Karyotypic abnormalities associated with Epstein-Barr virus status in classical Hodgkin lymphoma.

Classical Hodgkin lymphoma (CHL) is morphologically characterized by scattered malignant Hodgkin/Reed-Sternberg (HRS) cells that are far outnumbered by surrounding reactive hematolymphoid cells. Approximately half of all cases of CHL are associated with infection by Epstein-Barr virus (EBV), an oncogenic herpesvirus that expresses a number of proteins thought to contribute to transformation. While a small number of published studies have attempted to identify recurrent cytogenetic abnormalities in CHL, no large case series have explored karyotypic differences between EBV-positive and EBV-negative tumors. Here, we report a two-institution retrospective investigation of cytogenetic features characterizing CHL. In our cohort, cases of EBV-negative CHL were characterized by more complex routine karyotypes than their EBV-positive counterparts (24.6 versus 15.6 independent aberrations per case, P = 0.009). The increased complexity of EBV-negative cases was driven by a number of features suggestive of genomic instability, including a larger number of independent chromosomal breakpoints (P = 0.03) and apparently aneuploid autosomes (P = 0.008). Compelling but nonsignificant trends also suggest a larger modal number and increased marker chromosomes in EBV-negative cases (P = 0.13 and 0.06, respectively). While some of these differences are related to histologic subtype, others appear independent of histology. Finally, a significant subset of EBV-positive tumors has a surprisingly simple karyotype relative to what is normally seen in CHL, an observation suggesting considerable biological and genetic diversity in this disease.

Clonal karyotypic abnormalities associated with reactive lymphoid hyperplasia.

Cytogenetic abnormalities are important in the diagnosis and prognosis of hematolymphoid neoplasms. Although many recurrent karyotypic abnormalities are well-defined and known to underlie pathophysiologic processes contributing to malignancy, the significance of other cytogenetic changes is less clear. This uncertainty reflects an incomplete understanding of the frequency with which karyotypic abnormalities arise in benign processes. Numerous case reports and a small number of retrospective series have noted clonal cytogenetic changes in association with reactive-appearing lymph nodes. However, the incidence of such abnormalities has varied widely in published series. Here, we report the largest retrospective series of karyotypic abnormalities in association with reactive lymphoid hyperplasia published to date. Clonal karyotypic abnormalities were present in 6.3% of reactive lymph nodes with informative karyotypes and 5.1% of all reactive lymphoid tissues. These data suggest that karyotypic abnormalities are less frequently found in association with reactive lymphoid tissue than previously reported and provide a clearer picture of the baseline incidence of cytogenetic changes in benign lymphoid processes.