MUM1 expression dichotomizes follicular lymphoma into predominantly, MUM1-negative low-grade and MUM1-positive high-grade subtypes

We investigated the expression of MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) in 46 cases of follicular lymphoma (FL) and correlated this with grade and expression of CD10, Bcl-6 and Ki-67. The analysis suggests that MUM1 expression dichotomizes FL into low-grade FL of CD10+/Bcl-6+/MUM1−/Ki-67low pheno-type, and high-grade FL of CD10+/−/Bcl-6+/weak/MUM1+/Ki-67high phenotype

Posttransplant Lymphoproliferative Disorders

Posttransplant lymphoproliferative disorders (PTLDs) are a group of diseases that range from benign polyclonal to malignant monoclonal lymphoid proliferations. They arise secondary to treatment with immunosuppressive drugs given to prevent transplant rejection. Three main pathologic subsets/stages of evolution are recognised: early, polymorphic, and monomorphic lesions. The pathogenesis of PTLDs seems to be multifactorial. Among possible infective aetiologies, the role of EBV has been studied in depth, and the virus is thought to play a central role in driving the proliferation of EBV-infected B cells that leads to subsequent development of the lymphoproliferative disorder. It is apparent, however, that EBV is not solely responsible for the “neoplastic” state. Accumulated genetic alterations of oncogenes and tumour suppressor genes (deletions, mutations, rearrangements, and amplifications) and epigenetic changes (aberrant hypermethylation) that involve tumour suppressor genes are integral to the pathogenesis. Antigenic stimulation also plays an evident role in the pathogenesis of PTLDs. Plasmacytoid dendritic cells (PDCs) that are critical to fight viral infections have been thought to play a pathogenetically relevant role in PTLDs. Furthermore, regulatory T cells (Treg cells), which are modulators of immune reactions once incited, seem to have an important role in PTLDs where antigenic stimulation is key for the pathogenesis

Aberrant positivity for CD79a in erythroid lineage cells – a finding observed in a subset of re-staging bone marrow trephine biopsies after treatment

Aberrant expression of CD79a has been reported in neoplastic cells in peripheral T cell lymphoma, T-cell acute lymphoblastic leukemia and acute myeloid leukemia (especially those with t(8;21)). In this report, we document the first report of CD79a positivity in erythroid precursor cells in bone marrow. In all, we document this finding in five of 18 re-staging bone marrow trephine samples in patients of lymphoma treated with chemotherapy (one index case and 17 additional validation cases). It is important to appreciate this finding especially in rituximab treated patients where one tends to rely on CD79a to identify minimal marrow disease

HIV/AIDS-related non-Hodgkin’s lymphomas and confounders: preliminary report of the Sub-Saharan Africa Lymphoma Consortium (SSALC)

CITATION: Ayers, L.W. et al. 2012. HIV/AIDS-related non-Hodgkin’s lymphomas and confounders : preliminary report of the Sub-Saharan Africa Lymphoma Consortium (SSALC). Infectious Agents and Cancer, 7(Suppl 1):P11, doi:10.1186/1750-9378-7-S1-P11.The original publication is available at http://infectagentscancer.biomedcentral.comSSALC was established to characterize HIV/AIDS-related lymphoma and the indigenous background of malignant lymphomas (ML) in sub-Saharan Africa. Because WHO classified lymphoma subgroups can vary in prevalence African, Asian or European ancestry, we surveyed lymphoma heterogeneity in geographically diverse East, South and West sub-Saharan populations, particularly for HIV/AIDS associated immunophenotypes.http://infectagentscancer.biomedcentral.com/articles/10.1186/1750-9378-7-S1-P11Publisher's versio

No Evidence of XMRV or MuLV Sequences in Prostate Cancer, Diffuse Large B-Cell Lymphoma, or the UK Blood Donor Population

Xenotropic murine leukaemia virus-related virus (XMRV) is a recently described retrovirus which has been claimed to infect humans and cause associated pathology. Initially identified in the US in patients with prostate cancer and subsequently in patients with chronic fatigue syndrome, doubt now exists that XMRV is a human pathogen. We studied the prevalence of genetic sequences of XMRV and related MuLV sequences in human prostate cancer, from B cell lymphoma patients and from UK blood donors. Nucleic acid was extracted from fresh prostate tissue biopsies, formalin-fixed paraffin-embedded (FFPE) prostate tissue and FFPE B-cell lymphoma. The presence of XMRV-specific LTR or MuLV generic gag-like sequences was investigated by nested PCR. To control for mouse DNA contamination, a PCR that detected intracisternal A-type particle (IAP) sequences was included. In addition, DNA and RNA were extracted from whole blood taken from UK blood donors and screened for XMRV sequences by real-time PCR. XMRV or MuLV-like sequences were not amplified from tissue samples. Occasionally MuLV gag and XMRV-LTR sequences were amplified from Indian prostate cancer samples, but were always detected in conjunction with contaminating murine genomic DNA. We found no evidence of XMRV or MuLV infection in the UK blood donors

Lymphomas in sub-Saharan Africa - what can we learn and how can we help in improving diagnosis, managing patients and fostering translational research?

Approximately 30 000 cases of non-Hodgkin lymphoma (NHL) occur in the equatorial belt of Africa each year. Apart from the fact that Burkitt lymphoma (BL) is very common among children and adolescents in Africa and that an epidemic of human immunodeficiency virus (HIV) infection is currently ongoing in this part of the world, very little is known about lymphomas in Africa. This review provides information regarding the current infrastructure for diagnostics in sub-Saharan Africa. The results on the diagnostic accuracy and on the distribution of different lymphoma subsets in sub-Saharan Africa were based on a review undertaken by a team of lymphoma experts on 159 fine needle aspirate samples and 467 histological samples during their visit to selected sub- Saharan African centres is presented. Among children (age), BL accounted for 82% of all NHL, and among adults, diffuse large B-cell lymphoma accounted for 55% of all NHLs. Among adults, various lymphomas other than BL, including T-cell lymphomas, were encountered. The review also discusses the current strategies of the International Network of Cancer Treatment and Research on improving the diagnostic standards and management of lymphoma patients and in acquiring reliable clinical and pathology data in sub- Saharan Africa for fostering high-quality translational research

The alteration of lipid metabolism in burkitt lymphoma identifies a novel marker: adipophilin

Background: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. Methods and Results: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymphoma and in other B-cell aggressive lymphoma cases. Gene expression profile indicated a significant over-expression of the adipophilin gene and marked up-regulation of other genes involved in lipid metabolism in Burkitt lymphoma. These findings were confirmed by immunohistochemistry on a series od additional histological samples: 45 out of 47 BL cases showed strong adipophilin expression, while only 3 cases of the 33 of the not-Burkitt lymphoma category showed weak adipophilin expression (p<0.05). Conclusions: Our preliminary results suggest that lipid metabolism is altered in BL, and this leads to the accumulation of lipid vacuoles. These vacuoles may be specifically recognized by a monoclonal antibody against adipophilin, which may therefore be a useful marker for Burkitt lymphoma because of its peculiar expression pattern. Moreover this peptide might represent an interesting candidate for interventional strategies. © 2012 Ambrosio et al

In situ mantle cell lymphoma: clinical implications of an incidental finding with indolent clinical behavior

Background Cyclin D1-positive B cells are occasionally found in the mantle zones of reactive lymphoid follicles, a condition that has been called 'in situ mantle cell lymphoma'. The clinical significance of this lesion remains uncertain. Design and Methods The clinical and pathological characteristics, including SOX11 expression, of 23 cases initially diagnosed as in situ mantle cell lymphoma were studied. Results Seventeen of the 23 cases fulfilled the criteria for in situ mantle cell lymphoma. In most cases, the lesions were incidental findings in reactive lymph nodes. The t(11; 14) was detected in all eight cases examined. SOX11 was positive in seven of 16 cases (44%). Five cases were associated with other small B-cell lymphomas. In two cases, both SOX11-positive, the in situ mantle cell lymphoma lesions were discovered after the diagnosis of overt lymphoma; one 4 years earlier, and one 3 years later. Twelve of the remaining 15 patients had a follow-up of at least 1 year (median 2 years; range, 1-19.5), of whom 11 showed no evidence of progression, including seven who were not treated. Only one of 12 patients with an in situ mantle cell lymphoma lesion and no diagnosis of mantle cell lymphoma at the time developed an overt lymphoma, 4 years later; this case was also SOX11-positive. The six remaining cases were diagnosed as mantle cell lymphoma with a mantle zone pattern. Five were SOX11-positive and four of them were associated with lymphoma without a mantle zone pattern. Conclusions In situ mantle cell lymphoma lesions are usually an incidental finding with a very indolent behavior. These cases must be distinguished from mantle cell lymphoma with a mantle zone pattern and overt mantle cell lymphoma because they may not require therapeutic intervention