Epstein-Barr virus expression in Hodgkin's disease: correlation with histologic subtypes and T and B lymphocyte distribution

ABSTRACT

The pathogenesis of Hodgkin's disease [HD] has been linked to Epstein-Barr virus [EBV]. Some histologic subtypes show a high level of viral expression. These include mixed cellularity [MCHD] and nodular sclerosis [NSHD] subtypes. Grade II NSHD is a more aggressive variant of HD. Lymphocyte predominant [LPHD] is a B cell lymphoproliferative disorder that has not been associated with EBV expression. Infiltrating lymphocytes in HD are predominantly T-lymphocytes, with a minor component of B lymphocytes. In the current study, EBV expression was tested in cases of HD in relation to histologic subtypes. An attempt was made at correlating EBV expression with T and B lymphocyte distribution in lymph nodes involved by HD. Formalin-fixed paraffin-embedded tissue from 62 cases of HD were tested for EBV mRNA expression, using the EBER-1 probe and in situ hybridization. T and B lymphocyte distribution and their ratios were evaluated using antibodies to T and B lymphocytes [UCHL-1 [CD45 R0| and CD 20, respectively], and the immunoperoxidase technique. The cases were seen in 38 male and 24 female patients, with an age range of 3 to 72 years [median 25 years]. There were 30 cases of grade I and 15 cases of grade II NSHD, 9 cases of MCHD and 8 cases of LPHD. EBV mRNA expression was seen in 29 cases [46%]. This expression was seen in 8 cases of grade 1 NSHD [26%], 13 cases of grade II NSHD [86%] and 8 cases of MCHD [88%]. None of the cases of LPHD showed viral expression. T to B lymphocyte ratios in EBV-positive cases ranged from 1/6 to 8/1, and ranged from 2/1 to 20/1 in EBV-negative cases [P=0.06]. Nine of the 29 positive cases [31%] showed equal T/B lymphocyte ratios [n=4], or predominance of B lymphocytes [n=5]. None of the EBV-negative cases showed predominance of B lymphocytes. Our study confirms previously reported findings of the prevalence of EBV expression in MCHD and NSHD. Our findings also suggest that EBV expression may be more commonly seen in aggressive forms of HD. Decreased numbers of T-lymphocytes in these aggressive subtypes may suggest that a process of more profound T-lymphocyte depletion is occurring in these cases, leading to uncontrolled EBV replication and more aggressive disease