IGH gene rearrangement is most frequently determined by PCR analysis, which has a high rate of both false-positive and false-negative results in the context of immunodeficiency-related lymphomas. In the setting of SOT, monoclonal populations are identified by PCR but not by SBA in the low-grade or early lesions (PH) that frequently regress following a reduction of immunosuppres-sion. Similarly, in AIDS-related lymphadenopathies, monoclonal populations can be identified by PCR but usually not by SBA. These PCR-positive but SBA-negative results are probably due to strong antigenic stimuli from infectious agents such as EBV, giving rise to small mono clonal expansions that are identified by the more-sensitive PCR assay. False-negative results also are common, since many posttransplantation and AIDS-related lymphomas are of postgerminal center B-cell origin, where extensive somatic hypermutation of the IGH VDJ region has occurred. These mutations may be in the primer recognition site, precluding primer annealing and PCR amplification. SBA is sometimes helpful in eliminating false-negative and false-positive results but is impractical in a clinical molecular laboratory setting. SBA also can give false-negative results when the tumor cells comprise less than 1% to 5% of the population in the tissue being analyzed. It has been suggested that a significant proportion of AIDS lymphomas are polyclonal. By combining SBA and PCR, including analysis of IGLK and IGLL genes and EBV clonality, monoclonal populations can be documented in practically every case of histologically confirmed AIDS-related lymphoma. However, in the absence of such extensive analysis, the inability to demonstrate a monoclonal population should never be taken as an absolute criterion against the diagnosis of lymphoma. Similarly, the presence of a monoclonal population by PCR should not be considered diagnostic of lymphoma. Either a positive or a negative result should be correlated with clinical and pathologic information to establish the final diagnosis.
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