Cases Of Diffuse Malignant Mesothelioma Research Articles

Diffuse Malignant Mesothelioma

Diffuse malignant mesothelioma (DMM) is an uncommon cancer with great clinical significance because it currently remains an incurable disease, and most patients die within months after diagnosis. Although DMM incidence is leveling off or decreasing in developed countries because of the strict control of asbestos use, it is increasing in countries without adequate asbestos control. In some settings, benign, reactive mesothelial hyperplasias and organizing pleuritis can be difficult to differentiate from DMM and vice versa, and the variety of DMM's histopathologic features generates an extensive list of differential diagnoses with other malignancies, particularly, metastatic malignancies, which are more frequent in the pleura than are primary malignancies. These two issues are the topic of discussion in this review, along with a brief presentation of a case of DMM that presented in a 66-year-old man with recurrent, right pleural effusions, and in whom, diagnosis of DMM had not been suspected clinically, radiographically, surgically, grossly, or initially, on frozen section. It was not until focal invasion into the skeletal muscle was discovered on permanent sections that a diagnosis of DMM could be established.

Elucidation of Asbestos-induced Mesothelial Carcinogenesis toward Its Prevention

Human exposure to asbestos fibers has been associated with diffuse malignant mesothelioma (DMM) in the pleural and abdominal cavity. Despite advancements in the molecular analyses of human cases of DMM and animal models, the understanding of the carcinogenic mechanisms remains still limited. There are basically three hypotheses regarding the pathogenesis of asbestos-induced DMM, which may be integrated as follows; (1) the “oxidative stress theory” is based on the fact that phagocytic cells that engulf asbestos fibers produce large amounts of reactive oxygen species (ROS) due to their inability to digest the fibers, and that iron contained in crocidolite and amosite fibers works as a catalyst for the generation of ROS, (2) the “chromosome tangling theory” postulates that asbestos fibers impair the equivalent distribution of chromosomes during mitosis, and (3) the “theory of adsorbing many specific proteins as well as carcinogenic molecules” states that asbestos fibers in vivo concentrate specific proteins or chemicals including the components of cigarette smoke and radioactive chemical element. Recent studies suggest that local iron overload is a key event. Elucidation of the major mechanisms underlying DMM would be helpful for the development of strategies to prevent DMM generation in people who have been exposed to asbestos.

Absence of Evidence for a Significant Background Incidence of Diffuse Malignant Mesothelioma apart from Asbestos Exposure

The incidence of diffuse malignant mesothelioma is rising. Physicians can diagnose a disease only when they know that it exists, so one explanation for the rise in incidence is more widespread appreciation of the clinical and pathological features of the disease. Modern pathology has ascribed specific requirements for the diagnosis of diffuse malignant mesothelioma. A priori one cannot assume that these requirements have increased the likelihood of the diagnosis because the requirements also can serve to exclude the diagnosis depending on the findings. Most cases of diffuse malignant mesothelioma are suspected by macroscopic and routine microscopic techniques that have been available since the last part of the nineteenth century. Although single reported instances of some pulmonary diseases have survived from the nineteenth century, pathologists did not identify enough cases to convincingly establish the existence of diffuse malignant mesothelioma of the pleura as an entity until the 1930s or 1940s. One must conclude that the background level of diffuse malignant mesothelioma in Europe and in the United States prior to 1930 was extremely low. No case was detected at the Massachusetts General Hospital until 1946.

A case-series of diffuse malignant mesothelioma of the pleura and peritoneum

Nine cases of diffuse malignant mesothelioma of the pleura and peritoneum presented within an eight month period to our institution. The clinical, diagnostic and patholocical features of these cases were reviewed. In addition, a complete social and occupational history was obtained from the patients or their next-of-kin. A number of interesting points emerge from this case series including the low yield of diagnosis using cytolopical examination of serous fluids and blina pleural biopsy, and the diagnostic utility of a standard panel of monoclonal and polyclonal antibodies on tissue. There was a lack of a significant exposure history for asbestos in the majority of cases. The epidemiology of non-asbestos related mesotheliomas will be discussed.

Mesothelioma in man and experimental animals.

Asbestos has been established as the cause of most cases of diffuse malignant mesothelioma occurring in the industrialized world. The morphology of mesothelioma may be complex, and the employment of chemical, histochemical and ultrastructural studies are often helpful in identification. Diagnostic difficulties may to some degree blur the extent of its prevalence and reliance on exposure history may not reveal its association with asbestos. Reference panels can be useful in assessing the former and analysis of lung tissue asbestos content may help to clarify the latter, especially in the low dose range. Electron microscopy may prove to be of assistance in this respect, possibly with particular attention to the peripheral areas of the lung. Animal experimentation has supported epidemiologic conclusions and revealed the phenomenon of fiber carcinogenesis. The morphology of mesothelioma in experimental animals is very similar to that in humans, including ultrastructural and biochemical features.

Diffuse Malignant Mesothelioma

Thirteen cases of diffuse malignant mesothelioma, 12 pleural and one peritoneal, were examined and reviewed from the clinical and morphologic points of view. The most frequent symptom and sign were pain and effusion. Periods of survival varied, with one patient surviving 11 years despite morphologic features of the pleural tumor. The diagnosis can be made only on the basis of excised tumor tissue. The best control of the tumor is attained by repeated surgical removal. Neither radiation nor chemotherapy altered significantly the growth of the tumors.

Epidemiological and quantitative relationships between mesothelioma and asbestos on Tyneside.

Thirty-five necropsied cases of diffuse malignant mesothelioma of pleura and six cases of mesothelioma of peritoneum are reported. Occupational histories from 40 cases showed that 32 cases (80%) were definitely exposed to asbestos; six cases (15%) were probably exposed and two (5%) had no known exposure. The mean latent interval was 34 years. Occupational histories of 56 control patients matched in pairs for age and sex with 28 of the mesothelioma cases revealed definite exposure to asbestos in 12 controls (21%), probable exposure in 11 (20%), and no evidence of exposure in 33 (59%). The difference in incidence of exposure between mesotheliomas and controls is statistically highly significant. Six-micron histological sections of lung, available in 39 mesothelioma cases, contained coated asbestos fibres in 36 cases (92%). Sixteen cases of mesothelioma showing fibres were free of asbestosis; asbestosis was slight in 14 cases, moderately severe in five cases, and severe in one case. The incidence of asbestos bodies in sections from mesothelioma cases was significantly higher than in a previously reported series of routine necropsies examined by lung smear. Counts of coated and uncoated asbestos fibres were performed on samples of lung tissue from 33 mesothelioma cases. No fibres were identified in one case and only occasional coated fibres in a second case. The remainder gave counts ranging from 154 thousand to 684 million fibres per gram dry weight. Uncoated fibres were invariably present and usually comprised 50 to 80% of the count. No relationship was found between total fibre count and the latent period of the mesothelioma. Fibre counts were also performed on lung samples from 18 smear-positive and 30 smear-negative routine necropsies. Cases with numerous coated fibres in the smear gave total fibre counts similar to those of mesothelioma cases without asbestosis. Routine cases with only one fibre in the smear usually yielded only occasional fibres on analysis. Coated and uncoated fibres were found in 13 out of 30 smear-negative cases, indicating a true incidence of 56% of exposure to asbestos in the whole necropsy series. When compared with the mesothelioma series the difference in incidence of fibres remains statistically significant. The data suggest that, on Tyneside, exposure to asbestos sufficient to cause an appreciable risk of developing mesothelioma has usually occurred through occupational exposure rather than by general environmental pollution by asbestos.