Search

Despite efforts to ban asbestos mining and manufacturing, mesothelioma deaths in the United States have remained stable at approximately 2500 cases annually. This trend is not unique to the United States but is also a global phenomenon, associated with increased aging of populations worldwide. Although geoeconomic factors such as lack of regulations and continued asbestos manufacturing in resource-poor countries play a role, it is essential to consider biological factors such as immune senescence and increased genetic instability associated with aging. Recognizing that mesothelioma shares genetic instability and immune system effects with other age-related cancers is crucial because the impact of aging on mesothelioma is frequently assessed in the context of disease latency after asbestos exposure. Nevertheless, the long latency period, often cited as a reason for mesothelioma's elderly predominance, should not overshadow the shared mechanisms. This communication focuses on the role of immune surveillance in mesothelioma, particularly exploring the impact of immune escape resulting from altered TSG function during aging, contributing to the phylogenetic development of gene mutations and mesothelioma oncogenesis. The interplay between the immune system, TSGs, and aging not only shapes the immune landscape in mesothelioma but also contributes to the development of heterogeneous tumor microenvironments, significantly influencing responses to immunotherapy approaches and survival rates. By understanding the complex interplay between aging, TSG decline, and immune senescence, health care professionals can pave the way for more effective and personalized immunotherapies, ultimately offering hope for better outcomes in the fight against mesothelioma., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

We reviewed 354 cases of malignant diffuse mesothelioma (MM) in women from a database of 2858 histologically confirmed MM cases. There was a pleural predominance with 78% pleural MM and 22% peritoneal MM. The pleural tumors consisted of 72% epithelioid, 19% biphasic, and 9% sarcomatoid variant. The peritoneal tumors consisted of 82% epithelioid, 13% biphasic, and 5% sarcomatoid. The immunohistochemical profile was typical of what is well-accepted and previously described for MM. When examining tumor subtype and location, there was a trend toward epithelioid subtype and peritoneal location; however, this did not reach statistical significance. Age at the time of diagnosis ranged from 19 to 93 years with a mean of 60 years. The median age at time of diagnosis for pleural MM was 65 years and for peritoneal MM was 52 years. A further look at age and histologic subtype showed no statistically significant difference in age between MM subtypes. Survival was greatest for epithelioid variant, and this was magnified in the peritoneum. A majority of our cases were exposed to asbestos through a household contact. Asbestosis and parietal pleural plaque were present in 5% and 50% of cases with data, respectively. Fiber analysis data was available in 67 cases; 38 cases had elevated asbestos fiber burden, and tremolite was the most common asbestos fiber type detected. Commercial and noncommercial amphibole asbestos fibers were elevated in nearly equal numbers of cases.

Two cases of pulmonary alveolar proteinosis, including one death, occurred in workers at a facility producing indium-tin oxide (ITO), a compound used in recent years to make flat panel displays. Both workers were exposed to airborne ITO dust and had indium in lung tissue specimens. One worker was tested for autoantibodies to granulocytemacrophage-colonystimulating factor (GM-CSF) and found to have an elevated level. These cases suggest that inhalational exposure to ITO causes pulmonary alveolar proteinosis, which may occur via an autoimmune mechanism.

Asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive amounts of asbestos fibers. Pathologically, both pulmonary fibrosis of a particular pattern and evidence of excess asbestos in the lungs must be present. Clinically, the disease usually progresses slowly, with a typical latent period of more than 20 years from first exposure to onset of symptoms., Differential Diagnosis: IDIOPATHIC PULMONARY FIBROSIS: The pulmonary fibrosis of asbestosis is interstitial and has a basal subpleural distribution, similar to that seen in idiopathic pulmonary fibrosis, which is the principal differential diagnosis. However, there are differences between the 2 diseases apart from the presence or absence of asbestos. First, the interstitial fibrosis of asbestosis is accompanied by very little inflammation, which, although not marked, is better developed in idiopathic pulmonary fibrosis. Second, in keeping with the slow tempo of the disease, the fibroblastic foci that characterize idiopathic pulmonary fibrosis are infrequent in asbestosis. Third, asbestosis is almost always accompanied by mild fibrosis of the visceral pleura, a feature that is rare in idiopathic pulmonary fibrosis., Differential Diagnosis: RESPIRATORY BRONCHIOLITIS: Asbestosis is believed to start in the region of the respiratory bronchiole and gradually extends outward to involve more and more of the lung acinus, until the separate foci of fibrosis link, resulting in the characteristically diffuse pattern of the disease. These early stages of the disease are diagnostically problematic because similar centriacinar fibrosis is often seen in cigarette smokers and is characteristic of mixed-dust pneumoconiosis. Fibrosis limited to the walls of the bronchioles does not represent asbestosis., Role of Asbestos Bodies: Histologic evidence of asbestos inhalation is provided by the identification of asbestos bodies either lying freely in the air spaces or embedded in the interstitial fibrosis. Asbestos bodies are distinguished from other ferruginous bodies by their thin, transparent core. Two or more asbestos bodies per square centimeter of a 5- mu m-thick lung section, in combination with interstitial fibrosis of the appropriate pattern, are indicative of asbestosis. Fewer asbestos bodies do not necessarily exclude a diagnosis of asbestosis, but evidence of excess asbestos would then require quantitative studies performed on lung digests., Role of Fiber Analysis: Quantification of asbestos load may be performed on lung digests or bronchoalveolar lavage material, employing either light microscopy, scanning electron microscopy, or transmission electron microscopy. Whichever technique is employed, the results are only dependable if the laboratory is well practiced in the method chosen, frequently performs such analyses, and the results are compared with those obtained by the same laboratory applying the same technique to a control population.

Asbestos exposure is indisputably associated with development of mesothelioma. However, relatively few studies have evaluated the type of occupational exposure in correlation with asbestos fiber content and type. This study reports findings in 1445 cases of mesothelioma with known exposure history; 268 of these also had fiber burden analysis. The 1445 cases of mesothelioma were subclassified into 23 predominant occupational or exposure categories. Asbestos body counts per gram of wet lung tissue were determined by light microscopy. Asbestos fiber content and type were determined by scanning electron microscopy and energy dispersive x-ray analysis. Results were compared with a control group of 19 lung tissue samples. Ninety-four percent of the cases occurred among 19 exposure categories. Median asbestos body counts and levels of commercial and noncommercial amphibole fibers showed elevated levels for each of these 19 categories. Chrysotile fibers were detectable in 36 of 268 cases. All but 2 of these also had above-background levels of commercial amphiboles. When compared to commercial amphiboles, the median values for noncommercial amphibole fibers were higher in 4 of the 19 exposure groups. Most mesotheliomas in the United States fall into a limited number of exposure categories. Although a predominant occupation was ascertained for each of these cases, there was a substantial overlap in exposure types. All but 1 of the occupational categories analyzed had above-background levels of commercial amphiboles. Commercial amphiboles are responsible for most of the mesothelioma cases observed in the United States.

The experience of the US/Canadian Mesothelioma Panel with its first 200 cases is reviewed. The light microscopic diagnosis, histochemical findings, immunohistochemical findings, and electron microscopic features of malignant mesotheliomas are reviewed in the context of differential diagnosis. Reasons for referral of case material to the panel and lessons from follow-up of difficult and controversial cases are reported. Recommendations to general pathologists are made regarding evaluation and review of possible mesotheliomas.