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Accurate pathologic diagnosis and reporting in malignant pleural mesothelioma are essential for clinical care, and cancer registration. Practical guidelines for pathologists are provided in publications and textbooks but it is unclear how these recommendations are applied in routine practice. We investigated the characteristics of pathology reports, and the extent to which they meet guideline standards. We reviewed 819 pathology reports relating to a first diagnosis of malignant pleural mesothelioma. Data sources were a regional section of the Italian network of the Mesothelioma Registry (2001-2014) and a pathology archive (1990-2000). We evaluated tumor characteristics, the diagnosis field including terminology and immunohistochemistry (IHC) workup, and report completeness (the proportion of items recorded). We investigated also two IHC panels identified by the most used markers in current practical guidelines, one best suited for epithelioid mesotheliomas (combinations of at least 2 positive and at least 2 negative mesothelioma markers) and the other best suited for sarcomatoid mesotheliomas (positive mesothelioma markers plus cytokeratins). Reports (753 histology, 66 cytology, IHC-confirmed 86%) were 74% complete and always narrative. Missing data were related to clinical history (76%), tumor laterality (61%), specimen size (38%), and histological subtype (23%). The proportion of cases with IHC was higher for epithelioid (90%) than sarcomatoid mesothelioma (87%). Compliance to IHC recommendations was higher for epithelioid (59%) than sarcomatoid mesothelioma (11%). The mean number of stains was significantly higher for sarcomatoid than epithelioid mesothelioma (p

Malignant mesothelioma is a sporadic cancer linked to asbestos exposure. Its occurrence among blood relatives (familial mesothelioma) may point to genetic susceptibility or shared exposures. The burden of the familial disease is unknown. The aims of the study were to assess at population level the proportion of familial mesotheliomas among all mesotheliomas and to investigate the family history of cancer among relatives of mesothelioma cases. We actively searched familial clusters based on a mesothelioma registry from central Italy (5.5 million people, 10% of the Italian population) of the National Mesothelioma Register network (ReNaM) as well as a pathology-based archive. Among 997 incident mesotheliomas recorded in a 32-year-period (1980–2012), we detected 13 clusters and 34 familial cases, accounting for 3.4% of all mesotheliomas. The most common clusters where those with affected siblings and unaffected parents. Asbestos exposure was occupational ( n =7 clusters), household ( n =2), environmental ( n =1), or not attributable for insufficient information ( n =3). There were 25 additional cancers in nine families. Some were cancer sites for which there is sufficient evidence (lung and larynx) or limited evidence (stomach and colon) of causal association with asbestos. The results suggest potential genetic recessive effects in mesothelioma that interact with asbestos exposure, but it is not possible to estimate the specific proportion attributable to each of these components.

Familial malignant mesothelioma clusters are ideal candidates to explore BAP1 genomic status as a predisposing risk factor. We report data on BAP1 analysis in four families with multiple mesothelioma cases to investigate possible BAP1 alterations associated with an inherited cancer syndrome. We also recorded family history of cancer and assessed asbestos exposure. By genomic direct sequencing, we found no evidence of a BAP1 germline mutation in tumor DNA samples (one mesothelioma per family: n = 3 epithelioid; n = 1 biphasic). On the other hand, we identified a novel BAP1 somatic alteration (c.329_335delinsTC) in exon 5 (n = 1 biphasic), and we hypothesized the occurrence of somatic inactivating events not identifiable by sequencing in the other cases (n = 3 epithelioid), as demonstrated by the loss of nuclear BAP1 immunostaining. History of other cancers was in sites not typical of the BAP1 cancer syndrome. Asbestos exposure was occupational (n = 2 clusters), household (n = 1), and unknown (n = 1). These family units without inheritance of a BAP1 predisposing mutation expand the number of unmutated germline BAP1 families with multiple mesothelioma cases. This suggests that besides the exposure to asbestos other currently unknown genetic or epigenetic factors may be responsible for the high incidence of mesothelioma in BAP1 -unmutated families.

Aims and background Epidemiological studies on malignant mesothelioma have provided evidence on the etiologic role of occupational asbestos exposure and, to some extent, domestic and residential exposures. Less attention has been given to the occurrence of mesothelioma in urban areas where large quantities of asbestos have been employed in the past. The purpose of the study was to investigate the occurrence of mesothelioma in patients living in the urban area of Rome and in other parts of the Latium Region and the patterns of asbestos exposure. Methods and study design A pathology-based, malignant mesothelioma archive operating in Rome, Italy, was the source of cases. Included in the survey were cases resident in Latium and diagnosed in the period January 1, 1993, through December 31, 2001. Information on asbestos exposure was derived from interviews to the patient or his/her next of kin and from available medical records. Results The case series included: 114 males and 53 females; total, 167. Information on asbestos exposure was available for 138 cases (83%). Occupational exposure was ascertained or suspected for 33% of cases resident in Rome and 63% of those resident in other municipalities of Latium. Sex ratio was 1.6 in Rome and 3.3 in Latium. Conclusions The high prevalence of women among mesothelioma cases and lower proportion of occupational exposure in Rome versus the other municipalities of Latium suggest a possible role of environmental asbestos exposure in the urban area.

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 Dl expression defines a subset of thyroid papillary carcinomas, and might be a contributory factor to thyroid tumorigenesis.

The aim of this study was to compare the cytologic diagnosis and specimen adequacy of conventional Papanicolaou (CP) and fluid-based, thin-layer [ThinPrep (TP), Cytyc, Boxborough, MA] cervical cytology in a population from central Italy. CP and TP samples were collected simultaneously using a consecutive sampling method on women presenting for cervical screening. Colposcopy was performed as clinically indicated, and biopsy results were compared with cytologic diagnoses. Among the 461 patients included in the study, 413 were negative at both CP and TP, 9 had unsatisfactory results at both tests and 39 patients presented abnormal results at CP, TP or both. Cohen's Kappa was 0.77 showing good agreement between CP and TP test results. Histological data were available for 20 (51.28%) of the 39 patients with at least one positive test. Among the 13 patients with HSIL at histology, 7 had HSIL at CP (sensitivity 53.85%) and 5 at TP (sensitivity 38.46%). For all three patients with squamous cell carcinoma (SCC) at histology, CP and TP had shown the same diagnosis (sensitivity 100%). The positive predictive values were 33.33% for CP and 25.0% for TP regarding the LSIL diagnosis and 100% for both CP and TP regarding HSIL and SCC diagnoses. Our results may be influenced by the consecutive sampling procedure. Diagn. Cytopathol. 2009. © 2008 Wiley-Liss, Inc.

Malignant mesothelioma is indicative of past exposure to asbestos. In recent years an increase of incidence and mortality from malignant mesothelioma has been observed. Recent legislation in Italy requires nation-wide registration of asbestos-related pathologies. We conducted a preparatory study for systematic recording of cases of malignant pleural mesothelioma in the Lazio region.To register new diagnoses of malignant mesothelioma, to estimate the incidence in the Lazio region, and to evaluate possible survey instruments.We conducted a systematic study of hospital admissions in the region with diagnosis of cancer of the pleura (ICD-IX 163) in the period 1997-2000. Clinical information and results of diagnostic tests were requested for 530 patients from the hospitals involved. Using the capture-recapture method, it was possible to estimate the accuracy of the data we compiled using hospital admissions as the data source (76.8%, 95% C.I.=76.4-77.3).After careful review of clinical documentation, the diagnosis of malignant mesothelioma of the pleura was confirmed in 31.6% of cases (156 cases diagnosed). The percentage of confirmed cases has risen over the years (from 21% in 1997 to 45.1% in 2000) and it was higher in large public hospitals than in other types of health care facilities. On the basis of 156 confirmed cases of mesothelioma (116 males and 40 females), we estimated the annual incidence of the disease in the Lazio region as 1.73 new cases per 100,000 inhabitants among men and 0.47 new cases per 100,000 inhabitants among women.The results show that the incidence of mesothelioma in the region is consistent with national data, falling in the middle of the range for all Italian regions. However, some areas emerge (for example, Colleferro, Civitavecchia, Tarquinia, Ferentino, Gaeta, Aprilia, Pomezia) that have particularly high rates, probably in relation to past occupational asbestos exposure. The role of diffuse environmental exposure in Rome may warrant further investigation.

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 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.

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.

Malignant mesothelioma is associated with asbestos, yet its occurrence in genetically-related individuals suggests a role of host predisposition. We have identified a cluster of pleural malignant mesothelioma in three sisters and one cousin (male). The women had worked in the same confectionery shop as pastry cooks and/or pastry shop assistants; the use of an asbestos-insulated oven was the putative source of exposure. The man had occupational exposure as a heating system installation worker. The family history reported malignant cancers in first-degree (larynx, brother; pleura and lung, mother), second-degree (lung, aunt and uncle) and third-degree (lung, cousin) relatives. The study reveals the potential existence of the mesothelioma risk among pastry cooks and highlights the fact that inherited factors may be involved in the development of this tumour.

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.

Aim and background To evaluate the characteristics of a case-series of 79 malignant mesothelioma patients collected from the main teaching hospital of Rome, Italy, and other local clinics of Latium Region and to assess the role of asbestos exposure, since previous studies on the occurrence of the disease in this area were lacking. Methods The study included cytohistologically diagnosed malignant mesothelioma (71 pleural, 7 peritoneal, and 1 testicular tunica vaginalis) detected or referred for consultation during the period 1980-1995. Information regarding occupational and/or nonoccupational exposures was derived from clinical records and interviews, when available. Results Patients were resident in Rome and other towns of Latium; a few were from other parts of central and southern Italy. Exposure to asbestos was assessed for 45.5% of patients, another 45.5% had unknown exposure, and for the remaining 9% such information was lacking. Occupational exposure occurred in 53% of men for whom information was available and nonoccupational exposure occurred in 20% of women. The study identified two clusters of cases from an asbestos-cement plant and a facility where asbestos was ubiquitous. Furthermore, most exposed subjects reported occupations in the construction industry, which is particularly active in the Latium Region; others were railroad workers, naval mechanics and navy personnel, bakers, explosive workers and car mechanics. A few patients reported indoor exposure to asbestos at home and/or in the workplace. Conclusions The study confirmed that mesothelioma risk is present in several job titles of the construction industry, and it is no longer confined to workers employed in the manufacture or application of asbestos products. The occurrence of malignant mesothelioma in patients with unexpected occupational and nonoccupational exposures indicates the need for further investigation on previously underestimated exposures.

We describe the cytohistological, immunohistochemical and ultrastructural findings in a 55-yr-old-man with history of asbestos exposure and diffuse malignant mesothelioma (DMM) of the pleura, peritoneum, and tunica vaginalis presenting with chest pain and scrotal swelling. Pleural fine-needle aspiration (FNA) revealed mesenchymal elements and spindle-shaped epithelial-like cells, while biopsy showed pure sarcomatous tumor invading lung parenchymal. In both samples tumor cells coexpressed cytokeratin and vimentin. Peritoneal and hydrocele effusions contained aggregates of malignant mesothelial cells. Electron microscopy showed intermediate filaments, rare desmosomes and sparse microvilli. Morphological findings were consistent with a DMM, with a biphasic pattern in the pleura and an epithelial one in the peritoneum and tunica vaginalis. Although the possibility of a multicentric origin cannot be ruled out, clinical chronologic sequence suggests that the pleura was the primary involved site, followed by spread to peritoneum and tunica vaginalis.

Using a commercially available monoclonal antibody (Ks20.1) and the avidin-biotin peroxidase method on cytospins and cell blocks, we analyzed cytokeratin (CK) 20 expression in 169 serous effusions. Cytoplasmic staining was observed in 44/151 malignant fluids. Colon, gastric, and pancreatic adenocarcinomas and mucinous ovarian tumors were most frequently positive. Single cases of transitional-cell and squamous cell carcinomas were reactive as well. Lung and breast cancers were mostly negative. Nonmucinous ovarian tumors were invariably unlabeled as were mesotheliomas and normal mesothelial cells. the study shows that CK 20 is valuable in distinguishing tumor cell origin in effusions. in particular, it identifies a set of carcinomas with the majority arising from the gastrointestinal tract, and represents a highly characteristic marker for colorectal cancer. © 1995 Wiley- Liss, Inc.

Human herpesvirus-8 (HHV-8) has been associated with Kaposi's sarcoma, multicentric Castleman's disease and primary effusion lymphoma. Kaposi's sarcoma and multicentric Castleman's disease patients may develop body cavity effusions that, unlike primary effusion lymphoma, are poorly characterized. To better define these effusions, pleural and peritoneal fluids derived from 12 human immunodeficiency virus-seropositive and one seronegative patients affected by Kaposi's sarcoma or multicentric Castleman's disease were analyzed by a combination of morphologic, immunophenotypic, and DNA analyses, including polymerase chain reaction amplification of HHV-8, Epstein-Barr virus, and immunoglobulin heavy-chain (IgH) gene sequences. In addition, HHV-8 serologic status was assessed by using an immunofluorescence assay. All patients were adult men with high antibody titers to HHV-8; 11 of the 13 patients were homosexual/bisexual. Effusions revealed monocyte/macrophage-rich infiltration (10 patients) or large-cell lymphoma with CD45(+)/non-T/non-B phenotype (three of 13 patients); polymerase chain reaction analysis showed the presence of HHV-8 sequences (nine of 13 patients), germline IgH (seven of 12 patients) or clonal IgH rearrangements (four of 12 patients), and rarely Epstein-Barr virus sequences (two of 12 patients). In the setting of HHV-8 infection, two effusion types may occur. One fulfills the criteria for HHV-8-positive PEL (lymphoma-morphology, HHV-8-DNA(+), IgH rearrangement). The other seems more reminiscent of an HHV-8-associated nonneoplastic process (monocyte-macrophage morphology, HHV-8-DNA(+/-), germline IgH). Interestingly, a single case of the latter effusion type harbored a B-cell monoclonal proliferation, which suggests the hypothesis that a prelymphomatous effusion may precede overt body cavity lymphoma.