Malignant pleural mesothelioma
定义
Malignant pleural mesothelioma (MPM) is a malignant tumor that originates from the pleura, the membrane formed by two sheets (called visceral pleura and parietal pleura), in continuity between them. The two pleuras line the lungs (visceral pleura), the mediastinum (the portion of the thorax located between the two lungs that contains various structures including the heart, trachea, esophagus and large vessels) and the rib cage (parietal pleura).
MPM is a very rare neoplasm: in 2019, an incidence of 0.7 cases per 100,000 people/year was estimated in the US, more relevant in the male sex than in the female one.
Histologically, MPM can be classified into 3 distinct forms, characterized by different prognoses:
- epithelioid MPM: the most frequent form, accounting for between 70% and 85% of cases. The median survival of epithelioid MPM is approximately 14 months.
- sarcomatoid MPM: accounts for about 10% of cases. It is the form with the worst prognosis, with a median survival of only 3 months at diagnosis.
- biphasic MPM: diagnosed in about 10-25% of cases. Diagnosis is made when a combination of the above two variants, representing at least 10% of the total cellularity, is present in the biopsy specimen. The median survival of patients with biphasic MPM is about 12 months.
There are also rarer forms of the disease, some with pre-invasive features such as mesothelial hyperplasia and mesothelioma in situ, or minimally invasive forms such as localized mesothelioma and well-differentiated papillary mesothelioma. The diagnosis of these forms often requires the presence of an experienced anatomical pathologist and discussion in the context of the multidisciplinary chest oncology team to define the most appropriate course of treatment.
原因和风险因素
The main cause of the onset of MPM is exposure to asbestos fibers. The term asbestos refers to a large group of silicate minerals that have been used industrially since after World War II for their heat-insulating properties (asbestos). Several studies have shown a marked increase in the incidence of MPM among workers exposed to this substance, the use of which has been banned and a remediation process initiated since the 1990s. Once inhaled, asbestos particles are trapped in the lungs and then translocated to the pleura.
Asbestos fibers are capable of inducing both direct and indirect damaging effects (carcinogenesis) to pleural cells, which, however, occur several decades after exposure. In addition to those directly exposed to asbestos, an increased incidence has also been found in their cohabiting family members. MPM may more rarely be caused by exposure to ionizing radiation or thorium dioxide (formerly used as a radiographic contrast agent), or by a genetic predisposition (BAP1 gene mutation).
症状描述
Symptomatology in MPM patients is often insidious and nonspecific: clinically, the most frequent expression (about 90%) and especially the one that most affects the patient's quality of life is the occurrence of recurrent pleural effusion. This condition results in the appearance of aggravating dyspnea (i.e., “shortness of breath with air hunger”).
Other signs of the disease that may appear are:
- lack of strength (asthenia);
- major weight loss;
- chest pain (thoracodynia) accompanied by a “sense of weight” in the chest.
Less frequent symptoms may be:
- wheezing cough;
- hemoftoe (emission of blood with coughing);
- dysphagia;
- dystonia;
- fever.
如何诊断？
The diagnosis of malignant pleural mesothelioma is made by:
- chest X-ray: confirms the presence of a pleural effusion;
- pleural ultrasound and echo-guided thoracentesis: performed for the purpose of evacuating pleural fluid with the dual purpose of resolving the dyspnoic picture and collecting a sample of fluid for cytological (i.e., microscopic) analysis in order to obtain a diagnosis of the nature;
- CT (computed tomography) scan: documents the presence of solid pleural thickening/injuries and the possible presence of lung lesions;
- PET (positron emission tomography) scan: metabolically characterizes the disease and identifies any distant involvement (metastasis);
- videothoracoscopic pleural biopsy: this is the most important diagnostic procedure to obtain a definitive diagnosis of the disease, define the degree of intrathoracic spread of the disease, and possibly perform pleurodesis, a procedure in which an irritant substance (Asbestos-free talc) is instilled into the chest that can create adhesions between the two pleurae and prevent recurrence of effusion.
建议进行的检查
如何治疗？
The therapeutic approach to MPM is multimodal and involves different combinations of:
- surgery: in selected cases of limited disease, surgery can be performed to reduce the disease burden and improve the results of subsequent chemo-radiotherapy treatment. Pleurectomy and decortication (PD) involves the radical removal of the parietal and visceral pleura, along with the pericardium and diaphragm. In addition, pleuro-pneumonectomy involves the removal of the ipsilateral lung;
- chemotherapy: based on cisplatin and pemetrexed. The combination of bevacizumab increased disease-free survival in a trial. In addition, in some studies, the use of immunotherapy drugs (nivolumab and ipilimumab) increased 2-year survival by 14% compared with traditional chemotherapy;
- radiation therapy: for pain palliation in infiltrating disease. It is also used for prevention of recurrence at drainage sites and thoracoscopic access points.