Edmond Chiu

IgG4-related sclerosing disease is a recently recognized syndrome characterized by mass-forming lesions in exocrine glands or extranodal tissues due to lymphoplasmacytic infiltrates and sclerosis, a raised serum IgG4 level and increased IgG4+ plasma cells in the involved tissues. We report the morphologic features of the enlarged regional (n=3) and nonregional lymph nodes (n=3) in patients with this syndrome. The patients presented with autoimmune pancreatitis, lymphoplasmacytic sclerosing cholangitis, chronic sclerosing dacryoadenitis, or chronic sclerosing sialadenitis. The histologic features of the lymph nodes could be categorized into 3 patterns: Castleman diseaselike, follicular hyperplasia, and interfollicular expansion by immunoblasts and plasma cells. The percentage of IgG4+/IgG+ plasma cells was markedly elevated (mean 62% vs. 9.9% in 54 control lymph nodes comprising a wide variety of reactive conditions). We also report 6 cases of primary lymphadenopathy characterized by increased IgG4+/IgG+plasma cells (mean 58%). These cases share many clinical and pathologic similarities with IgG4-related sclerosing disease. In fact, 2 of these patients developed lymphoplasmacytic sclerosing cholangitis or lacrimal and submandibular gland involvement during the clinical course. These cases therefore probably represent primary lymph node manifestation of the disease. The importance of recognition of the lymphadenopathic form of IgG4-related sclerosing disease lies in the remarkable response to steroid therapy, and the potential of mistaking the disease for lymphoma either clinically or histologically.

Some immunosuppressed patients with hepatitis C virus infection do not have detectable levels of antibody to hepatitis C virus on second-generation enzyme immunoassay. Antibodies to the envelope and nonstructural region 5 proteins have not been examined. Four groups of patients with hepatitis C virus infection were studied: (a) 20 immunocompetent patients, (b) 15 hemodialysis patients, (c) 17 kidney transplant recipients and (d) 3 acute leukemia patients who underwent bone marrow transplantation. Serum samples were tested for antibody to hepatitis C virus with a second-generation enzyme immunoassay and multi-antigen enzyme immunoassays and for hepatitis C virus RNA with a nested polymerase chain reaction assay. All the immunocompetent patients reacted to C25, C22 and C33C; 90% reacted to nonstructural region 5 antigen and 80% reacted to C100-3. Only 55% reacted against yeast-derived e1 and e2 antigens, but all reacted against vaccinia virus--expressed N e1 and e2 antigens, indicating that the envelope epitopes are conformational and glycosylated. Sixty-five percent to 90% of dialysis and kidney transplant patients reacted to C25, C22 and N e1 and e2, but only 12% to 60% reacted to C100-3, C33C and nonstructural region 5 antigen. Diminution or loss of reactivity to hepatitis C virus antigens was observed after kidney and bone marrow transplantation, with C25 and N e1 and e2 less affected. Our data suggest that incorporation of C25 and N e1 and e2 antigens in the assay for antibody to hepatitis C virus would improve the detection of hepatitis C virus infection in immunosuppressed patients.

This paper reviewed the clinical characteristics and treatment outcome of 484 lymphoma patients with known hepatitis B status. Comparisons were made between the hepatitis B surface antigen positive and negative patients. Also, the effect of treatment for lymphomas, including cytotoxic chemotherapy, in the hepatitis B antigen positive patients were analysed. The hepatitis B status was determined in 484 Chinese lymphoma patients at the time of initial diagnosis. Hepatic complications occurring during therapy for lymphomas were analysed. Although our lymphoma patients had a similar prevalence of hepatitis B markers of 42 per cent, they had a strikingly higher positive rate of 22 per cent for hepatitis B surface antigen and a relatively lower positive rate of 20 per cent for antibody, as compared to the respective figures of 9.5 per cent and 33 per cent in the control population. The hepatitis B surface antigen positive patients were younger than the negative patients but their treatment outcomes were similar despite the higher incidence of hepatic complications (21 per cent) in the hepatitis B surface antigen positive patients during therapy for lymphomas. None of the clinical parameters analysed appeared to be useful in predicting the development of these complications which included fatal liver failure (5.7 per cent), icteric hepatitis (5.7 per cent) and anicteric hepatitis (9.5 per cent). The high prevalence of hepatitis B surface antigen in our lymphoma patients may be related to the immunosuppressive effect of lymphomas. There is no definite evidence to suggest that hepatitis B infection has an aetiological or promoting role in the pathogenesis of lymphomas. Hepatitis B infection has contributed to the high incidence of hepatic complications during therapy for lymphomas and possible ways of prevention need to be investigated.

The risk of secondary central nervous system (CNS) was estimated in 833 cases of non-Hodgkin's lymphoma diagnosed between January 1975 and December 1988. Fifty-one of them had CNS disease (51/833, 6.1 per cent). No case of low grade lymphoma developed CNS disease. However, 6.5 per cent and 16.7 per cent of patients with intermediate and high grade lymphomas, respectively, had secondary CNS involvement. Stage IV disease and the presence of B symptoms were also associated with an increased risk of CNS disease. Significantly higher incidence of CNS disease was seen in patients with lymphoma involving orbit (43 per cent), testis (40 per cent), peripheral blood (33 per cent), bone (29 per cent), nasal/paranasal sinuses region (23 per cent) and bone marrow (20 per cent). CNS prophylaxis is recommended to patients with an increased risk of CNS disease.