Pathogenesis and risk factors of Mesothelioma Cancer

Mutation of the BAP-1 tumor suppressor genesis a predictive factor that individuals may be at risk of becoming ill. Mutations can be congenital or acquired, with up to 70% of mesothelioma patients present. The products of this gene regulate the membrane protein channel responsible for the entry of calcium into the cell. People with a positive BAP-1 mutation are more resistant to treatment and more aggressively treated. It is hoped that a way to stabilize and fixate this calcium channel will be developed and thus compensate for the loss of regulation by the BAP-1 gene product. Mutation of the BAP-1 gene can be found in healthy individuals, and it is of the utmost importance as such individuals must be closely monitored as they have a high chance of developing mesothelioma. Screening a population exposed to asbestos dust for a BAP-1 gene mutation provides valuable insight into who is potentially more likely to get this malignancy within this at-risk population. Sometimes healthy individuals with a BAP-1 defect develop a benign melanocytic intradermal tumor that may resemble the young and thus visually indicate the mutation present.

Family history of mesothelioma and chest radiotherapy are also risk factors. Family members of asbestos-exposed persons and residents in the vicinity of the mine are also at risk. 

Clinical presentation and manifestation

The symptomatology of mesothelioma is very nonspecific. The early stages give no symptoms and are rarely detected, mostly by accident. The late stages give non-specific symptomatology and are mainly due to the pressure of the surrounding organs and healthy tissues by the growth and spread of the tumor mass. It is very easy for manifestations to mislead doctors by giving a picture of common and harmless diseases such as colds or flu. With the development of the disease, the symptoms worsen and impede the quality of life. The first symptoms are pleural effusion, chest pain, and dyspnea where the discharge is once the only manifestation I of high importance is the evaluation of patients with recurrent effusions. The most common manifestations of mesothelioma are:

·         Pleural effusions (are recurrent and impair quality of life and may lead to impaired pulmonary function even lung collapse)

·         Difficulty breathing (initially with exertion later as the tumor progresses with growth and during rest)

·         Chest pain (increased by inhalation)

·         Dry and persistent cough, sometimes coughing up blood

·         A lump under the skin on the chest

·         Back and rib pain

·         General symptoms: weakness, malaise, fever, night sweats

In differential diagnosis, the following can be considered:

·         Asbestosis – occurs bilaterally while mesothelioma occurs unilaterally

·         Pneumonia – the onset of symptoms of mesothelioma

·         Lung cancer

·         Congestive heart failure – recurrent pleural effusions

·          Lung embolism

·         Fibrous plaques and plaques in the lungs

·         Fibrosarkom i fibrohistioicitom

Classification I Histology

Mesotheliomas are divided into cell types, of which they are composed of three major types: epithelial, sarcomatoid, and biphasic, which is composed of a mixture of the first two types. When diagnosing and planning therapy, it is mandatory to determine which histological type the patient’s tumor is made of. Each type has a different prognosis and treatment plan. The most common and with the best prognosis and therapeutic response is the epithelial mesothelioma, while the most aggressive with the worst prognosis and the shortest survival is sarcomatoid mesothelioma.

Epithelial mesothelioma accounts for about half of the total number of these malignancies. Better prognosis and easier to treat with longer survival. It is composed of anamorphic epithelial malignant cells that are close to each other and thus contract more slowly to the surrounding structures and thus to metastasize more slowly. Histologically it resembles lung adenocarcinoma, so it is very important to do immunohistochemistry and thus exclude adenocarcinoma. Subtypes of epithelial mesothelioma are: Tubulopapillary (most common subtype), Adenomatoid, Solid, Glandular, Well-differentiated papillary (this subtype is more common in women)

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