Cutaneous lymphatic amyloid deposits in "Hungarian-type" familial transthyretin amyloidosis: a case report.

Multiple transthyretin (TTR) mutations have recently been identified and implicated in the development of familial systemic amyloidoses, but early diagnosis of these disorders is still largely unresolved. We investigated the presence and tissue distribution of TTR-derived amyloid in skin biopsies of a 59-year-old woman carrying the "Hungarian-type" mutation of TTR (Asp18Gly). Clinical symptoms involved severe central nervous system dysfunction without signs of polyneuropathy, also referred to as the "central form" of TTR-related systemic amyloidosis. Skin biopsy was also evaluated as a tool in order to diagnose this type of TTR amyloidosis. Biopsy samples were collected from the infra-axillary region. Light microscopy using Congo red and polarized light was used to diagnose amyloid deposits. Subsequently, electron microscopic analysis was performed to correlate the amyloid deposits with vicinal dermal structures. The amyloid class was determined by means of immunocytochemistry. TTR amyloid was primarily localized to lymphatic microvessels in the present case, whereas arterioles were devoid of TTR amyloid deposits. In addition, the well-known association of TTR amyloid with neural structures along the erector pilorum and around the sebaceous and serosal (sweat) glands was also evident. Electron microscopic analysis of amyloid deposits revealed characteristic amyloid fibrils that were irregular in shape, and exhibited a heterogeneous density and a random deposition pattern. Immunocytochemistry confirmed the cutaneous accumulation of TTR amyloid. In conclusion, amyloid deposits were abundantly present in the skin of a patient with "Hungarian-type" TTR amyloidosis; skin biopsy seems to be appropriate for the diagnosis of this disorder. We showed that besides the erector pilorum, sweat glands and nerve terminals, lymphatic microvessels are also severely infiltrated by TTR amyloid. Whether these pathological alterations can exclusively be found in "Hungarian-type" TTR amyloidosis should still be investigated. If such changes are not specific for the Asp18Gly mutation, they may be considered as diagnostic markers for "central" TTR amyloid disorders.

[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.

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.

[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.

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.

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.

Changes in adhesion molecule expression and function in B-cell chronic lymphocytic leukaemia after in vitro interferon-alpha stimulation.

Peripheral blood mononuclear cells (PBMCs) from 10 B-CLL patients were investigated after 24 hours of in vitro interferon-alpha (IFN-alpha) stimulation. The constitutional expression of the L-selectins (LECAM-1), LFA-1/CD11a, VLA alpha-4/CDw49d and ICAM-1/CD54 adhesion molecules was detected, and changes in their density after IFN-alpha stimulation were compared to results obtained by the high endothelial venule (HEV)-binding assay and a carbohydrate (phosphonomannan core polysaccharide: PPME and fucoidin) immobilization test. The LECAM-1 and ICAM-1 molecules were expressed on the great majority of CLL cells, while the LFA-1 and VLA-4 alpha-chains were expressed by only a small number of cells. Statistically significant changes (p < 0.001) were observed in LECAM-1 antigen density (changes in mean cell fluorescence), as well as in functional tests (HEV-, PPME- and fucoidin-binding; p < 0.01) after in vitro IFN-alpha stimulation. Based on a prior study (Jewell et al., Leukemia 1992: 6: 400-404) and on the present findings, not only an increased expression but also an enhanced function of the L-selectins seem to be well substantiated after IFN-alpha stimulation, which may explain the therapeutic effect of IFN-alpha in reducing the accumulation of leukaemic B cells in the blood. The remarkably high expression of ICAM-1 in this series necessitates further studies to clarify the exact expression rate and role of this molecule.

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.

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.

Expression and function of L-selectin molecules (LECAM-1) in B-cell chronic lymphocytic leukemia.

BACKGROUND: The notion that adhesion molecules play a crucial role in lymphoma/leukemia dissemination is widely accepted. Individual cases of B-cell chronic lymphocytic leukemia (B-CLL) show well-defined variables in the extent and pattern of peripheral blood and nodal involvement. The L-selectin adhesion molecule (TQ1/Leu-8, LAM series and LECAM-1) initiates the attachment of lymphocytes to the high endothelial venules (HEVs), and as a consequence the entrance of lymphocytes from the blood into the peripheral lymph node (recirculation which may be operative in lymphoma/leukemia dissemination as well). MATERIALS AND METHODS: The constitutional expression of L-selectin molecules (LECAM-1) on peripheral blood mononuclear cells (PBMCs) from B-CLL (16 cases) was examined and correlated with receptor function in an HEV-binding assay and in a ligand immobilization test. RESULTS AND CONCLUSIONS: A correlation was found between constitutional expression and function of the L-selectins, namely the higher the number of cells expressing L-selectin molecules at a measurable level on the cell surface, the greater the number of cells showing attachment in the tests. It is suggested that many aspects of the biological and clinical heterogeneity of B-CLL will be explained by revealing the exact adhesion profile and function in different subtypes of the disease.

Presence of Epstein-Barr virus in extranodal T-cell lymphomas: differences in relation to site.

T-cell lymphomas with similar morphology but with different sites of origin have a different clinical behavior. The theoretical explanation for this finding originates from the hypothesis that non-Hodgkin's lymphomas (NHLs) are neoplastic equivalents of immunological reactions involving tissue-restricted lymphocytes. This hypothesis also implies that T-NHLs originating from different sites differ in their genesis, and thus may differ in oncogen expression, expression of adhesion molecules, or presence of certain DNA/RNA viral sequences. Therefore, we have investigated in T-cell lymphomas with similar morphology originating from different sites, ie, nose (n = 5; all pleomorphic small- or medium- and large-cell T-cell lymphomas [PTL]), skin (PTL, n = 6; anaplastic large-cell [ALCL], n = 11), gut (PTL, n = 8; ALCL, n = 4), and lung (PTL, n = 6), the presence of Epstein-Barr virus (EBV) at the DNA, RNA (EBER 1 and EBER 2), and protein level (LMP-1). A double-staining technique was used to detect EBER 1/2, LMP-1, and differentiation markers at the single-cell level. High numbers of EBER 1/2-positive tumor cells (> 100 per medium power field [mpf]) were found in five of five nasal T-cell lymphomas, none of 17 primary cutaneous T-cell lymphomas, one of 12 gastrointestinal T-cell lymphomas (ALCL), and two of six pulmonary T-cell lymphomas. These lymphomas are therefore called EBV-associated lymphomas. In contrast to our earlier findings in lymph nodes, no extranodal lymphomas were found, with only a few EBV-positive tumor cells. Five gastrointestinal cases positive for EBV by polymerase chain reaction (PCR) showed that EBER 1/2 was only found in sporadic nonneoplastic, ie, reactive lymphocytes. Angiocentricity was present in 18 PTL and one ALCL, but not associated with the presence of EBV. These results indicate that the presence of EBV in extranodal T-cell lymphomas is site-restricted and argues for a different pathogenesis of T-cell lymphomas with similar morphology but originating from different sites. The presence of EBV in most tumor cells in these EBV-associated lymphomas suggests that when present, EBV might be important in the pathogenesis of these lymphomas.

Expression of an adhesion molecule and homing in B-cell chronic lymphocytic leukaemia: I. Application of the HEV-binding assay to a clinical series.

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.

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.

Expression of an adhesion molecule and homing in B-cell chronic lymphocytic leukaemia: II. L-selectin expression mediated cell adhesion revealed by immobilized analogue carbohydrates in B-cell chronic lymphocytic leukaemia and monoclonal lymphocytosis of undetermined significance.

The L-selectin mediated adhesion of freshly isolated peripheral blood mononuclear cells (PBMCs) to phosphonomonoester core polysaccharide (PPME) and fucoidin derivatized gels was investigated in seven cases of monoclonal lymphocytosis of undetermined significance (B-MLUS) and 12 cases of chronic lymphocytic leukaemia: B-CLL, patients with peripheral lymphocytosis (LY-patients), lymph node enlargement (LN-patients) and splenomegaly (SM-patients). PBMCs isolated from the peripheral blood of 10 healthy donors served as controls. The binding to PPME and fucoidin correlated well (n = 19, P = 0.01). Adhesion of PBMCs from B-MLUS and B-CLL showed a greater variability than controls. A higher number of cells, on average, bound to PPME and fucoidin derivatized polyacrylamide gels in B-MLUS than in B-CLL. However, the differences observed were not statistically significant. In four cases with B-CLL, the stimulatory effect of interferon-alpha on the function of L-selectin and some other accessory molecules was also studied. The increased binding of PBMCs to immobilized analogue molecules (PPME, fucoidin) and to high endothelial venules (HEVs) in the in vitro HEV-binding assay supports the notion that interferon-alpha not only increases the expression of the adhesion molecules, but also results in an enhanced adhesive function.

[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.

[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.

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.

[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.