Biphasic Malignant Mesothelioma with Brain Metastasis

 Malignant pleural mesothelioma is a malignant neoplasm of mesodermal origin and arises from multipotent mesothelial or subserosal cells of the pleura, pericardium or peritoneum. On microscopic examination it can be differentiated into three forms: epitheloid (60%), sarcomatoid (10-20%) and biphasic patterns (20-30%) [1]. Metastasis to brain is rare. The most common sites for metastasis in men are the lungs (27%), kidneys (13%) and skin (13%); in women, the common sites include breast (24%) and genital organs (17%), followed by bone (10%) and kidney (10%) [2]. Work-related asbestos exposure has been associated in 70% of all pleural mesothelioma cases [3]. The tumor is commonly seen in patients during their fifth and sixth decades. The latency between exposure and clinical presentation of mesothelioma takes approximately 20 to 40 years. Median survival from the time of presentation is 9 to 12 months [4].

A 40-year-old female patient presented with complaints of chronic dry cough for 4 months without any specific aggravating and relieving factors. She also complained of right sided severe stabbing localized chest pain, consistent with pleuritic chest pain for 3 months prior to her presentation. Her pain was worsened by coughing and deep inspiration. Pain was so severe that it affected her sleep. Chest pain was associated with progressive persistent shortness of breath with MMRC (Modified Medical Research Council) grade 4, that is, dyspnea during dressing and undressing. Patient also complained of blurry vision without diplopia and sharp occipital headache without any specific aggravating factors for 15 days prior to her presentation. Clinical examination revealed decreased respiratory movement and dull percussion note all over the right side of the chest with decreased vesicular breath sounds consistent with right sided massive pleural effusion. She also had a right sided firm, mobile supraclavicular lymph node. Pleural fluid, obtained during thoracocentesis, examination showed lymphocytic exudative (protein 5.33 gm/dl, glucose 90 mg/dl)

effusion with adenosine deaminase of 11.3 U/L. Contrast enhanced CT scan of the thorax showed irregular costal and mediastinal pleural thickening, exceeding 10 mm with encasement of the lung in between (Figure 1). There was also evidence of mediastinal lymphadenopathy, peribronchial cuffing of right main bronchus and esophagus along with right sided pleural effusion. Bronchoscopy showed right lower lobe and middle lobe bronchi narrowed by external compression; however, malignant cells were not detected on bronchial brush and bronchoalveolar lavage fluid examination. Ultrasonography guided pleural biopsy revealed a piece of fibrofatty tissue infiltrated by a biphasic tumor containing both epitheloid (due to the presence of round, cube-like cells that have long and slender microvilli) and sarcomatous (due to presence of spindle-shaped cells arranged in a disorganized fashion) properties suggestive of malignant biphasic mesothelioma (Figure 2). On immunohistochemistry, the tumor cells expressed calretinin, CK-5/6, WT-1, HBME-1 and were immunonegative for Ber ep4. Contrast enhanced CT scan of brain showed an enhancing lesion in the left occipital region. Overall, the data was consistent with biphasic malignant mesothelioma with brain metastasis in occipital lobe without prior history of asbestos exposure (Figure 3). The patient presented with stage IV disease due to the presence of occipital metastasis, and thus surgery had no role in her case. Palliative chemotherapy was given with combination regimen of pemetrexed and cisplatin. After 5 days of chemotherapy, she developed severe respiratory distress with vomiting.

Supportive management was started with fluid resuscitation and bronchodilators but patient died 7 days after presentation due to sudden cardiac arrest.

The occurrence of mesothelioma is often associated with prior exposure to asbestos, and occasionally due to endemic erionite exposure as in Turkey, ionizing radiation or chest injuries [5]. Pleural effusion, usually with dyspnea and often with chest wall pain, is the most common presentation in mesothelioma patients [6]. A fixed hemithorax on clinical examination, that is, unilateral lack of chest expansion, is usually a late sign. Clubbing is rare. Metastatic deposits of mesothelioma are commonly found during post mortem but are usually not detected before death [7]. The conventional chest X-ray typically shows pleural effusion. An encircling ring of tumor and/or extensive lobulated pleural-based tumor can be seen early but are usually a late feature [8]. Thoracic CT scan usually shows pleural effusion only. Pleural-based masses with or without thickening of interlobular septa can also be seen at presentation. Classical picture of mesothelioma on CT scan thorax is thickening of pleura, with an irregular, often nodular internal margin, most pronounced at the base of the lung [9]. At times, pleural thickening is seen predominantly along the mediastinum. Malignant mesothelioma should be suspected on CT scan thorax when there is ring-like pleural involvement, mediastinal pleural involvement, and pleural thickness more than 1 cm, as seen in our patient [10].