1. Pathology of the pleura
Pleural disorders are always in the shadow of lung diseases. The discussion of these diseases has been neglected in relation to other diseases although the symptoms of pleural effusion always accompany lung as well as heart diseases.
Inflammation of the pleura may be acute or chronic, of nonspecific or specific type. Prolonged, chronic effusion causes reactive changes on mesothelial cells that can be histologically misdiagnosed as malignancy. Tuberculosis inflammation causes pleural effusion characterized by the presence of large numbers of lymphocytes and a small number of mesothelial cells. Tuberculous pleuritis is the most common form of extrapulmonary tuberculosis .
Pleural tumors originate from mesenchymal cells of the epithelial type and submesothelial cells of the mesenchymal type. The most common pleural mesenchymal tumor is a solitary fibrous tumor of the pleura. The biological behavior of this tumor of the pleura is predicted by the proliferation marker, protein Ki-67, and when its index is more than 4 mitoses at 2 mm2 or >4/10 high power fields, it may be considered as a malignant alteration that creates dilemmas about the treatment [8, 9].
We will pay particular attention to reactive mesothelial cells as well as to tumors of the pleura.
Reactively altered mesothelial cells are difficult to distinguish morphologically from malignant mesothelial cells both on biopsy and on effusion (Figure 1) [8, 9]. Recently, a monoclonal antibody, bap-1, which is mainly expressed in reactive mesothelial cells has been used (Figure 2). It is also expressed in malignant mesothelial cells but not in malignant cells of another origin, such as lung adenocarcinoma .
According to the latest WHO classification of pleural tumors , they are divided into mesothelial tumors, mesenchymal tumors, and lymphoproliferative disorders.
2. Classification of pleural tumors
Diffuse malignant mesothelioma
Localized malignant mesothelioma
Other tumors of mesothelial origin
Well-differentiated papillary mesothelioma
Primary effusion lymphoma
Pyothorax—associated with lymphoma
Solitary fibrous tumor
Calcifying tumor of pleura
Desmoplastic round cell tumor
We will consider the most common types, in the group of mesothelial tumors—pleural mesothelioma and in the group of mesenchymal tumors—solitary fibrous tumor.
Pleural mesothelioma is divided into the most common, monophasic, epithelioid type (Figure 3); sarcomatoid type (Figure 4); biphasic, epithelioid/sarcomatoid (Figure 5) and the rarest, difficult-to-diagnose, desmoplastic type (Figure 6). Epithelioid mesothelioma is diagnosed and differentiated from carcinoma that involve pleura with monoclonal antibodies: podoplanin (D2-40) (Figure 7), HBME-1 (Figure 8), cytokeratin 5 (Figure 9), calretinin (Figure 10), and WT-1 (Figure 11). By using several of these antibodies, epithelioid mesothelioma can be diagnosed with great certainty. Sarcomatoid mesothelioma can be diagnosed by using the following antibodies: cytokeratin, vimentin, HBME-1, and Fascin, but this type can be differentiated from pulmonary sarcomatoid carcinoma only by clinical findings [4, 5, 6, 7, 8].
Solitary fibrous tumor is fibroblastic neoplasm, consisting of primitive connective tissue cells, which can therefore mimic morphological picture of neurofibroma or hemangiopericytoma with zones of hypercellularity (Figure 12) and hypocellularity (Figure 13). However, solitary fibrous tumor is characterized by immunophenotype of tumor cells. These cells express vimentin, CD34, bcl-2, and Stat-6 (Figure 14). The proliferation index of these cells is low in benign phase, less than 2 mitosis/10 HPF (Figure 15). If this tumor recurs and proliferation index is elevated, it is advised that tumor is treated as a sarcoma [11, 12].
Rare mesenchymal tumors are epithelioid hemangioendotheliomas which can be bilateral, both in the lungs and in the pleura. Monophasic and biphasic types of synovial sarcoma are also rare. These tumors have a specific immunophenotype, where epithelioid hemangioendothelioma (Figures 16–18) expresses vascular markers, while synovial sarcoma expresses (Figures 19 and 20) itself as synovial sarcoma of the joints but with a specific genetic mutation [13, 14, 15].