A 75-year-old Caucasian male with a past medical history of coronary artery disease status post coronary artery bypass grafting 11 years prior, congestive heart failure with an ejection fraction of 25%, atrial fibrillation, hypertension, and hyperlipidemia presented to the hospital with dyspnea and chest pain. He has no history of tobacco use. He worked as a lawyer all his life and had no occupational exposures. On exam, the patient had diminished breath sounds over the left lung. Chest x-ray revealed a large left-sided pleural effusion (Fig. 1). Of note, he had previously been evaluated by his primary care doctor four months prior with similar symptoms and was found to have a left-sided pleural effusion. At that time, he underwent a thoracentesis at an outside facility with unknown pleural fluid analysis (PFA).
He was admitted to the hospital for further evaluation and underwent both a diagnostic and therapeutic thoracentesis (Fig. 2). PFA revealed a lymphocytic predominant, exudative effusion with total triglyceride level of 1406mg/dL consistent with a chylous effusion. Microbiology was negative. Cytology of the pleural fluid revealed reactive appearing mesothelial cells as evidenced by positive calretinin and Wilms tumor-1 (WT-1) immunohistochemical (IHC) stains. Adenocarcinoma was ruled out by negative BerEP4 and MOC-31 IHC stains (Fig. 3).
Computed tomography (CT) of the chest after the thoracentesis was performed revealing left lung airspace disease, pleural calcifications and mediastinal adenopathy (Fig. 4). Due to concern for a possible malignancy, he underwent an endobronchial ultrasound guided fine needle aspiration (EBUS-FNA) biopsy of station 7 lymph node and transbronchial biopsy (TBBX) of the left lung infiltrate. Cytology of the EBUS-FNA lymph node specimen revealed abundant bland mesothelial cells with minimal amounts of lymphoid tissue. Interestingly, histologic examination of the concomitant TBBX specimen showed only rare atypical epithelioid cells floating within lymphatic spaces that stained with mesothelial markers. These findings were suspicious for a malignant process; however, limited sampling precluded a definitive diagnosis. A thoracoscopy was performed but an additional specimen could not be obtained due to extensive adhesions. A lymphangiogram was also performed. The contrast injected into the femoral vein did not progress to the level of the cisterna chyli suggesting an obstructive process in the lymph nodes. Due to concern for malignancy, the patient was offered a video-assisted thoracoscopic surgery, but he declined.
He returned to the hospital 3 months later with progressive dyspnea. CT chest revealed progression of the left lung infiltrate, a new right-sided pleural effusion and persistent mediastinal adenopathy (Fig. 5). Thoracentesis on the right sided revealed a chylothorax. He underwent another EBUS-FNA biopsy of station 7 lymph node and a TBBX of the left lung infiltrate. Cytologic examination of the lymph node FNA specimen again showed abundant bland mesothelial cells in the lymphatic spaces. Given the concern for MPM, the lymph node specimen was sent for additional ancillary testing - BRCA1 associated protein (BAP-1) IHC stain and CDKN2A/p16 homozygous deletion by fluorescent in situ hybridization (FISH). BAP-1 staining was lost in the mesothelial cells supporting MPM; the CDKN2A/p16 FISH study did not show a homozygous deletion. A third TBBX specimen of the left lung infiltrate was obtained which confirmed the diagnosis of MPM, epithelioid subtype.
Due to the patient's poor functional status, no treatment was offered. An indwelling pleural catheter was placed for palliative measures. Four months after his diagnosis, the patient presented with worsening dyspnea. He expired during that hospitalization. Autopsy examination demonstrated diffusely thickened pleura bilaterally, concentrated mostly of the left side, and measuring up to 1cm thick. Histologic sections confirmed the presence of dyscohesive malignant mesothelial cells, epithelioid subtype, with bland appearance throughout the pleura. The malignant mesothelial cells invaded the lung parenchyma minimally. While MPM is known to invade the lung parenchyma, in our case, tumor cells were present predominately within lymphatics in lung sections. Furthermore, metastatic tumor cells were evident in multiple mediastinal lymph nodes (Fig. 6).
Computed tomography of the chest 3 months after initial admission showed worsening left lung infiltrate and a new right sided pleural effusion. Lung window settings: thickness 1mm, width 1600.