THE NATURE OF REED-STERNBERG CELLS - PHENOTYPE, GENOTYPE, AND OTHER PROPERTIES

The most recent sophisticated investigations have provided new and rev ealing but also contradictory and controversial information on the bio logical nature and the cellular origin of Hodgkin and Reed-Sternberg ( H-RS) cells. Immunophenotypic analyses have shown consistent expressio n of CD15, CD30, CD74, and HLA-Dr antigens, but generally lack of T- o r B cell-associated markers in H-RS cells. The H-RS cells are also dev oid of many monocyte/macrophage-associated antigens. Molecular genetic studies have demonstrated heterogeneous findings with respect to rear rangements of T-cell receptor and immunoglobulin genes. Only a small p ercentage of the cases have rearrangements; this cannot always be attr ibuted to the threshold of sensitivity of the method and/or the scarci ty of the malignant cells in tissues examined. The H-RS cells do not e xpress transcription factors such as BSAP, TCF-1, and GATA-3, known to be associated with lymphoid cells. It appears that evidence to suppor t a lymphoid origin for H-RS cells is still lacking. On the contrary, the mechanism responsible for the unique clinical and histopathologic alterations associated with this disease has become clear. The H-RS ce lls have been shown to secrete IL-1, IL-5, IL-6, IL-9, TNF-a, M-CSF, a nd TGF-b, and, less frequently, IL-4 acid C-CSF. These cytokines are l ikely to be responsible for the increased cellular reaction and fibros is observed in tissues involved by HD and for the immunosuppression in patients with HD. Like most lymphomas, the etiology or pathogenesis o f HD remains unknown, The Epstein-Barr virus (EBV) genomes are clonall y integrated in the H-RS cells of about half the cases. The significan ce of these findings, whether EBV is a causative agent or an epiphenom enon, remains to be elucidated.