No abstract

The proto‐oncogene c‐kit encodes a transmembrane tyrosine protein kinase receptor for an unknown ligand and is allelic with the murine white‐spotting locus (W). Mutations at the W locus affect various aspects of hematopoiesis, the proliferation and migration of primordial germ cells and melanoblasts during development. The original W mutation and W37 are severe lethal mutations when homozygous. In the heterozygous state the W mutation has a weak phenotype while W37 has dominant characteristics. Wv and W41 are weak W mutations with dominant characteristics. We have characterized the molecular basis of these four W mutations and determined their effects on mast cell differentiation by using a fibroblast/mast cell co‐culture assay. We show that W37, Wv and W41 are the result of missense mutations in the kinase domain of the c‐kit coding sequence (W37 E‐‐‐‐K at position 582; Wv T‐‐‐‐M position 660 and W41 V‐‐‐‐M position 831), which affect the c‐kit associated tyrosine kinase to varying degrees. The c‐kit protein products in homozygous mutant mast cells are expressed normally, although the 160 kd cell membrane form of the c‐kitW37 protein displays accelerated turnover characteristics. The W mutation is the result of a 78 amino acid deletion which includes the transmembrane domain of the c‐kit protein. A 125 kd c‐kit protein was detected in homozygous W/W mast cells which lacks kinase activity and is not expressed on the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Patients with nasal lymphoma, especially those with advanced disease, seemed to have a poor prognosis, and their clinical outcome was not improved significantly by the use of chemotherapy instead of radiotherapy or the use of doxorubicin-containing chemotherapeutic regimens.

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.