Primary mucosa-associated lymphoid tissue lymphoma of the gallbladder: report of a case harboring API2/MALT1 gene fusion.

The genetic alterations underlying extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type are heterogeneous and show variation according to the tumor site. Here, we report a case of mucosa-associated lymphoid tissue lymphoma of the gallbladder with genetic characterization. This lymphoma, diagnosed in a 75-year-old woman who underwent cholecystectomy for suspected acute cholecystitis, presented as diffuse thickening of the gallbladder wall. The morphology was typical of mucosa-associated lymphoid tissue lymphoma, and by immunophenotype, the tumor cells were CD20+ CD5- CD10- CD23- CD43- BCL6- BCL2+ IgM+ IgD- lambda+, with moderate nuclear expression of BCL10. Interphase fluorescence in situ hybridization analysis on paraffin sections, using a fusion probe for API2/MALT1, demonstrated 2 fusion signals in most nuclei, bringing the first documentation of a t(11;18)(q21;q21) in this exceptional primary disease location.

Limited usefulness of CA125 measurement in the management of Hodgkin's and non-Hodgkin's lymphoma.

BACKGROUND: Several papers have reported an association of high CA125 serum levels with advanced non-Hodgkin's lymphoma (NHL) as well as a relationship between high CA125 values and poor outcome. PATIENTS AND METHODS: Ninety-nine patients with NHL or Hodgkin's disease (HD) underwent serum CA125 assessment at diagnosis. Gender, age, presence of B symptoms, performance status (PS), histology, sites of tumor involvement, presence of effusion, clinical stage, age-adjusted International Prognostic Index, C-reactive protein (CRP), Hb, lactate deshydrogenase (LDH) and beta2-microglobulin were evaluated for their association with serum CA125 levels. The impact of CA125 levels and other features on overall (OS) and progression-free (PFS) survival was also assessed. RESULTS: CA125 serum levels were elevated in 34% of the patients, including 19% of patients with aggressive NHL, 45% of patients with indolent NHL, and 29% of patients with HD. Univariate analyses showed that CA125 levels correlated with poor PS, the presence of B symptoms, advanced clinical stage, abdominal, bone marrow or mediastinal involvement, presence of effusions, high aaIPI, low Hb levels and high CRP, LDH or beta2-microglobulin levels. In multivariate analysis, bone marrow involvement, the presence of effusions, and high aaIPI were all associated with high CA125 serum levels. In univariate analyses, OS and PFS were affected by age (PFS only), poor PS, B symptoms, advanced clinical stage, bone marrow or abdominal involvement (PFS only), high aaIPI, low Hb, high CRP or beta2-microglobulin levels. OS and PFS were not different in patients with normal or elevated CA125 levels. Multivariate analyses showed significantly inferior OS and PFS in patients with high beta2-microglobulin but no influence of CA125. CONCLUSION: While CA125 serum level correlates significantly with a number of features associated with more aggressive disease, it does not enhance the performance of standard prognostic markers in the management of patients with NHL or HD.

Establishment and characterisation of two novel human KSHV- and EBV-negative Burkitt cell lines, GAL-01 and GAL-02, from a primary lymphomatous effusion.

OBJECTIVES: Burkitt's lymphoma (BL) is a highly aggressive mature B-cell neoplasm comprising endemic, sporadic and immunodeficiency-associated variants. Human cell lines constitute a very useful tool to investigate the biology of lymphoid neoplasia. In this study, we succeeded in establishing two human cell lines, GAL-01 and GAL-02, from a HIV-negative patient with Epstein-Barr virus (EBV) -negative sporadic BL presenting as an effusion. GAL-01 and GAL-02 were established at diagnosis and after one course of polychemotherapy, respectively. The in vivo effusion occurred in a very peculiar clinical setting; the patient having a previous history of intestinal diffuse large B-cell lymphoma. METHODS: The morphologic, immunophenotypic and molecular genetic features of GAL cell lines are reported and compared with those of the parental tumour. The findings clearly demonstrated that the Burkitt effusion did not represent disease progression of the intestinal tumour, but represented a second primary haematological malignancy. The in vivo tumorigenic properties of the cells were tested by subcutaneous injection to NOD/SCID mice. RESULTS: Both cell lines were composed of medium-sized lymphoid cells with clumped chromatin, multiple medium-sized nucleoli and moderate amounts of vacuolated cytoplasm. GAL cells display the phenotype and genotype of a B-cell lineage (positive for CD20, CD79a and clonal rearrangement of Ig heavy chain), carry the c-MYC rearrangement by t(8;22)(q24;q11) translocation and are characterised by the expression of the germinal centre-associated antigens CD10, BCL6, CD38 and absent to low BCL2 expression. EBV and HHV8 were not identified within parental tumour or in cultured cells. Subcutaneous injection of both cell lines to NOD/SCID mice induced tumour formation. CONCLUSIONS: GAL-01 and GAL-02, two novel EBV-negative human BL cell lines represent a potentially useful experimental model to study the biology of BL possibly including the resistance to chemotherapy.

18F-FDG PET in children with lymphomas.

PURPOSE: The aim of this study was to retrospectively evaluate the performance of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) in children with lymphomas, at various stages of their disease. METHODS: Twenty-eight children (mean age 12.5 years, 14 girls, 14 boys) with Hodgkin's disease (HD, n=17) or non-Hodgkin's lymphoma (NHL, n=11) were evaluated. Patients were investigated at initial staging (n=19), early in the course of treatment (n=19), at the end of treatment (n=16) and during long-term follow-up (n=19). A total of 113 whole-body PET studies were performed on dedicated scanners. PET results were compared with the results of conventional methods (CMs) such as physical examination, laboratory studies, chest X-rays, computed tomography, magnetic resonance imaging, ultrasonography and bone scan when available. RESULTS: At initial evaluation (group 1), PET changed the disease stage and treatment in 10.5% of the cases. In early evaluation of the response to treatment (group 2), PET failed to predict two relapses and one incomplete response to treatment. In this group, however, PET did not show any false positive results. There were only 4/75 false positive results for PET among patients studied at the end of treatment (group 3, specificity 94%) or during the systematic follow-up (group 4, specificity 95%), as compared with 27/75 for CMs (specificity 54% and 66%, respectively). CONCLUSION: 18F-FDG-PET is a useful tool for evaluating children with lymphomas. Large prospective studies are needed to appreciate its real impact on patient management.

Primary central nervous system lymphoma report of 32 cases and review of the literature.

We retrospectively analyzed 32 cases of primary central nervous system lymphoma (PCNSL). Five cases were diagnosed in the period 1987-1994, for 27 cases in the period 1995-2002. There were 17 men and 15 women whose median age was 69 years. Three patients were immunodeficient. The commonest symptoms were focal deficit (16 patients) and cognitive/behaviour disturbances (14 patients). Radiologically, a total of 47 contrast-enhancing lesions were observed in 32 patients; 18 patients had deep-seated lesions. All but two patients underwent histological diagnosis following craniotomy (11 patients) and/or stereotaxic biopsy (22 patients); diagnosis was obtained on CSF cytology in one patient with a third ventricle tumour. In the last patient, the diagnosis was based on the finding of marked tumour shrinkage under corticotherapy, despite two negative histological examinations. Treatment included surgical resection (10 patients), chemotherapy (25 patients) and/or radiotherapy (12 patients). According to the therapeutic recommendations of the GELA (Groupe d'Etude des Lymphomes de l'Adulte), 19 patients received at least two courses of high-dose methotrexate; intrathecal chemotherapy was used in 20 patients with methotrexate and/or cytosine arabinoside. Radiation therapy consisted of whole brain irradiation followed by a boost on tumour site. Nine patients received a combined treatment of chemotherapy and radiotherapy. Twelve patients showed rapid progression to death. At the time of last contact, 28/32 patients (88%) had died, all from PCNSL disease or from complications due to its treatment. The median survival time was 13.9 months. We conclude that PCNSL is an increasingly frequent tumour. The diagnosis is obtained by stereotactic biopsy in the majority of cases. The prognosis appears dismal despite an intensive multidisciplinary therapeutic approach.

Whole-body tumor imaging using PET and 2-18F-fluoro-L-tyrosine: preliminary evaluation and comparison with 18F-FDG.

UNLABELLED: 18F-FDG PET imaging is now established as a valuable tool for evaluating cancer patients. However, a limitation of (18)F-FDG is its absence of specificity for tumor. Both protein synthesis and amino acid transport are enhanced in most tumor cells, but their metabolism is less affected in inflammation. We therefore decided to evaluate the ability of PET with 2-(18)F-fluoro-L-tyrosine ((18)F-TYR) to visualize cancer lesions in patients compared with (18)F-FDG PET. METHODS: (18)F-FDG PET and (18)F-TYR PET were performed on 23 patients with histologically proven malignancies (11 non-small cell lung cancers (NSCLCs), 10 lymphomas, and 2 head and neck carcinomas). Fully corrected, whole-body PET studies were obtained on separate days. (18)F-FDG studies were performed after routine clinical fashion. (18)F-TYR studies were started 36 +/- 6 min after tracer injection and a second scan centered over a reference lesion was acquired after completion of the whole-body survey-on average, 87 min after injection. Standardized uptake values (SUVs) were calculated for all abnormal foci and for various normal structures. Results were compared with pathologic or correlative studies. RESULTS: (18)F-FDG PET correctly identified 54 malignant lesions, among which 36 were also visualized with (18)F-TYR (67%). (18)F-TYR did not detect any additional lesion. Tumor SUVs (SUV(bw), 5.2 vs. 2.5), tumor-to-muscle (7.4 vs. 2.7), and tumor-to-mediastinum activity ratios (3 vs. 1.4) were higher with (18)F-FDG than with (18)F-TYR. Two of 11 NSCLCs and 4 of 10 lymphomas were understaged with (18)F-TYR compared with (18)F-FDG. Although the NSCLC lesions missed by (18)F-TYR PET were small, several large lymphoma lesions did not accumulate the tracer. In 4 patients, (18)F-TYR-positive lesions coexisted with (18)F-TYR-negative lesions. There was a high physiologic (18)F-TYR uptake by the pancreas (average SUV(bw), 10.3) and the liver (average SUV(bw), 6.3). Muscle and bone marrow uptakes were also higher with (18)F-TYR than with (18)F-FDG: average SUV(bw), 1 versus 0.7 and 2.6 versus 1.8, respectively. There was no change over time in the (18)F-TYR uptake by the tumors or the normal structures. CONCLUSION: (18)F-TYR PET is not superior to (18)F-FDG PET for staging patients with NSCLC and lymphomas.

Phase III randomized study comparing 5 or 10 microg per kg per day of filgrastim for mobilization of peripheral blood progenitor cells with chemotherapy, followed by intensification and autologous transplantation in patients with nonmyeloid malignancies.

BACKGROUND: It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells (PBPC) and leads to faster hematopoietic engraftment after autologous transplantation. STUDY DESIGN AND METHODS: A randomized, open-label, multicenter trial was carried out in patients with breast cancer, multiple myeloma, and lymphoma, in which patients were randomized to receive 5 or 10 microg per kg per day of filgrastim after standard chemotherapy to mobilize PBPCs. After high-dose chemotherapy, the components from the first two leukapheresis procedures were returned, and all patients received 5 microg per kg day of filgrastim after transplantation. RESULTS: A total of 131 patients were randomized, of whom 128 were mobilized (Group A, 5 microg/kg, n = 66; Group B, 10 microg/kg, n = 62) and 112 were transplanted. Only six patients were not transplanted because of insufficient CD34+ cell numbers. The median number of CD34+ cells collected in the first two leukapheresis procedures tended to be higher in Group B than in Group A (12.0 vs. 7.2 x 10(6)/kg, NS), but after transplantation there was no significant difference in median times to platelet (9 days in both groups) or neutrophil (8 days in both groups) engraftment or the number of platelet transfusions (three in both groups). A subsequent subgroup analysis separating patients transplanted after first- or second-line chemotherapy also showed no measurable impact of filgrastim dose on the median CD34+ cell yield or on platelet engraftment in either subgroup. CONCLUSION: PBPC mobilization with chemotherapy and 5 microg per kg of filgrastim is very efficient, and 10 microg per kg of filgrastim does not provide additional clinical benefit.