José-Luis Mate

Hepatosplenic T-Gammadelta Lymphoma in a Patient with Crohn's Disease Treated with Azathioprine

Hepatosplenic γ δ T-cell lymphoma (HS γ δ TCL) is an uncommon type of peripheral T-cell lymphoma, which has been associated in some cases with immunosuppression, mainly after solid organ transplants. We describe a case of HS γ δ TCL with a leukaemic course in a patient with Crohns disease who had received azathioprine during the previous 55 years. Sinusoidal infiltration by atypical lymphocytes was observed in the liver, spleen and bone marrow and the typical cytogenetic abnormalities (isochromosome 7 and trisomy 8) were found. The patient did not respond to intensive chemotherapy. This case shows the importance of ruling out HS γ δ TCL in patients with hepatosplenomegaly, B-symptoms and any immunosuppressive condition.

Translocation (3;8)(q27;q24) in two cases of triple hit lymphoma.

Unclassifiable lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma is a new category of B-cell lymphoma appearing in the new World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. This lymphoma usually shows MYC rearrangements with non-IGH genes in the setting of a complex karyotype possibly involving BCL2 and, less frequently, BCL6 rearrangements. According to the presence of two or three rearrangements, these lymphomas are called double-hit lymphomas or triple-hit lymphomas (THL), respectively. Here we report two cases of THL with MYC, BCL2, and BCL6 rearrangements and t(3;8)(q27;q24) diagnosed in one center in the last two years.

Decrease in the frequency of meningeal involvement in AIDS-related systemic lymphoma in patients receiving HAART

We evaluated the frequency of primary central nervous system lymphoma and leptomeningeal involvement in systemic non-Hodgkin’s lymphoma (NHL) in HIV-infected patients. Those receiving highly active antiretroviral therapy (HAART) showed a decrease in leptomeningeal involvement in systemic NHL (0/30 vs. 12/87; p=0.023). Therefore HAART could prevent CNS involvement in systemic NHL.

Usefulness of tumor markers CA 125 and CA 15.3 at diagnosis and during follow-up in non-Hodgkin's lymphoma : study of 200 patients

CA 125 and CA 15.3 serum levels were measured at diagnosis, after treatment and at the time of recurrence in 200 consecutive patients (114 males, median age 56 years) with non-Hodgkins lymphoma (NHL) to explore its usefulness in the evaluation of response to treatment and survival in patients with NHL compared to lactate dehydrogense (LDH) and β2-microglobulin (β2-M). Their association with the clinical – biologic parameters at diagnosis, response to treatment, event-free survival (EFS) and overall survival (OS) was analysed. Eighty-six patients (43%) had elevated CA 125 levels and 35 (17.5%) had elevated CA 15.3 levels at diagnosis. CA 125 was associated with advanced stage, lung, pleural or gastrointestinal tract involvement and CA 15.3 was correlated with advanced stage, bone involvement, aggressive histology and bulky disease. LDH had the highest predictive value for failure to achieve complete remission (P = 0.001). A shorter OS was associated with increased LDH (P < 0.0001), β2-M (P = 0.013) and CA 125 (P = 0.025) whereas CA 15.3 was associated with a shorter EFS (P = 0.027). When elevated at diagnosis, CA 125 and CA 15.3 should be monitored during follow-up of patients with NHL.

Favorable Impact of Virological Response to Highly Active Antiretroviral Therapy on Survival in Patients with AIDS-related Lymphoma

We have retrospectively studied the influence of highly active antiretroviral therapy (HAART) on the outcome of AIDS-related lymphomas (ARL) as well as the possible influence of the virological response to HAART on complete response (CR) rate and survival in our series of ARL treated with CHOP. Two groups of patients were studied: (1) 44 patients who did not take HAART when the lymphoma was diagnosed, and (2) 26 patients treated with HAART concomitantly and after chemotherapy. There were 4 (9%) women in group 1 versus 11 (42%) in group 2 (P =0.01), and serum lactate dehydrogenase (LDH) level was lower in group 2. The response rate to CHOP was higher in group 2 patients (15 out of 23, 65%) than in those of group 1 (16 out of 44, 36%) (P =0.025). The factors associated with improvement of CR in the multivariate analysis were the administration of HAART (P =0.004) and International Prognostic Index (IPI) score ≤ 2 (P =0.006). Among group 2 patients, those with a virological response to HAART and with IPI score ≤ 2 had better response rate to chemotherapy (odds ratios 9.3 and 11.8, respectively). The median (95% CI) overall survival (OS) for group 1 patients was 7 (3-11) months, whereas it has not been reached for group 2 (P =0.002). The only parameters influencing OS in the multivariate analysis were HAART (0.003), as a protective factor and IPI score>2 (P =0.015) with negative influence. Among patients treated with HAART, those with virological response had higher OS probability (P =0.004), whereas those with IPI score>2 had an unfavorable prognosis (P =0.014). The only variable with statistical significance for disease free survival (DFS) in the univariate and multivariate analyses was HAART (P =0.0168 and P =0.028, respectively). We conclude that HAART is an independent prognostic factor for CR attainment, OS and DFS in patients with ARL treated with CHOP. Those patients with virological response to HAART had a better survival.

MYC protein expression is associated with poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

MYC and BCL2 gene translocations and protein expression have recently demonstrated to be of prognostic significance in systemic diffuse large B‐cell lymphoma (DLBCL). However, their role in primary central nervous system DLBCL (CNS‐DLBCL) prognosis has been scarcely analyzed. We studied the immunophenotype, the status of the MYC, BCL2, and BCL6 genes and the clinical features of a series of 42 CNS‐DLBCL and evaluated their prognostic significance. We found high MYC protein expression in 43% of cases, and this was associated with lower overall survival (OS). Cases with concurrent expression of MYC and BCL2 showed a lower OS, although the difference did not reach statistical significance. Translocations involving the MYC or BCL2 genes were not detected. The BCL6 gene was frequently translocated, but was unrelated to survival. We conclude that MYC protein expression detected by immunohistochemistry identifies a CNS‐DLBCL subset with worse prognosis and may contribute to a more accurate risk stratification of CNS‐DLBCL patients.

Primary myeloid sarcoma of the gynecologic tract: a report of two cases progressing to acute myeloid leukemia.

Primary gynecologic myeloid sarcomas are rare, and their diagnosis is often difficult. Differential diagnosis includes lymphomas and carcinomas of the gynecologic tract. We report the clinical, morphological, immunohistochemical and cytogenetic features of two cases of chloromas of the female genital tract, which progressed to acute myeloid leukemia in spite of aggressive therapy.

Immunohistochemical expression profile and prognosis in patients with diffuse large B-cell lymphoma with or without human immunodeficiency virus infection.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype in non-immunosuppressed and in human immunodeficiency virus (HIV)-positive patients. The prognosis of DLBCL with germinal center (GC) phenotype is better than that of the non-germinal center (non-GC) phenotype by immunohistochemical expression profile (IHC) in some studies but not in others. The frequency and the prognosis of these phenotypic subtypes in DLBCL related to HIV infection is not well known. The objectives of this study were to characterize the IHC by tissue microarray in 98 patients with DLBCL, 34 of whom were HIV-positive, and to evaluate their prognosis. Patients with HIV-related DLBCL with a non-GC pattern had poorer prognosis than patients with non-HIV-related DLBCL with the same pattern, but this difference disappeared when we considered only patients receiving HAART.

Effectiveness of Local Radiotherapy in Primary Extranodal Marginal Zone B-cell Lymphoma of MALT or MALT Lymphoma of Conjunctiva: Study of Four Cases

Primary lymphomas of the conjunctiva are extremely infrequent and usually belong to extranodal marginal zone B-cell lymphoma of MALT or MALT lymphoma. Radiotherapy with lens shielding is one of the most employed therapeutic options. Four patients with MALT lymphomas of the conjunctiva with complete and maintained response to radiotherapy are reported. The effectiveness as well as the lack of significant toxicity of radiotherapy are emphasized.

Plasma Epstein-Barr viral load measurement as a diagnostic marker of lymphoma in HIV-infected patients.

BACKGROUND AND OBJECTIVES To assess the use of the Epstein-Barr virus (EBV) viral load as a marker for lymphoma diagnosis in HIV-infected patients. We also aimed to identify the relationship between EBV viral load in plasma and the presence of EBV in lymphoma cells. PATIENTS AND METHODS Retrospective observational study of two HIV-infected populations: one of patients diagnosed with lymphoma and a control group. Thirty-nine patients with AIDS-related lymphoma (ARL) (32 non-Hodgkins and 7 Hodgkins lymphomas) and 134 HIV-positive individuals without neoplasia or opportunistic infections were studied. Blood samples were collected before lymphoma treatment in ARL patients. EBV viral load was measured in plasma by real-time quantitative PCR and the presence of EBV-EBER mRNA in lymphoma tumor was investigated by in situ hybridization. RESULTS Patients with ARL had higher EBV viral loads than those without lymphoma: 24,180.5 (±73,387.6)copies/mL versus 2.6 (±21.6)copies/mL (p<0.001). HIV-infected patients without lymphoma had negative or very low EBV load values. Among ARL patients, no correlation was found between EBV viral loads and CD4+ lymphocyte counts or between EBV and HIV RNA loads, or any other clinical or biological parameter. Cases with an EBV-EBER-positive lymphoma had higher EBV viral loads than those with EBER-negative tumors. CONCLUSIONS EBV viral load is a useful marker of lymphoma in HIV-infected patients, and may be a useful tool for early diagnosis and treatment.