Adhesion receptors on peripheral blood leukemic B cells. A comparative study on B cell chronic lymphocytic leukemia and related lymphoma/leukemias.

The expression of a series of adhesion receptors: L-selectins (CD62L): Leu-8, several integrins (LFA-1: CD11a/CD18, VLA-4: CD49d/CD29 and VLA-5: CD49e/CD29), ICAM-1(CD54) and the 'homing receptor' (CD44) were investigated by a dual color flow cytometry in 56 cases of B cell disorders namely, 39 chronic lymphocytic leukemias (CLL), four hairy cell leukemia (HCL), seven splenic lymphoma with villous lymphocytes (SLVL) and six other non-Hodgkin's lymphoma (NHL). The functional activity of L-selectins was assessed with L-selectin ligand analogs (polyphosphomonester core polysaccharide: PPME and fucoidin). Leukemic B cells were identified with phycoerythrin-conjugated monoclonal antibodies (McAbs) anti-CD19, anti-kappa/lambda investigated simultaneously for the expression of adhesion receptors estimated with fluorescein-isothiocyanate (FITC) conjugated McAbs. The percentage of leukemic cells expressing L-selectins (Leu-8) was high in CLL (52% of positive cases) and integrin expression (LFA-1, VLA-4, 5) was low (19 and 33%, respectively), while a reverse pattern, low Leu-8 (17%), and a high VLA-4 (77%), was observed in non-CLL cases. The expression of LFA-1 alpha-chain was variable in non-CLL cases, and the LFA-1 heterodimer was expressed on most clonal B cell in NHLs (92%). LFA-1 alpha-chain was detected on cells from only one HCL case, while beta2 integrin was regularly expressed on hairy cells. VLA-5 integrin was found on a relatively small number (26%) of mature B cell leukemias. A remarkable finding was the detection of ICAM-1 in all CLL cases albeit the number of positive cells was significantly lower (P < 0.05) compared to non-CLL cases. CD44 was expressed on a high number of neoplastic cells in all the investigated categories. There was no correlation between the expression of the adhesion molecules and clinical and laboratory parameters except for CD18 which was expressed on a significantly (P < 0.05) higher number of leukemic cells in CLL with more advanced stages. This study demonstrates that even closely related B cell leukemia/lymphomas have a certain well defined and strictly variable adhesion profile which is characteristic of the disease entity and therefore, the adhesion profile may offer additional information useful for differential diagnosis and study of disease pathogenesis.

Endothelial cell receptors on leukemic plasma cells.

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.

Blood vessels in human immunodeficiency virus-related lymphoadenopathy: high endothelial venules and lymphocyte migration.

The vasculature of 25 lymph nodes of patients with human immunodeficiency virus-related lymphadenopathy was investigated morphometrically. The number of small vessels, the morphological features of high endothelial venules and the migratory index of the lymphocytes passing through the high endothelial venules, as well as the stage-dependent change of each parameter, were analysed. Twenty reactive lymph nodes served as controls. The total number of vessels in the HIV-infected lymph nodes was relatively stable. However, the small vessels with flat endothelium increased in number, while the number of high endothelial venules decreased as the disorder progressed, and the decrease in the lymphocyte migration seemed to precede the change in the morphology of high endothelial venules. The presumptive role of these alterations in the pathogenesis of the investigated disorder is emphasized.

High endothelial venules and cell adhesion molecules in B-cell chronic lymphocytic leukaemia and related low grade B-cell lymphoma/leukaemia: II. Expression of cell adhesion molecules in lymph nodes biopsies.

The expression of cell adhesion molecules (LECAM-1, LFA-1, VLA-4, ICAM-1 and CD44) of lymph nodes from B-cell chronic lymphocytic leukaemia (B-CLL; mature: 16 cases, immature: 8), lymphocytic lymphoma (LL; M:5, IM:2) and reactive lymph nodes (10) were investigated in frozen tissue sections. In order to assess the B- and T-cell compartments of the lymph nodes some additional markers CD3, CD20, CD45 RO were used, and for follicular dendritic reticulum cells (FDCs) CD35. The expression of the LECAM-1 molecule was correlated to the expression of activation (CD23, CD25) and proliferation (Ki67) markers. Findings, in accordance with the relevant data of the literature, indicate that B-CLL and LL show and identical adhesion profile to the mantle zone of the germinal centres of reactive lymph nodes; namely, they were CD44+/LECAM-1+/VLA-4+. The T-zones of the reactive lymph nodes were characterized by an LFA-1+ and the follicles by an ICAM-1+ pattern, while in B-CLL and LL cases the LFA-1+ and ICAM-1+ were detected without coexpression of these molecules in only a small number of cases. The ratio and location of CD3+ and LFA-1+ cells was very similar in lymph nodes from B-CLL and LL, and from this fact may arise the suspicion that LFA-1+ reported in LL cases derive from the sometimes significant T-cell compartment of the diseased lymph nodes. The LECAM-1 molecule did not show any correlation with the investigated activation/proliferation markers.

High endothelial venules and cell adhesion molecules in B-cell chronic lymphocytic leukaemia and related low grade B-cell lymphoma/leukaemia: I. High endothelial venules and lymphocyte migration.

The high endothelial venule (HEV)-content and the lymphocyte migration index (LMI) of reactive lymph nodes and lymph nodes from patients with B-cell chronic lymphocytic leukaemia (B-CLL), as well as some related B-cell malignancies (lymphocytic lymphoma -LL-, prolymphocytic leukaemia -PLL-) were determined and statistically analyzed. The HEV-content and the LMI were significantly higher in reactive lymph nodes than in the low grade B-cell lymphomas and leukaemias (p < 0.001). The number of HEVs among lymphoma/leukaemia cases was the highest in LL independently of the maturation. However, the maturation of the process seems to determine the intensity of lymphocyte migration; i.e. a significantly higher LMI was found in mature (B-CLL, PF, mature; M and LL, M) than in immature subtypes (B-CLL, PF, immature -IM-; diffuse -D- and LL, IM) subtypes (levels of significance varied from p < 0.05 to p < 0.001). Based on these findings, a more intense migration of lymphocytes from blood to peripheral lymph nodes may be supposed in LL than in B-CLL, thus explaining the nodal sites of involvement in LL and the peripheral blood in B-CLL. Within the same histological categories the morphometric features in mature subtypes may implicate an enhanced HEV-lymphocyte interaction when compared to the immature subtypes.

Biotinylated L-selectin ligand analogs as cytochemical probes in cytospin preparations.

Amino-derivatives of L-selectin ligand analogs: phosphonoester core polysaccharide (PPME) and fucoidin were biotinylated with the use of biotinyl-N-succinimide ester, and these biotinylated analogs b-PPME and b-fucoidin were demonstrated as useful tools to investigate the functional activity of L-selectins in cytospin preparations obtained from healthy human donors and from patients with chronic lymphocytic leukemia (CLL). The avidin/biotin system adds a new alternative to the application of the L-selectin ligand analogs (PPME, fucoidin) which have been formerly used as fluoresceinated, solid phase or immobilized probes.

Renal angiomyolipoma: report of three cases with regional lymph node involvement and/or with renal cell carcinoma.

AIMS AND BACKGROUND: Angiomyolipomas (AMLs) are benign hamartoid tumors which frequently occur in tuberous sclerosis (TS). They may be manifest at different organ sites such as kidneys, lymph nodes, liver and lung and may be associated with renal cell carcinoma (RCC). The nature of multiple organ involvement in AML (metastasis versus multicentric synchronous tumors), the malignant transformation and the relation of AML to RCC have not been sufficiently clarified. STUDY DESIGN: Three cases of renal AMLs in patients with tuberous sclerosis associated with lymphangioleiomyomatosis of the paraaortic lymph nodes and/or with RCC are reported. The concise clinical history of the patients as well as the findings of histology, immunohistochemistry and quantitative DNA analysis are presented. RESULTS: The multicentric form of AML and coincidence of renal AML and RCC were observed in 2 patients. AML and RCC were found within the same focus in one of the cases. RCCs were either aneuploid or "near diploid", whereas one of the multicentric AMLs showed a discordant DNA ploidy pattern, namely aneuploidy in the kidney and diploidy in the lymph nodes. CONCLUSIONS: The presented cases (all of them underwent periaortic lymphadenectomy) suggest that lymph node involvement in renal AML may be more frequent than expected (1-2% of all AMLs) on the basis of the few reported cases. The discordant DNA ploidy (renal versus lymph node lesions) observed in one of the cases with multicentric AML implies synchronous tumor growth at different sites rather than metastatic disease. The intimate coexistance of RCC and AML (RCC revealed by immunohistochemistry within a larger mass of renal AML) may indicate that malignant transformation of an AML should only be accepted, if such a coincidence is unequivocally excluded.

L-selectins revealed by immobilized analogue molecules on human peripheral blood lymphocytes.

The lymphocyte-endothelial interaction is initiated by selection type adhesion molecules on the surface of the lymphocytes (L-selectins) and by their carbohydrate ligands (addressins) in the glycocalyx of the endothelial cells. Under experimental conditions they can be substituted by analogue sugars, such as polyphosphonomonoester core polysaccharide and fucoidin. In this study, the expression of phosphomannosyl and fucoidin receptors is demonstrated on lymphocytes from human peripheral blood by polyacrylamide immobilized analogues. Based on adhesion and sugar inhibitory experiments, authors suggest that lineage and probably species specific differences exist in the expression and activity of the selectins responsible for binding of the two analogue molecules.

[Relationship between histological prognostic indices and clinical course in prostatic carcinoma]. / A szövettani prognosztikai indexek és a klinikai kórlefolyás összefüggése prostata carcinomában.

The authors have summarized the relationship between histological differentiation indices and survival rate, hormonal sensitivity time, hormonal resistance time for the past 10 years. The classifications have been made according to Dhom and Gleason. 130 patients have been followed from the time of diagnosis to the time of their death. 95 patients died because of tumour. They found that there is a relationship between the survival rate and indices in those cases who were early diagnosed and they had no metastasis. There was no relationship between hormonal sensitivity time, hormonal resistance time and histological prognostic differentiation indices.

[Primary (B-cell) mediastinal lymphoma]. / Primer (B-sejtes) mediastinalis lymphoma.

The authors present two cases of a new pathological entity--primary (B-cell) mediastinal lymphoma. The disease both clinically and histologically differ from the known lymphomas. Its diagnosis is possible only with the use of immunhistochemical methods. The low age incidence, the unusual course and the bad prognosis of the disease merits its publication.

[Symptomless amniotic infection related to pregnancy outcome]. / Tünetmentes peteürfertözödés kapcsolata a szüléskimenetellel.

Placental histology in 984 pregnancies (758 term and 226 preterm) occurring during the years 1995 to 1998 was investigated and amniotic cavity cultures were taken during 918 cesarean sections. Histology revealed placental infection in 20.3% of placentas. Chorioamnionitis was confirmed in 119 out of 758 term pregnancies (15.7%) while in 81 out of 226 preterm pregnancies (35.8%); the difference is highly significant (chi 2 = 26.6, p < 0.01). Bacteriological culture resulted in bacterial growth in 19.7% of all cases (181/918), its frequency was significant higher in premature births (54/133, 40.3% chi 2 = 25.2, p < 0.01) as compared with pregnancies carried to term. Recovery of any organism from the amniotic cavity was strongly associated with chorioamnionitis confirmed by histology. Comparison of the rates of indicating placental infection found in this study and a study performed between 1981 and 1983, showed that the program aiming at detection and treatment of silent intrauterine infection has only partially been successful.

[Angiocentric T-cell lymphoma of the lung]. / A tüdö angiocentrikus t-sejtes lymphomája.

Angiocentric T-cell lymphoma of the lung. The case history of a patient with primary angiocentric T-cell lymphoma of the lung having an unusually long survival period (> 10 years) is presented. Attention is paid to the possibilities of differential diagnosis that should be taken into account in the analysis of certain lymphocytic infiltrates of the lung. In accordance with relevant data of the literature, this case shows that pleiomorphic small cell T-lymphomas may have a protracted course, and the disease free periods repeatedly achieved in this patient by irradiation and chemotherapy are thought to be noticeable. Authors refer to some recent findings which may give new insights in the pathobiology of extranodal T-cell lymphomas, and result in recognition of new disease entities.

[Actinomycosis with abdominal manifestation]. / Abdominális manifesztációjú actinomycosis.

During the last 4 years the authors observed 3 actinomycotic cases with abdominal localization. The disease was found in all the three cases to be localized to those parts of the intestinal tract where stasis of fecal contents may occur, i. e. to the appendix, to Meckel's diverticle and to the left colonic flexure. The relatively rare incidence and preoperative diagnostic difficulties make publication of these cases worthwhile. Based on own experience and literary data they describe natural history, clinical picture, histology and treatment of the disease, respectively.

[Peanut agglutinin binding of lymph node follicles]. / Nyirokszöveti csíracentrumok paenut agglutinin kötése.

The peanut-agglutinin binding of lymph node follicles was studied in frozen and paraffin sections of human tonsils. In a substantial fraction (10-25%) of follicles focal zones of high PNA receptor expression were encountered which were more readily recognizable in paraffin sections and corresponded to the centrocytous, "light" zone of the follicle. Results suggest that divergent lectin binding of follicles reflects their different functional states.

Antigen-induced changes in the lymphocyte-high endothelial venule interaction.

The sequential changes of some morphometric parameters (lymph node weight, high endothelial venule (HEV)-content) after an antigenic challenge (sheep red blood cell; SRBC) and the alterations of HEV-function (HEV-adhesiveness measured with a HEV binding assay) were studied in rat lymph nodes over a period of seven days with daily measurements. Authors suggest that the proper estimation of the HEV-content of a lymph node in a HEV binding assay allows to express the HEV-adhesiveness numerically, and to compare the data obtained by this assay quantitatively. The HEV-adhesiveness is the strongest on day 6 after the antigenic challenge, the early increase in weight on day 2 is attributed to an increased blood flow and the changes in the HEV-content are presumed to reflect a simple dilation of HEVs (on day 2) and later (on days 4 and 5) an increase in the height of high endothelial (HE) cells. A crucial role is ascribed to the altered HEV-adhesiveness in the increase of lymphocyte migration to the challenged lymph nodes.

Antigen-induced changes in the lymphocyte-high endothelial venule interaction.

The sequentional changes of some morphometric parameters (lymph node weight, high endothelial venule (HEV)-content) after an antigenic challenge (sheep red blood cell; SRBC) and the alterations of HEV-function (HEV-adhesiveness measured with a HEV binding assay) were studied in rat lymph nodes over a period of seven days with daily measurements. Authors suggest that the proper estimation of the HEV-content of a lymph node in a HEV binding assay allows to express the HEV-adhesiveness numerically, and to compare the data obtained by this assay quantitatively. The HEV-adhesiveness is the strongest on day 6 after the antigenic challenge, the early increase in weight on day 2 is attributed to an increased blood flow and the changes in the HEV-content are presumed to reflect a simple dilation of HEVs (on day 2) and later (on days 4 and 5) an increase in the height of high endothelial (HE) cells. A crucial role is ascribed to the altered HEV-adhesiveness in the increase of lymphocyte migration to the challenged lymph nodes.

[Malignant lymphomas: pathomorphology and experiment]. / A malignus lymphomákról: pathomorphologia és experimentum.

The last fifteen years have provided a significant development in pathomorphological diagnosis of malignant lymphomas (ml), in clinical fellow-up of patients and in its therapy. Diagnosis is built on functional morphological basis (immunohistology). New methods have reslited in identification of new types of mls. On the basis of high number of cases registered in Lymphoma Reference Centre, specific organic distribution new entities can be determined. Perifollicular B-cellular mls of MALT type are frequent in gastrointestinal tract and are rare in Waldeyer ring and in lymph nodes. Flow cytometric determination of DNA content of cells proved to be very useful in diagnostics of mls, so the probably determination of aneuploid and proliferative activity, respectively. These parameters are of prognostic significance. Recirculation of lymphocytes may play a role in dissemination os nHmls. It can be studied in immunomorphological (in vitro) test ased on the interaction (adherence) of lymphocytes and of endothelial cells of high endothelial postcapillary venule. Our observations present that B-cellular CLL and clonal cells of plasma cellular leukemia show endothelial adherence, while multiple cells of myeloma do not.

Lectin histochemical characterization of the mouse, rat and human lymphoid tissues.

The authors performed a comparative lectin histochemical study on lymphoid organs of three species with 12 different lectins. The T and B cell regions and the accessory cells of lymphoid tissues were studied. The species differences show that the BALB/c mouse can be a valuable tool in modelling human lymphoid tissues, whereas Wistar rats exhibit great differences in lectin binding patterns as compared with human tissues. The positivity of peanut agglutinin binding of cortical and the negativity of medullar thymocytes in mice can be regarded as an indicator of cell differentiation. The focal distribution of peanut agglutinin positivity in the centrocytic region of human and rat germinal centres marks a small B cell subpopulation at the early stage of differentiation, while Bandeira simplicifolia binding is characteristic of a broader B cell lineage, but only in rats and mice. Canavalia ensiformis lectin seems to be a reliable marker of accessory cells (dendritic and interdigitating reticulum cells as well as macrophages) in all species studied.