methods, we identified 145 genes associated with outcome, which were grouped into 4 signatures representing genes expressed by either the tumoral cells (genes involved in the regulation of mitosis and cell growth/apoptosis) or the tumor microenvironment. The relationship between the expression of 8 representative genes and survival was successfully validated in an independent series of 235 patients by quantification of protein expression levels on tissue microarrays. Analysis of centrosomes and mitotic checkpoint confirmed the existence of an abnormal transition through mitosis in HL cells. Therefore, genes related to tumor microenvironment, cell growth/apoptosis, and regulation of mitosis are associated with treatment response and outcome of patients with HL.

Celiac disease and lymphoma risk: a multicentric case--control study in Spain.

Celiac disease is a highly prevalent condition frequently misdiagnosed because of heterogeneity of the clinical symptoms. It is well recognized that enteropathy-associated T-cell lymphoma is an uncommon lymphoma type linked to celiac disease; it has also been suggested that other types of lymphomas may be associated with celiac disease. Our aim was to estimate the risk of all lymphoma associated with celiac disease. Serological markers and personal interviews were obtained from 298 consecutive lymphoma cases and 251 matched controls recruited in four Spanish hospitals. Celiac disease was detected in two cases (0.67%; n = 298) and in three controls (1.2%; n = 251). Treated celiac disease was observed in one patient with lymphoma and in two control subjects. In our series, there was no evidence that celiac disease was a risk factor for lymphoma (OR = 0.62, 95% CI = 0.10-3.79). Serological screening for CD is not recommended in people with lymphoma.

Lack of serological evidence for an association between simian virus 40 and lymphoma.

Recent studies have implicated simian virus 40 (SV40) in non-Hodgkin's lymphomas based on detection of SV40 DNA sequences. We employed a virus-like-particle (VLP)-based enzyme immunoassay for antibodies to SV40 to test sera from 520 lymphoma cases and 587 controls in Spain. The SV40 seroprevalence was 9.5% in controls and 5.9% in cases. Antibody levels of the positive sera were low. There was no association of SV40 seropositivity with any subtype of lymphoma. VLPs of the human BK virus substantially inhibited the SV40 reactivity of human sera. There was no serological evidence of widespread SV40 infection and no association of SV40 seropositivity with human lymphomas in Spain.

CD38 expression in B-chronic lymphocytic leukemia: association with clinical presentation and outcome in 155 patients.

BACKGROUND AND OBJECTIVES: To investigate whether CD38 expression at diagnosis is an independent predictor of survival and assess its associations with other clinical parameters used in the staging of B-cell chronic lymphocytic leukemia (B-CLL). DESIGN AND METHODS: CD38 expression was analyzed in 155 consecutive unselected patients newly diagnosed with B-CLL from January 1991 to July 1997. In all cases CD38 expression was evaluated at diagnosis and patients were classified into two groups: those with > or = 30% were considered positive (CD38+) and those with < 30% were considered negative (CD38-). Statistical differences between each group were analyzed using c2 tests for categorical variables and Student's t-tests for continuous variables. Survival analysis was performed at the univariate level by the Kaplan Meier technique and at the multivariate level by Cox hazard models. RESULTS: Thirty (19%) patients were CD38+. CD38+ was associated with atypical morphology (p=0.004), a diffuse bone marrow pattern (p=0.016), Rai stage > or =2 (p=0.009), high lactate dehydrogenase (p=0.02), high b2 microglobulin (p=0.004), and higher lymphocyte count (p=0.02). Furthermore, CD38+ patients required treatment more frequently (p=0.006) and CLL-related mortality was significantly higher (p=0.012). When we divided the study group into patients with Rai 0-1 and Rai 2-4 stages, CD38 positivity was only significantly associated with mortality in the early stage patients (p= 0.012 vs p= 0.68). CD38 expression in the multivariate analysis lost its statistical significance. None of these results was modified when the CD38 cut-off was set at 20%. INTERPRETATION AND CONCLUSIONS: CD38 expression identifies a subgroup of B-CLL patients with aggressive clinical presentation and worse outcome. Its expression is probably associated with other prognostic factors, but the feasibility of determining this parameter makes it easily reproducible and adds prognostic information at diagnosis to aid prediction of the clinical course and outcome of B-CLL.