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.

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.

Expression of ras and myc oncogenes in human hepatocellular carcinoma and non-neoplastic liver tissues.

An immunohistochemical assay was used to assess expression of ras p21 and myc p62 oncogene products in human hepatocellular carcinoma (HCC) and non-neoplastic liver tissues. The monoclonal antibodies Y13 259 and Myc1-9E10, specific for ras p21 and myc p62 oncoproteins, were employed on paraffin-embedded sections. Most HCCs showed enhanced ras p21 and myc p62 expression, as indicated by staining intensity. Cirrhotic livers revealed increased myc p62 and occasionally increased ras p21 expression. HBsAg+ hepatocytes showed intense immunostaining for ras p21. Fibrotic, cholestatic, fetal and normal adult liver did not present enhancement of oncoprotein production. We suggest that combined over-expression of ras and myc oncoproteins may be important for the malignant phenotypic alteration in human HCC.

Hepatocellular dysplasia: immunohistochemical and morphometrical evaluation.

Hepatocellular dysplasia, first described by Anthony et al. [J. clin. Path. 26: 217-223, 1973], is considered a peculiar pattern of proliferation process mainly observable in cirrhotic nodules in patients with hepatocellular carcinoma. Its precancerous meaning has been variously evaluated in the past. In the present study, immunohistochemical data concerning the presence of alpha-fetoprotein, alpha 1-antitrypsin, carcinoembryonic antigen, hepatitis B surface antigen and hepatitis B core antigen did not show meaningful differences between carcinomatous cells and normal and dysplastic hepatocytes. On the contrary, morphometric analysis seems to be useful to discriminate dysplastic cells by means of parametrical indexes of shape and symmetry of the nuclei and could probably offer in the future an objective evaluation of hepatocellular dysplasia.

Presence of cells with argyrophil granules in normal, hyperplastic, and neoplastic endometrium.

Cells with argyrophil granules were searched for in 131 consecutive specimens obtained from endometrial curettage. Particular care was taken with the fixation methods to avoid a false positivity to the silver impregnation according to Grimelius. We did not consider the grossly argyrophilic positivity on the cellular apex or of the whole cytoplasm, which was partially reduced by diastase digestion and probably due to the presence of glycogen and secretory mucoproteins. Cells with thin argyrophilic granules similar to those observed in endocrine APUD cells were present among glandular cells and/or among stromal cells in 15 of 131 examined specimens. They concerned 5 cases of proliferative endometrium, 3 of secretive endometrium, 5 of hyperplasia, and 2 of carcinoma. In 8 of the 15 cases with argyrophilic cells, immunohistochemical studies with the PAP method showed cells with the presence of FSH, S-100 protein, somatostatin, vasoactive intestinal peptide (VIP), gastrin, and neuron-specific enolase (NSE). The significance and origin of these cells in normal and neoplastic endometrium are discussed.

Struma cordis. Ectopic thyroid goiter in the right ventricle.

Intracardiac thyroid goiter (struma cordis) is an exceptionally rare finding. To our knowledge, only two cases have been reported in the literature to date. A middle-aged woman was the subject of our case, in which an intracardiac tumor was clinically diagnosed and surgically resected. The mass, adhesive to the ventricular septum and obstructing the right ventricular outlow tract, histologically was formed by thyroid tissue, separated from the myocardium by fibrous tissue. The woman died of renal failure two weeks after the operation, and at autopsy the thyroid gland showed strumous changes. The similarity to previously reported cases suggests a dysembryologic origin of this ectopia.