Simple karyotype and bcl-6 expression predict a diagnosis of Burkitt lymphoma and better survival in IG-MYC rearranged high-grade B-cell lymphomas.

Rearrangement of MYC with immunoglobulin genes is a hallmark of Burkitt lymphoma. However, this rearrangement is not entirely specific and is often accompanied by varying numbers of additional cytogenetic abnormalities. This study aimed to assess the impact of karyotypic complexity, in correlation with comprehensive immunophenotypic analyses on the diagnosis and clinical outcomes of 34 cases of MYC-IG rearranged lymphomas that included Burkitt lymphoma (twenty-two cases), diffuse large B-cell lymphoma (three cases), unclassifiable B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (six cases), and plasmablastic lymphoma (three cases). Additional cytogenetic abnormalities were observed in 26 of 34 cases (76%), including four cases (12%) that harbored dual translocations involving BCL-2 or BCl-6. Burkitt lymphoma cases had a significantly lower number of additional abnormalities (mean of 1.7), compared with unclassified B-cell lymphoma (3.3), diffuse large B-cell lymphoma (21.7), and plasmablastic lymphoma (6.7). Cases with simple karyotype (< or =2 additional abnormalities) were more likely to have a diagnosis of Burkitt lymphoma (89 versus 33% in patients with >2 additional abnormalities, P<0.01) and express bcl-6 (95 versus 47%, P<0.01). In addition, Burkitt lymphoma, bcl-6 expression, and simple karyotype were individual predictors of better overall survival. However, in multivariate analyses, only bcl-6 expression remained an independent predictor, although survival could be further stratified by karyotypic complexity in bcl-6(+) patients. We conclude that simple karyotype and bcl-6 expression suggest a diagnosis of Burkitt lymphoma and may portend better overall survival. These results may be very useful in the diagnosis and stratification of MYC-IG rearranged high-grade B-cell lymphomas.

A 3-way collision tumor of the upper respiratory tract: a composite of 2 immunophenotypically distinct mantle cell lymphomas and a plasmacytoma.

Composite lymphoma (CL) is composed of 2 or more morphologically and immunophenotypically distinct lymphomas in a single anatomical site. Here we report a unique CL of the upper respiratory tract in an elderly male patient. Morphologically, the lymphoma was composed of 2 distinct and well-demarcated areas consisting of monotonous small to medium-sized lymphocytes and sheets of mature-appearing plasma cells. Immunophenotyping by both flow cytometry and immunohistochemistry revealed that the small to medium-sized lymphocytes were composed of 2 distinct subpopulations sharing a CD5(+)/CD19(+)/CD20(+)/CD22(+)/CD23(-)/FMC-7(+)/cyclin D1(+) immunophenotype but with different immunoglobulin (Ig) light and heavy chain expression, consistent with 2 immunophenotypically distinct mantle cell lymphomas (MCLs); the plasma cells were composed of CD38(bright +)/CD138(+)/IgG kappa-restricted plasma cells, consistent with a plasmacytoma. Fluorescence in situ hybridization showed the t(11;14) translocation present in the lymphocyte region but absent in the plasma cell area. Ig heavy chain gene rearrangement studies on manually dissected populations showed 2 distinct patterns for the MCL and plasmacytoma. To our knowledge, this is the first report of a 3-way CL consisting of 2 immunophenotypically distinct MCLs and a plasmacytoma.

Multiparameter flow cytometric analysis reveals low percentage of bone marrow hematogones in myelodysplastic syndromes.

Diagnosis of myelodysplastic syndromes (MDS) could be difficult. We explored the usefulness of the enumeration of maturing B-lineage precursors (hematogones) by multiparameter flow cytometric analysis in the diagnosis of MDS in bone marrow (BM) specimens. We evaluated 111 MDS, 120 non-MDS (most with cytopenias; control group 1), and 41 noncytopenic lymphoma staging BM (control group 2) specimens. The percentage of total hematogones was significantly lower in MDS (median, 0%; mean, 0.10%) compared with non-MDS (control group 1, median, 0.38%, and mean, 0.91%; control group 2, median, 0.38%, and mean, 0.60%; P < .0001), as was the percentage of the most immature (stage I) hematogones. Thus, hematogone enumeration may serve as a biomarker to aid in the diagnosis of MDS. Interestingly, the percentage of hematogones was not significantly different between MDS subgroups or patients with MDS with and without chromosomal abnormalities, implying that a defect in maturing B-cell precursors may be an early event in the pathogenesis of MDS.

Estimating mutant microsatellite allele frequencies in somatic cells by small-pool PCR.

Identifying microsatellite instability (MSI) by partitioning DNA into multiple small pools containing only single genome amounts of DNA results in trapping both progenitor and low-frequency mutant alleles into pools where they can be identified and counted following PCR. Statistical approaches determining both the frequencies and the significant differences between frequencies of these Poisson-distributed alleles are presented. Results indicate a level of sensitivity and quantification not possible by standard PCR methods. Using material from colon cancer patients with high levels of MSI in their tumors, we also present the molecular and robotic methods for carrying out such studies. Validation experiments indicated mutants detectable at frequencies >0.03 above background. Frequencies obtained in tumor tissue (>0.25) met the expectations of the approach. Significant levels of MSI were detected in the constitutive tissue of the patient carrying a germ-line mutation for mismatch repair, suggesting both mechanistic and clinical applications of the procedure.