Sarcomatous Mesothelioma - Diagnosis of Mesothelioma
Pathology
Mesothelioma tissues have the singular potential of producing tumors of epithelial or mesenchymal type, or both. Such a duality can be explained by embryology. The mesothelium is made of a coelomic epithelium developed from the mesoderm, not the mesenchyme, and is supported by mesenchymal tissue.143 Tissue culture experiments have confirmed this hypothesis.254 It is not entirely clear, however, whether the malignant cells arise from the mature mesothelial cells or from undifferentiated mesenchymal cells of the submesothelial tissues.238
As a result, mesothelioma can be classified under three major histologic types: epithelial or tubulopapillary, the most frequent (50 to 70% of cases); mesenchymal or fibrosarcomatous, the least common (7 to 20% of cases); and mixed or biphasic, intermediate in frequency (20 to 35% of cases). The mixed type is the most characteristic, containing both epithelial and mesenchymal elements (Plate 19, Fig. 89.1); the transition is either abrupt or gradual.214 Synoviosarcoma is the only other tumor that can produce a pathologic picture similar to that of mixed mesothelioma.305
This dual appearance of mesothelioma has been shown in tissue culture studies. A change from one morphology to the other may be related to artificial conditions of the media used,145 since no such conversions have been observed in human mesothelioma growing in nude mice despite repetitive transplantations over >1 year.258,259 Other subtypes of mesothelioma have been described: desmoplastic with prominent fibrosis43 and lymphohistiocytoid with intense lymphoplasmacytic infiltration,122 both most often in sarcomatous mesothelioma. Psammoma bodies can be seen, although rarely, in mesotheliomas.69,137
Another remarkable property of the mesothelial cell is the production of hyaluronic acid, a glycosaminoglycan which stains weakly with muci-nucleation, cytoplasmic vacuolization, and irregular chromatin pattern, which are not constant.148,304 Electron microscopy can be helpful, if available.258 The diagnosis of mesothelioma by fluid cytology or needle biopsy often presents a great challenge, as discussed below.
Another difficult task which may lead to considerable clinical problems is the distinction between malignant mesothelioma, particularly of the desmoplastic type, and benign reactive mesothelial hyperplasia, which can appear atypical in a number of conditions, including pulmonary infarction, cirrhosis of the liver, uremia, and metastatic carcinoma.124
In such cases, even electron microscopy may not be helpful.260 Suspicion of malignant mesothelioma should arise in case of invasion of surrounding structures, of focally necrotic and avascular areas, and subtle microscopic features, such as piling and aggregation of mesothelial cells, variability in size, nuclear hyperchromasia, mitotic activity, irregular chromatin pattern, and cytoplasmic vacuolization, or in the presence of any florid mesothelial proliferation.
1,144,148,240 Some of these changes have been described several years before the development of mesothelioma; it is not clear whether the tumor is preceded by such preneoplastic mesothelial proliferations, 144 or if it arises directly as a diffuse microscopic neoplasm.113A recently described argyrophil stain, the 'AgNOR technique" which detects 'nucleolar organizer" regions of ribosomal DNA, seems to be effective in differentiating malignant from normal or reactive mesothelial cells.18 Cytogenetic analysis to detect clonal chromosome aberrations is also of great interest.100
Mesotheliomas spread by contiguity over the parietal and visceral serosal surfaces. Pleural mesothelioma extends over the diaphragm, mediastinum, pericardium, and, eventually, the peritoneum. It also extends into the interlobar fissures and into the lung itself by contiguity or by interstitial and alveolar spread.64 Seeding along the track of needle biopsy channels occurs in 10 to 20% of cases.63,127
Peritoneal mesothelioma involves mainly the parietal and visceral surfaces, the omentum, and the mesentery with tumor nodules and/or infiltration causing thickening. Involvement of the serosa overlying the small and large bowel, the liver, the spleen, and other organs leads to encasement of these organs in tumor tissue. Lymphatic dissemination is common, and mediastinal nodes are involved in about 50% of cases of pleural mesothelioma.214,305 Distant blood-borne metastases are more common than was previously thought and are seen at autopsy in 50 to 80% of cases.214 They can occur in any organ, including the brain.209 A peculiar pattern of massive hepatic calcifications, attributed to degenerative and necrotic liver metastases, has been described.42,196
Clinical Features
The onset of mesothelioma is usually insidious; a common presenting symptom is persistent localized pain.