A 79-year-old man presents to the clinic for worsening shortness of breath, dry cough, and chest pain for the past 5 months. He also states that for the past few months, he has been feeling exhausted throughout the day and has had 15 pounds of unintentional weight loss. Past medical history is significant for mediastinal Hodgkin lymphoma diagnosed 20 years ago that was treated successfully with chemotherapy and radiation therapy. His other medical conditions include hypertension and hyperlipidemia. Current medications include lisinopril and rosuvastatin. He has consumed 4-5 alcoholic beverages per day and smoked 1 pack of cigarettes per day for the past 30 years. He had worked in the local shipyard since his early adulthood and retired 19 years ago. Vital signs are temperature 37.1°C (98.8°F), blood pressure 138/88 mmHg, pulse 97 beats/min, and respirations 19/min. Body mass index (BMI) is 18.2 kg/m2. Physical examination reveals dullness to percussion and reduced breath sounds on the right side of the chest. An electrocardiogram shows normal sinus rhythm. A chest x-ray reveals marked diffuse opacification of the right middle and lower hemithorax with blunting of the costophrenic angle. A contrast-enhanced CT scan shows circumferential nodular pleural thickening of the right lung. Pleurocentesis is performed and reveals a bloody exudate. The patient subsequently undergoes a thoracoscopic biopsy. Histological analysis shows invasive epithelioid cells with enlarged, hyperchromatic nuclei and prominent nucleoli. The cells are positive for calretinin and cytokeratin 5/6 on immunohistochemistry.
Which of the following had the most significant role in the development of the patient’s current condition?
C) Prior occupational exposure
This patient with long-standing shortness of breath, cough, and chest pain has imaging and histopathological findings consistent with malignant pleural mesothelioma. Mesothelioma is a malignancy of the pleura, which is the thin membrane that lines the surface of the lungs. Pleural mesothelioma usually develops in older males and most often presents with chest pain and dyspnea due to an underlying pleural effusion, which is the most common initial finding in these patients.
After an initial chest x-ray, which usually shows a pleural effusion, further evaluation may include thoracocentesis (which classically yields a bloody tap), a contrast-enhanced CT scan of the chest (which usually shows pleural thickening), and a pleural biopsy.
Histology may show psammoma bodies, although these are nonspecific for mesothelioma. On immunohistochemistry, calretinin and cytokeratin 5/6 are positive in mesotheliomas and negative in most carcinomas. This is an important distinguishing feature between mesothelioma and lung carcinomas. Electron microscopy classically shows polygonal tumor cells with desmosomes, tonofilaments, and microvilli.
By far, the most important risk factor for the development of pleural mesothelioma is exposure to asbestos, usually in the workplace. The lifetime risk of developing mesothelioma among asbestos workers is thought to be as high as 10%. The use of asbestos in the United States has ceased, but any exposure at any point in life can still put a patient at risk of developing mesothelioma, even long after the exposure has ended. Some of the occupations associated with asbestos exposure include shipbuilding, roofing, mining, plumbing, and insulation work.
Answer choice A: Alcohol consumption, is incorrect. There is no evidence that alcohol consumption increases the risk of developing mesothelioma. Heavy alcohol consumption does, however, increase the risk of hepatocellular carcinoma, breast cancer, and esophageal carcinoma, among others.
Answer choice B: History of prior malignancy, is incorrect. The patient had mediastinal Hodgkin lymphoma 20 years ago that was successfully treated. A relapse could present as new-onset painless supra-diaphragmatic lymphadenopathy, the return of B symptoms such as fever, night sweats, and weight loss, and imaging and biopsy findings consistent with Hodgkin lymphoma. The current imaging and biopsy findings suggest that a different malignancy has developed in the patient.
Answer choice D: Radiation exposure, is incorrect. The patient had chemotherapy and radiation therapy 20 years ago for Hodgkin lymphoma. Although there is evidence that radiation therapy to the chest might increase the risk of developing mesothelioma even after long latency periods, it is not the primary risk factor in this patient, who has a likely history of occupational exposure to asbestos.
Answer choice E: Tobacco smoking, is incorrect. Although smoking increases the risk of developing lung cancer and many other cancers, it is not implicated in the causation of mesothelioma. A current consensus view is that asbestos exposure and tobacco smoking interact synergistically for the causation of lung cancer.
Key Learning Point
Pleural mesothelioma often causes hemorrhagic pleural effusion, which is the initial presentation in most patients. Histology can show psammoma bodies, and electron microscopy classically shows polygonal tumor cells with desmosomes, tonofilaments, and microvilli. Calretinin and cytokeratin 5/6 are positive in mesotheliomas and negative in most carcinomas. Asbestos exposure is the strongest risk factor, whereas tobacco smoking does not independently increase the risk of developing mesothelioma.
