Mesothelioma is a disease that begins with accumulation of water in the chest cavity before the lung. The accumulation of water in the lungs is the sum of the edema of the lungs.
Malignant tumors of the lung membrane (pleura).
The so-called asbestos and erionite are usually found in people who have been exposed for many years.
Many patients do not have any asbestos or erionite exposure.
Familial predisposition has been reported.
Significant reduction in the disease has been observed since asbestos has been prohibited from being used in the industry.
Frequent cases of severe chest pain, weight loss, and cough occur in patients.
Water usually collects in the chest cavity, and the effect of this water can cause breathlessness.
In the picture below, we see a 52 year-old male patient with computed tomography and thoracoscopy images of mesothelioma on the right side.
Mesothelioma is the type of cancer that occurs in tissues that cover the surface of some internal organs. It is also called “lung cancer” because it usually appears in the lung. However, it rarely starts and spreads in the midge, the heart and other organs.
What are Mesothelioma Symptoms?
The indication for lung cancer is usually a few years after exposure to triggering factors. Some of the symptoms are:
Pain under the rib cage
Night sweats, high fever
Unexplained weight loss
The indications of mesothelioma seen in the mesothelioma are:
Pain, swelling or tuber formation in the abdominal region
Loss of appetite, unexplained weight loss
Diarrhea or constipation.
Pleural mesothelioma was first described in 1960 as a rare cancer type. Epidemiological studies indicate that the incidence has increased over the last 20 years (1). Diagnosis of the disease is usually delayed and despite all treatment modalities, the chance of complete treatment is very low.
The association between asbestos and malignant mesothelioma was first reported by Wagner and colleagues in 1960 (2). This relationship was later shown by many researchers. Malignant mesothelioma is reported at a very low rate in places where asbestos fibers are not found. Asbestos is responsible for one out of every 100 deaths in areas with asbestos, while in regions that do not contain asbestos, it falls to 1 in 10,000 deaths (3). In a UK study, it has been reported that exposure to asbestos in the occupational setting accounts for 90% of all mesothelioma cases (4). One of every 10 workers exposed to asbestos in the environment they are working for has been reported to have caught mesothelioma and lost their lives (5). Asbestos is a kind of silicate fiber and can be examined in 2 major subgroups: Amphibole and serpentine fibers. While chrysotile asbestos is examined in the serpentine group, amphibole fibers are divided into different subgroups as crocidolite, amosite, tremolite, anthrofilite and actinolite groups. Serpentine fibers are large fibers that can not go beyond the major airways, while fine amphibole fibers travel through the lung lymphatics and reach interstitial spaces and subpleural spaces and remain attached there. Asbestos fibers can even be transported from these subpleural areas to the perithecia with lymphatics. Most amphibole fibers, among them cricodolite asbestos is the most common cause of mesothelioma. Amphibole fibers demonstrate the formation of mesothelioma when applied to experimental animals, indicating that this material alone may cause mesothelioma. Nevertheless, it has been found that asbestos-free erionite fibers are the most important cause of mesothelioma in Turkey. Erionite fibers are found in a type (zeolite) volcanic rock and are widely found especially in central Anatolia. Peace and colleagues reported that between 1970 and 1981, 62 people lost their lives due to mesothelioma on the 604-population Karain village of Konya, where the erionite fibers are very dense (6). The fact that people in the 20s and 30s who live in this village are the most frequently detected group of mesothelioma is also shown as evidence that this cause causes the disease with an exposure of at least 20 years. Simian Virus 40 (SV 40) has also been shown to be another cause of mesothelioma. Findings that exposure to radioactive bacteria cause mesothelioma have also been published (7). Smoking alone is not the cause of the disease, but smoking and exposure to asbestos or erionite are synergistic.
Malignant mesothelioma is seen in 2 distinct age groups: Especially in the Central Anatolia region, the disease occurs clinically in the regions between 20 and 30 years of age in areas exposed to erionite fibers since birth, but at least 20 years of exposure to occupationally exposed asbestos fibers, 60 Mesothelioma is found at these ages when it is full of age.
Formation Mechanism and Carcinogenesis:
Studies on the mechanism of mesothelioma formation have been made mostly in relation to asbestos. Findings have been published that this mechanism is similar to mesotheliomas which are related to other factors, but this issue has not yet reached full enlightenment.
Asbestos causes a chronic inflammatory and fibrotic reaction mediated by cytokines and active macrophages (8). It is observed that protooncogenes such as C-cis (the beta-chain of platelet-derived growth factor) are extensively ex- pressed in alveolar macrophages in the fibrotic lung. This leads to excessive proliferation of mesothelial cells. In addition, asbestos has been shown to directly alter its cell DNA (8). It has been found that asbestos fibers enable the formation of oncogenes such as c-fos and c-jun in cells in tissue culture (9). Increased cytokine secretion in the inflammatory tissue, especially Interleukin 6, has been found to contribute to the growth and progression of the tumor (10). In addition, Dhaene and colleagues reported that telomerase activity may be increased in the mesothelium as well as in many other tumor types, which may also play a role in carcinogenesis (11). In summary, these findings indicate that oxidative stress (overexpression of free oxygen radicals) caused by asbestos fibers plays a major role in cytotoxicity, DNA damage, mutation, gene expression, or carcinogenesis.
Benign inflammatory or reactive formations that cause mesothelial cell hyperplasia or other malignant tumors may mimic mesothelioma in a pathological examination (12). The diagnosis of malignant mesothelioma is difficult even for experienced pathologists. Despite the presence of an active tumor, repeated cytological examinations and biopsies may not detect a tumor. When a tumor is detected, adenocarcinoma and mesothelioma are usually indistinguishable, although it is proven that the tumor is a light microscope. In most cases, further histochemical, immunohistochemical, and sometimes electron microscopy studies may be required to ensure complete resolution. The histological classification of malignant mesotheliomas is shown in Table 1.
Table 1. Histopathological subclasses of malignant mesothelioma
Large cell (giant cell)
Sarcomatoid (fibrous, sarcomatous, mesenchymal)
Mixed epithelial-sarcomatoid (biphasic)
Localized fibrous mesothelioma
A large serrate has been reported to have approximately half of the diagnosed mesotheliomas in the epithelial type, 34% in the mixed type and 16% in the sarcomatoid type (13). The most important diagnostic problem faced by pathologists is to distinguish epithelial mesothelioma from metastatic adenocarcinoma, in addition to the diagnosis of malignancy. Apart from the standard methods for this, some additional histopathological studies are needed:
1) Histochemical methods: Neutral mucopolysaccharides are strongly positive in periodic acid-Schiff (PAS) diastasis. This feature can often be detected in adenocarcinomas. Adenocarcinomas are strongly positive with Mayer’s musikarmin method and leave the epithelium mesothelioma. Alcian blue pigmentation is found positively in both mesotheliomas and adenocarcinomas.
2) Immunohistochemical methods: Immunoperoxidase staining against the Leu M1 antigen gives a negative result in the mesothelium, but most of the adenocarcinomas have a positive result. Carcinoembryonic antigen (CEA) counter staining has a moderately strong effect on adenocarcinomas, as well as in the mesothelium, but also in the renal, prostate, some over, endometrial cancers. While low molecular weight keratins can be detected on the surface of mesothelioma cells, this type of staining is negative in sarcomas. When muscarinic dyeing results in adenocarcinomas, mesothelioma cells are not stained.
3) Electron microscopy: Despite all standard and histochemical staining, mesothelioma diagnosis may not be very rare. Thus, in some centers where this pathology is intensively diagnosed, electron microscopy is recommended as a standard method, while taking a biopsy specimen, it is recommended that a separate vessel be taken in ‘glutaraldehyde’ and ready for electron microscopic examination if necessary.
In the epithelial mesothelium, polygonal, long, surface microvilli, desmozomes, dense tonofilaments and intracellular lumen formations of cells can be observed. In primary lung, breast, or gastrointestinal adenocarcinoma cells, short and rare microvilli, several tonofilaments, microvilli roots, and lamellar bodies are observed. The long nuchal and large coarse endoplasmic reticulum are sarcomatoid type.
It usually occurs after exposure to asbestos for at least 20 years, aged between 50 and 70 years. For this reason, it can be detected in the ages of 20-30 in people who are in asbestos-containing environments since birth or in the soil where erionite is present as in Turkey. The male to female ratio is 5/1. Patients usually refer first to dyspnea and chest pain complaints. Patients rarely have complaints despite a very advanced stage, and usually have a pleural effusion that is unilaterally determined by chance, which can move freely. Nadie may be admitted to the pneumothorax from the first complaints of the patient. The disease is right-sided with a rate of 60% and bilateral in 5%. The pulmonary function test indicates a restrictive restriction of the disease to the circumference of the lung. In laboratory studies, there is no significant change except erythrocyte sedimentation rate and thrombocytosis. In rare cases, cough, hemoptysis, dysphagia, hoarseness, fever and Horner’s syndrome occur. It is noteworthy that physiological examination of respiratory sounds decreased and widespread maturation was taken on the patient side in periscus. On further occasions, the patient may be seen to have a contralateral thorax. A tumor of pleural origin may grow outward from the intercostal space and form masses that can be palpable in some cases. In some cases, supraclavicular or axillary metastatic lymph nodes may be palpable. Mesothelioma can also be detected in the peritoneum, and ascites can be seen in such cases.
Hypercoagulopathy without autoimmune hemolytic anemia, hypercalcemia, hypoglycemia, thrombocytosis, inappropriate antidiuretic hormone (ADH) secretion syndrome are paraneoplastic syndromes detected in patients with mesothelioma but reported to be seen in a small number of cases (14). Non-specific ECG changes are monitored in the majority of patients. Wadler and colleagues recorded a sera, 42% of sinus tachycardia, 17% of cases of ventricular or atrial arrhythmia (15). In cases where the tumor is pericardial or myocardial, abnormal findings on echocardiography may be present.
Hyaluronic acid may be useful in diagnosis and follow-up, but it has no specific features (16). C-reactive protein, alpha-1-acid glycoprotein and fibrinogen are higher in patients with mesothelioma compared to patients with adenocarcinoma, but no specific threshold value was found. Serum Interleukin 6 (IL-6) levels correlate with the level of acute phase proteins and the platelet count. IL-6 in the pleural fluids of mesothelioma patients is found to be 60 to 1400 times the serum level. Although high levels of pleural IL-6 may be detected in tuberculous pleurisy, high levels may be considered as an important adjunct to differential diagnosis of adenocarcinoma (17).
The disease occurs in the early stages, with parietal pleural localized masses and pleural effusion. Even in this stage, chest pain and dyspnea can be. However, as the disease progresses, mesothelioma, which is the tumor of the pleural tissue as the major, is diagnosed in a way that diffusely surrounds the entire lung and envelops the lungs, trapping it. As the disease progresses, the visceral pleura can also be held, so that the pleural effusion surrounding the locus or the entire lung can be observed. In this period, patients describe dyspnea due to restriction.
Precipitation may be detected on PA chest X-ray in 20% of patients with complete unilateral opacity, pleural plaques or interstitial fibrosis in advanced stage. In advanced cases, contracture of the ipsilateral hemithorax and scoliosis PA grafite may be seen. If treatment is planned, chest tomography or thoracic MR is very helpful in showing the disease’s condition. As a characteristic CT image, pleural thickening (86% in patients with intralober fissures), pleural effusion in 74% of patients and pleural calcification in 20-50% patients are seen in 92% of patients (18,19). Mediastinal adenopathy can be seen on CT, direct invasion of the tumor to the mediastinum, pericardial effusion to the pericardium, invasion to the chest wall or diaphragm. However, MR imaging has been reported to be more sensitive in showing chest wall and diaphragm invasion (20). Coronal planar MR shows better spread of interlobar fissure and invasion to bone tissue, whereas pleural calcifications can be better seen in CT than MR. However, the standard examination method in the mesothelioma is accepted as thorax CT.
Positron emission tomography (PET) with 2-fluoro-2-deoxy-d-glucose (FDG) is very helpful in differentiating malignant lesions from benign lesions. The standard ‘uptake’ value was found to be inversely proportional to survival (21).
It has been found that pleural thick- ness associated with pleural thick- ness of 6 mm is associated with Gallium-67 ‘uptake’ scan (22). Single photon emission CT (SPECT) is a useful method for determining tumor localization (23).
Routine investigation of brain, bone, or liver metastases or other serosal surfaces is not recommended, although 50% of autopsy studies have been reported, but there is no symptom or laboratory finding on patients’ initial applications. However, examination of CEA levels in pleural fluid or serum may be helpful in differential diagnosis of adenocarcinoma.
Pancreas made from pleural effusion found in the majority of patients when a physician admitted is the first diagnostic method. Cytologic examination of the pleural fluid involves 20% to 50% of patients. Percutaneous biopsy of the pleura can be used to diagnose a third of the patients. More than half of the patients with negative cytologic findings are diagnosed with cytogenetic examination of the pleural fluid. Needle biopsy can not provide adequate material for further histochemical examinations, especially for separating adenocarcinoma, even if it introduces malignancy diagnosis. For this reason, with diagnostic surgical procedures, it is often necessary to obtain larger tissue fragments. Bronchoscopy, mesothelioma, is suspected in every patient to assess the possibility of an endobronchial lesion.
In particular, if surgery is not planned for treatment, adequate tissue sampling should first be performed with videothoracoscopic intervention. Since the tumor usually obliterates diseased hemithorax, the standard approach with VATS may not be sufficient. In such cases, a small incision can reach the thorax with a biopsy taken there. Generally, it is observed that the pleural mass or the lung is trapped with a thick parietal pleura in each side in the chorus, with irregular edgewise, mostly nodular, in advanced cases. However, incisions made for both thoracotomy incisions and VATS ports may result in a mass attached to the tumor after the procedure. For this reason, in some centers these regions are irradiated prophylactically. If stage I mesothelioma is predicted with preoperative studies and surgical treatment is considered, the procedure for treatment immediately after the diagnostic intervention can be planned in the same seansta. Such a plena should be sent as large as possible to the ‘frozen section’ to allow differential diagnosis from the adenocarcinoma. At the same time, precise pathologic diagnosis should be provided as far as possible before an unforeseen, radical surgical procedure involving the risk that the patient with a metastatic adenocarcinoma can be oppressed unnecessarily in this disease, where the ectoplasmic thoracotomy can be difficult to definitively diagnose. Considering the difficulties of definitive diagnosis, a separate biopsy specimen for glutaraldehyde to be examined for electron microscopy should also be provided.
Bone scintigraphy, abdominal and brain CTs, and, if necessary, ultrasound can be used to illuminate the direct or metastatic spread of the disease.