BackgroundCyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors.

Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon, but aggressive nodal peripheral T-cell lymphoma. Little is known of its biology and its natural history has been poorly studied. We report the first comprehensive study on the natural history/histologic progression of AITL by reviewing consecutive biopsies in 31 cases. Immunostaining for CD3, CD20, CD10 and CD21, CD23, CNA-42, CD4, CD8, and Ki 67, in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA and polymerase chain reaction for T-clonality and B-clonality were performed. Histologic progression from AITL with limited nodal involvement and hyperplastic follicles (pattern I) to typical AITL with or without regressed follicles (patterns II and III) was observed in 7 cases, one of which relapsed subsequently as pattern I. Thirteen cases showed typical AITL at presentation and follow-up. Eleven cases where polymerase chain reaction results for T-cell receptor-gamma gene rearrangement were directly compared showed an identical band-size in the initial and follow-up biopsies. Seven cases (23%) developed EBV-associated B-cell lymphomas [5 diffuse large B-cell lymphoma (DLBCL) and 2 classic Hodgkin lymphoma]. In 4 cases, a dominant B-cell clone was observed in biopsies lacking evidence of DLBCL. A single case was complicated by EBV-negative DLBCL, whereas another with large cell transformation had a T-cell phenotype. In conclusion, AITL represents a clonal T-cell proliferation with a stable T-cell clone throughout the disease. Partial nodal involvement with hyperplastic follicles is seen in early AITL and at relapse. When "morphologic high-grade transformation" occurs, it is usually due to a secondary (often EBV-associated) B-cell lymphoma, rather than a T-cell neoplasm.

In approximately 5% to 10% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas, evidence of Helicobacter pylori infection is absent, and their pathogenesis is poorly understood. We reviewed the clinical data and histology, and we examined t(11;18)(q21;q21) and BCL10 expression pattern in 17 such cases. In each case, the absence of H pylori was confirmed by negative serology and histology/immunohistochemistry. Five cases with stage I E disease were first treated with antibiotics, and none of them showed any endoscopic or histologic response. Review of the histology failed to identify any apparent difference between gastric MALT lymphomas with and without H pylori infection. Reverse transcription-polymerase chain reaction (RT-PCR) showed t(11;18)(q21;q21) in 9 (53%) of 17 cases, more frequent in lymphomas at stage II E or above (5 of 6) than those at stage I E (3 of 10). Two t(11;18)(q21;q21)-positive lymphomas were treated by partial gastrectomy and more than 16 years later showed lymphoma relapse in the gastric stump with dissemination to other mucosal sites, poorly responsive to therapy. BCL10 nuclear expression was observed in 7 of 8 t(11;18)(q21; q21)-positive cases and 4 of 7 t(11;18)(q21; q21)-negative cases, including one case suspicious for a BCL10-involved chromosomal translocation. Our results show that t(11;18)(q21;q21) occurs at a high frequency in H pylori-negative gastric MALT lymphomas. Translocation-positive gastric MALT lymphomas tend to be aggressive, and patients with such lymphomas might benefit from prompt treatment and close follow-up.

Summary The clinical and histological presentations of angioimmunoblastic T‐cell lymphoma (AITL) often mimic an infectious process. Epstein–Barr virus (EBV) and human herpes virus (HHV6) are known to be associated with AITL, but whether these viral infections play a role in its pathogenesis is unclear. It also remains to be investigated whether there might be other viruses associated with AITL. We first screened 26 well‐characterised cases of AITL for herpesvirus by polymerase chain reaction (PCR) with universal primers and found evidence of only EBV and HHV6B infection. Subsequent PCR using virus‐specific primers demonstrated EBV and HHV6B infection in 40/49 biopsies (36/42 cases) and 21/49 biopsies (19/42 cases) of AITL respectively with both viral infections found in 17/49 specimens (15/42 cases). Importantly, simultaneous infection with both viruses was found only in specimens showing histological pattern II (n = 2) or III (n = 15). Interestingly, among specimens containing both viruses, there was a tendency towards an inverse correlation between the EBV and HHV6B viral load as shown by quantitative PCR. In specimens positive only for EBV, the viral load was significantly higher in specimens with histological pattern III than those with pattern II. High EBV load was also significantly associated with B‐cell monoclonality. Double EBV encoded small RNA (EBER) in situ hybridisation and immunohistochemistry indicated that EBV‐infected B cells had a late postgerminal centre immunophenotype. Our results demonstrate an association between EBV and HHV6B infection and the histological progression of AITL, suggesting that these viruses may play a role in the pathogenesis of this lymphoma.