A 66-year-old Japanese woman with complaint of chest dullness was referred to Chiba University Hospital. She was a housewife with no history of smoking or any other complications. She had not been exposed to asbestos in her life, not even for a short period of exposure. Her residential area has not been contaminated with asbestos and her family had not been engaged to any works dealing with asbestos. These suggest the para-exposure or environmental exposure to asbestos was quite unlikely. Until the first visit to our hospital, she had no previous medical history of pneumonia, tuberculosis, or thoracic trauma that may cause pleural effusion. At the first visit, she complained left-sided dull pain, extending from lateral chest to back (grade 2 of the Numerical Rating Scale) and slight dyspnea on effort (grade 1 of the MRC dyspnea scale). These complaints continued thereafter for 11 years without any deterioration. Weight loss, continuous fever, and nocturnal sweat were not observed.
Chest X-ray showed left-sided pleural thickening and pleural effusion. The mild pleural effusion of unknown etiology was already detected 7 years ago before her visit to the hospital. Chest computed tomography (CT) on admission demonstrated left-sided thickened pleural of 13 mm at the lower thorax with some pleural effusion. Pleura thickening was not extended to the mediastinal side and there was no finding of fissure thickening or lung parenchyma involvement. Pleural plaques, pleural implantation, and thoracic wall invasion were not detected. Typical radiological finding of malignant pleural mesothelioma was therefore absent. Nevertheless, it is sometimes difficult to make differential diagnosis between malignant pleural mesothelioma and non-mesothelioma diseases, since mesothelioma does not demonstrate these typical features, especially in the earlier stage.
Even though she had no history of asbestos exposure, malignant pleural mesothelioma was suspected based on CT scan findings and an abnormally high concentration of hyaluronic acid (2,030,000 ng/mL) in the pleural fluids. A pleural biopsy was performed with video-assisted thoracoscopic surgery (VATS) under local anesthesia and the pathological diagnosis with the specimens was epithelioid malignant pleural mesothelioma. The patient refused to take surgery and chemotherapy and was carefully monitored in the outpatient clinic. Four months after the VATS biopsy, the pleural effusion increased (Figure 1) and the CT scan detected a nodule with 4 cm in size (Figure 2(a)), which were compatible with mesothelioma or dissemination of lung cancer into the thoracic cavity. The patient then consented to a surgical pleural biopsy under general anesthesia in order to obtain an additional tissue for further analysis, and we conducted several examinations as described below. A positron emission tomography (PET) scan did not show fludeoxyglucose (FDG) accumulation in the nodule, but detected a round-shaped atelectasis (Figure 2(b)). The patient survived 3 years after the last biopsy without any respiratory symptoms and more than 11 years from the first manifestation of pleural effusion.
In summary, we presented a rare case of diffuse pleural thickening that was indistinguishable from mesothelioma with routine immunohistochemical examinations. Number of this type of marginal case will increase in the future according to expansion of asbestos-related disease. We presume that large biopsied samples by open surgery and p16 FISH analysis and BAP1 immunohistochemistry are crucial for differential diagnosis between mesothelioma and the benign diseases, in order to avoid misdiagnosis which leads to highly invasive medical interventions.