Comparative genomic hybridisation in malignant deciduoid mesothelioma.

BACKGROUND: Malignant deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. This tumour generally has poor prognosis, and can be asbestos related. AIM: To identify peculiar genetic changes responsible for critical phases in pathogenesis of malignant deciduoid mesothelioma and their prognostic relevance. METHODS: Comparative genomic hybridisation was carried out in six cases of malignant pleural deciduoid mesothelioma, four sporadic and two familial. All cases were found to be asbestos related. Four patients died during follow-up and the mean survival was 29.5 (SD 14.2, range 12-43) months. RESULTS: Genetic abnormalities were found in all the tumour tissues, the most frequent being chromosomal gains at 1p, 12q, 17, 8q, 19 and 20 and losses at 13q, 6q and 9p. Survival was found to be longer in those patients who presented a smaller number of losses (< or =2) in the tumorous chromosomes. CONCLUSIONS: Although numerous genetic changes are presented by deciduoid mesotheliomas, certain chromosomal regions are preferentially affected. The clinical outcome for this mesothelioma subtype is predicted by the number of losses.

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival.

AIMS: To present two rare cases of malignant mesotheliomas with deciduoid features arising in the pleura, both with long survival. METHODS AND RESULTS: These two cases of deciduoid mesotheliomas were observed in adult patients (one 73-year-old male and one 23-year-old female). Only the male had a history of occupational asbestos exposure, whereas the woman had a history of familial mesothelioma. A deciduoid morphology was predominant and focal areas with tubular-papillary features were noted. The tumour cells were positive for cytokeratins, HMBE-1, calretinin, EMA and mitochondrion antibodies. The follow-up data did not suggest a particularly poor prognosis; the mean survival observed was 23 months (17 and 39 months, respectively). CONCLUSIONS: This deciduoid mesothelioma histological subtype does not appear to represent an unfavourable prognostic category.

[Polycystic mesothelioma of the peritoneum. Description of 4 cases]. / Mesotelioma multicistico del peritoneo. Descrizione di quattro casi.

Cystic mesothelioma is a rare tumor of the peritoneal cavity arising from mesothelial cells. About 130 cases have been reported in the literature. The tumor is more frequent (85%) in adult women and rarely occurs in children. It is benign but recurrences are often described. The differential diagnosis with adenomatoid tumors, lymphangiomas, cystic malignant mesotheliomas and metastatic serous cystic tumors of the ovary is supported by immunohistochemistry. We describe four cases of cystic mesothelioma of the peritoneum; two of the cases occurred in pregnant women, one in a 45-year-old man and one in a 5-year-old boy. Asbestos exposure was not documented. The mesothelial origin of the neoplasms was supported by immunohistochemical analysis. Furthermore, tests for simian virus 40 (SV40 T antigen), to determine whether this virus was also present in the lesions, were negative.

Helicobacter heilmannii gastritis: a histological and immunohistochemical trait.

AIM: Biopsies of the gastric antrum were reviewed over a period of 10 years to determine the prevalence of Helicobacter heilmannii in symptomatic subjects from this geographical area and to relate its presence to distinctive histopathological and immunohistochemical features. METHODS: Biopsies from 7926 symptomatic patients were reviewed. Ten serial sections were stained with haematoxylin and eosin for conventional histology. Another 10 sections were stained with the Gram method for spiral bacteria. When H heilmannii was suspected, 10 additional serial sections were stained with methylene blue to obtain homogeneous colouring. An equal number of sections from patients affected by isolated H heilmannii or H pylori gastritis were analysed by immunohistochemistry to evaluate lymphoid aggregate/mucosal lymphocyte clonality (CD20 and CD3) and tumour necrosis factor alpha (TNF-alpha) in stromal cells. RESULTS: The prevalence of H heilmannii was 0.1% (eight of 7926), whereas H pylori was present in 60.7% of patients (4813 of 7926). In two of the eight H heilmannii positive patients both helicobacters were found. In all subjects infected by H heilmannii only, distinctive histology (lymphocyte exudation into gastric foveolae) was seen. Lymphoid aggregates, chronic mucosal inflammation with patchy activity, and the absence of epithelial mucus depletion were regular features of H heilmannii gastritis. Immunohistochemistry did not reveal different lymphocyte clonal patterns between H pylori and H heilmannii gastritis: CD20 positive cells were predominant in the centre of aggregates and mucosal infiltrates, whereas CD3 positive cells were prevalent at the periphery of follicles. Only H pylori gastritis showed a significant increase in TNF-alpha positive stromal cells. CONCLUSION: These data suggest that an unusual lymphocyte reaction, with the tendency to invade the foveolar lumen, is a distinctive histopathological aspect of H heilmannii chronic gastritis, although further studies in a larger series are necessary to confirm this fact. Nevertheless, lymphocyte clones do not differ qualitatively from those found in H pylori infection. Moreover, compared with H heilmannii, H pylori provokes a more intense release of TNF-alpha, suggesting that different inflammatory responses exist to these two organisms.

Immunohistochemical detection of Helicobacter pylori vacuolating cytotoxin in the hepatocytes of patients with isolated hypertransaminasaemia.

BACKGROUND AND AIM: Even if different Helicobacter species can colonise animal livers and induce hepatitis, there is no evidence that Helicobacter pylori can damage this organ and only a potential capacity of cytotoxic strains to increase transaminases in humans has been suggested. We have, therefore, carried out an immunohistochemical study on vacuolating cytotoxin in the hepatocytes of subjects with isolated hypertransaminasaemia. PATIENTS, METHODS AND RESULTS: Five male patients with isolated hypertransaminasaemia without signs of known causes of liver diseases were studied. Endoscopy demonstrated diffuse mucosal hyperaemia in 3 patients and duodenal ulcer in one. Histology revealed active chronic pangastritis in all. Helicobacter pylori was assessed by histology and culture and its cytotoxity, demonstrated by positive immunoblotting for both anti-CagA and VacA. Percutaneous liver biopsy showed minimal changes. Hepatic and gastric sections were tested either with autologous serum and rabbit antibody to VacA toxin. Immune reaction was revealed by immunoperoxidase. Both autologous sera and anti-VacA toxin antibody showed a reaction with a similar pattern which involved 60% of hepatocytes. Anti-VacA toxin showed a reaction to gastric epithelial cells and autologous sera to parietal cells in 4/5 patients. All patients received triple therapy and eradication of Helicobacter pylori was assessed by urea breath test. Serum transaminase levels 3 months after eradication, are still abnormal. CONCLUSIONS: Our immunohistochemical findings suggest that vacuolating cytotoxin could reach the hepatocytes of patients suffering from both isolated hypertransaminasaemia and infection by cytotoxic strains of Helicobacter pylori. Nevertheless, a clear relationship between these two condition remains uncertain.

Angiogenesis in hepatocellular carcinoma: an experimental study in the chick embryo chorioallantoic membrane.

Ten samples of human hepatocellular carcinoma and three of a laceration injure of the liver (controls) were grafted onto the chick embryo chorioallantoic membrane (CAM) to investigate their possible angiogenic activity. The angiogenic response in pathological and control implants was assessed on histologic sections by a morphometric method, 4 days after grafting. The vascular count in the CAMs treated with the pathological implants was significantly higher compared to control ones and the angiogenic response induced by pathological implants was comparable to that of a well known angiogenic molecule, namely basic fibroblast growth factor. The role played in vasoproliferative response by angio-genic cytokines released by tumor cells, by CAM extracellular matrix and by the perivascular mononuclear cells was supported by this study.

Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology.

Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and both its biological features and its prognostic behavior are still under investigation. DNA content and proliferative activity of the tumor have been considered as biological parameters related to the tumor's aggressiveness. The present study attempts to investigate the possible association between histologic subtype, DNA content, and proliferative indices in HB. DNA content and the proportion of cells in the S-phase were assessed by flow cytometry in 34 cases of HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin-fixed, paraffin-embedded archival samples. The proliferative cell nuclear antigen (PCNA) labeling index was also evaluated by immunohistochemistry, and both the flow cytometry (FC) and the immunohistochemical data were correlated with tumor pathology. A significant association was found between histological type, DNA content and the percentage of cells in the S-phase, with aneuploidy and the highest proportions of S-phase cells significantly associated with embryonal tumors. The PCNA labeling index was found to be significantly higher in embryonal than in fetal phenotype. The biological heterogeneity of HB is Confirmed by the different nuclear content of the fetal (diploid) and embryonal (aneuploid) epithelial components of the tumor, also ruling out the likelihood of fetal (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since the highly proliferative neoplastic clones (i.e., embryonal) are thought to be more sensitive to antimitotic drugs, further studies are indicated to determine the relationship between ploidy, proliferative indices and chemoresponsiveness.

[Asbestos fiber count in extra-pulmonary tissues]. / Riscontro di fibre di asbesto in tessuti extrapolmonari.

Most autoptic tissues of three men (two with pulmonary asbestosis and one without any exposure to asbestos) were analyzed by transmission electron microscopy and energy dispersion spectrometry for the quantitative and qualitative evaluation of asbestos fibers. Preliminary results indicate that only in cases with occupational exposure were found asbestos fibers (in lung, pleura , bladder, kidney and liver). These results allow interesting speculations on some environmental pathogenetic questions and deserve further investigations.

Biliary malformation with renal tubular insufficiency in two male infants: third family report.

We report two male sibs, born to non-consanguineous healthy parents, who showed arthrogryposis, cholestatic jaundice and tubular renal insufficiency. The liver biopsy of the first case showed scanty hypoplastic biliary ducts. This association, first reported by Lutz and Richner in 1973, is a distinct syndrome, characterized by intra-extrahepatic biliary hypoplasia, and described in McKusick's catalogue under the number 210550. All reported cases were males and consanguinity was found in two families. For these reasons, the possibility of an autosomal recessive or of an X-linked transmission should be considered. A similar association, in reports by Nezelof, Di Rocco, and Saraiva, without intra-extrahepatic atresia but with a cholestatic pigmentary liver disease was considered as another condition (no. 301820) by McKusick in 1992.

[Concentration of asbestos fibers in urothelial tumors and in the neoplasm-free bladder wall]. / Concentrazione di fibre di asbesto nei tumori uroteliali e nella parete vescicale esente da neoplasia.

The aim of our study was to search the eventual presence of asbestos fibers in the neoplastic tissue of 13 cases of bladder carcinoma and in the normal vesical tissue of 12 control cases without neoplasia and operated upon for other urologic pathologies. To all patients a standardised questionnaire has been administered in order to ascertain the entity of the eventual exposition to asbestos. The organic component of the tissues has been oxidated at low temperature in atomic oxygen plasma and the residual inorganic component has been analysed by transmission electronic microscopy and energy dispersion spectrometry. We have found asbestos fibers only in two over the 25 examined samples; in both cases they belonged to patients affected by the neoplasia and in one of them also by pulmonary asbestos. The procedures that we used in this study, in respect to our other experiences, allowed us to reduce the risk of contamination of the tissues by asbestos, as it is shown by the lower number of cases with positive finding of fibers and by lower concentration of fibers in the positive cases.

Insulin-like growth factor 1 (IGF-1) in multinodular goiters: a possible pathogenetic factor.

In order to support previous in vitro studies which had stressed a possible autocrine role for Insulin-like Growth Factor 1 (IGF-1) in thyroid growth regulation, we have investigated the presence of IGF-1, as detected by means of radioimmuno assay and of immunocytochemistry, in thyrocytes from normal thyroid and from multinodular goiter. Our study revealed that IGF-1 is detectable in thyroid cells from multinodular goiter and, to a lesser extent, from normal thyroid. Both techniques used in this study demonstrated that thyrocytes are the site of accumulation of IGF-1 and that stromal cells contain lower amounts of this growth factor. The findings of the present study seem to suggest that thyrocytes could produce IGF-1 in vivo. This feature gives further support to the hypothesis that IGF-1 may regulate thyroid growth and therefore it might be involved in the pathogenesis of multinodular goiter.

Treatment of chronic hepatitis C with recombinant human interferon-alpha 2a: results of a randomized controlled clinical trial.

Sixty consecutive patients with chronic hepatitis C were included in a randomized controlled trial of recombinant human interferon-alpha 2a vs. no treatment. Treated patients received tapering doses of interferon thrice weekly for 1 yr. Twenty treated cases (66.7%) normalized serum aminotransferase levels within the first 4 mo of treatment, but reactivation or breakthrough frequently occurred afterward (20% in both cases). Only one of the untreated patients showed spontaneous normalization of serum aminotransferase levels. Liver histology did not improve in patients without a biochemical response or with breakthrough during therapy, whereas it did not worsen in long-term responders and reactivating patients. Lack of response does not appear to be related to serum interferon antibodies, although their early appearance is more frequent in patients who showed reactivation later on. No biochemical parameter was found to be predictive for positive response to treatment. Antibody to c100 became negative in 62.5% of long-term responders, whereas no change was recorded in other treated patients or controls. Reactivation and breakthrough often occur during treatment, and further studies are needed to determine the most effective schedule (dose and time) of interferon treatment. Loss of c100 antibody during therapy may be a marker of long-term maintenance of response to interferon therapy.

Vimentin- and GFAP-immunoreactivity in developing and mature neural microvessels. Study in the chicken tectum and cerebellum.

The expression of the cytoskeletal filaments vimentin and GFAP has been analyzed by immunocytochemical techniques in endothelial cells, pericytes, and astrocyte perivascular endfeet of microvessels of chicken optic tectum and cerebellum during embryonic development and in adulthood. Endothelial cells and pericytes were characterized by strong vimentin-immunoreactivity in both tectum and cerebellum only in early developmental stages (11-15 incubation days, i.d.). Astrocyte processes closely associated with the vessel wall were vimentin stained in the 11 i.d. cerebellum and vimentin-and GFAP-reactive in 15 i.d. tectum. These perivascular endfeet became GFAP-immuno-stained in the tectum and cerebellum by the 21st i.d. The results indicate that intermediate filament expression in the cells of the brain microvasculature is developmentally regulated, and suggest that the vimentin to GFAP transition in perivascular astrocytes parallels the vessel wall maturation.

Anti-HBe-positive chronic hepatitis B with HBV-DNA in the serum response to a 6-month course of lymphoblastoid interferon.

Eighteen heterosexual HBsAg carriers with anti-HBe- and HBV-DNA-positive chronic hepatitis B (CHB) were randomly assigned to receive human lymphoblastoid interferon (ly-IFN) at a dose of 5 MU/m2 i.m. three times a week for 6 months (ten cases) or no treatment (eight cases). All patients were followed for 24 months after IFN discontinuation and received a second liver biopsy. During the 6 months of treatment all patients had a progressive reduction of serum HBV-DNA levels, and at the end of therapy nine out of ten were HBV-DNA-negative and had normal ALT values. None of the untreated patients became persistently HBV-DNA-negative or showed significant variations of ALT levels. During the post-treatment follow-up, from 1 to 17 months after ly-IFN discontinuation, eight of the nine responders (89%) had recurrent or persistent reappearance of HBV-DNA in the serum and reactivation of the liver disease activity, with an ALT peak in four of them. On the post-trial liver biopsy seven of the eight relapsed patients showed persistence of HBcAg reactivity with no significant difference in the percentage of positive cells with respect to the pre-treatment liver specimen. Histological features improved in four treated patients, worsened in one untreated case and were unchanged in the remaining patients. These results indicate that ly-IFN shows a transient antiviral effect in the therapy of anti-HBe- and HBV-DNA-positive CHB. The 6-month treatment regimen employed in this study seems insufficient for eradicating the replicating virus from the liver cells in the majority of patients and consequently does not appear to prevent HBV reactivation after IFN discontinuation.

Hepatoblastoma: a clinico-pathologic review.

Hepatoblastoma, the most common and peculiar tumor of the liver in infancy and childhood, has recently been the object of an international protocol of the European (SIOP) Histopathological Study Group in order to establish common anatomicoclinical criteria provided with therapeutic and prognostic significance. A general review of hepatoblastoma concerning its possible association with congenital anomalies, endocrine and metabolic disorders, as well as physical and laboratory data, macroscopic and histological patterns, is reported. The different histotypes of hepatoblastoma, represented by anaplastic, embryonal, fetal, mixed (epithelial and mesenchymal) and teratoid, are described, and hypothesis of the pathogenesis of this tumor is discussed, based upon immunohistochemical investigations.

Differential diagnosis between thyroid follicular adenoma and carcinoma. Analytic morphometric approach.

In this study some nuclear dimensional and analytical parameters were evaluated in order to distinguish follicular atypical adenoma from follicular carcinoma of the thyroid. Eighty nuclei from carcinomas, 80 from adenomas and 80 from normal thyroid were studied. Analytical parameters obtained by the nuclear shape study (by S.A.M. system) as well as dimensional parameters were submitted to univariate statistical analysis. On the ground of our results atypical adenoma could be considered as an intermediate aspect of a progressive change from benign to malignant even if they are closer to normal thyroid than to carcinoma.