Franco Mollo

Reliability of death certifications for different types of cancer. An autopsy survey.

A series of 1000 cases was selected, on the basis of a clinical and/or post-mortem diagnosis of cancer, out of 4927 autopsies performed at the Institute of Pathologic Anatomy and Histopathology of Turin University. The comparison between clinical and post-mortem diagnoses pointed to an overall concordance with regard to the correct identification of a malignancy as the underlying cause of death of 75%; if the correct identification of type and primary site of the tumor was also taken into account, the concordance was only 56%. The rate of false-positive and false-negative diagnoses, the confirmation rate and sensitivity index of clinical diagnoses, and the error of estimate of the overall frequency of the different types of tumors were computed. Pancreas, liver and biliary tract tumors appear to be the most difficult to identify correctly during life; also lung, stomach and colorectal cancers, lymphomas and leukemias show fairly high rate of clinical errors. Breast cancer, tumors of the nervous system and colorectal cancers appear to be overnotified. These results seem to underscore the necessity of being very careful in drawing conclusions on the frequency and distribution of the different types of cancer on the basis of current mortality statistics.

Asbestos lung burden and asbestosis after occupational and environmental exposure in an asbestos cement manufacturing area: a necropsy study

OBJECTIVE: The largest Italian asbestos cement factory had been active in Casale Monferrato until 1986: in previous studies a substantial increase in the incidence of pleural mesothelioma was found among residents without occupational exposure to asbestos. To estimate exposure to asbestos in the population, this study evaluated the presence of histological asbestosis and the lung burden of asbestos fibres (AFs) and asbestos bodies (ABs). METHODS: The study comprises the consecutive series of necropsies performed at the Hospital of Casale Monferrato between 1985 and 1988. A sample of lung parenchima was collected and stored for 48 out of 55 necropsies. The AF concentration was measured with a TEM electron microscope with x ray mineralogical analysis. The ABs were counted and fibrosis evaluated by optical microscopy. The nearest relative of each subject was interviewed on occupational and residential history. Mineralogical and histological analyses and interviews were conducted in 1993-4. RESULTS: Statistical analyses included 41 subjects with AF, AB count, and interview. Subjects without occupational exposure who ever lived in Casale Monferrato had an average concentration of 1500 AB/g dried weight (gdw); Seven of 18 presented with asbestosis or small airway lung disease (SAL). G2 asbestosis was diagnosed in two women with no occupational asbestos exposure. One of them had been teaching at a school close to the factory for 12 years. Ten subjects had experienced occupational asbestos exposure, seven in asbestos cement production: mean concentrations were 1.032 x 10(6) AF/gdw and 96,280 AB/gdw. Eight of the 10 had asbestosis or SAL. CONCLUSION: The high concentration of ABs and the new finding of environmental asbestosis confirm that high asbestos concentration was common in the proximity of the factory. Subjects not occupationally exposed and ever living in Casale Monferrato tended to have higher AB concentration than subjects never living in the town (difference not significant). The concentrations of ABs and AFs were higher than those found in other studies on nonoccupationally exposed subjects.

Role of iron in asbestos-body-induced oxidant radical generation.

Asbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TBA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thiourea (DMTU) and mannitol (MN) also effectively blocked TBA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TBA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. In the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.

Recurrence of hepatitis D (delta) in liver transplants: Histopathological aspects

BACKGROUND The viral/pathological correlates of recurrent hepatitis delta virus (HDV) disease in orthotoptic liver transplants are reported. METHODS We examined the histological features of recurrent HDV disease in nine patients with transplants for terminal HDV cirrhosis were examined; intrahepatic HDV and hepatitis B virus (HBV) antigens were detected by immunoperoxidase techniques. Sera were tested for the battery of HDV and HBV markers. RESULTS In four patients, HDV reinfection was accompanied by the recurrence of an HBV infection with features of active viral replication. In the other five, HDV reinfection was accompanied by an atypical recurrence of HBV infection without evidence of active HBV replication (no expression of intrahepatic hepatitis B core antigen). In four of the latter patients, the atypical HBV pattern changed during the follow-up into a pattern of active viral replication accompanied by chronic necroinflammation detected during histology. CONCLUSION The pattern of recurrent HBV infection can influence the pathological aspects of the relapses of HDV disease in liver grafts.

The attribution of lung cancers to asbestos exposure: A pathologic study of 924 unselected cases

We studied a series of 924 nonselected surgical cases of lung carcinoma (without occupational history in clinical records) by histologic examination and light microscopic determination of asbestos body (AB) concentration to determine cancers attributable to asbestos exposure. Lower lobes showed higher concentrations, but no significant associations were recorded between concentrations and histologic type of the lung carcinomas. Histologic asbestosis was demonstrated in 56 cases considered definitely asbestos-related. In 12 of them, the demonstration of asbestosis was attained only after repeated examination of additional sections, suggested by thefinding of more than 1,000 ABs per gram of dry weight (gdw), an indicator of occupational asbestos exposure. In the 56 cases, the media

Minimal pathologic changes of the lung and asbestos exposure.

A group of 199 autopsy subjects was investigated for minimal pathologic pulmonary changes possibly resulting from asbestos exposure. According to the standards proposed by the Pneumoconiosis Committee of the College of American Pathologists, features consistent with asbestosis grade 1 (AG1) include findings of bilateral pleural plaques, high concentrations of asbestos bodies (ABs) in digested lung tissue, and a history of occupational risk. Similar changes without evidence of ABs on histologic section and referred to as small airway lesions (SALs) present a less well-correlated association. In this study, SALs showed significant differences when compared with the features observed in subjects without possible asbestos-related pulmonary fibrotic changes. Minimal bronchioloalveolar fibrotic changes with concomitant presence of ABs can be considered a mild pneumoconiotic lesion (AG1), and SALs may be regarded as an additional indicator of asbestos exposure.

Human Peripheral Lung Tumours: Light and Electron Microscopic Correlation

Thirteen human peripheral lung tumours have been studied in both light and electron microscopy. They were classified as epidermoid carcinoma, mucus-secreting cell adenocarcinoma, and alveolar cell adenocarcinoma, the latter made up of granular pneumocytes. Alveolar cell cancer, as defined by ultrastructural features, could assume different gross histological patterns in light microscopy, and therefore electron microscopy is required for its identification.Since neither squamous nor mucous metaplasia was observed in any alveolar cell tumour, it is tentatively suggested that all peripheral lung tumours which lack these features may be derived from granular pneumocytes, irrespective of whether they appear to be adenocarcinomata or large cell carcinomata when examined by light microscopy.

Pleural plaques and risk of cancer in Turin, Northwestern Italy. An autopsy study

The relationship between the occurrence of neoplastic diseases and the presence of pleural plaques was studied in a series of 1097 autopsies performed in Turin from the adult general population. In men, pleural plaques showed an association with the presence of laryngeal, pulmonary, esophageal, and colorectal cancer. Only cancer of the larynx was strongly related to the occurrence of such pleural changes. This autopsy investigation confirms previous observations by others based on x‐ray findings, and suggests that pleural plaques may be regarded as risk indicators of possibly asbestos‐related tumors in the general population.

Dark Reticular Cells in Human Lymphadenitis and Lymphomas

ZusammenfassungVierzig menschliche Lymphknoten (16 Fälle von Hodgkinscher Krankheit, 9 Fälle von Lymphosarkom, 5 Fälle von Retothelsarkom, 4 Fälle von chronischer lymphatischer Leukämie, und 6 Fälle von Lymphadenitis) wurden licht- und elektronenmikroskopisch studiert. Die Gewebsstückchen der Lymphknoten wurden in 5 Fällen in OsO4 fixiert, in den anderen 35 Fällen hingegen wurden sie erst in Aldehyd und dann in OsO4 fixiert. Eigenartige dunkle Zellen fand man in allen aldehydfixierten Tumoren und Lymph-adenitiden. Man konnte sie lichtmikroskopisch in Semi-Dünnschnitten sehen und sie erschienen spindelförmig oder auch in unregelmäßigen Sternformen. Elektronenmikroskopisch zeigten sie oft dünne und verschiedentlich verzweigte Plasmafortsätze. Manchmal schienen die dunklen Zellen in Beziehung zu den kollagenen Fasern zu stehen. Einige zeigten phagozytische Aktivität. Degenerative Veränderungen von Kern und/oder Cytoplasma konnten in verschiedenen dunklen Zellen beobachtet werden. Es wird angenommen, daß die dunklen Zellen eine funktioneile, besondere Phase von retikulären Zellen darstellen und dabei eine besondere Neigung zu degenerativen Veränderungen zeigen.SummaryForty human lymph nodes (16 cases of Hodgkin’s disease, 9 cases of lymphosarcoma, 5 cases of reticulum cell sarcoma, 4 cases of chronic lymphoid leukemia, and 6 cases of lymphadenitis) were studied by light and electron microscopy. In 5 cases the specimens were fixed in OsO4, in the other 35 cases the tissues were fixed in aldehydes and then in 0OsO4. Peculiar dark cells were found in all aldehyde-fixed neoplastic and non-neoplastic lymph nodes, and could be seen in light microscopy on semi-thin sections and appeared fusiform or irregularly star-shaped. In electron microscopy the dark cells often showed thin and variously branched cytoplasmic processes. They appeared sometimes to be related to collagen fibres, and some of them showed phagocytic activity. Nuclear and/or cytoplasmic degenerative changes could be observed in several dark cells.The findings are discussed; the hypothesis is suggested, that the dark cells are a particular functional state of reticular cells with frequent degenerative changes.

The Role of Asbestos Fiber Dimensions in the Prevention of Mesothelioma

Abstract A recent interpretation of the pathogenetic role of asbestos fiber size in the development of mesothelioma and in the possibility of mesothelioma prevention needs clarification. This point of view is based on a biased interpretation of the literature. Epidemiologic, experimental, and molecular evidence suggests that the arguments for the role of fiber size relative to dose, dose-response effect, and genetic susceptibility are scientifically unsound. Their proponent also states that means available in the past for the implementation of dust-control measures and/or personal protective equipment would not have contributed to reducing the frequency of mesothelioma among exposed subjects, an argument again based on invalid assumptions.