Malignant pleural mesothelioma is an uncommon cancer with a characteristic long latency period between exposure to asbestos and clinically apparent disease.1–3 Asbestos bodies are inhaled and travel from the lung to the pleura, where they accumulate and induce genetic damage to the mesothelial cells that comprise the pleura. Clinically evident disease usually occurs 3 to 4 decades after the initial exposure to asbestos.1,3
The clinical features of malignant pleural mesothelioma are nonspecific, but the most common presenting symptoms are dyspnea and nonpleuritic chest pain, often described as a severe boring pain. Radiographically, a unilateral effusion with associated pleural thickening is the most common finding, and mesothelioma is more likely if there is mediastinal pleural involvement, rind-like pleural involvement, or if the pleural thickening is greater than 1 cm.3 The diagnostic test of choice is a medical thoracoscopy.4–7 We present a case of a patient who had massive exposure resulting in very severe involvement of the pleura.
An 86-year-old white man presented to the emergency department with anorexia, fatigue, cough, and rapidly progressive dyspnea. A large right pleural effusion was found on chest-computed tomography (Fig. 1). His history was remarkable for atrial fibrillation, diabetes, and colon cancer with status post hemicolectomy 26 years earlier. His family history was significant for a brother with dementia who died in his 70s from mesothelioma. Our patient was a nonsmoker who worked in construction with his eldest brother during his 20s and 30s. He was in the US navy during World War II and both brothers had significant recurrent exposure to loose asbestos in buckets. In addition, they cut asbestos tiles with a band saw, resulting in heavy exposure to asbestos dust.
His physical examination was normal, except for right hemithorax dullness to percussion and absent breath sounds on the right. Laboratory evaluation including a complete blood count, complete metabolic profile, thyroid-stimulating hormone, and urinalysis was remarkable only for normocytic anemia with hemoglobin of 10.3 g/dL and mild glucosuria. A computerized tomographic scan of the thorax revealed a large right pleural effusion with compressive atelectasis (Fig. 1). This also revealed pleural plaques.
He underwent a thoracentesis, and 100 mL of exudative bloody pleural fluid was aspirated. Pleuroscopy was subsequently performed, and 3.6 L of bloody pleural fluid was aspirated from the right pleural cavity. The parietal pleural surface had countless areas of patchy deeply erythematous irritation and there were multiple areas of hemorrhage, white nodules, and pachypleuritis. The visceral pleural surface had 2 areas of pearly white nodularity (Figs. 2–4). Multiple visceral and parietal pleural biopsies were obtained. It took just over 24 hours for the right lung to reexpand after the procedure.
The histology revealed large clusters of epithelioid cells with prominent atypia and increased mitotic activity. Immunohistochemical stains suggested mesothelial differentiation. They were strongly positive for calretinin and epithelial membrane antigen, focally positive for cytokeratin (CK) 5/6, and negative for CD15, CK20, meso marker, CEA, TTF-1, and B72.3. A mucarmine stain was negative. The histology was consistent with malignant mesothelioma, epithelioid type. After successful pleurodesis, the patient declined any further intervention.
Asbestos exposure has been steadily declining in the United States over the last 20 years and so has the prevalence of asbestos pulmonary disease.1,2 What makes this patient unique was his massive exposure to asbestos. In our patient, a thoracentesis was attempted to aid in diagnosis before medical thoracoscopy, a technique advocated by Blanc.7 The thoracentesis fluid was negative on cytologic analysis. More than 3 L of pleural fluid were sent from the pleuroscopy, and this too was negative. This is in accordance with several large series, where the thoracoscopic pleural fluid cytology was positive in only 18.5% to 44% of cases.5,7,8
Closed pleural biopsy yields this diagnosis in up to 60% of patients,7 but medical thoracoscopy can change the closed pleural biopsy diagnosis in up to 44% of the cases.8,9 Medical thoracoscopy has been shown to be as reliable as thoracotomy7 and is performed without the risk of general anesthesia.5,9 We prefer thoracoscopy because direct visual inspection improves tissue sampling and allows for the staging of malignant pleural mesothelioma. It also enables talc poudrage, minimizing the need for future procedures. It is generally well tolerated. The limitation of medical thoracoscopy would be the presence of dense adhesions necessitating a video-assisted thoracoscopy or thoracotomy under general anesthesia.7 In addition, parietal seeding from the interventional entry tract may occur. Prophylactic irradiation to each entry site with 21 Gy divided over 3 sessions is currently controversial.4,10,11
The neoplasm had a solid growth pattern with large clusters of atypical epithelioid cells with increased mitotic activity (Fig. 5A). There was no gland formation or mucicarmine production. The World Health Organization Histologic Classification12 was used to identify the subtype as “epithelioid.” Recommendations by the International Mesothelioma Panel13 were followed in the selection of an appropriate panel of antibodies to identify the immunohistochemical expression profile. Tumor cells were negative for broad-spectrum CK (AE1/AE3), CK20, CD15, TTF-1 (Fig. 5B), Ber-EP4, Leu-M1, B72.3, CEA, focally positive for CK5/6 (Fig. 5C) and epithelial membrane antigen, and strongly positive for calretinin (Fig. 5D).
Medical thoracoscopy is the procedure of choice in malignant cases as it can provide a diagnosis and help decide on a definitive treatment in the appropriate patient.5–9 As thoracoscopy is a safe and well-tolerated procedure with excellent results, we encourage its use in patients in whom pleural biopsies are required.5–9
This patient had very severe involvement of the pleural space with significant thickening and hemorrhage formation. This is probably due to the excessive exposure. Both the patient’s brother and his wife died of asbestos-related diseases.
1. Weill H, Hughes JM, Churg AM. Changing trends in the US mesothelioma
incidence. Occup Environ Med. 2004;61:438–441
2. Welsh L, Haile E, Dement J, et al. Change in the prevalence of asbestos-related disease among sheet metal workers 1989 to 2004. Chest. 2007;131:863–869
3. Metinas M, Ucgun I, Elbek O, et al. Computed tomography features in malignant melanoma and other commonly seen pleural diseases. Eur J Radiol. 2002;41:1–9
4. Boutin C, Schlesser M, Frenay C, et al. Malignant pleural mesothelioma
. Eur Respir J. 1998;12:972–981
5. Scherpereel A, Astoul P, Bass P, et al. Guidelines of the European Respiratory Thoracic society and European Thoracic society for the management of malignant pleural mesothelioma
. Eur Respir J. 2010;35:479–495
6. Tassi GF, Marchetti GP, Fattibene F, et al. Thoracoscopy
in malignant pleural mesothelioma
diagnosis. Diagn Ther Endosc. 1997;3:147–151
7. Blanc FX, Atasi K, Bignon J, et al. Diagnostic value of medical thoracoscopy
in pleural disease: a 6 year prospective study. Chest. 2002;121:1677–168
8. Boutin C, Rey F. Thoracoscopy
in pleural malignant mesothelioma
: a prospective study in 188 consecutive patients. Part 1, Diagnosis. Cancer. 1993;72:389–393
9. Loddenkemper R. Thoracoscopy
—State of the art. Eur Respir J. 1998;11:66–69
10. Nagendran M, Palis A, Patel M, et al. Should all patients have mesothelioma
diagnosed by video-assisted thoracoscopy
surgery have their intervention sites irradiated? Interact Cardiovasc Thorac Surg. 2011;13:66–69
11. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. 2004 Lyon, France IARC Press
12. Husain AN, Colby TV, Ordonez NG, et al. Guidelines for pathologic diagnosis of malignant mesothelioma
: a consensus statement from the International Mesothelioma
Interest Group. Arch Pathol Lab Med. 2009;133:1317–1331
13. Rusch VW. A proposed new international TNM staging system for malignant pleural mesothelioma
from the International Mesothelioma
Interest Group. Chest. 1995;108:1122–1128