Multicentric study on malignant pleural mesothelioma and non-occupational exposure to asbestos.

Insufficient evidence exists on the risk of pleural mesothelioma from non-occupational exposure to asbestos. A population-based case-control study was carried out in six areas from Italy, Spain and Switzerland. Information was collected for 215 new histologically confirmed cases and 448 controls. A panel of industrial hygienists assessed asbestos exposure separately for occupational, domestic and environmental sources. Classification of domestic and environmental exposure was based on a complete residential history, presence and use of asbestos at home, asbestos industrial activities in the surrounding area, and their distance from the dwelling. In 53 cases and 232 controls without evidence of occupational exposure to asbestos, moderate or high probability of domestic exposure was associated with an increased risk adjusted by age and sex: odds ratio (OR) 4.81, 95% confidence interval (CI) 1.8-13.1. This corresponds to three situations: cleaning asbestos-contaminated clothes, handling asbestos material and presence of asbestos material susceptible to damage. The estimated OR for high probability of environmental exposure (living within 2000 m of asbestos mines, asbestos cement plants, asbestos textiles, shipyards, or brakes factories) was 11.5 (95% CI 3.5-38.2). Living between 2000 and 5000 m from asbestos industries or within 500 m of industries using asbestos could also be associated with an increased risk. A dose-response pattern appeared with intensity of both sources of exposure. It is suggested that low-dose exposure to asbestos at home or in the general environment carries a measurable risk of malignant pleural mesothelioma.

[The cervico-vaginal cytology workload. A complex task in planning laboratory activities]. / Il carico di lavoro in citologia cervico-vaginale. Un compito complesso nella pianificazione dell'attività di laboratorio.

Measurement of professional work efforts are desired by health care administrators as a means of comparing the efficiency of the laboratory activities in an attempt to predict proper staffing levels and funding. In view of the complexity of measuring pathology workload, it is not surprising that the evaluation of this effort has never been adequately quantitated and that, as a consequence, literature data are scant. We reviewed all available information on cervical cytology workload. Most data refer to cytoscreener workload while very few indications concerning the cytopathologist's performance can be obtained. The vast majority of reported figures derive from the English literature and show extreme variability: for cytoscreener/cytotechnologist, the workload figures are between 3,000-15,000/year, 40-150/day and 3-20/hour. In addition, data are scarcely comparable since the true "object" of the workload measurement is not always evident: just Pap-test microscopic screening or pre- and post-analytical procedures too? In the Italian milieu , a reasonable cytoscreener workload would range from 6 slide/hour (i.e. 45-50/day or 10,000/year) if the duty is limited to the screen only, to 4 slide/hour (i.e. 30-35/day or 7,000/year) for people involved in slide preparation or ancillary duties. For both events, upper and lower workload limits are suggested. We conclude that professional attention must be given to determine appropriate workloads in order to minimize suboptimal performance and improve the cost-effectiveness of laboratory activities.

Cancer risk among female agricultural workers: a multi-center case-control study.

BACKGROUND: Cancer risk among women engaged in farming has been poorly investigated. This group of female workers is of particular interest, however, since they may experience exposure to several potential agricultural hazards. METHODS: A hospital-based case-control study was conducted in five Italian rural areas to examine the association between cancer and farming among women. The areas selected were located in three different regions (i.e., Piedmont, Tuscany, and Emilia-Romagna). The following cancer sites were selected for the study: stomach, colon, rectum, lung, skin melanoma, skin non-melanoma, breast, cervix and corpus uteri, ovary, bladder, kidney. Cases of non-Hodgkin's lymphoma were also included. Altogether, 1,044 newly diagnosed cases aged 20-75 years were ascertained from hospital records from March 1990 to September 1992, and for 945 of them detailed information was collected by a standard questionnaire. The analyses of data were performed comparing each case series to a reference group drawn from among the other sites. Unconditional logistic regression models were used in the statistical analyses. RESULTS: Statistically significant increased risks in association with farming were estimated for skin melanoma (OR 2.7, 95% CI 1.2-5.8) and bladder cancer (OR 2.7, 95% CI 1.2-6.1). Lung cancer was also found increased but not at a statistically significant level (OR 1.7, 95% CI 0.7-4.4). An OR lower than unity was observed for postmenopausal breast cancer (OR 0.4, 95% CI 0.3-0.7). CONCLUSIONS: The present study suggests that women in farming might experience increased risk of cancers, not usually found in excess among male farmers, as well as a protective effect for postmenopausal breast cancer. The role of different patterns of exposure or gender specific responses should be considered in further studies.

Villoglandular papillary adenocarcinoma of the uterine cervix: report of a case.

Villoglandular papillary adenocarcinoma is a recently described form of adenocarcinoma of the uterine cervix, which apparently affects young women and seems to have a favorable course with an excellent prognosis. We report on a case of villoglandular papillary adenocarcinoma in a 26-year-old woman. The patient was treated by conization alone and is disease free after a 40-month follow-up.

Malignant mesothelioma of the pleura. The reproducibility of the immunohistological diagnosis.

The reproducibility of the histopathological diagnosis of pleural malignant mesothelioma (MM), after supplementing routine H&E stain by immunohistochemistry (IH) in 77 cases of original diagnoses of MM, was assessed by examining interobserver variation between five pathologists. A battery of commercial antibodies (cytokeratins, vimentin, HMFG-2, anti Leu-M1 [CD15], BerEP4, B72.3 [TAG-72], carcinoembyonic antigen), considered to be useful in enhancing diagnostic accuracy, was used. The number of definitively classified tumors (accepted MM plus rejected MM) increased from 57 on H&E stain to 60 after IH, with 59 (76.6%) cases being accepted as true MM. Based on IH, the chance-adjusted interobserver agreement was poor (kappa w = 0.29) and lower than that observed on previous H&E alone. The intraobserver agreement for four of the five pathologists was rather good (kappa w = 0.54-0.56). The inter- and intraobserver concordance was higher in accepting than excluding the cases as MM. A larger number of cases were classified by all reviewers as mixed or sarcomatous variants after IH. In the interpretation of each immunostain, kappa values ranged from 0.19 for B72.3 to 0.62 for HMFG-2, which were respectively the least and the most consistently interpreted immunostains. The information additionally contributed by IH did not seem to change the pathologists' diagnoses very much in comparison with those made by routine H&E stain. Until highly specific and sensitive probes for the positive identification of MM become available, a careful scrutiny of routinely stained preparations still remains the most rewarding component of the diagnostic pathway.

[Audit of histopathology activities at the pathology departments of 7 general hospitals. 2. Response time]. / Audit dell'attività istopatologica nei servizi di sette ospedali generali. 2. Tempi di risposta.

A retrospective analysis of 1,000 consecutive cases was conducted in each histopathology lab of seven general hospitals. The collected information included the date of specimen withdrawal (six labs only), receipt in the laboratory, and reporting. Time intervals between withdrawal and receipt. Two labs, received 3/4 of cases the same day, while the others had a very low prevalence of receipt. All labs but one, received 80-90% of cases within 48 hours. In one lab, 17% of cases arrived five days after from the withdrawal. Time intervals between receipt and reporting. The mean observed in the seven labs ranged from 3.1 to 6.1 days. Two labs were able to report within 24 hours, but this occurred only in 6% of their cases. The reporting prevalence within three days ranged between 5 and 64%, with a mean for the seven labs of 37%. The reporting prevalence within 6 days was about 95% (four labs), 60-70% (two labs) and 20% (one lab). All labs but one reported 95-100% of cases within ten days. Time intervals between withdrawal and reporting. Our labs were not able to report within 24 hours from the withdrawal (frozen sections excluded). The reporting prevalence within 2-3 days was about 35-40% (three labs), 16% (one lab), 2% (two labs), and within six days it was about 90% (three labs), and 61%, 38% and 14% (the remaining). These latter reported 95% of their cases within twenty days. The turnaround times we found are unsatisfactory. Probably, there are many sources of delay, and these are multifactorial. However, a major factor involved in these delays seems to be related to poor arrangements in the allocation and managing of human resources.

[Audit of histopathological activities in the laboratories of 7 general hospitals. 1. Types of resources and quantitative aspects of the workload]. / Audit dell'attività istopatologica nei servizi di sette ospedali generali. 1. Tipi di risorse e aspetti quantitativi delle prestazioni.

Following a major reorganization of the National Health Service, competition for resources will depend to a great extent on the quality of the service offered, and audit will be of increasing importance. The present investigation deals with the quantitative aspects of the histopathology workload. A retrospective analysis of the biopsy handling of 1,000 consecutive cases was conducted in each histopathology lab of seven general hospitals. The data collected included information on specimen type, diagnosis, block/section/stain details for each specimen, as well as information about human resources, total workload and technical equipment. Among the seven labs, the histopathology workload ranged between 6,600 and 15,600 cases/year. The workload per person/year ranged between 1,400 and 2,600 (mean 1,900) for pathologists, between 800 and 3,000 (mean 1,500) for technicians, and between 2,200 and 8,300 (mean 4,400) for secretarial staff. The prevalence of biopsy fragments (endoscopic, endometrial curettage , etc.), "small" surgery (skin, appendix, gallbladder, etc.) and surgery was, respectively, between 42 and 50%, 34 and 47%, 9 and 21%. In all labs but one, 80% of cases were within 1-3 blocks; the seven labs had a mean of blocks/case ranging from 1.8 to 4.0 (total mean = 2.8). Differences in performing special stains were astonishing: one lab performed special stains in about 40%, and another in only 0.6% of cases (mean of the seven labs = 15%). Finally, the labs performed immunohistochemical stains within a range of 2.7-8% of cases (mean of the seven labs = 4.6%). The data we have collected provided baseline information on the laboratory running, and this is likely to be an integral part of laboratory administration in the near future.

Malignant mesothelioma of the pleura: interobserver variability.

AIMS: To assess the consistency of histopathological diagnosis of pleural malignant mesothelioma by estimating interobserver agreement between five pathologists. METHODS: Eighty eight histological sets pertaining to original diagnoses of pleural malignant mesothelioma were reviewed separately by each pathologist. Diagnostic likelihood was graded as definite (A), probable (B), possible (C), improbable (D), and definitely not (E) malignant mesothelioma. The following indexes were estimated: observed proportion of agreement (Po), kappa statistics and proportion of agreement for "positive" (Ppos) and "negative" (Pneg) diagnoses. RESULTS: Sixty cases (68.2%) were rated by at least three reviewers as A or B and by none of the others as D or E. Five (5.7%) were rated by at least two reviewers as D or E and by none of the others as A or B. Nine (10.2%) showed a serious disagreement, rated A or B and D or E. Agreement for sets obtained at necropsy/surgery (median kappa w = 0.57) was similar to that for endoscopic material (median kappa w = 0.54). Agreement was poor on material obtained by needle biopsy (median kappa w = 0.21). The median value of Ppos varied between 0.94 (necropsy/surgery) and 0.67 (needle biopsy) and that of Pneg between 0.78 (necropsy/surgery) and 0.34 (unspecified biopsy). Interobserver agreement on histological typing was good overall (median kappa = 0.59). CONCLUSIONS: Of the original histological diagnoses, 70% were consistently reproduced through panel review. Most indexes of agreement between pathologists ranged from poor (needle biopsy) to moderate (necropsy/surgery). Agreement in confirming malignant mesothelioma was greater than that regarding exclusion of this diagnosis. Of the cases finally considered to have malignant mesothelioma, the reproducibility of histological typing was relatively satisfactory.

Pleural malignant mesothelioma and non-occupational exposure to asbestos in Casale Monferrato, Italy.

OBJECTIVES: To assess and quantify the occurrence of pleural malignant mesotheliomas in people who neither experienced occupational exposure to asbestos nor were married to (or known to live with) workers exposed to asbestos in the workplace. The study was conducted in the area of the local health authority of Casale Monferrato, in north western Italy, where a large factory that produced asbestos cement was active up to 1985. No other major activities related to asbestos have ever been present in the area. METHODS: A retrospective survey covering the period 1980 to 1991 identified 126 incident pleural malignant mesotheliomas histologically diagnosed among residents in the local health authority (population at the 1981 census 98,000). Submission of 83 of 95 cases diagnosed during 1980-9 for revision by a panel of five expert pathologists led to the exclusion of 21. The 31 cases diagnosed in 1990-1 were not submitted for revision. For 64 of the 105 retained cases, information derived from different sources (rosters of the employees in the asbestos cement factory dated back to 1907, list of their spouses, clinical records) did not suggest occupational or paraoccupational exposure to asbestos. RESULTS: Incidence excludes cases for which there was some suggestion of occupational or paraoccupational exposure to asbestos. Incidence of histologically confirmed malignant mesothelioma among residents in the local health authority (annual x 100,000; age adjusted) was 4.2 in men and 2.3 in women (based on 26 and 18 cases respectively). In both sexes, rates in 1985-9 were higher than in the previous quinquennium. Corresponding estimates for 1990-1 (based on unrevised diagnoses) suggest similar rates in men and women. CONCLUSION: Rate ratios which are four to six times those measured by conventional Italian cancer registries can hardly be totally explained by bias produced by lack of recognition of occupational or paraoccupational exposure. The problem of proving this type of negative data is common to other circumstances of alleged cancer clusters of environmental (non occupational) origin.

What's new in managing health hazards in pathology departments.

Health hazards related to activities performed in pathology departments have represented, in recent years, an increasing concern among pathologists and pathology technicians. The major occupational health problems encountered in pathology departments are reviewed. They include biological hazards (tuberculosis, hepatitis, HIV, other infectious diseases), chemical hazards (formaldehyde, xylene(s), aromatic amines, methacrylates, glutaraldehyde, latex) and physical hazards (cut injuries, accidental fires, radiation). Current data suggest that infections (particularly, tuberculosis and hepatitis) still represent the more relevant risk. Exposure to HIV and Creutzfeldt-Jakob agent may be highly harmful but containment measures have been proven to be effective. The actual adverse effects due to chemicals seem to be less alarming than was previously believed. Attaining a safe work environment is an inherent element of good quality assurance management. This task is largely a matter of information, education, organization and common sense. Well-designed premises, efficient equipment and well-trained personnel are the keys to preventing and minimizing hazardous exposures. In order to provide current information that may be used by pathology staff to implement the functional quality of the workplace, organizational and preventive measures are described.

Clear cell ("sugar") tumor of the lung is a lesion strictly related to angiomyolipoma--the concept of a family of lesions characterized by the presence of the perivascular epithelioid cells (PEC).

We report a comparative study of 3 clear cell tumors of the lung (CCTL) and 3 angiomyolipomas (AML) of the kidney. Morphological analysis shows that the cells of CCTL are identical to the perivascular epithelioid component of AML. Phenotypically they both consistently expressed melanoma-associated antigens recognized by Moabs HMB45 and HMSA-1, while they were negative for HMSA-5. A minority of cells also expressed S-100 protein, vimentin and actin. In addition, one case of CCTL showed mature adipose tissue entrapped in the proliferation, thus suggesting an intermediate form between CCTL and AML. Based on morphological and phenotypical similarities, it is suggested that CCTL and AML belong to the same family of lesions, characterized by the presence of a peculiar muscle cell, expressing different melanoma-associated antigens.

Malignant peritoneal mesothelioma mimicking mesenteric inflammatory disease.

A case of malignant peritoneal mesothelioma mimicking mesenteric inflammatory disease (MID) is presented. The patient had mesenteric and omental lesions characterized at biopsy by extensive fibrosis of fat tissue with mild to moderate inflammation. One year later, post-mortem examination revealed a well-differentiated epithelial mesothelioma. Immunohistochemical stains for keratin and vimentin were diffusely positive, whereas EMA showed a membranous staining of scattered cells. CEA, Ber-EP4, B72.3 and Leu-M1 were negative. In addition, actin monoclonals decorated groups of cells pertaining to the tumoural component. Immunostains of sections from retrieved paraffin blocks of the previous biopsy showed that the bulk of the spindle-shaped and histiocytic-like cells present in the fibrous streams was strongly labeled by low-molecular-weight keratin, and coexpressed vimentin and actin. EMA showed a membranous staining of sporadic spindle and round cells. The other immunostains were invariably negative. This immunohistochemical pattern closely corresponded to the immunophenotype of the mesothelial tumour detected at autopsy and was very suggestive of myofibroblastic/submesothelial cell origin. The quantitative evaluation of silver nucleolar organizer regions (Ag-NORs) demonstrated high levels of cell proliferation in both surgical and autopsy tissue samples.

Malignant peritoneal mesothelioma in a 17-year-old boy with evidence of previous exposure to chrysotile and tremolite asbestos.

We describe a case of malignant peritoneal mesothelioma arising in a 17-year-old boy. The diagnosis was based on a comprehensive study including light microscopy, histochemistry, immunohistochemistry, evaluation of the clinical course, and autopsy examination. Analytical transmission electron microscopy showed a concentration of 510,000 asbestos fibers/g dry lung tissue. The fibers were represented by chrysotile (62%) and tremolite (38%) asbestos. About 40% of the total fibers were longer than 5 microns. The presence of tremolite fibers was probably due to environmental exposure to contaminated cosmetic talc. This is the first reported case of pathologically proven exposure to asbestos dust in malignant mesothelioma of childhood and adolescence.

Ki-67 scores and AgNor counts in transitional cell carcinoma of the bladder: apparent lack of prognostic value.

The cellular proliferative state of 18 incident cases of transitional cell carcinomas of the bladder treated with transurethral resection was blindly determined by two independent observers using Ki-67 monoclonal antibody and silver stain for nucleolar organizer regions (AgNORs). Ki-67 scores were significantly related to histological grade (WHO) (rs = 0.65, p < 0.01) and clinical stage (UICC) (rs = 0.46, p < 0.05). However, the follow-up analysis over a six year period did not demonstrate significant relationship between Ki-67 values and survival. AgNOR counting did not show significant association with any of the variables under study. The results of this investigation and the review of the pertinent literature suggest that the assessment of cell proliferation of bladder carcinoma by means of Ki-67 and AgNOR techniques is far from having immediate direct influence on patient management.

Hyaline splenic and hepatic plaques. Correlation with cirrhosis, pulmonary tuberculosis, and asbestos exposure.

Nine hundred twenty-five unselected autopsies were investigated for the presence or absence of hyaline peritoneal (splenic or hepatic) plaques, hyaline pleural plaques, asbestos, liver cirrhosis, heart failure, previous peritoneal dialysis or abdominal surgery, chronic peritonitis, splenomegaly, splenic infarcts, and pulmonary or abdominal tuberculosis. Lung asbestos body concentrations were calculated in 570 subjects. Peritoneal plaques were recorded in 163 cases. In both univariate and multivariate analyses, they were associated with cirrhosis, pulmonary nonactive tuberculosis, pleural plaques, and asbestosis. Association with asbestos body counts was also found, with a significant trend. Peritoneal plaques were described long ago in different pathologic conditions, for some of which (cirrhosis and nonactive pulmonary tuberculosis) the association is confirmed by the present analysis. It is suggested that they are significantly associated, moreover, with indicators of asbestos exposure.

[Chorioangioma (placental hemangioma): anatomo-pathologic identification and possible clinical relevance]. / Corioangioma (emangioma placentare): identificazione anatomo-patologica e possibile rilevanza clinica.

Chorioangioma (Placental hemangioma): Anatomo-pathological identification and possible clinical importance. Chorioangioma is found in about 1% of all placentas. However, many small tumours are missed in routine examination or easily mistaken for infarcts. Cases of large chorioangiomas may be related with a number of feto-maternal pathological conditions. Here we report a case of chorioangioma with a brief review on the possible several complications related to its occurrence.