The clinical manifestations of MM are non-specific, irrespective of the site of mesothelioma development. With regard to pleural mesothelioma, dyspnea may be recognized in up to 90% of all cases. Patients may also suffer from chest pain. Rare symptoms of pleural mesothelioma include phrenic nerve palsy, which contributes to shortness of breath and may result in orthopnea, as well as irritative cough and paraneoplastic phenomena [1]. Those suffering from peritoneal mesothelioma often claim abdominal pain. Distension may be noted and is partially due to ascites. Additionally, intestinal obstruction may occur, and patients may experience loss of appetite and weight. In some cases, the tumor is palpable [2].

• Abdominal Lymphadenopathy

  Abdominal computed tomography revealed one 8-cm intrahepatic mass adjacent to the abdominal wall with peritoneal thickening, multiple smaller nodules in the peritoneal cavity, and intra-abdominal lymphadenopathy. [ncbi.nlm.nih.gov]

• Fatigue

  […] of Fullness Weight Loss Anemia Fever Diarrhea Constipation Bowel Obstruction Nausea Vomiting Fatigue Pericardial Mesothelioma Irregular Heartbeat Heart Palpitations Trouble Breathing Heart Murmurs Weight Loss Shortness of Breath Chest Pains Fatigue Coughing [mesothelioma.net]

  Symptoms can include chest pain, shortness of breath and general fatigue. Navigate through the sections below and click on a topic for more in-depth information on mesothelioma. [mesothelioma.com]

  […] symptoms Abdominal (belly) pain Swelling or fluid in the abdomen Nausea and vomiting Constipation Pericardial mesothelioma symptoms Chest pain Irregular heart rhythm Heart murmur Shortness of breath General mesothelioma symptoms Fever Excessive sweating Fatigue [cancer.org]

  Early signs of pleural mesothelioma include: Trouble breathing Long-lasting cough Pain under the rib cage or in the abdomen Pain while breathing Weight loss and fatigue Diagnosis Images may be taken of your bodily structures. [cancer.uvahealth.com]

• Inguinal Mass

  We report a case of malignant mesothelioma of the spermatic cord in 80-year-old man presented with retained testis, hydrocele, and right inguinal mass. The patient had a long history of asbestos exposure as a railway worker. [ncbi.nlm.nih.gov]

• Laboratory Technician

  Three men had been working as dental laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one woman had been helping her husband for 30 years in manufacturing dental prostheses. [ncbi.nlm.nih.gov]

• Inguinal Hernia

  Herein, we report a case of an elderly patient who presented with an inguinal hernia which pathologically had features of deciduoid malignant mesothelioma. [ncbi.nlm.nih.gov]

• Abdominal Pain

  Abstract A 62-year-old man presented with clinical signs of acute abdominal pain and adrenal insufficiency. Computerized tomographic scans revealed bilateral adrenal tumors and the left adrenal tumor was surgically resected. [ncbi.nlm.nih.gov]

  Symptoms may include abdominal pain and swelling, nausea, and vomiting. Cell Types of Mesothelioma Malignant mesothelioma can also be described by cell type. There are three primary types. [nyulangone.org]

• Nausea

  She presented to our department with a 2-week history after the last chemotherapy of progressive dizziness related to head movement, nausea, vomiting, ataxia and unsteady gait. [ncbi.nlm.nih.gov]

  Symptoms may include abdominal pain and swelling, nausea, and vomiting. Cell Types of Mesothelioma Malignant mesothelioma can also be described by cell type. There are three primary types. [nyulangone.org]

  Pain in the side of the chest or lower back Shortness of breath Cough Trouble swallowing (feeling like food gets stuck) Hoarseness Swelling of the face and arms Peritoneal mesothelioma symptoms Abdominal (belly) pain Swelling or fluid in the abdomen Nausea [cancer.org]

  The typical side effects from surgery, chemotherapy, and radiation are as follows: Hair thinning and hair loss Nausea with or without vomiting Easily prone to infections Bruising and bleeding easily Bladder changes–urinating more frequently or less frequently [mesotheliomalawyercenter.org]

  The five most frequently reported TEAEs (all grades) were fatigue (32%), decreased appetite (28%), dyspnea (28%), nausea (27%), and cancer pain (26%), regardless of relationship to study drug. [globenewswire.com]

• Epigastric Mass

  An epigastric mass was palpated through systemic physical examination and MR scanning demonstrated an 8 6 cm-sized, well-defined elliptic mass at gastric corpus. [ncbi.nlm.nih.gov]

• Right Shoulder Pain

  We report a case of a 66-year-old man who presented with shortness of breath, right shoulder pain, and peripheral edema of the lower limbs. [ncbi.nlm.nih.gov]

• Short Arm

  Deletion mapping of the short arm of chromosome 3 in human malignant mesothelioma. Genes Chromosom. Cancer 9, 76–80 (1994). 14. Murthy, S.S. & Testa, J.R. [nature.com]

• Diplopia

  The patient presented with diplopia following a 2-week history of malaise, myalgia, mild headache and diarrhoea. Clinical examination found global areflexia, cerebellar ataxia and bilateral sixth nerve palsies. [ncbi.nlm.nih.gov]

• Impulsivity

  Physical examination revealed a well-circumscribed, hard, non-reducible swelling palpable along the medial extent of the inguinal canal with no cough impulse. Fine-needle aspiration cytology suggested metastatic carcinoma. [ncbi.nlm.nih.gov]

• Meningism

  Differential diagnoses included the Miller-Fisher variant of Guillain-Barre syndrome, malignant meningitis and infectious meningitis. [ncbi.nlm.nih.gov]

• Areflexia

  Clinical examination found global areflexia, cerebellar ataxia and bilateral sixth nerve palsies. Differential diagnoses included the Miller-Fisher variant of Guillain-Barre syndrome, malignant meningitis and infectious meningitis. [ncbi.nlm.nih.gov]

• Cerebellar Ataxia

  Clinical examination found global areflexia, cerebellar ataxia and bilateral sixth nerve palsies. Differential diagnoses included the Miller-Fisher variant of Guillain-Barre syndrome, malignant meningitis and infectious meningitis. [ncbi.nlm.nih.gov]

• Dysarthria

  It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. [ncbi.nlm.nih.gov]

Most patients have a history of occupational asbestos exposure, whereby the latency period between the respective activities to the time of MM diagnosis may range from 15-50 years [3]. Affected individuals may have been working in mining and crushing decades ago, been manufacturing products, constructing and demolishing buildings, eliminating waste, or realizing maintenance work of asbestos-containing material, products, or buildings [4]. In some cases, anamnestic data may reveal non-occupational exposure to asbestos, and in very few patients, no evidence of asbestos exposure can be obtained [5].

Diagnostic imaging may provide important hints as to the origin of symptoms. Radiography, ultrasonography, computed tomography, and magnetic resonance imaging may be used to obtain further support for the suspected diagnosis, to assess the extent of the tumor and the presence of lymph node metastases. Due to its augmented sensitivity, positron emission tomography is increasingly used for the detection of distant metastases [1].

• In patients with pleural mesothelioma, mostly unilateral pleural effusion and pleural thickening are commonly reported [1].
• Peritoneal mesothelioma often provokes ascites. The tumor itself appears as a solid, heterogeneous soft-tissue mass with irregular margins. Enhancement is seen after venous contrast administration. Furthermore, a diffuse distribution throughout the abdominal cavity should raise suspicion as to MM [2].

The cytological examination of pleural or peritoneal fluid may reveal abnormalities that back up the suspicion of MM, but the absence of anomalies does not rule out mesothelioma [6]. MM diagnosis can only be definitively established by biopsy, and the respective samples should be obtained under image guidance. Concerning the histological features of mesothelioma, there are epithelioid, biphasic, and sarcomatoid subtypes, and the immunohistochemical confirmation of the cells' origin is mandatory. MM tend to stain positive for calretinin, cytokeratin 5/6, and Wilms tumor antigen 1, while staining against p63, MOC-31, and Ber-EP4, as expressed by distinct types of carcinoma, usually yields negative results [2] [7].

If doubts remain as to the nature of the disease, thoracoscopy or thoracotomy should be carried out. Indeed, thoracoscopy should be performed for the reliable diagnosis of pleural mesothelioma except in the case of pre-operative contraindication or pleural symphysis, according to the guidelines for the management of malignant pleural mesothelioma [7].

• Ovarian Mass

  Though the ovarian involvement may be seen in the background of a diffuse peritoneal involvement, the presentation of MPM as a primary ovarian mass is rare. Here we present such a case who underwent surgery but had residual progressive lesion. [ncbi.nlm.nih.gov]

MM patients should be cared for by a multidisciplinary team. While surgery, chemotherapy, and radiotherapy may be employed to fight the disease, additional measures must be taken to alleviate pain and other symptoms and to preserve the patients' quality of life.

• The total resection of pleural mesothelioma is generally hampered by the diffuse growth of the tumor, but surgery remains the mainstay of treatment. Pleurectomy and decortication with en bloc resection of the parietal and visceral pleura may be performed to this end and at the same time serves to relieve a possibly entrapped lung and restrictive ventilatory deficits. Extrapleural pneumonectomy with en bloc resection of pleura, lung, pericardium, and diaphragm and systematic nodal dissection constitutes a more radical approach to MM therapy. The procedure is associated with high morbidity, and it remains unclear whether it provides an advantage in terms of survival [1] [7]. Chemotherapy may be applied instead of surgery, but may work better on smaller tumors and should thus be considered a complementary measure. The combination of cisplatin with pemetrexed or raltitrexed has been shown to prolong progression-free and overall survival times, although little is known about possible second-line treatments [8]. Radiotherapy is recommended only in the setting of palliative treatment and pain management. Furthermore, palliative care may comprise thoracoscopy with pleurodesis to control pleural effusions and alleviate pain, or talcum pleurodesis in the case of recurrent pleural effusions [1].
• Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the standard therapy of peritoneal mesothelioma. Combined platinum-based regimens have been shown to be most effective, with best results being achieved after complete cytoreduction. Chemotherapy, mostly cisplatin or carboplatin with pemetrexed, is also used to treat inoperable patients [2].

So far, molecular-targeted therapies have not been proven effective in MM therapy. However, recent clinical trials have shown bevacizumab and nintedanib to improve progression-free and overall survival in mesothelioma patients under chemotherapy [9] [10].

MM is an aggressive type of cancer. It is associated with a poor prognosis and median survival times are below one year for those diagnosed with malignant pleural mesothelioma. Here, the histological subtype and the Karnofsky score are the main prognostic factors. Biphasic and sarcomatoid mesotheliomas are related to unfavorable outcomes, as is a low Karnofsky score [1]. For patients with malignant peritoneal mesothelioma who are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, median survival times of about five years have been reported. Similar to pleural tumors, the biphasic and sarcomatoid subtypes imply a worse prognosis [11].

The degeneration of mesothelial cells in the pleural or abdominal cavity may give rise to the development of mesothelioma. In rare cases, mesothelioma originates from the pericardium, perimetrium, or tunica vaginalis testis. The vast majority of MM develops in the pleural cavity and is related to occupational asbestos exposure. Furthermore, exposure to this mineral may induce MM in non-pleural mesothelium, and people who are exposed to asbestos in their domestic environment, who are living with asbestos workers or near asbestos mines and manufacturing plants are at increased risks, too [4]. Besides asbestos, asbestos-like compounds such as erionite, fluoro-edenite, silicon carbide whiskers, and carbon nanotubes have been implied in mesothelial cancerogenesis [3].

Beyond that, little is known about predisposing factors other than asbestos exposure. Both genetic and environmental factors may contribute to the individual risk of MM, but reliable data are scarce [5]:

• Exposure to ionizing radiation may augment the likelihood of developing MM.
• The diagnostic use of thorium dioxide, an insoluble source of α particles, has also been related to the development of this type of malignancy.
• Furthermore, certain pathogens have been discussed in this context. Avian leukosis virus strain MC29 may be able to induce degenerative changes in mesothelial cells, and simian virus 40 has been demonstrated to act as cocarcinogen of asbestos in animals, yet its potential role in MM remains unproven.
• Finally, chronic or recurrent serosal inflammation and severe scarring have been associated with MM development.

The overall incidence of MM has been estimated at 1-3 per 100,000 inhabitants but differs greatly between those parts of the population that have been exposed to asbestos and people who haven't. Indeed, the general incidence in the absence of asbestos exposure may be below 1 per 1,000,000 individuals, while values 40 times as high may be reached among asbestos workers. As for those who have been exposed to asbestos before it was banned in most industrialized nations, a peak in the incidence of MM is expected between 2015 and 2030 [1].

The majority of patients is male, a fact that is likely attributable to the etiology of MM, and most diagnoses are made in the elderly, in patients aged 65 to 85 years [12]. By far the most common type of MM is malignant pleural mesothelioma. It accounts for up to 80% of all cases [3]. While about 20% of MM arise in the peritoneum, malignancies derived from the pericardium, perimetrium, or tunica vaginalis testis are rare.

There are distinct types of asbestos that differ in their physical properties, namely amphiboles and serpentine, and the carcinogenicity of asbestos is related to the diameter and size of the respective fibers. In this context, amphiboles like amosite and crocidolite have been shown to be most hazardous to human health. They are composed of particularly long and fine fibers, measuring more than 5 µm in length and less than 0.25 µm in diameter. If inhaled, these fibers pass from the alveoli to the pleural space, from where they cannot be eliminated via parietal pleural stomata and lymph vessels. The latter constitute narrow openings for pleural fluid drainage that may even be blocked by asbestos fibers. These fibers persist and accumulate within the pleural space, cause pleural irritation and chronic mesothelial inflammation. As a result, patients exposed to long asbestos fibers are predisposed to a variety of pleural disorders, e.g., pleural effusion, pleural fibrosis, and pleural mesothelioma [13].

The translocation of asbestos fibers from the pleural cavity to the abdominal cavity has been postulated as a possible mechanism of peritoneal mesothelioma development [14]. Another hypothesis is based on the idea that the excessive and persistent production of proinflammatory cytokines in the pleural space may affect mesothelial cells at distant sites. Indeed, preliminary studies indicate an increased risk of systemic autoimmune diseases in patients who have been exposed to asbestos [15] [16]. Further research is required to link these findings and shed more light on the pathogenesis of non-pleural mesothelioma.

The avoidance of asbestos exposure is the single most effective measure of MM prevention, and in the interest of public health, asbestos has been banned in 55 countries worldwide. Notwithstanding, it continues to be used in large quantities around the world. An estimated 2 million tons of asbestos are still used every year, mainly in the United States, Russia, India, China, and some developing countries. It is the task of politics to further reduce the production and use of asbestos, and to limit its role as a commodity in global trade [17].

On the other hand, protocols must be established for the safe removal and management of asbestos that is still present in many private and public buildings. The application of such protocols should always be left to experts. Both sanitary and environmental issues should be considered in the context of asbestos disposal, and the ultimate goal should be to employ physical, chemical, and biological treatments to detoxify asbestos waste instead of dumping it in landfills [18].

With regard to former asbestos workers and those otherwise exposed to this carcinogen, no recommendations can be given to prevent the onset of MM. These patients may, however, be enrolled in health surveillance programs in order to facilitate the early diagnosis of MM and related disorders [19]. Other authors disagree with the efficacy of such programs and argue they may not improve the patient's prognosis but rather imply possibly harmful interventions in unaffected individuals [7].

Malignant mesothelioma is a rare but aggressive and rapidly fatal type of cancer. Both environmental and genetic factors may contribute to the malignant degeneration of mesothelial cells in the pleura, peritoneum, or elsewhere in the body, and further research is required to fully understand the pathophysiological events behind MM development. The majority of cases, however, can unequivocally be related to prior exposure to asbestos. MM may thus be classified as an occupational disease. The diagnosis is usually made decades after the cessation of asbestos exposure and is related to a poor prognosis with median survival times of about one year. This fact highlights the need for the implementation of effective safety measures in the respective industries and the importance of global efforts to reduce the production and use of asbestos and asbestos-like compounds.

The mesothelium is an epithelial structure that lines the body's serous cavities and internal organs. It is composed of a monolayer of specialized cells forming a thin membrane that provides a non-adhesive surface and thus facilitates the frictionless movement of the heart, lungs, intestines, and other organs. If mesothelial cells degenerate and give rise to cancer, malignant mesothelioma (MM) is diagnosed. Most cases are related to the exposure and inhalation of asbestos fibers and affect the pleura, which lines the thoracic cavity. Affected individuals may experience symptoms such as shortness of breath and chest pain. On the other hand, MM may develop in the abdominal cavity and induce abdominal pain and distension. Neither of these symptoms is specific, and a thorough workup is required to make a definite diagnosis.

The best way to prevent the onset of MM is to avoid asbestos exposure. This means for the laymen that they should not handle asbestos or asbestos-containing products, and that they should consult the respective authorities if doubts arise as to a possible environmental burden.

1. Neumann V, Löseke S, Nowak D, Herth FJ, Tannapfel A. Malignant pleural mesothelioma: incidence, etiology, diagnosis, treatment, and occupational health. Dtsch Arztebl Int. 2013; 110(18):319-326.
2. Broeckx G, Pauwels P. Malignant peritoneal mesothelioma: a review. Transl Lung Cancer Res. 2018; 7(5):537-542.
3. Hiriart E, Deepe R, Wessels A. Mesothelium and Malignant Mesothelioma. J Dev Biol. 2019; 7(2).
4. Goldberg M, Luce D. The health impact of nonoccupational exposure to asbestos: what do we know? Eur J Cancer Prev. 2009; 18(6):489-503.
5. Jasani B, Gibbs A. Mesothelioma not associated with asbestos exposure. Arch Pathol Lab Med. 2012; 136(3):262-267.
6. Meister T, Birkfellner T, Poremba C, et al. Papillary mesothelioma of the peritoneum in the absence of asbestos exposure. Z Gastroenterol. 2003; 41(4):329-332.
7. Scherpereel A, Astoul P, Baas P, et al. Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J. 2010; 35(3):479-495.
8. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003; 21(14):2636-2644.
9. Grosso F, Steele N, Novello S, et al. Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial. J Clin Oncol. 2017; 35(31):3591-3600.
10. Zalcman G, Mazieres J, Margery J, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet. 2016; 387(10026):1405-1414.
11. Salo SAS, Ilonen I, Laaksonen S, Myllarniemi M, Salo JA, Rantanen T. Malignant Peritoneal Mesothelioma: Treatment Options and Survival. Anticancer Res. 2019; 39(2):839-845.
12. Delgermaa V, Takahashi K, Park EK, Le GV, Hara T, Sorahan T. Global mesothelioma deaths reported to the World Health Organization between 1994 and 2008. Bull World Health Organ. 2011; 89(10):716-724, 724a-724c.
13. Donaldson K, Murphy FA, Duffin R, Poland CA. Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma. Part Fibre Toxicol. 2010; 7:5.
14. Donaldson K, Borm PJ, Castranova V, Gulumian M. The limits of testing particle-mediated oxidative stress in vitro in predicting diverse pathologies; relevance for testing of nanoparticles. Part Fibre Toxicol. 2009; 6:13.
15. Noonan CW, Pfau JC, Larson TC, Spence MR. Nested case-control study of autoimmune disease in an asbestos-exposed population. Environ Health Perspect. 2006; 114(8):1243-1247.
16. Reid A, Franklin P, de Klerk N, et al. Autoimmune antibodies and asbestos exposure: Evidence from Wittenoom, Western Australia. Am J Ind Med. 2018; 61(7):615-620.
17. Frank AL, Joshi TK. The global spread of asbestos. Ann Glob Health. 2014; 80(4):257-262.
18. Spasiano D, Pirozzi F. Treatments of asbestos containing wastes. J Environ Manage. 2017; 204(Pt 1):82-91.
19. Chellini E, Battisti F, Cristaudo A, Sartorelli P, Calà P. Health surveillance for former asbestos exposed worker: a specific programme developed in an Italian region. J Thorac Dis. 2018; 10(Suppl 2):S383-s389.