Disease relevance of Lymphoma, High-Grade

• Some aggressive variants have been recognized with a blastic or large cell morphology, higher proliferative activity, and shorter survival. p53 gene mutations in lymphoid neoplasms have been detected mainly in high grade lymphomas and have been associated with tumor progression in follicular and small lymphocytic lymphomas [1].
• Low-grade lymphoma patients had a higher sensitivity in LL2 imaging (82% versus 71%), and high-grade lymphoma patients in 67Ga citrate scanning (100% versus 75%) [2].
• Epstein-Bar virus DNA was detected by polymerase chain reaction in the biopsy specimen of the high grade lymphoma but bcl-2/JH protooncogene rearrangement, t (14:18), was not identified in either the low or high grade lymphoma specimens tested [3].
• This case raises questions about the optimum time of imaging for thallium in high-grade lymphoma, whether delayed imaging is essential, about previous reports of low sensitivity of thallium in undifferentiated lymphoma and about the mechanism of thallium uptake in this type of tumor [4].
• Proportions of cells staining with the monoclonal antibody OKT9 showed a correlation between levels of cellular expression of transferrin (trf) receptor and the histological grade of malignancy, OKT9+ cells being elevated in high grade lymphomas, and in some cases of transforming lymphoma of low grade histological class [5].

High impact information on Lymphoma, High-Grade

• Half of the immunoblastic high-grade lymphomas had a rearranged c-myc gene [6].
• Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for patients older than 60 with high-grade lymphoma: results of a BNLI randomized trial of PAdriaCEBO versus PMitCEBO [7].
• Previously, we have reported an enhanced expression of TIMP-1 by normal reactive B cells and high-grade lymphomas [8].
• These results suggest that high-dose therapy and ASCT during first remission may improve the survival and prognosis of patients with poor-risk intermediate- and high-grade lymphoma [9].
• The CD22 antigen was found in tissue sections in most B cell-derived neoplasms, the major exceptions being myeloma (all cases negative) and a small proportion of high-grade lymphoma (6% of cases negative) [10].

Chemical compound and disease context of Lymphoma, High-Grade

• Epirubicin was administered at doses of 120 mg/m2, 150 mg/m2, and 180 mg/m2 every 3 weeks (maximum four doses) to groups of six patients with previously treated intermediate- and high-grade lymphoma [11].
• Between September 1983 and April 1985, 15 patients with previously untreated intermediate and high grade lymphoma were treated with COMLA/ABP (cyclophosphamide, vincristine, cytarabine, methotrexate, leucovorin, adriamycin, bleomycin, prednisone) [12].
• Five additional cases were diagnosed as high-grade lymphoma but could not be further subclassified because of the small biopsy size or formalin fixation [13].
• A larger inorganic phosphate (Pi) peak was seen in high grade NHL relative to phosphomonoesters (PME) or beta adenosine triphosphate (beta ATP), producing significant differences in the PME/Pi and Pi/beta ATP metabolite ratios, and probably reflecting a larger hypoxic cell fraction within the high grade lymphomas [14].
• We performed a prospective randomised placebo-controlled trial using topical oral r-metHuG-CSF (filgrastim) in high-grade lymphoma patients treated according to the B-NHL protocol, which contains high-dose methotrexate and causes severe oral mucositis (WHO grades I-IV) in >50% of patients [15].

Biological context of Lymphoma, High-Grade

• A new member of the proprotein convertase gene family (LPC) has been identified at a chromosome translocation breakpoint occurring in a high grade lymphoma [16].
• However, secondary high-grade lymphomas showed a significant down-regulation of bcl-2 protein (p<0.0001) and, conversely, an up-regulation of p53 protein (p<0.0001) as compared with their low-grade tumour components [17].
• In this setting, the strong correlation between PARP and p53 suggests that the high expression of PARP may be associated with ongoing DNA damage in high-grade lymphomas [18].
• Furthermore, polymerase chain reaction across the t(14;18) major breakpoint region in both tumors amplified nucleotide fragments of identical size, confirming the clonal identity of the low- and high-grade lymphomas despite the divergent immunoglobulin gene studies [19].
• The rate of cell proliferation as measured by Ki-67 immunostaining varied between 4-25% and 30-80% for low- and high-grade lymphomas, respectively [20].

Anatomical context of Lymphoma, High-Grade

• Proliferative activity, as measured by proliferative index and S-phase fraction, was significantly increased in lymphomas, compared with controls, and was significantly higher in morphologically high-grade lymphomas, compared with low-grade lymphomas and control lymph nodes (P less than 0.05) [21].
• High-dose treosulfan in patients with relapsed or refractory high-grade lymphoma receiving tandem autologous blood stem cell transplantation [22].
• The highest percentage of MIB1 positive T cells was observed in high grade lymphoma [23].
• Cerebrospinal fluid (CSF) neopterin levels were determined by high-pressure liquid chromatography in 48 normal children and in 15 children with meningeal relapse of hematologic malignancies (13 acute lymphoblastic leukemia and 2 high-grade lymphomas) [24].
• CONCLUSIONS--These data support the notion that Hodgkin's disease can be regarded as a high grade lymphoma, the large Hodgkin's and Sternberg-Reed cells being the (PCNA positive and AgNOR rich) neoplastic elements with high proliferative capacity [25].

Gene context of Lymphoma, High-Grade

• With time, a fraction of follicular lymphoma accumulates mutations of p53 and of p16 and evolves into a high grade lymphoma [26].
• Loss of p16 was identified in 14 of 55 evaluable high-grade lymphomas but not in any of the low-grade lesions [27].
• We conclude that staining formalin-fixed, paraffin-embedded, high-grade lymphomas with anti-cyclin D-1 antibody is useful in confirming the diagnosis of MCL-BV, whereas positive reactions with CD99, CD34, and particularly TdT are more characteristic of LBL [28].
• When one considers the differential diagnosis of a high-grade lymphoma/acute lymphoblastic leukemia, positive reactions with 12E7, TdT, bcl-2, and CD34 support the diagnosis of LyL/ALL over SNCL [29].
• While all proliferating cells expressed both genes, BCL2 expression was increased two- to threefold in follicular lymphomas with t(14;18) and MYC expression was increased two- to four-fold in high-grade lymphomas with t(8;14) [30].

Analytical, diagnostic and therapeutic context of Lymphoma, High-Grade

• The markedly increased Ki-67 staining (proliferation fraction) in the lymph node biopsy specimen compared to the earlier splenectomy specimen indicated the transformation of a low-grade leukemia to a high-grade lymphoma [31].
• Serial studies in a patient with high grade lymphoma receiving combination chemotherapy showed changes in phosphorus spectra, with an increase in the phosphodiester/beta adenosine triphosphate ratio [32].
• Forty-one patients with advanced Hodgkin's disease or intermediate or high-grade lymphoma, after having received standard salvage chemotherapy, were treated with a nonablative high-dose regimen of paclitaxel, etoposide and cyclophosphamide (D-TEC) to optimally cytoreduce their disease and simultaneously mobilize peripheral blood stem cells [33].
• Flow cytometry on paraffin, formalin-fixed tissue revealed tetraploidy and high proliferative fractions that are characteristic of high-grade lymphomas [34].

References