The celomic cavity develops early in embryogenesis and is divided by partitioning membranes into the pleural, pericardial and peritoneal cavities. These body cavities are lined by tissue referred to as serosa that have a visceral and parietal layer. The serosal tissue is composed of a layer of epithelial mesothelial cells separated from the underlying connective tissue component by a basement membrane. Mesotheliomas arise from cells forming this serosal membrane. The majority of mesotheliomas (90-95%) arise in the pleural cavity whereas about 5 to 10% arise in the peritoneal cavity. Primary pericardial mesotheliomas are extremely uncommon. Mesotheliomas can arise in the tunica vaginalis which is an invagination of the peritoneum.
Serosal tissue is an extremely reactive type of tissue and shows a prominent reaction to almost any form of injury. Epithelial mesothelial cell hypertrophy and hyperplasia can become extremely severe and be confused with epithelial mesothelioma. Likewise, multipotential subserosal cells proliferate forming a highly cellular invasive appearing type process. One of the most difficult areas in “mesothelioma pathology” is differentiating reactive epithelial mesothelial cell proliferation from an epithelial mesothelioma and from differentiating reactive multipotential subserosal cell proliferation from a sarcomatoid or desmoplastic mesothelioma.
At the time most pleural mesotheliomas are diagnosed, they are composed of multiple small nodules studding the visceral and parietal pleural surface. These nodules range from 1 mm. to occasionally 1 cm. In the majority of cases, this proliferation is associated with a pleural effusion, the pleural fluid usually having the features of an exudate.
As time progresses, the nodules coalesce to form solid tumors that in the case of pleural mesotheliomas encase the lung and obliterate the pleural cavity. Mesotheliomas frequently invade chest wall skeletal muscle and sometimes directly invade skin and subcutaneous tissue. They likewise invade lung parenchyma. It is not uncommon for mesotheliomas to show variability in the thickness of the rind of tumor that encases the lung. In general, the tumor is usually much thicker at the base of the pleural cavity than it is at the apex. Frequently, mesotheliomas have a nodular morphology and if the rind of tumor is relatively thin, these nodules can be confused with primary lung cancers. Occasionally, mesotheliomas metastasize to hilar lymph nodes and produce a hilar mass that is significantly more recognizable radiographically than the thin rind of tumor that encases the lung. Mesotheliomas also frequently directly invade pericardium and sometimes myocardium. It is not uncommon for pleural mesotheliomas to invade through the hemidiaphragms and extend into the abdominal cavity.
Some epithelioid mesotheliomas produce excess amounts of hyaluronic acid and proteoglycans. Tumors that produce these substances are “slick” and “slimy”. They often have large cystic areas filled with a tannish gelatinous material.
Peritoneal mesotheliomas are similar to pleural mesotheliomas in that they also begin as multiple small nodules that over a period of time coalesce to form a rind of tumor tissue that encase various organs within the abdominal cavity. Sometimes this can be so extensive that the bowel and other organs are compressed to the point of being nonexistent. As with pleural mesotheliomas, most peritoneal mesotheliomas initially are associated with an effusion.
Primary mesotheliomas that arise in the tunica vaginalis often present as a mass in that location. They sometimes remain localized, although not infrequently invade the peritoneal cavity and extensively involve it.
Primary pericardial mesotheliomas are rare. To diagnose a primary pericardial mesothelioma, one has to be certain that the tumor involving the pericardium does not represent an extension of a pleural mesothelioma. Pericardial mesotheliomas are like other mesotheliomas in that they start out as small nodules that coalesce to form a rind of tumor around the heart with obliteration of the pericardial cavity.
Rarely, mesotheliomas occur as localized masses rather than diffusely involving a body cavity. These occur most frequently in the pleural cavity and are called localized malignant mesotheliomas.
Symptoms referable to the site that mesotheliomas begin are often so dominating that metastases are not searched for in mesothelioma. However, metastases are relatively common in mesothelioma, although not as common as one sees in primary lung cancers. The most common site mesotheliomas metastasize to is bronchopulmonary and hilar lymph nodes. The next most common site is to the pleural surface of the lung not involved by tumor. Mesothelioma metastases can involve almost any organ, including adrenal glands, liver, kidneys, etc. There have been about 20 or 25 reported cases of mesotheliomas metastasizing to brain. Desmoplastic mesotheliomas have a propensity to metastasize to bone and can be a diagnostic dilemma because they resemble benign fibrous tissue.

Mesotheliomas are subtyped into four major categories: 1. Epithelial 2. Sarcomatoid – fibrous 3. Biphasic – mixed 4. Desmoplastic (this is considered a variant of a sarcomatoid mesothelioma) This classification scheme is extremely simple compared to what actually exists. There are numerous subtypes of epithelial mesothelioma (Table 1) and there are numerous patterns that one sees with sarcomatoid mesotheliomas and biphasic mesotheliomas. When large tissue samples are available such as a pleural pneumonectomy specimen or an autopsy specimen, it is common to see variable differentiation. One can often see five or six histologic types of differentiation by the tumor and the more sections one takes, the more likely the tumor is found to be biphasic. Sarcomatoid mesotheliomas can show homologous or heterologous differentiation including osteocartilaginous and lipomatous differentiation. It is debatable whether they show vascular differentiation.
Desmoplastic mesotheliomas are probably the most difficult of all mesotheliomas to diagnose. They should not be diagnosed from a needle core biopsy. The primary differential diagnosis is fibrosing pleuritis. The criteria for diagnosing desmoplastic mesothelioma include: 1. Over 50% of the tumor has to be composed of relatively dense hypocellular fibrous tissue that not infrequently forms vague nodules. 2. Areas of increased cellularity that have the features of a sarcomatoid mesothelioma. 3. Focal areas of stellate necrosis. 4. Invasion of subparietal pleural fat/chest wall or invasion of the lung (most important). In fibrosing pleuritis, there are more reactive tissue changes with capillary proliferation, inflammation and fibrin deposition. The capillaries that proliferate in the pleura are usually perpendicular to the surface of the pleura which is not seen in desmoplastic mesothelioma.
One has to remember that when desmoplastic mesotheliomas invade or metastasize, they can look extremely bland and can be misdiagnosed as benign fibrous tissue.