Lymphocyte-depleted classic Hodgkin lymphoma-a neglected entity?

Changes in the definition of lymphocyte-depleted classic Hodgkin lymphoma (LDcHL) have recently led to reclassification of many cases as other pleomorphic lymphomas. We have set out to identify LD cases in our cohort of cHL patients and determine their clinical and biological characteristics properties. We defined the morphologic picture of LDcHL according to selected criteria and determined how its features differ from those of other subtypes of cHL. Twelve of 201 cHL patients (5.9%) were diagnosed as showing LDcHL histology, a higher percentage of LDcHL than in most recent series. The LD cases were most often positive for Epstein-Barr virus and for sialyl-CD15. Defining the cases as either reticular (eight) or as diffuse fibrosis (three) variants was critical to the diagnostic approach. We conclude that LDcHL may be a neglected entity.

Selectins and anti-CD15 (Lewis x/a) antibodies transmit activation signals in Hodgkin's lymphoma-derived cell lines.

OBJECTIVE: The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in a variety of normal and tumor cells and recognized by selectins. The detection of CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic marker of Hodgkin's lymphoma (HL). Retrospective studies suggest that the expression of nonsialylated CD15 molecules on HRS cells has a positive prognostic value while presence of sialylated CD15 may correlate with a poor outcome. However, the relevance of the CD15 antigen expression to the pathobiology of the disease is not clear. In this work, we studied the contribution of CD15 to cell adhesion and the activation of signaling cascades in two HL-derived cell lines, KMH-2 and L428. METHODS: Immobilized anti-CD15 monoclonal antibodies and recombinant E- and P-selectins were used to activate KMH-2 and L428 cells. Immunoblotting, immunoprecipitation, and the electrophoretic mobility shift assay were performed to detect tyrosine phosphorylation of c-Cbl, c-Jun nuclear translocation, and AP-1 DNA binding. RESULTS: Treatment of cells with antibodies against the sialylated and nonsialylated forms of CD15, or with immobilized selectins, induced changes in cell morphology. Tyrosine phosphorylation of c-Cbl, together with tyrosine phosphorylation of multiple protein substrates, was also induced. In addition, binding of the CD15 molecules induced nuclear translocation of c-Jun and an increase in AP-1 DNA binding activity. CONCLUSIONS: We suggest that CD15 has a dual physiological role, both as an adhesion molecule recognized by selectins and as a regulatory molecule upstream to specific intracellular signaling cascades with implications to the pathogenesis of HL.

Is classical Hodgkin's disease indeed a single entity?

We present a retrospective clinicopathological study on the significance of the histologic type of classical Hodgkin's disease (HD) in a cohort of patients from southern Israel. This was performed to critically evaluate the generally accepted view that classical HD is a single clinicopathological entity and the resultant impression that its segregation into four different histologic types remains essential only for the pathologist in his diagnostic endeavor. We confirmed the existence of a uniform response of nodular sclerosis (NS), and mixed cellularity-lymphocyte depletion (MC-LD)-HD to treatment, consideration being given to other classical prognostic factors. We also accept the fact that histological type is not a significant independent factor in terms of survival. Our findings, however, do suggest that NS-HD, on the one hand, and MC-LD-HD, on the other, are distinct biologic entities. Cases of NS differ significantly from those of MC-LD-HD with regard to sex and age distribution, and in the expression of several antigens and gene products, including sialylated-CD15, CD30, LMP1 and the p53 and mdm-2 gene products.