Cytologic re-evaluation of negative effusions from patients with malignant mesothelioma.

BACKGROUND: Cytology is a controversial means of diagnosing malignant mesothelioma due to the high rates of negative samples. The aim of the present study was to review effusions originally reported as "negative" in patients with histologically-proven mesothelioma to evaluate possible pitfalls. METHODS: We reviewed the cytologic slides of 25 specimens that refer to 15 epithelioid, 5 biphasic, 4 sarcomatoid and 1 well-differentiated papillary mesotheliomas. For comparison, we also reviewed 23 specimens from non-neoplastic conditions. For each effusion, we evaluated the background and calculated a score considering the following items: amount of mesothelial cells, architectural pattern and atypical features, and a revised diagnosis was rendered. RESULTS: More than half of the effusions initially called "negative" (but mesothelioma by histology) were considered atypical/ suspicious (false-negative diagnosis); the remaining cases were true-negative or inadequate. Almost all effusions initially called "negative" (but non-neoplastic by histology) were considered negative. The only item that seems to discriminate between the two groups is atypia of mesothelial cells. CONCLUSIONS: The present study has highlighted the following pitfalls: (i) to report effusions devoid of mesothelial cells as negative that instead should be reported as inadequate/non-diagnostic; (ii) to underestimate low cellular effusions containing atypical mesothelial cells or high cellular effusions containing bland mesothelial cells with a morular pattern; (iii) to consider that an inflammatory background may obscure a scant number of mesothelial cells. A categorized system (inadequate (M1), negative (M2), atypical (M3) and suspicious (M4)) for reporting effusion cytology may be of help in the diagnostic work-up of patients with effusions suspicious for mesothelioma.

A one-generation cluster of malignant mesothelioma within a family reveals exposure to asbestos-contaminated jute bags in Naples, Italy.

Substantial evidence supports the role of asbestos in malignant mesothelioma. Clustering for this malignancy among relatives not only suggests genetic susceptibility as a relevant component but also provides a clue to investigate non-occupational sources of exposure. We identified five cases of malignant mesothelioma within one family with exposure to asbestos experienced during childhood, as 'next door' residents of a workshop recycling asbestos-contaminated jute sacks in Naples, Italy. This cluster discloses the health risk in the reuse of bags that previously had contained asbestos. Furthermore, it emphasizes the role of asbestos in the genetic-environmental interaction issue of malignant mesothelioma.

Malignant pleural mesothelioma in bakers and pastry cooks.

BACKGROUND: The occurrence of malignant pleural mesothelioma (MPM) among bakers and pastry cooks has never been documented. CASE REPORTS: We detected eight cases of MPM in bakers, pastry cooks, and biscuit cooks engaged in making, baking/cooking, and selling pastry/bread in two hospital-based series (Rome and Orbassano/Turin, Italy; period 1990-1997; 222 cases). Field-investigations revealed asbestos-containing material (ACM) in ovens for baking bread, that were manufactured prior to the 1980s. CONCLUSIONS: It is suggested that there is a possible new association of the risk of having worked as a baker or pastry cook and MPM. Presumptive source of exposure to asbestos was the use of asbestos-insulated ovens.

DNA copy number changes in familial malignant mesothelioma.

Malignant mesothelioma (MM) is predominantly a sporadic malignancy linked to exposure to asbestos. Clustering of MM in families suggests genetic susceptibility as a contributing factor. We performed comparative genomic hybridization (CGH) analysis on tumor samples from members of a family with MM of the pleura and a history of parental cancer. Our specific aim was to find a recurrent copy number loss indicating the chromosomal area to which a gene underlying the development of MM could be assigned according to the Knudson two-hit hypothesis. We found losses at 1p, 6q, 9p, 13q, and 14q. The copy number changes were very similar to those reported in sporadic cases. Our findings and results from sporadic cases highlight the importance of cloning the genes in the loss sites at 1p, 6q, 14q, and 22q.

[Malignant mesothelioma in the industrial area of Colleferro]. / Mesotelioma maligno nel comprensorio industriale di Colleferro.

The study describes the occurrence of pleural and peritoneal malignant mesothelioma in the Colleferro industrial area (Province of Rome, 9 municipalities, population 63,000, period 1993-98) which is the site of a large chemical plant (BPD) producing organic chemicals, acid mixtures, insecticides, explosives and dynamite, and was involved in manufacturing/maintenance of railroad rolling stock. Asbestos was extensively used in these plants in the past. Mesothelioma cases were actively searched from data in files of pathology archives, hospital admission and discharge (records), and death certificates recorded at local health authority register. 23 potential cases were identified for whom clinical charts and pathological slides were reviewed. A multidisciplinary evaluation of all collected information confirmed 18 cases of cyto-histologically proven malignant mesothelioma (pleural/peritoneal ratio of 2.75:1) among residents and/or workers at BPD. The remaining 5 cases were defined as not mesothelioma; however, two were cases of lung cancer (both occupationally exposed to asbestos). All subjects with malignant mesothelioma had been occupationally exposed to asbestos (14 males and 3 females), except one (1 female with domestic exposure). No mesothelioma case was attributable to environmental exposure. Of the 17 cases with occupational asbestos exposure, 15 occurred in BPD workers employed in manufacturing/maintenance of railroad rolling stock (3 cases), general maintenance services (5 cases), or in the armaments sector (7 cases) and 2 in residents but not BPD workers (1 baker, 1 pipefitter). The incidence rate in residents of the 9 municipalities was 5.5 in males and 1.3 in females (standardized on the Italian population x100,000, census 1981). For Colleferro municipality only, the incidence was 10.1 in males and 4.1 in females, which are the highest rates reported so far in Italy. Besides confirming the risk of mesothelioma risk in railroad rolling stock manufacturing and asbestos-insulated pipe maintenance workers, this study identifies a cluster of malignant mesothelioma in explosives production workers.

Absence of HHV-8 DNA sequences in malignant mesothelioma.

Human herpesvirus 8 (HHV-8) associated primary effusion lymphomas arise and grow in the body cavities as effusions, but it is not known whether the lining of body cavities and mesothelium derived malignancies are potential targets of HHV-8 infection. We examined a series of 13 diffuse malignant mesotheliomas and four mesothelial cell rich effusion samples of non-neoplastic aetiology from non-immunodepressed patients using the polymerase chain reaction to detect HHV-8 specific sequences. HHV-8 amplification products were absent in diffuse malignant mesotheliomas and in non-neoplastic effusions samples. These results suggest that HHV-8 has a selective tropism among body cavity based tumours, being confined to primary effusion lymphomas.

Cyclin D1 and Cyclin E expression in malignant thyroid cells and in human thyroid carcinomas.

Evidence of the involvement of cyclin gene alterations in human cancer is growing. In this study, we sought to determine the pattern of expression of cyclin D1 and cyclin E in normal and malignant thyroid cells. Quiescent rat thyroid cells in culture, induced to synthesize DNA by thyrotropin (TSH), expressed cyclin D1 gene after 6 hr and cyclin E gene with a peak at 18 hr from the stimulus; K-ras-transformed rat thyroid cells, which grew without addition of hormones necessary for normal cell proliferation, expressed elevated levels of cyclin D1 and cyclin E, compared with normal differentiated thyroid cells. Human benign and malignant thyroid tumors and their relative normal tissues were then analyzed. Neither major genetic alterations nor amplifications for cyclin D1 and cyclin E genes were found by Southern blot analysis in genomic DNAs extracted from all types of thyroid tumors. Moreover, statistical analyses of densitometric values from Northern blots did not show increased levels of cyclin D1 and E mRNAs in the tumor samples, compared with normal thyroid. Immunohistochemical analyses of formalin-fixed paraffin-embedded sections of tissues with specific antibodies revealed a prevalent cytoplasmic cyclin E staining in the thyroid tissues analyzed. Cyclin D1, instead, was present in the cytoplasm of normal thyroids and adenomas, but in 31% of thyroid papillary carcinomas analysed, it was overexpressed, with a localization in the nucleus. Our in vivo observations suggest that unlike cyclin E, elevated nuclear cyclin D1 expression defines a subset of thyroid papillary carcinomas, and might be a contributory factor to thyroid tumorigenesis.

Utility of HBME-1 immunostaining in serous effusions.

HBME-1 is an anti-mesothelial cell monoclonal antibody derived from human mesothelioma cells. We investigated 227 body cavity effusions to test its utility in differentiating mesothelioma from adenocarcinoma. HBME-1 outlined cell membranes in non-neoplastic mesothelial cells. Thick surface staining was observed on all mesotheliomas. HBME-1 reactivity was also detected in 24% of metastatic carcinomatous effusions. Most ovarian carcinomas (83%) reacted with this antibody, showing surface staining. Cytoplasmic HBME-1 immunoreactivity was observed in a small proportion of non-ovarian adenocarcinomas (14%). Despite its limited specificity, HBME-1 might be added to the battery of other markers of epithelial and/or mesothelial differentiation to be used in cases of suspected mesothelioma. Evaluation of suspicious cells should include careful study of the pattern of immunostaining.