Morphologically normal, CD30-negative B-lymphocytes with chromosome aberrations in classical Hodgkin's disease: The progenitor cell of the malignant clone?

A recent study observed that numerical chromosome abnormalities in Hodgkin' s disease (HD) are detected not only in morphologically abnormal Hodgkin/Re ed-Sternberg cells, but also in a fraction of morphologically normal cells. However, the phenotypic constitution of these genetically abnormal, morpho logically normal cells and their relationship to the malignant Hodgkin/Reed -Sternberg cells could not be established in the earlier cases studied, bec ause of the low frequency of these cells. The present study investigated tw o cases of classical Hodgkin's disease containing a relatively large popula tion of such apparently normal cells with aberrant chromosome copy numbers. The phenotype and their position within the developmental route of the mal ignant compartment were examined by a combined in situ hybridization and im munocytochemistry approach. Numerical abnormalities for chromosome 1 in one case and for chromosomes X, Y, and 1 in the Other case were observed not o nly in CD30-positive Hodgkin/Reed-Sternberg cells, but also in CD30-negativ e, morphologically normal cells. It was shown that these genetically aberra nt cells expressed the B-cell antigen CD19, thus confirming their B-cell na ture. These studies indicate a relationship between the genome aberrations in these genetically abnormal, morphologically normal B-cells and the Hodgk in/Reed-Sternberg cells, suggesting that they are progenitor cells of the m alignant cell fraction. Copyright (C) 1999 John Wiley & Sons, Ltd.