Unique morphological spectrum of lymphomas in Nijmegen breakage syndrome (NBS) patients with high frequency of consecutive lymphoma formation.

Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, radiation hypersensitivity, chromosomal instability and increased incidence of malignancies. In Poland 105 NBS cases showing mutations in the NBS gene (nibrin, NBN), have been diagnosed, approximately 53% of which have developed cancer, mainly (>90%) lymphoid malignancies. This study is based upon the largest reported group of NBS-associated lymphomas. The predominant lymphoma types found in these 14 NBS children were diffuse large B cell lymphoma (DLBCL) and T cell lymphoblastic lymphoma (T-LBL/ALL), all showing monoclonal Ig/TCR rearrangements. The spectrum of NBS lymphomas is completely different from sporadic paediatric lymphomas and lymphomas in other immunodeficient patients. Morphological and molecular analysis of consecutive lymphoproliferations in six NBS patients revealed two cases of true secondary lymphoma. Furthermore, 9/13 NBS patients with lymphomas analysed by split-signal FISH showed breaks in the Ig or TCR loci, several of which likely represent chromosome aberrations. The combined data would fit a model in which an NBN gene defect results in a higher frequency of DNA misrejoining during double-strand break (DSB) repair, thereby contributing to an increased likelihood of lymphoma formation in NBS patients.

Expression of antigens homologous to human retrovirus molecules in normal and severely atrophic thymus.

An immunopathologic study of normal and severely atrophic thymuses (STA) was undertaken in order to evaluate the expression of human retrovirus (envelope and core) molecules in thymic epithelial cells (TEC) in HIV negative children. Both normal and STE thymuses disclosed p19, p24, p39, p45 and p55 viral core proteins as well as gp46, gp63 glicoprotein of envelope origin. No evidence of gp160, gp120 and gp41 molecules were observed in TEC which suggested endogenous lack of receptor molecules for HIV. The results are discussed in the context of possible thymus oriented autoimmune reaction in HIV and non-HIV bearing patients and in consequence, severe injury of TEC forming microenvironment.

Secretory component, alpha 1-antitrypsin and lysozyme in IgA deficient children. An immunohistochemical evaluation of intestinal mucosa.

Nine children with IgA deficiency were studied in order to evaluate by the immunoperoxidase technique the behaviour of secretory component (SC), alpha 1-antitrypsin (alpha 1-AT), lysozyme and esterase in biopsies of intestinal mucosa. In none of the studied patients was SC found to be lacking, suggesting that the epithelial transport mechanism of IgA across enterocytes was relatively normal. The distribution of SC activity in immunodeficient children differed however from that seen in control intestinal mucosa in its non-uniform distribution on the villus, abnormal retention in the Golgi region of enterocytes or exclusive activity confined to the proliferating compartment of the villus. The staining of alpha 1-AT in enterocytes was clearly obvious in all studied cases with no alteration in zonal distribution when compared with normal human mucosa. The lysozyme staining pattern was seen exclusively in Paneth cells. The non-specific esterase positive enterocytes observed in control mucosa failed to stain in biopsies from IgA deficient children. The results of this study of SC, alpha 1-AT, lysozyme and esterase may indicate that IgA deficiency is not related to a defect in enterocyte transport of immunoglobulins and confirms previously reported findings indicating the lymphoid B-cell compartment to be altered.

Light and immunoelectronmicroscopic study of Hodgkin's disease: evidence of immunoglobulin synthesis by tumor cells.

The direct immunoperoxidase technique with peroxidase-conjugated F(ab')2 fragments was used at the light and electron microscopic levels to identify intracytoplasmic immunoglobulin (CIg) components in malignant cells of Hodgkin's disease. In each of the 27 cases studied, Hodgkin and Reed-Sternberg cells contained either IgG or IgM, with both light chains often present simultaneously. The number of IgG-positive malignant cells was inversely related to changes in the lymphoid compartment, as defined by the Rye grading system. The evolution from lymphocytic predominance to lymphocytic depletion was paralleled by a decrease of IgM-positive cells and by a substantial increase (to exclusiveness) of IgG-containing cells. These immunoelectronmicroscopic studies disclosed definite morphologic evidence of CIg synthesis by Hodgkin, Reed-Sternberg and lacunar cells. The immunoglobulin components were also synthesized by lymphoid B cells at different levels of modulation. Immunoglobulin synthesis by malignant cells was localized in perinuclear zone, on free cytoplasmic ribosomes and profiles of rough endoplasmic reticulum. The results of this joint light and electron microscopic study support the view that Hodgkin, Reed-Sternberg and lacunar cells belong to the B-cell compartment within Hodgkin's disease.

Cytoplasmic immunoglobulins in giant lymph node hyperplasia (Castleman's tumour).

The immunohistologic features were studied in 6 cases of giant lymph node hyperplasia (GLNH) and the cytoplasmic immunoglobulin (CIg) characteristics were compared with those of follicular lymphoma and non-specific follicular lymph node hyperplasia. By use of the peroxidase - antiperoxidase (PAP) technique it was shown that GLNH comprised a mosaic, polyclonal population of CIG-producing cells, the CIg pattern being comparable with that observed in follicular lymphadenitis. In contrast, follicular lymphomas disclosed a definite monoclonal pattern, the cytoplasmic Ig containing only one light chain of kappa type. This led to the conclusion that GLNH is not a neoplastic change, but has the characteristics of a reactive process within the B-cell compartment.