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Background: Non-Hodgkin’s Lymphoma (NHL) is the third most common childhood malignancy representing nearly 10% of all childhood cancers diagnosed in the US. Diffuse Large B-cell Lymphoma (DLBCL), the most common subtype of adult NHL, is rare in children and represents less than 5% of all pediatric NHL. These lymphomas express B-cell markers, have a low risk of second malignancy and good prognosis when treated for short periods with aggressive chemotherapy.
Objectives: There are only rare reports defining chromosomal abnormalities in pediatric DLBCL and genetic changes that are distinct for pediatric DLBCL are not known.
Design: We have collected cytogenetic data from 12 pediatric and young adult patients with histologically confirmed DLBCL that presented with abnormal karyotypes. The patients with ages ranging from 9.3 to 24.9 years (mean age 18 years) were referred for cytogenetic analysis to UNMC during the past 20 years.
Results: Karyotypic analysis showed that all cases were polyploid with modal chromosome numbers ranging from 47-90. Numeric abnormalities were more common than structural abnormalities and chromosome loss, relative to ploidy, was more frequent than gain. Loss of chromosomes 2, 3, 4, 12, 15, 16, and 17 and gain of 12, 18, and X were observed in ≥20% (≥ 3 cases)of the cases. Sex chromosome anomalies were observed in more than 80% of the cases (10/12). Recurrent breakpoints (≥3 cases)included 14q32 and 17p13, however, the clustering of breakpoints was observed mainly in the young adult age group (14q32, 4/5 cases; 17p13, 2/3 cases). Also since fewer cases were studied, we considered it worthwhile to note the breakpoints that were observed in 2 cases each, 7q35-36, 9p24, 13q34, and 16p24. The 14q32 (IGH) and 17p13 (P53) are both implicated in adult DLBCL. Although these cases were not investigated specifically for IGH, BCL2 and BCL6 gene disruptions, cytogenetic analysis showed that 50% of the cases (6/12) did not involve 14q32 (IGH), 3q27 (BCL6) or 18q21 (BCL2). Increasingly, 5/6 cases were young adults (≥20 years)and only one case belonged to the pediatric age group. Further, gain of chromosome 7, which is frequently observed in adult DLBCL, was not observed in this pediatric DLBCL subset. Unidentifiable chromosomes or segments were observed in more than 80% of the cases (10/12). A thorough analysis using multi-color fluorescence in situ hybridization might prove useful and reveal more genetic changes.
Conclusion: In summary, although this cytogenetic investigation has been performed in a small number of cases, it provides a distinctly different picture than adult DLBCL. Continued studies with cytogenetic and molecular techniques will help elucidate the pathogenesis and progression of this subset of NHL. This information is integral for developing enhanced treatment modalities for improved prognosis among these patients.
