[Barrett's neoplasia: where is the problem?]. / Barrett-Neoplasie: Wo liegt eigentlich das Problem?

The Barrett mucosa is characterised by metaplastic transformation in the distal oesophagus from squamous epithelium into columnar-lined cells and shows an increased risk for progression into adenocarcinoma. Up to date an international definition of Barrett's oesophagus is still lacking and it is also difficult to separate low-grade dysplasia/intraepithelial neoplasia from high-grade dysplasia/intraepithelial neoplasia. The present review describes the criteria for the histological diagnosis, discusses the possibilities of endoscopic diagnosis and highlights the biomarkers of the Barrett mucosa.

Two malignant tumours in the anterior mediastinum positive for CD5.

To our knowledge, the simultaneous involvement of the anterior mediastinum by a thymic carcinoma and a B-cell chronic lymphocytic leukaemia has not been reported previously. The authors describe the case of a 62-year-old man, suffering from severe bronchitis. Chest x-ray and CT scan showed a mediastinal tumour, resected short-time after diagnosis. First, standard based histological examination revealed a thymic carcinoma admixed by a dense lymphatic infiltrate. Additional immunohistochemical staining for CD5-labelled epithelial thymic carcinoma cells as well as neoplastic B cells and led in combination with blood tests to confirm the diagnosis of the composite occurrence of a thymic carcinoma and a B-cell chronic lymphocytic leukaemia.

Kaposi sarcoma in solid organ transplant recipients: a single center report.

BACKGROUND: Human herpes virus (HHV8) is associated with Castleman's disease, primary effusion lymphoma, and the Kaposi's sarcoma (KS). PATIENTS AND METHODS: Among 3815 solid organ transplants performed at our center between 1977 and 2003, five patients (0.1%) were identified with KS. RESULTS: There were one cardiac, one liver, and three renal allograft recipients of median age of 52 (range 38 to 60) years, three of whom were females. Three patients were of Italian and one of Turkish descent; only one patient was a native Austrian. The onset of the disease was 2.0, 7.5, 7.8, 9.4 months, and 22 years posttransplant. Diagnosis of KS was based in all cases on histology. The heart recipient developed a tumor on the planta pedis; one renal recipient, on both legs. The liver and the two remaining renal recipients presented with disseminated disease. Treatment in all cases consisted of reduction in immunosuppression, together with surgery (n = 1), chemotherapy (n = 1), or irradiation (n = 2). Furthermore, immunosuppression was switched in two cases from Tacrolimus to Sirolimus. In the liver recipient a complete response was achieved; he died, however, due to noncompliance followed by graft failure. One renal recipient died without evidence of recurrent disease from myocardial infarction. The cardiac and two renal recipients are alive between 4 months and 17 years with well-functioning grafts and no evidence of recurrent disease. DISCUSSION: HHV8-associated lesions seem to be extremely rare in the Central European transplant population. Nevertheless, awareness of KS is important for early diagnosis and optimal treatment.

Sensitive detection of tumour cells in effusions by combining cytology and fluorescence in situ hybridisation (FISH).

Diagnosis of malignant cells in effusions is important for staging procedures and resulting therapeutic decisions. Cytodiagnostics in effusions is sometimes difficult since reactive mesothelial cells can mimic malignant cells. We used fluorescence in situ hybridisation (FISH) in single-colour or if appropriate in dual-colour evaluation to detect chromosomal aberrations in effusion cells as markers of malignancy, to raise the diagnostic yield. Cytologic and FISH evaluations--by using probes representing several chromosomes always including chromosomes 11 and 17--were performed in 358 effusion fluids. Cytology was positive for malignancy in 44.4% of all effusions, whereas FISH was positive in 53.9% (P=0.0001). The combination of cytology and FISH was diagnostic for malignancy in 60.9% of effusions. Diagnostic superiority of FISH was demonstrated in effusions from breast cancer, lung cancer, pancreatic cancer, and in effusions from the entire group of gynaecological and gastrointestinal carcinomas. In transudates (effusion protein <2.5 g dl(-1)), malignant cells were detectable by cytology, FISH, and combined use of both methods in 18.6, 30, and 37.1% of effusions, respectively, suggesting that cytologic and molecular analysis should be performed also with transudates. In conclusion, FISH in combination with conventional cytology is a highly sensitive and specific diagnostic tool for detecting malignant cells in effusions.

Unfavourable prognosis of patients with trisomy 18q21 detected by fluorescence in situ hybridisation in t(11;18) negative, surgically resected, gastrointestinal B cell lymphomas.

BACKGROUND: The most frequent cytogenetic alteration in gastrointestinal (GI) B cell lymphoma (BCL) is t(11;18)(q21;q21). GI B cell non-Hodgkin lymphomas lacking this translocation vary in their biology and clinical outcome. The t(11;18) negative subgroup shows increased numerical changes of chromosome 18, although its clinical relevance remains unknown. METHODS: Thirty surgically resected primary GI BCLs were examined-11 low grade marginal zone mucosa associated lymphoid tissue (MALT) lymphomas, four marginal zone lymphomas with diffuse large BCL (DLBCL), and 15 de novo DLBCLs. Chromosome 18 aberrations were examined using interphase fluorescence in situ hybridisation. Trisomy 18 was studied applying a centromere 18 probe and a dual colour probe for the MALT1 gene at 18q21. RESULTS: Using the MALT1 probe, only one marginal zone MALT lymphoma had a break apart pattern, indicating t(11;18) or variants. In the GI BCLs lacking MALT1 breaks, trisomy 18q21 was seen in seven patients (four with complete trisomy 18 and three with partial trisomy of 18q21). Trisomy 18q21 was found in two of 10 low grade MALT lymphomas and five of 19 GI BCLs with large cell component. Six of 17 patients with trisomy 18q21 presented with >/= stage II and one of 12 with stage I disease. Trisomy 18q21 was associated with significantly shorter disease specific survival in the whole group and GI BCLs with large cell component, but not in the low grade group. CONCLUSIONS: Trisomy 18q21, including MALT1, may be associated with advanced tumour stage and may be a predictor of poor outcome in surgically resected primary GI BCLs.

Heparanase-1 gene expression in normal, hyperplastic and neoplastic prostatic tissue.

Heparanase-1 (Hpa-1) has been implicated in tumour invasion and metastasis. In the present study, we evaluated the clinicopathological significance of Hpa-1 mRNA expression in prostate cancer and non-cancerous prostatic tissue by one-step polymerase chain reaction (PCR) of laser microdissected prostatic gland cells. In addition, cell type-specific expression of Hpa-1 mRNA in prostatic tissue was analysed by in situ hybridisation. Hpa-1 mRNA expression was found in 50% of normal and 40% of hyperplastic prostatic tissue. In situ hybridisation showed that Hpa-1 mRNA was strongly expressed in prostate gland cells. Of the 26 prostate carcinomas tested, 42% were positive for Hpa-1 mRNA. However, in non-cancerous prostatic tissue, Hpa-1 mRNA was significantly more often expressed than in less differentiated or more invasive prostate cancers (P<0.05). In situ hybridisation revealed only focal Hpa-1 mRNA expression in the neoplastic gland cells. Hpa-1 mRNA expression in the tumours significantly correlated with tumour differentiation and tumour stage (P<0.05). Our data indicate that Hpa-1 gene expression may be lost during dedifferentiation of prostatic gland cells.

Intravascular large B-cell lymphoma with a fulminant clinical course: a case report with definite diagnosis post mortem.

A patient is described who presented with pancytopenia, splenomegaly and excessively elevated lactate dehydrogenase levels in concurrence with signs of extramedullary hematopoiesis. Although initially considered in the differential diagnostic spectrum, a highly aggressive lymphoma could not be identified before the patient died, 6 weeks after admission. Even an intensive diagnostic work-up including splenectomy and repeated bone marrow biopsies was inconclusive. Finally, the diagnosis of an intravascular large B-cell lymphoma, a highly aggressive clinical subtype of a diffuse large B-cell lymphoma, spreading within vascular structures of multiple organs was established by autopsy. Intravascular large B-cell lymphoma is often not diagnosed before death due to the exclusive intravascular growth pattern of the tumor cells and a fulminant clinical course. The heterogeneous clinical features of this lymphoma subtype are discussed.

Primary gastrointestinal B-cell lymphoma. A clincopathological and immunohistochemical study of 61 cases with an evaluation of prognostic parameters.

We hereby present a retrospective clinicopathological and immunohistochemical study of surgically resected primary gastrointestinal (GI) lymphoma with an analysis of parameters of potential prognostic relevance. From a larger series of 144 cases of primary GI lymphomas, we chose 61 cases with sufficient clinical follow-up (mean 60, range 1-219 months), classified either as extranodal marginal zone B-cell lymphoma of MALT type (MALT lymphoma) or diffuse large B-cell lymphoma (DLBCL), after having excluded other subtypes. In addition to conventional clinical and morphological parameters, the expression levels of Ki-67 (MIB-1), bcl-2 and p53 were evaluated for prognostic significance. Twenty-one (34.4%) cases were classified as pure low grade marginal zone B-cell lymphoma of MALT type, 12 (19.7%) cases as low grade MALT lymphoma with a high grade component (mixed type), and 28 (45.9%) cases as primary extranodal DLBCL. Most of the lymphomas (53/61; 86.9%) were localized in the stomach, 3 (4.9%) in the small bowel, 3 (4.9%) multifocal in both stomach and small intestine and 2 (3.3%) in the large bowel. MIB-1 expression in more than 30% of tumor cells was detected in 42 (68.6%), bcl-2 expression in 20 (32.8%) and p53 accumulation in more than 10% of neoplastic cells in 16 (26.2%) lymphomas. Both high Ki-67 expression and p53 accumulation were more prevalent in the DLBCL. 30 (49%) patients showed lymph node involvement at surgery, 14 (23%) patients suffered tumor recurrence, and 24 (38.5%) died during the follow-up period. Tumor recurrence occurred primarily in patients who had presented lymph node involvement (9/14, 64.3%). The 5-year survival rate was 66.1% for all patients. Important prognostic factors for overall survival were tumor stage (p < .004) and p53 accumulation (p < .05) in univariate analysis, and tumor stage in multivariate analysis (p < .001). Although p53 accumulation did not reach statistical significance in our small study group, it may be both important in the transformation of low grade MALT lymphoma and an indicator for aggressive behavior in high grade tumors.

Regulation of transforming growth factor-beta secretion by human peritoneal mesothelial and ovarian carcinoma cells.

This study was conducted to compare the secretion of TGF-beta isoforms by human ovarian carcinoma (OVCA) cell lines (n=12) and human peritoneal mesothelial cells (HPMC;n=6) and to examine the regulation of their production by inflammatory cytokines. TGF-beta isoforms were furthermore analysed in OVCA-associated ascitic fluids. HPMC constitutively produced considerable amounts of TGF-beta1 (median 42 pg/10(5)cells; range 7-98) but only minimal amounts of TGF-beta2 (median 0.8 pg/10(5)cells; range 0-1.5). Treatment of HPMC with IL-1beta (10 ng/ml) resulted in a significant elevation of the secretion of both TGF-beta1 (median 187 pg/10(5)cells; range 71-264;P<0.001) and TGF-beta2 (median 1.8 pg/10(5)cells; range 0-13;P<0.01). In OVCA TGF-beta1 and TGF-beta2 were detected in 7/12 and 11/12 of the cell lines, respectively. The levels detected varied widely for TGF-beta1 (median 25 pg/10(5)cells; range 0-410) as well as for TGF-beta2 (median 14 pg/10(5)cells; range 0-419) and there was no correlation between the two isoforms. In contrast to HPMC, TGF-beta secretion by OVCA was not affected by any of the inflammatory cytokines tested. TGF-beta3 could not be detected in supernatants, neither in OVCA nor in HPMC. In ascitic fluids the median level of TGF-beta1 (median 5443 pg/ml; range 737-14687) was 10-fold higher than the level of TGF-beta2 (median 545 pg/ml; range 172-3537). The present data provide a model for the analysis of the molecular mechanisms of aberrant TGF-beta production by OVCA and support the hypothesis that HPMC are an important source of ascitic TGF-beta.

Epstein-Barr virus-associated Hodgkin's lymphoma and legionella pneumophila infection complicating treatment of juvenile rheumatoid arthritis with methotrexate and cyclosporine A.

We describe the case of a 53-month-old girl with juvenile rheumatoid arthritis (JRA), complicated by the occurrence of Hodgkin's lymphoma and Legionella pneumophila infection during immunosuppressive treatment with methotrexate (MTX) and cyclosporine A (CSA). The girl had received variable anti-inflammatory combination therapy, including MTX for 28 months and CSA for 3 months. Thirty-six months after the onset of arthritis, the girl presented with an enlargement of the lymph nodes of the mediastinum, the hilum of the lungs, and the abdomen. Concomitantly, a diagnosis of Legionella pneumonia was rendered. Autopsy showed Epstein-Barr virus (EBV)-associated nodular sclerosing Hodgkin's lymphoma. The neoplastic cells were positive for CD15, CD 30, and latent membrane protein 1 (LMP 1). The present case is the second reported to occur in a child, and it lends support to the hypothesis that immunosuppressive treatment may contribute to an increased risk of the development of EBV-associated lymphoproliferative disorders (LPD) in pediatric patients suffering from JRA.

Thymic Hodgkin's disease--a histological and immunohistochemical study of three cases.

Thymic Hodgkin's disease (HD) shows some peculiar histological features different from nodal disease which are a result of the interaction with the specific thymic microenvironment. We describe the histological and immunohistochemical findings in three cases presenting as a primary thymic neoplasm both clinically and radiologically. Histological hallmarks were the prominent formation of epithelium-lined cysts, inflammatory changes, a marked proliferation of thymic epithelium in association with Hodgkin- and Reed-Sternberg (RS) cells and the occurrence of the nodular sclerosing subtype in all cases. The immunophenotype of the neoplastic cells was that of classical HD. They expressed CD30, CD15 and lacked CD45. In two cases CD20 expression was observed. All cases were negative for the latent membrane protein (LMP) of the Epstein-Barr virus (EBV). The accompanying inflammatory infiltrate was rich in mature T-cells, but also showed a significant number of B-cells with frequent formation of follicles and proliferation of follicular dendritic cells. Thymic HD develops in a microenvironment with features of thymic medulla as defined by the morphology and pattern of the proliferating epithelial cells and the mature immunophenotype of the admixed thymocytes. These findings, especially the CD20 positivity in Hodgkin and RS-cells, may point to the possible origin of thymic HD from medullary B-cells.

High prevalence of a 30-base pair deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 gene and of strain type B EBV in Mexican classical Hodgkin's disease and reactive lymphoid tissue.

Depending on geographic location and patient age Hodgkin's disease (HD) is associated with Epstein-Barr virus (EBV), mostly type A EBV, in 20% to 100%. The highest prevalence occurs in children of developing countries. Molecular analysis of the oncogene coding for the latent membrane protein 1 (LMP-1) revealed a 30-base pair (bp) deletion in up to 46% of EBV-positive HD. We investigated the presence of EBV in a series of Mexican classical HD (n = 57) and reactive lymphoid tissues (n = 20) from a private and a public hospital with special emphasis on the prevalence of the 30-bp deletion and the type of EBV. EBV infection was analyzed at the cellular level by Epstein-Barr encoded early RNA transcripts (EBER) in situ hybridization (ISH) and by LMP-1 protein immunohistochemistry (IHC). Molecular analysis of the LMP-1 gene configuration was performed by polymerase chain reaction (PCR) with primers spanning the site of the deletion and subsequent Southern and/or dot blot hybridization using wild-type and deletion-specific probes. The prevalence of type A and type B EBV was investigated by PCR-analysis for divergence in the coding region of Epstein-Barr nuclear antigen (EBNA)-2. EBV was detected in Hodgkin- and Reed-Sternberg cells (H-RS) by LMP-1 IHC and/or EBER ISH in 35/57 (61%) Mexican HD including 18/32 (56%) with nodular sclerosis, 15/20 (75%) with mixed cellularity and 2/4 (50%) with lymphocyte depletion. In addition, LMP-1 gene sequences were detected by PCR in 9 cases of HD without LMP/EBER expression by H-RS cells and in 17/20 (85%) reactive lymph nodes, supposedly originating from rare latently infected B cells. Surprisingly, the 30-bp LMP-1 deletion was found in 28/35 (80%) EBV-positive HD. This deletion, however, was also found in all 9 (100%) HD with H-RS cells negative for EBV and in 10/17 (59%) reactive lymph nodes. Thus, the overall LMP-1 del prevalence in reactive tissue is 73% (19/26). Typing of EBV was successful in 26 cases of EBV-positive HD, 10 of these were infected by type B EBV (38%). Of the reactive lymphoid tissue, 9 (47%) were infected by type A, and 10 (53%) by type B; All 20 cases (100%) associated with type B, whether neoplastic or reactive, displayed the LMP-1 del variant compared with 18/25 (72%) infected by type A EBV. To our knowledge, this is the highest incidence for both the LMP-1 deletion variant and the infection by type B EBV in HD reported so far worldwide. Our data suggest that EBV infection contributes to the pathogenesis of the majority of Hodgkin's disease cases in Mexico. The specific tumorigenic role of the LMP-1 deletion variant, however, is doubtful with regard to its high frequency in nonneoplastic lesions. Moreover, type B infection frequently occurs in Mexican HD and reactive lymphoid tissue and is consistently associated with the deletion variant pointing to a pathogenetic role of this combined genotype.

DNA-ploidy analysis correlates with the histogenetic classification of thymic epithelial tumours.

The ploidy values of the epithelial component were determined in a series of thymomas and organotypic thymic carcinomas using image cytometry and the results were compared with the histological tumour subtypes according to the histogenetic classification introduced by Marino, Müller Hermelink, and Kirchner (MMHK). Forty-six cases of thymic epithelial tumours were included in the study. After reclassification according to the MMHK classification, the distribution among the subtypes was as follows: three medullary, nine mixed type, five predominantly cortical (organoid), 16 cortical thymomas, and 13 well-differentiated thymic carcinomas. Single cell preparations were made from paraffin-embedded tumour tissue and stained according to Feulgen. Ploidy analysis was performed using an automated image analysis system. In five cases, DNA cytometry could not be performed, for technical reasons. The remaining 41 cases consisted of 11 diploid and 30 non-diploid tumours. The percentage of aneuploid tumours in the different subtypes increased from medullary (0 per cent) through mixed type (44.4 per cent), predominantly cortical (75 per cent), cortical (83.3 per cent) to well-differentiated thymic carcinomas (100 per cent). DNA-ploidy determination using image cytometry correlates with the concept of the MMHK classification of thymomas.

Peroxide treatment changes activity of non specific esterase in vascular endothelium of isolated pig aorta in vitro.

The effect of hydrogen peroxide on certain enzymes contained in endothelial cells was investigated in vitro. Specifically in this study the influence of hydrogen peroxide on the non-specific esterase activity in endothelial cells of the perfused pig aorta was examined. We perfused an isolated segment of the pig aorta for 10 h and added 5, 10, 12, 15 ml 10% hydrogen peroxide to 100 ml perfused medium. In unperfused pig aorta 99.34% of the endothelial cells reacted positive. After 10 h of perfusion without hydrogen peroxide administration 93.25% endothelial cells still showed positive enzyme reactivity. In presence of hydrogen peroxide in the perfusion medium the activity of non-specific esterase was progressively inhibited, finally causing complete inactivation.

[Histologic classification and morphologic prognostic factors in malignant ovarian tumors]. / Histologische Klassifikation und morphologische Prognosefaktoren bei malignen Ovarialtumoren.

Most cases of death in genital neoplasms of females are caused by ovarian cancer. Prognostic factors are the postoperative tumor, tumor stage (FIGO, pTNM), age, tumors among family, and the reproductive history. On the basis of 710 malignant ovarian tumors we describe the histogenetic classification and compare the morphologic diagnosis with additional prognostic factors by literature to give a practical review of ovarian neoplasms. The morphologic prognostic factors are the histological subtype, tumor grading and perhaps the receptor status. Worse prognosis, despite of tumor grading, show undifferentiated carcinomas, followed by the serous and mucinous subtype. Endometrioid carcinomas have the best prognosis. Malignant Mullerian tumors show a very aggressive behavior. After the introduction of polychemotherapy the sex-cord- and germ cell-tumors show better prognoses. New prognostic factors are DNA-parameters (ploidy, S-phase-fraction), detection of oncogenes and tumor suppressor genes, cellular adhesion molecules (integrins, CD 44-splicing variants), and the proliferation rate of the tumor. Perhaps, these factors show prognostic relevance for individual treatment. A correct histologic classification with consideration of all morphology related prognostic factors and the knowledge about them is necessary for oncologists to choose the optimal individual therapeutic treatment.

The effect of peroxides on the vascular endothelium of isolated pig aorta in vitro.

The effect of peroxide on endothelial cells (perfused pig aorta) was examined using an in vitro perfusion model. Hydrogen peroxide was added to the perfusion medium (pig serum together with a buffer solution) which was expected to lead to an increased oxidation of lipids and lipoproteins. Oxidation processes of this type play a decisive role in the pathogenesis and progression of arteriosclerosis. The aim of the present investigation was to demonstrate by introducing hydrogen peroxide (H2O2) in varying concentrations (0.5-1.5%), the destructive impact of peroxides on the endothelium, while these cells are believed to play a key role in the pathogenesis of arteriosclerosis. The extent of endothelial cell impairment was assessed by means of silver staining visualisation of endothelial cell borders as well as light- and scanning-electronmicroscopic investigation. It was discovered that the endothelial cells show increasing impairment after 10 h of perfusion due to the effect of peroxide (hydrogen peroxide).