Array-based comparative genomic hybridization (array CGH) provides a powerful method for simultaneous genome-wide scanning and prognostic marker assessment in chronic lymphocytic leukemia (CLL). In the current study, commercially available bacterial artificial chromosome and oligonucleotide array CGH platforms were used to identify chromosomal alterations of prognostic significance in 174 CLL cases. Tumor genomes were initially analyzed by bacterial artificial chromosome array CGH followed by confirmation and breakpoint mapping using oligonucleotide arrays. Genomic changes involving loci currently interrogated by fluorescence in situ hybridization (FISH) panels were detected in 155 cases (89%) at expected frequencies: 13q14 loss (47%), trisomy 12 (13%), 11q loss (11%), 6q loss (7.5%), and 17p loss (4.6%). Genomic instability was the second most commonly identified alteration of prognostic significance with three or more alterations involving loci not interrogated by FISH panels identified in 37 CLL cases (21%). A subset of 48 CLL cases analyzed by six-probe FISH panels (288 total hybridizations) was concordant with array CGH results for 275 hybridizations (95.5%); 13 hybridizations (4.5%) were discordant because of clonal populations that comprised less than 30% of the sample. Array CGH is a powerful, cost-effective tool for genome-wide risk assessment in the clinical evaluation of CLL.
Context.-D-dimer is widely used for exclusion, or as an aid in diagnosis, of venous thromboembolism (VTE); however, the D-dimer assay methods available from manufacturers and the laboratory application of those methods vary widely.Objective.-To describe the current laboratory practice regarding the assay and reporting of D-dimer.Design.-Laboratories' D-dimer proficiency testing data were analyzed and laboratory practices regarding the performance and reporting of D-dimer were surveyed.Results.-Initial grading of D-dimer proficiency testing demonstrated high variability within and among methods. This variability continued to be present for several years after attempts to intervene. The number of laboratories using D-dimer to exclude VTE grew from 1500 in 2004 to more than 3500 in 2012. Survey and proficiency testing data demonstrated that 33% of laboratories changed the type or magnitude of units from that recommended by the manufacturer, a practice associated with as much as a 20-fold increase in the failure of proficiency testing. Many laboratories used a threshold for the exclusion of VTE that is higher than that recommended by the manufacturer. Many laboratories continue to use qualitative assays with insufficient sensitivity for exclusion of VTE.Conclusions.-There is considerable variability both within and among quantitative methods used to assay Ddimer by laboratories. Laboratory practice continues to vary widely regarding the type and magnitude of units reported and the setting of the threshold for the exclusion of VTE. Although improved, the variability continues despite initial efforts to intervene.
Context.—Beginning with the immunologic classifications of Lukes and Collins and Kiel and culminating in the Revised European-American Lymphoma and World Health Organization classifications, the diagnosis of lymphoid tumors relies heavily on the determination of cell lineage, maturation, and function, based on antigen expression in addition to morphology and clinical features. Technologic advances in immunology, antibody production, genetic analysis, cloning, and the identification of new genes and proteins by microarray and proteomics have provided pathologists with many antibodies to use in routine diagnosis. Objective.—To provide guidance to the practicing pathologist in the appropriate selection of an antibody panel for the diagnosis of lymphoma based on morphology and relevant clinical data and to avoid pitfalls in the interpretation of immunohistochemical data. Attention is given to some of the newer antibodies, particularly against transcription factors, that are diagnostically and prognostically useful. Data Sources.—The information presented in this article is based on review of the literature using the OVID database (Ovid MEDLINE 1950 to present with daily update) and 20 years of experience in diagnostic hematopathology. Conclusions.—Immunophenotyping is required for the diagnosis and classification of lymphoid malignancies. Many paraffin-reactive antibodies are available to the pathologist but most are not specific. To avoid diagnostic pitfalls, interpretation of marker studies must be based on a panel and knowledge of a particular antigen's expression in normal, reactive, and neoplastic conditions.
Results of this trial suggest that the use of a powered bone marrow biopsy device significantly reduces needle insertion pain and procedural time when compared to a manual technique. The superior size and overall quality of core specimens retrieved by the powered device provides more material for pathologic evaluation, thereby increasing diagnostic yield and reducing the need for repeat procedures.
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