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Autoimmune diseases are defined as specific, adapted immune reactions against self-antigens. These antigens were attacked by activated, autoaggressive T-Cells in most cases. However, since introduction of the MALT concept it became clear, that particularly in the autoimmune diseases of the MALT specific subpopulations of B-cells play an important role. In this study, the B-cells in the thyroid gland of 40 patients suffering from Hashimoto's disease and 25 patients with Sjögrens syndrome and enlargement of the salivary glands were immunophenotyped and molecular-genetically investigated. The molecular-genetical investigation included PCR based amplification of immunoglobulin heavy chain CDR III region and the T-cell receptor gamma chain (TCR-gamma). By immunophenotyping, in the salivary glands monocytoid B-cells could be identified as intraepithelial effector cells in nearly all cases, whereas in the thyroid gland mostly marginal zone cells in the follicle epithelium were observed. In 13 biopsy specimen from salivary gland, clonal rearrangements of TCR-gamma, and in 9 cases of patients with Sjögren's syndrome JH rearrangements could be detected. Monoclonal TCR-gamma rearrangements were identified in 9/40 patients suffering from autoimmunethyroiditis Hashimoto. In 8/40 thyroid gland biopsies a monoclonal JH-rearrangement could be found. Within 11/25 patients with Sjögren's syndrome and in 23/40 patients with M. Hashimoto polyclonal rearrangements were observed. Within all biopsy specimen of patients with monoclonal rearrangements, lymphoepithelial lesions or lymphoepithelial destructions could be identified immunohistochemically. Additionally, in 2 biopsies from salivary gland and in one specimen from thyroid gland the transition from autoimmune disease into a secondary high grade lymphoma was observed. In 26/40 patients with M. Hashimoto and in 11/25 patients with Sjögren's syndrome the transition in a subsequent low grade B cell lymphoma of MALT-type was found. These results lead to the following conclusions: 1. clonal rearrangements of tumor forming B-cells in both autoimmune diseases investigated can be interpreted as facultative malignant. 2. Intraepithelial B-cells probably are the promotors of the autoimmune process and--in case of clonal evolution and immortalisation--can be regard as causative agent in the development of primary extranodal B-cell lymphoma.

With the establishment of the MALT concept in immunology it became obvious that B cells play an important role in the autoimmune diseases of the MALT. We immunophenotyped the intraepithelial B cells occurring in Hashimoto's disease, Sjögren's syndrome and Helicobacter pylori-associated gastritis and looked for clonal T-cell receptor gamma chains (TCR-gamma) and immunoglobulin heavy chains (JH). Immunophenotypically, we identified predominantly monocytoid B cells as the effector cells in the salivary glands of patients with Sjögren's syndrome, whereas in the thyroid and stomach the effector cells were marginal zone cells. Polyclonal rearrangements were found in 11/25 patients with Sjögren's syndrome, 23/40 patients with Hashimoto's disease and 19/24 patients with gastritis. Accordingly, 14 of the patients with Sjögren's syndrome, 17 of the patients with Hashimoto's disease and 5 of the patients with gastritis showed monoclonal rearrangements. Immunohistochemically, all patients with clonal rearrangements were found to have lymphoepithelial lesions. In these patients a transition to a low grade MALT lymphoma could be diagnosed. From these results we can conclude that in these two autoimmune diseases clonal rearrangements must be considered at least potentially malignant and that intraepithelial B cells should probably be considered the promoters of autoimmune diseases and of the development of primary extranodal B-cell lymphomas.

Purpose: To evaluate a large group of patients with Castleman's tumours (Castleman's disease = MC) with regard to age, sex and tumour localisation., Patients and Methods: 338 cases of MC were evaluated. All cases were registered by the Lymphknotenregister of the German Society of Pathology, Kiel., Results: 292 MC of the hyaline vascular type (MC-HV) and 46 of the plasma cell type (MC-PC) were found, 259 (76.6%) in nodal and 79 (23.4%) in extranodal localisation. Main nodal localisation were the neck (25.5%) and the axilla (12.8%). The mediastinum was involved in only 6.2%. There was a slight preference of female (56%) compared to male (44%). Patients with MC-PC (mean age: 50 +/- 16.9 years) were significantly older (p < 0.001) than patients with MC-HV (mean age: 39 +/- 18.9 years)., Conclusions: The main localisation of MC is the neck. MC-HV is more common than MC-PC. There is a slight preference for women. Mean age of patients with MC-PC is approximate 10 years higher than for MC-HV.

One of the goals of the study NHL-BFM 90 was to investigate the distribution and prognosis of the different subtypes of Non-Hodgkin's Lymphoma (NHL) in children and adolescents according to histological, cytomorphological and immunological characteristics. From 4/1990 to 12/1992, 346 patients (pts) (84 females, 262 males) were enrolled (median age: 9.1 years; range: 0.8-17.9 years). Histology was available from 290 pts (84%), cytomorphology from 155 (44%), and immunophenotyping from 245 (70%). Cases with L1 oder L2 cytomorphology according to the French-American-British Classification were classified as lymphoblastic lymphoma and those with L3 cytomorphology as Burkitt-Type lymphoma or acute B-cell leukemia (B-ALL) if a histological classification was not available. By means of the combined analysis of all three diagnostic criterias the classification of the NHL according to the updated Kiel-classification was possible in 312 cases: 49% were classified as Burkitt-type-lymphoma (incl. B-ALL), 22% als lymphoblastic lymphoma, 10% as large cell anaplastic lymphoma (LCAL), 6% as centroblastic lymphoma, only few cases were classified as NHL of other subtypes, 3 pts (1%) suffered from low grade malignant lymphomas, and in 34 pts (10%) the NHL was not further classified. Patients were stratified according to NHL-subentities in 3 branches (Non-B-NHL, B-NHL, LCAL) of different treatment modalities. The estimated probability of a 3-year event free survival (pEFS) was 88 +/- 2% for the whole group (follow up 7 to 40 months, median 23 months) while pEFS of different subtypes was: lymphoblastic lymphoma: 91 +/- 4%; Burkitt-type-lymphoma/B-ALL: 90 +/- 2%; centroblastic lymphoma: 94 +/- 6%, LCAL: 88 +/- 6%. We conclude that the stratification of treatment modalities in study NHL-BFM 90 according to biological entities provided patients of different NHL-subtypes an equal chance to survive event free. The efficacy of the treatment strategy for rare subtypes, however, is not evaluable yet.

Malignant non-Hodgkins lymphoma with primary involvement of the thyroid is a rare disease. Nearly all these lymphomas are of B-cell phenotype, and they represent a broad morphological spectrum of high and low grade entities. We investigated 18 cases of Hashimotos disease and 95 cases of thyroid non-Hodgkins lymphoma including 16 cases of MALT-lymphoma. This type of lymphoma is often hardly distinguishable from reactive lesions, even by immunohistochemistry. Therefore, we introduced a new molecular genetic technique based on the polymerase chain reaction (PCR) combined with temperature-gradient gel electrophoresis to demonstrate monoclonal populations of B cells in a polyclonal background of reactive B lymphocytes. With this approach we found monoclonality in 4 of 18 cases of Hashimotos disease. In our opinion, these 4 cases demonstrate clearly the transition from autoimmune disease into non-Hodgkins lymphoma.

A 39 year old man had been suffering from chronic bowel symptoms of changing intensity. At the age of 37 the diagnosis of nontropical sprue was made. After institution of a gluten free diet the patient improved, but soon diarrhea started again. In the examination of peripheral blood smear, bone marrow and small intestinal mucosal biopsies a dominant eosinophilia was found. Since several attacks of abdominal colics and finally an acute abdomen occurred, a laparotomy was indicated. This operative intervention showed a perforation of the intestine and tumors in the bowel wall as well as numerous lymphomas spread over the whole mesentery. The histological examination of both the small intestine resect and the lymphomas proved the diagnosis of a highly malignant Non Hodgkin lymphoma (middle and large cell pleomorphic T-cell lymphoma with transition into a large cell anaplastic lymphoma [ki-1 lymphoma]). The patient received a chemotherapy with COEP but died 4 weeks after the surgery.

Lymph node sinuses consist mainly of sinus lining cells with clear dendritic morphology. Enzyme cytochemical and immune phenotypical analysis classify sinus lining cells as an intermediate cell type linking monocyte/macrophage to follicular dendritic cells, which are accepted immune accessory cells to humoral immune response. Labeling studies indicate sinus lining cells to hematogenous and possible monocytogenous in origin. In functional term sinus lining cells bind and present soluble antigen as the first cell type following antigen pulse. In addition sinus lining cells bind carcinoma cells and may play a role in metastasis. Sinus lining cells give rise to a well defined entity of neoplasia which is proposed to be termed sinus lining cell reticulosarcoma. In this presentation a case report exemplifies such a new entity.

Plasmacytoid, T cells (PTC) occurring in cases of chronic non-specific lymphadenitis were investigated using a panel of monoclonal antibodies and cryostat sections. From the typical T cell antigens only CD4 was detectable on PTC. Antibodies directed against myelo-monocytic antigens such as Ki-M2, Ki-M6 (CD68), and Ki-M7 revealed positive reaction with these cells. The recently established monoclonal antibody Ki-M1P reactive with monocyte/macrophages shows a surface and granular cytoplasmic reactivity with PTC. This observation may indicate the myelo-monocytic origin. Ki-M1P detects a formalin resistant antigen and is thus applicable to conventionally processed paraffin sections as demonstrated in twenty cases of hystiocytic necrotizing lymphadenitis (KIKUCHI).