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In the course of a routine clinical check up of the 54 year old male a splenic well circumscribed tumor like mass of 12 cm in diameter was discovered. Splenectomy with removal of splenic hilar lymph nodes and liver wedge biopsy were performed. Four years later the patient is symptom free. In the removed spleen the tumor like lesion showed a pattern consistent with the diagnosis of inflammatory pseudotumor. However, besides lymphocytes, plasma cells, macrophages, eosinophils and myofibroblasts a high number of slightly polymorphic, frequently binucleated cells positive for CD21 and CD23 were seen. These cells which were scattered or formed smaller or larger groups and fascicles were considered to represent follicular dendritic reticulum cells (FDRCs) and the lesion a FDRC tumor. Flow cytometric DNA ploidy analysis showed a hyperdiploid cell population inside the tumor like lesion. Besides FDRC tumors of high and of intermediate malignancy the present case may represent a low grade type of moderate proliferation activity. The FDRCs of the lesion and a few smaller spindle cells were EBER positive indicative of the presence of EBV. No EBER positive cells were seen in the uninvolved spleen.

A patient who had primary gastric B-cell non-Hodgkin's lymphoma, invasive ductal breast cancer and a basocellular carcinoma of the forehead in her medical history was studied. Three years after polychemotherapy and irradiation of the breast cancer, a rapidly enlarging, ulcerated violaceous tumour developed on the patient's left leg. The tumour was identified by the histopathological, immunohistochemical and immunoglobulin gene rearrangement analyses as a cutaneous large B-cell lymphoma. No signs of extracutaneous involvement were detectable. Despite surgical excision, interferon-alpha2b treatment and chlorambucil + prednisone chemotherapy, a relapse occurred in the previously affected site, whereafter the patient received radiotherapy. She was lost to follow-up, and died approximately 14 months after the surgical intervention without autopsy. We discuss the clinical and histologic features and outcome of the large B-cell lymphoma of the leg, its coincidence with other diseases, and the uncommon occurrence of primary multiple malignant tumours.

This report presents an experience of polymerase chain reaction (PCR) analysis of T-cell receptor g- and bgene (TCR g, TCR b), and immunoglobulin heavy chain (IgH) gene rearrangements in 9 cases of primary systemic anaplastic large cell lymphoma. We showed 2 clonal IgH, 2 TCR g, 1 TCR b rearrangements. The genotype was B/T-cell in 1, T-cell in 1, B-cell in 1 and null cell-type in 6 cases. We used reverse transcriptase PCR (RT-PCR) to detect t(2;5)(p23;q35) and t(1;2)(q25;p23) translocations. T(2;5) translocation was demonstrated in 2 cases, there was no t(1;2) translocation. In most cases the molecular genetic results were found to be in agreement with immunophenotypic data.

Intravascular (angiotropic) lymphoma is a unique and rare cutaneous lymphoma in which the malignant T or B lymphoid cells proliferate within the lumens of small blood vessels, primarily in the skin and central nervous system. Erythematous, tender nodules, tumors, and telangiectases are the most common skin symptoms in addition to various neurologic signs. Progression of the disease produces secondary organ involvement with variable symptoms and can be fatal. We describe a case of a 74-year-old woman with edematous, infiltrated, orange-like skin with multiple telangiectases, generalized edema, severe weakness, and extremely high values of lactate dehydrogenase. Skin biopsy specimens revealed atypical large cells filling up the lumens of dermal capillaries. Immunohistochemical investigation results identified them as B cells with CD20, CD45, CD79a, Ki-67, and HLA-DR positivity. After administration of diuretics, colchicine, and systemic PUVA therapy, the patient lost her edema, her skin became tender and free of telangiectases, and laboratory alterations normalized. Because of heavy neuralgia in her legs, oral monochemotherapy was introduced with chlorambucil, and now the patient is in remission.

To characterise the nature of the cellular origin of the blastic variant of mantle cell lymphoma (MCL-BV), we analysed the immunoglobulin (Ig) heavy chain variable region (V(H)) genes in four cases of MCL-BV. The rearranged V(H)-D J(H) genes were PCR-amplified, cloned and sequenced. In one case, the comparison of the rearranged V(H) gene sequence to known germline V(H) gene templates showed no somatic mutations suggesting a pre-germinal centre B-cell origin for tumour cells. In the other three cases, the V(H) gene sequences showed varied number of point mutations relative to the putative germline V(H) gene sequences but the point mutations were not associated with intraclonal diversification. In one of the mutated cases, the distribution and type of the mutations indicated that tumour cells had been selected by an antigen. Since somatically mutated Ig genes are expressed by B-cells that have reached a germinal centre/post-germinal centre stage of development, these findings suggest that the MCL-BV cell of origin may also be a germinal centre or a post-germinal centre B-cell. Taken together, our findings suggest that the development of MCL-BC may not be restricted to one stage of B-cell differentiation and that they may represent transformants of B-cells at different stages of ontogeny.

In virus associated diseases identification of viruses in cells can contribute to the understanding of the pathogenesis and may also help to establish the diagnosis. In the present communication, the effects of the microwave pretreatment (MWP) and that of the proteinase-K enzymatic predigestion (PKD) on EBER RNA oligonucleotide in situ hybridization (EBER-RNA-ISH) (EBER: Epstein-Barr-Encoded-(Early)-RNA) were studied. The efficacy of two EBV detecting methods, latent membrane protein-1 (LMP-1) immunohistochemistry and EBER-RNA-ISH were also compared. Our results show that microwave pretreatment enhances the intensity of the ISH signals and preserves significantly better the structure of the tissues compared with enzymatic predigestion. EBER-RNA-ISH, mainly in the nasopharyngeal carcinoma cases, showed a more frequent positivity than the immunohistochemical reaction for LMP-1, however in case of the Warthin's tumor only the LMP-1 protein was expressed.

We have reported that, in A/J (A) (H-2a) mice, a partial tolerance to C57BL/10ScSn (B10) (H-2b) skin allografts and a high incidence of lethal lymphoproliferative disorders (LPD) can be induced by the neonatal i.v. injection of 2 x 10(7) semiallogeneic (B10 x A)F1 spleen cells (SC) (Végh, P., Baranyi, L. and Jánossy, T., Cell. Immunol. 1990, 129: 56). In this study, we show that the incidence and mortality of LPD were continuously growing from 1 month of age until the end of the experiment at 1 year (64% and 36%, respectively). Based on histology, 27% of the diseased mice suffered from lymphoid malignancies. In the remaining cases (73%), reactive histopathological changes were seen in the spleen, lymph nodes (LN), liver and kidneys. The proportion of CD4+ T cells in the spleen and LN as well as that of splenic B cells decreased, while the percentages of mature and immature myeloid cells doubled. The total cell number of each (sub)population, however, was elevated in both lymphoid organs. The cells taking part in the lymphoproliferation were of host (A) and not of donor (F1) origin. Preceding the development of apparent LPD, the SC, LN cell and thymus cell suspensions of 1-month-old tolerized mice showed reduced in vitro proliferative responses to T cell and T cell-dependent B cell mitogens (Con A or PWM), while their reactivity to a T cell-independent B cell mitogen (lipopolysaccharide) was essentially unimpaired. This hyporeactivity seems to be functional, because neither histology nor immunophenotyping by flow cytometry revealed significant alterations in the spleen and thymus of such animals, apart from a slight reduction in the ratio of CD4+/CD8+ T cell subpopulations in the spleen. The in vivo T cell-mediated immune response of the tolerized mice was practically normal to third party CBA/Ca (H-2k) allografts. Antithymocyte autoantibodies (ATA) were detected in the sera of 76% of the tolerized mice at 1 month of age (i.e., even before the mass appearance of LPD). ATA as well as antinuclear Ab were present in 65% of the adult tolerized mice, independently of the presence of LPD. Taken together, in A mice neonatally injected with (B10 x A)F1 SC, a partial, specific allograft tolerance and a chronic host-vs.-graft disease-like syndrome developed. The latter is manifested in hyporeactivity to T cell mitogens, development of autoantibodies and, subsequently, in progressive LPD and lymphoid malignancies.

High endothelial venule (HEV)-binding of peripheral blood mononuclear cells (PBMCs) from 43 patients with B-cell chronic lymphocytic leukaemia (B-CLL) was investigated with a HEV-binding in vitro assay. Immunophenotyping of HEV-adherent PBMCs proved that most of them belonged to the B-cell proliferation. B-CLL cells stringently expressed CD44 molecules (Hermes-1, -3 and H90). The patients were subgrouped according to Binet's classification, as well as according to the organ manifestations, i.e. patients with B-cell monoclonal lymphocytosis of undetermined significance (B-MLUS) and patients with lymphocytosis (LY), lymph node enlargement (LN) and splenomegaly (SM). The HEV-binding activity of the cells was the highest in Binet stage A patients and in patients with B-MLUS (p < 0.05 in B-MLUS versus B-CLL LY, LN, SM). Based on these findings it is suggested that B-CLL patients show not only a clinical and immunophenotypical heterogeneity, but a diverse function of adhesion molecules.

Primary non-Hodgkin malignant lymphomas (ml) of the breast are infrequent (0.05-0.5% of all malignant breast tumours). In the present series, 10 cases seen between 1980-1989 from the files of the Malignant Lymphoma Reference Center, Pécs, Hungary, were re-evaluated. Nine out of the 10 cases were of B-cell origin, 4/10 of low grade and 6/10 of high grade malignancy. In the latter group there were 4 centroblastic ml-s. In one of them transformation of a low grade MALT-type ml to centroblastic ml was suspected. Another high grade B-cell ml was similar to the recently described mediastinal clear cell ml, B-cell type. At presentation, 7 out of 10 patients were in clinical stage IE. In the same period (1980-1989), 5 further cases with clinical suspicion of breast tumor had reactive lesions (florid follicular hyperplasia).

In diagnostic pathomorphology of lymphoproliferative diseases, immunohistochemical methods are of great importance. These methods help to elucidate the following issues: reactive or malignant nature of a lesion, origin of atypical cells (lymphoreticular or other), type of malignant lymphoma (Hodgkin's disease or malignant non-Hodgkin lymphoma, NHL), grade of malignancy, T- or B-cell origin and subtype of NHLs. All results of immunohistochemistry should be carefully scrutinized in the light of routine pathomorphological findings. The possibilities of immunohistochemistry are demonstrated by two examples: 1. Origin and stage of differentiation of B-cell chronic lymphocytic leukaemia cells with special emphasis on the presence of follicular dendritic reticulum cells in the lymph nodes of a few, otherwise typical cases of CLL. 2. Description of two cases of a new type of NHL that contains intrasinusoidal B-cells. Monoclonal plasma cells with immunoglobulins of the same isotypes as those of intrasinusoidal B-cells were observed in both cases. These findings suggest that the intrasinusoidal B-cells may be plasma cell precursors.

In a 26-year-old male suffering from haemophagocytic sinus histiocytosis with massive lymphadenopathy (SHML) five biopsies were performed during a period of 60 months. It seemed that the first change in SHML is the appearance of foamy histiocytes in the subcapsular sinuses at a time when accumulation of and haemophagocytosis by the histiocytes in the intermediary and medullary sinuses are not conspicuous. Progression of the lesions is indicated by the accumulation of haemophagocytic histiocytes in all sinuses and by the development of subcapsular xanthofibrous tissue areas, first focal, later confluent. Regression of the lymphadenomegaly may be due to gradual obliteration of the lymph node parenchyma by the subcapsular xanthofibrous tissue and by scarring. Even in the early phases of the disease the paracortical areas were underdeveloped. The immunophenotype of the foamy histiocytes populating the sinuses and the xanthofibrous areas is S-100+, Leu-M3+, VIM-13+ (CD 14), MAC 387+ N-PNA+, OKIa+, Leu-M1- (CD 15) and OKM1- (CD 11).

The binding of peripheral blood mononuclear cells of 7 patients with plasma cell leukemia to rat lymph node high endothelial venules has been studied in vitro. The mononuclear cells adhered selectively to the high endothelial venules. Their neoplastic origin was proved by in situ demonstration of their monoclonal cytoplasmic immunoglobulins. The in vitro binding of bone marrow mononuclear cells of 4 patients with multiple myeloma to high endothelial venules was also studied. In two patients there was no high endothelial cell binding. In the two others some adhering cells were observed. The plasmacytoid nature of these cells was, however, excluded for lack of cytoplasmic immunoglobulins. Since cells at the end stage of B-cell differentiation lose their surface receptors associated with lymphocyte recirculation, the presence of endothelium-recognizing structures on leukemic plasma cells seems to be remarkable.

Cetylpyridinium chloride (CPC) and cetyltrimethylammonium bromide (CETAB) are bound to polyanionic substances by ionic bonds between the positively charged nitrogen of the quaternary salts and the negative groups of polyanions. The mast cell granules and some other structures treated with CPC or CETAB react selectively with acid dyes and fluorochromes. In ultrathin sections treated with CPC, phosphotungstic acid (PTA) greatly enhances the electron density of the granules of mast cells. The possible mechanism of acid dye and PTA binding by CPC or CETAB treated tissues is discussed.

In a retrospective study of 202 cases of multiple myeloma (MM) were studied cyto- and histomorphologically. In 62 cases only bone marrow smears, in 60 only histological preparations and in 80 both types of material were available. According to the differentiation of myeloma cells, a plasmocytic (n = 127), a mixed cellular (n = 35) and a plasmoblastic type (n = 32) could be distinguished. Besides, 8 cases with predominance of giant cells were found (giant cell MM). The comparative cytological and histological typing into the four types of MM proved to be reproducible. The medium survival time and survival curves of the described types showed a statistically significant difference. The survival times were 39.7 months with the plasmocytic type, 16.1 months with the mixed cellular type, and 9.8 months with the plasmoblastic type. The prognostic relevance of the morphological classification was supported by the frequency of extramedullary infiltrates (20% in the plasmocytic, 67% in the mixed cell, 69% in the plasmoblastic and 100% in the giant cell type).

In the present paper, the more important data on malignant lymphoma cases seen by the Malignant Lymphoma Reference Centres of the GDR, Hungary and Poland in 1979 are summarized. Altogether 655 new malignant lymphomas were diagnosed pathohistologically, 141 of them (21.5%) representing Hodgkin's disease and 514 (78.5%) non-Hodgkin's malignant lymphomas. Besides, 16 cases of malignant histiocytosis were recorded in the three Centres. The ratio of Hodgkin's disease to non-Hodgkin's malignant lymphoma (see above) and that of low-grade to high-grade tumours (68.5% vs 31.5%) were similar in the three Centres. Ways of further development of the collaboration of the Centres and the measures necessary to increase the comparability of the accumulated material are discussed.

In a 34-year-old woman a non-Hodgkin malignant lymphoma with extreme splenomegaly and monoclonal IgM paraproteinaemia was seen. The removed spleen and splenic hilar lymph glands showed a nodular centroblastic-centrocytic malignant lymphoma with large numbers of plasmocytoid cells containing monotypical (monoclonal) IgM-kappa type immunoglobulin. The case represents a borderline non-Hodgkin malignant lymphoma with features of a follicular tumour and an immunocytoma. The appearance of peculiar intracytoplasmic inclusions would support this assumption. Therapeutic measures (splenectomy and/or cytostatic treatment) and prognostic features (nodularity of the tumour) are discussed.

The reactivity of 38 anaplastic tumours for cytokeratin, vimentin, desmin, milk fat globule membrane antigen. Ia antigen as well as peanut agglutinin and Ulex europaeus I lectins were investigated immunohistologically in paraffin embedded tissue samples. By this typing of tumours establishment of the histogenesis of 34 out of 38 neoplasms was possible. Among the epithelial markers milk fat globule membrane antigen proved to be superior to cytokeratin. Vacuolar or intraluminal binding of peanut lectin was found to be more sensitive than PAS reaction for detecting early secretory activity. Our study substantiates the previous data that binding of Ulex europaeus I lectin is indicative of nasopharyngeal carcinoma. In this study we also provide evidence for vimentinization in solid metastases as well as for shift in the cytokeratin profile upon malignant transformation.

In 74 cases of acute leukaemia and of the blastic phase of chronic granulocytic leukaemia (CML), monoclonal antibodies of the "VI" series and a few commercially available antibodies proved to be of valuable help in establishing a definite diagnosis. In 4 out of 35 cases of AML (FAB-M 1-5), and in 2 out of 16 of the blastic phase of CML only the use of monoclonal antibodies secured the diagnosis. In the group of acute lymphoid leukaemias subtypes corresponding to various levels of differentiation, were defined. The blasts of 3 patients out of the 74 did not express any of the markers studied. Two additional cases were investigated for platelet peroxidase and studied with the antiplatelet antibodies VIPL 1, 2 and 3 by the electron microscope. These cases proved to be acute megakaryoblastic leukaemias (acute myelofibrosis).

Fifteen cases of primary gastrointestinal lymphoma diagnosed over 8 years are reviewed. In the period 1980 to 1982 there was a cumulative appearance of GI lymphomas, nine out of 15 cases were diagnosed in that period. According to its localization, lymphoma occurred in 12 cases in the stomach, and in 3 in the small intestines and the colon. One case of gastric lymphoma was Hodgkin type, the others were non-Hodgkin types. The clinical symptoms were not characteristic of lymphoma. The age of the patients was, on the average, ten years lower than the mean age of carcinoma patients. Preoperative diagnosis by gastric biopsy was successful in four cases. In patients with lymphoma of the colon not subjects to surgery, colonoscopy verified the origin of lymphoma. Exact clinical classification in the majority of cases was made intraoperatively. In the non-operated cases, sonography and lymphography were performed. In general, operation was attempted, but patients in stage II, in very poor condition, were possibly not operated. The possibility and indications of the "second look" operation are discussed. Histological typing was made according to the Kiel classification. In the literature, in the most controversial question of therapy, individual consideration of the cases is recommended. Based on our experience, in devising therapy or therapeutic strategy as well as concerning prognosis, the degree of malignancy according to histological type, clinical stage and anatomical localization seem to be the most decisive factors. In exceptionally malignant cases a protocol with doxorubicine + bleomycin + teniposide and prednisolone was applied.

The kinetics of 51Cr-tagged platelets was studied in 10 patients with idiopathic thrombocytopenic purpura and in 8 patients with congestive splenomegaly. The surgically removed spleens were examined for their platelet content and for their microscopic structure. In idiopathic thrombocytopenic purpura the life-span of platelets was reduced, the number of platelets washed out from the spleen averaged 4.36 X 10(10)/100 g splenic tissue (intrasplenic platelet reserve). The index platelets per g splenic tissue/platelets per ml whole blood reflecting the tendency of platelets to concentrate in the spleen was 8.06. Microscopically, extensive phagocytosis of platelets by macrophages and a preserved lienal architecture were seen. In the group of congestive splenomegaly the life-span of platelets was not significantly shortened and the intrasplenic platelet reserve agreed with the figure found in idiopathic thrombocytopenic purpura. The spleen was characterized by fibroid degeneration and endothelial hypertrophy causing partial obstruction of the sinusoids. It is concluded that while the intrasplenic platelet reserve is nearly the same in idiopathic thrombocytopenic purpura and congestive splenomegaly, in idiopathic thrombocytopenic purpura hypersequestration while in congestive splenomegaly platelet storage predominates.

In the period between 1960--1978 36 children dead with acute lymphoblastic leukaemia (ALL) were studied. Nine cases were found to be in pathological remission, i.e., without any leukaemia infiltrations (7 of these were seen in the last 5 years). The remaining 27 could be divided into two groups on the basis of nuclear structure: in 20 cases the lymphoblastic nuclei were round or oval and their convolution was pycnotic, "highly convoluted", or lobulated, in 7 the nuclei were round or oval and their convolution was slight. The survival was 10.8 months in the first and 3.6 months in the second group. Although the origin and the degree of differentiation of the cells of these two groups are not clearly known, it seems that the two types represent different stages of T-lymphoblast evolution.

The haematopoietic tissue in the supraneural organ of the freshwater river lamprey (Lampetra fluviatilis L. Gray) was studied in sexually immature animals. Besides erythro- and granulopoietic elements, macrophages, reticular cells, fibroblasts and glycogen-rich fat cells were seen. Developing granulocytes of the lamprey contain one type of azurophil granules originating from small cytoplasmic (Golgi) vesicles. The lamprey's azurophil granulocytes seem to be homologous with those of fishes. However, the granulocytes of fishes, studied thus far, show granules with only one type of inclusion, whereas in lamprey the granulocyte inclusions are variable in size and shape. Thus, lamprey granulocytes are, in this respect, reminiscent of similar cells of higher vertebrates. The PAS and alkaline phosphatase reactions, common markers of vertebrate neutrophil leucocytes, are very weak in the haematopoietic tissue granulocytes of the lamprey, and intense in the blood cells of the same animal. Lamprey granulocytes, similarly to the granulocytes of Chondrostei and Elasmobranchiata, do not stain with peroxidase, naphthol-AS-D-chloroacetate esterase and sudan black B. The haematopoietic tissue contains a relatively high number of degenerated granulocytes.