- Email: [email protected]
A Rare Cause of Dysphagia: Malignant Pleural Mesothelioma in the Posterior Mediastinum
1358
CASE REPORT HAYAMA AND MAEDA MEDIASTINAL MALIGNANT MESOTHELIOMA
Ann Thorac Surg 2010;90:1358 – 61
surgery. If our hypothesis is true that MBL deficiency may affect the outcomes of patients undergoing open heart surgery with aortic cross clamping, preoperative screening for MBL deficiency will become important, and necessary perioperative management should be implemented. Further investigations are needed to delineate the correlation and possible predictive value of MBLmediated inflammatory response with clinical outcomes.
Fig 1. Perioperative mannan-binding-lectin (MBL) changes in patients who had MBL deficiency and who were undergoing cardiac surgery. Plasma samples were collected at 7 time points preoperatively, intraoperatively, and postoperatively: (1) preoperatively before skin incision, (2) after skin incision and prior to the sternotomy, (3) 5 minutes after cardiopulmonary bypass (CPB) started, (4) 5 minutes after stopping aortic cross clamping, (5) 5 minutes after CPB cessation, (6) postoperatively on day 1, and (7) postoperatively on day 2. The MBL enzyme-linked immunosorbent assay (ELISA) was performed using a human MBL ELISA kit according to the instructions by the manufacturer (Cell Sciences, Caton, MA).
FEATURE ARTICLES
MBL deficiency and who underwent cardiac surgery with CPB. Two of these patients expired with similar postoperative changes of MBL. Taken together, our results indicated the postoperative pattern of abrupt increase followed by decrease of MBL may be related with an unfavorable outcome after cardiac surgery. One possible mechanism to explain our findings is that the sudden influx of exogenous MBL into these MBL deficient patients activates a complement cascade, thus leading to systemic inflammation. The MBL may target certain patterns of carbohydrate structures or natural immunoglobulin-M ischemic antigen complex [4], which are likely exposed during the global heart ischemia through aortic cross clamping. This hypothesis is supported by a recent report that reperfusion of regionally ischemic hearts had a favorable clinical outcome in MBL-deficient patients [5]. It is interesting to note that reperfusions in these patients were achieved without blood transfusion; thus no exogenous MBL were infused. In our study, the patient who had favorable recovery had a sustained postoperative MBL level, indicating that infused exogenous MBL was not consumed and activated as with the other patients. A possible explanation is that in this patient the target(s) for MBL was not fully exposed in cardiac surgery. Supporting this hypothesis is that this patient had the shortest aortic clamping duration and CPB time. Therefore, the patient had the least global heart ischemia in comparison with the others. Although this study is descriptive, it cannot claim causality, as our interpretation of findings merely supports previous experimental models and justifies the need for future studies. The MBL deficiency is not uncommon and occurs in about 5% of normal human population [6, 7]. However, MBL deficiency is not routinely tested before open heart © 2010 by The Society of Thoracic Surgeons Published by Elsevier Inc
The authors would like to thank Dr James Cottrell for his continued support through Brooklyn Anesthesia Research, Inc, and Lawrence Lai, Michael Lee, Amy Gleed, Hsiao-ying Chin, Donna Newman, Chris Johnson, and Downstate CT-ICU staffs for their valuable assistance. The research was funded in part by the National Institutes of Health, Grant No. 1R21HL088527 (MZ) and the Empire Clinical Research Investigator Program (ECRIP) Award of New York State Department of Health (KS and MZ). Yunfang Joan Hou is an ECRIP fellow.
References 1. Carroll MC. The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol 1997;16:545– 68. 2. Lai LT, Lee DC, Ko W, Shevde K, Zhang M. Deficiency of complement factor MBL in a patient required cardiac surgery after an acute myocardial infarction with underlining chronic lymphocytic leukemia. Int J Cardiol 2010;139:e24 – 6. 3. Bilgin YM, Brand A, Berger SP, Daha MR, Roos A. Mannosebinding lectin is involved in multiple organ dysfunction syndrome after cardiac surgery: effects of blood transfusions. Transfusion 2008;48:601– 8. 4. Zhang M, Takahashi K, Alicot EM, et al. Activation of the Lectin Pathway by Natural IgM in a Model of Ischemia/ Reperfusion Injury. J Immunol 2006;177:4727–34. 5. Trendelenburg M, Theroux P, Stebbins A, Granger C, Armstrong P, Pfisterer M. Influence of functional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Eur Heart J 2010;31:1181–7. 6. Sorensen GL, Petersen I, Thiel S, et al. Genetic influences on mannan-binding lectin (MBL) and mannan-binding lectin associated serine protease-2 (MASP-2) activity. Genet Epidemiol 2007;31:31– 41. 7. Presanis JS, Kojima M, Sim RB. Biochemistry and genetics of mannan-binding lectin (MBL). Biochem Soc Trans 2003;31: 748 –52.
A Rare Cause of Dysphagia: Malignant Pleural Mesothelioma in the Posterior Mediastinum Makio Hayama, MD, and Hiroya Maeda, MD Department of Thoracic Surgery, Mitoyo General Hospital, Kagawa, Japan
A 69-year-old man presented to the emergency room with dysphagia and vomiting. A computed tomographic scan Accepted for publication March 22, 2010. Address correspondence to Dr Hayama, Department of Thoracic Surgery, Mitoyo General Hospital, 708 Himehama, Toyohama-cho, Kanonji-City, Kagawa, 769-1695, Japan; e-mail: [email protected].
0003-4975/$36.00 doi:10.1016/j.athoracsur.2010.03.082
revealed a posterior mediastinal mass surrounding the lower portion of the esophagus. Endoscopic examination demonstrated narrowing of the lower esophagus without malignant mucosal lesions. Thoracoscopic biopsies of the mediastinal mass failed to yield a pathologic diagnosis. The hyaluronic acid concentration in the left pleural effusion was remarkably high (755 mg/L), which is a finding strongly suggestive of malignant mesothelioma. Four months after the initial admission, a subcutaneous nodule was found in the left chest wall and a biopsy was taken. The histopathologic and immunohistochemical findings of the biopsy were consistent with the diagnosis of pleural malignant mesothelioma. (Ann Thorac Surg 2010;90:1358 – 61) © 2010 by The Society of Thoracic Surgeons
M
alignant pleural mesothelioma usually develops diffusely along the parietal and visceral pleura. This report describes a relatively rare case of malignant pleural mesothelioma in which the patient presented with dysphagia as the initial symptom. In this case, the
CASE REPORT HAYAMA AND MAEDA MEDIASTINAL MALIGNANT MESOTHELIOMA
1359
tumor had formed a mass in the lower posterior mediastinum and had surrounded the esophagus, resulting in the development of dysphagia. A 69-year-old man visited our emergency room complaining of dysphagia and vomiting. He had experienced these symptoms for several months. He was currently a heavy smoker, but had no history of occupational asbestosis exposure. A chest roentgenogram showed a moderate amount of pleural effusion with pneumothorax. The patient was admitted into our hospital for further evaluation and treatment. The results of routine laboratory tests were within normal limits, although the serum level of cytokeratin 19 fragment was high at a concentration of 6.0 ng/mL (normal range ⬍ 3.5). A computed tomographic scan of his chest and abdomen revealed a posterior mediastinal mass surrounding the lower portion of the esophagus, which was causing esophageal stenosis (Fig 1A). In the same computed tomographic scan, no pleural thickening (as in cases of diffuse malignant pleural mesothelioma) was observed in either pleural cavity, Fig 1. (A) A chest computed tomographic scan shows a posterior mediastinal mass surrounding the lower portion of the esophagus. (B) Thoracoscopic examination revealed that the surface of the posterior mediastinal mass (arrow) was smooth. (C) A positron emission tomographic and computed tomographic scan shows that the standardized uptake value of the mediastinal mass is high at 5.2 (arrow).
FEATURE ARTICLES
Ann Thorac Surg 2010;90:1358 – 61
1360
CASE REPORT HAYAMA AND MAEDA MEDIASTINAL MALIGNANT MESOTHELIOMA
Ann Thorac Surg 2010;90:1358 – 61
cutaneous nodule were consistent with the diagnosis of malignant pleural mesothelioma (epithelioid type). To relieve his symptoms, a self-expanding esophageal metal stent (Ultraflex; Boston Scientific Japan Corporation, Tokyo, Japan) was deployed endoscopically. After this procedure there was a marked improvement in the patient’s dysphagia. The patient received cisplatin and pemetrexed combination chemotherapy, but this did not result in any symptomatic or radiographic improvement. The patient died 6 months after the first admission.
Comment
Fig 2. Microscopic findings indicate a diffuse epithelial tumor cell proliferation with a condensed or palisading pattern in the fibrous tissue. (Hematoxylin and eosin stain; ⫻40.)
FEATURE ARTICLES
even though there were small to moderate amounts of pleural effusion on both sides and the pneumothorax on the right side. Endoscopic examination revealed narrowing of the entire lower portion of the esophagus. There were no malignant mucosal lesions in the esophagus or stomach. At this point, he underwent thoracoscopic surgery to treat the right pneumothorax, and a surgical biopsy was taken from the mediastinal mass. Thoracoscopic examination revealed no obvious mass formation in the visceral and parietal pleura. Furthermore, no bullae or blebs were observed. The surface of the mediastinal mass was smooth (Fig 1B). We performed surgical biopsies of the mass, but failed to reach a pathologic diagnosis. A positron emission tomographic and computed tomographic scan showed that the standardized uptake value of the mediastinal mass was high (5.2) and that the tumor had invaded the diaphragm and extended to the peritoneal cavity at the level of the abdominal aorta (Fig 1C). A repeated cytological examination of both pleural effusions was negative; however, the hyaluronic acid concentration in the patient’s left pleural effusion was remarkably high at 755 mg/L. We made a tentative diagnosis of malignant pleural mesothelioma. However, the patient refused to undergo another surgical biopsy of the mediastinal mass. Therefore, he was discharged from the hospital without a determined diagnosis, even though he could only consume liquid food. Two and a half months later, he began to experience difficulty in swallowing any type of food. On his second admission, we noticed that he had a subcutaneous nodule in his left chest wall, in a location where a pleural drainage tube had been previously placed. Immediately a pathologic examination was performed on the surgical biopsy of the nodule. Hematoxylin and eosin staining of the specimen (Fig 2) revealed diffuse epithelial tumor cell proliferation with a condensed or palisading pattern in the fibrous tissue. Immunohistochemistry was positive for calretinin, vimentin, epithelial membrane antigen, and cytokeratin. These histopathologic findings from the implanted sub-
Malignant mesothelioma, which usually originates from the pleura and peritoneum, was once rare. However, currently the incidence of this type of tumor is increasing worldwide [1], which is probably a result of occupational or environmental exposure to asbestos, as first described by Wagner and colleagues [2]. The largest series [3] of malignant mesothelioma cases revealed that dyspnea, chest pain, or a combination of these were usually the initial symptoms of the malignant pleural mesothelioma, which accounted for 90% of all patients. Dysphagia only occurs in 1.4% of pleural malignant mesotheliomas and is very rare as the initial symptom [3]. Johnson and colleagues [4] reported the first case of malignant pleural mesothelioma presenting as dysphagia in 1983. According to a previous report, pleural mesothelioma is a rare cause of malignant pseudoachalasia, which accounts for 7.6% of all diagnoses [5]. The pathogenesis of pseudoachalasia continues to remain unclear; however, as the most common mechanism, it is believed that the tumor might directly infiltrate the nerves within the myenteric plexus of the esophagus [5]. In this case, pseudoachalasia (as previously described) might have occurred as the initial event, or the mass in the posterior mediastinum itself may have simply obstructed the free passage of the esophagus. Mesothelioma usually develops diffusely along the parietal and visceral pleura. In our case, the tumor formed a mass in the lower posterior mediastinum and surrounded the esophagus concentrically without mucosal invasion. Mesothelioma has a propensity to spread within tissue planes [4]. This aspect might explain the tumor growth and clinical presentation of our case. Malignant mesothelioma with pleural or abdominal effusion is diagnosed cytologically in 33% to 84% of cases [6]. However, in our case, even repeated cytologic examinations of the pleural effusions failed to yield a diagnosis of malignant pleural mesothelioma. An extremely high concentration (⬎100 mg/L) of hyaluronic acid in the pleural effusions makes the diagnosis of malignant mesothelioma very likely, even though cytologic inspections might be negative [7]. At this point, we were highly suspicious of malignant mesothelioma in our case, even before pathologic confirmation was obtained from the subcutaneous tumor implanted in the left chest wall. Although it is extremely difficult to treat malignant mesothelioma, there has been significant progress during the last few years [1]. We administered pemetrexed plus
CASE REPORT AFSHAR ET AL PERICARDIAL CONSTRICTION AFTER LUNG TRANSPLANTATION
cisplatin chemotherapy after esophageal stent placement. In a multicenter phase 3 study, those patients treated with pemetrexed plus cisplatin had a longer overall median survival (12.1 months) than those treated with cisplatin only (9.3 months) [8]. This report describes a relatively rare case of malignant pleural mesothelioma presenting as dysphagia as the initial symptom. This type of mesothelioma is extremely difficult to treat at an advanced stage. Therefore it is critical to reach a confirmative diagnosis at an early stage.
References 1. Robinson BWS, Lake RA. Advances in Malignant Mesothelioma. N Engl J Med 2005;353:1591–1603. 2. Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med 1960;17:260 –271. 3. Ruffie P, Feld R, Minkin S, et al. Diffuse Malignant Mesothelioma of the Pleura in Ontario and Quebec: A Retrospective Study of 332 Patients. J Clin Oncol 1989;7:1157–1168. 4. Johnson CE, Wardman AG, McMahon MJ, Cooke NJ. Dysphagia complicating malignant mesothelioma. Thorax 1983; 38:635– 636. 5. Liu W, Fackler W, Rice TW, Richter JE, Achkar E, Goldblum JR. The Pathogenesis of Pseudoachalasia A Clinicopathologic Study of 13 Cases of a Rare Entity. Am J Surg Pathol 2002;26:784 –788. 6. Whitaker D. The cytology of malignant mesothelioma. Cytopathology 2000;11:139 –151. 7. Welker L, Müller M, Holz O, Vollmer E, Magnussen H, Jörres RA. Cytological diagnosis of malignant mesothelioma— improvement by additional analysis of hyaluronic acid in pleural effusions. Virchows Arch 2007;450:455– 461. 8. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21:2636 –2644.
Pericardial Constriction After Lung Transplantation Kamyar Afshar, DO, Mark J. Cunningham, MD, Richard G. Barbers, MD, and Paul Michael McFadden, MD Divisions of Pulmonary and Critical Care Medicine and Cardiothoracic Surgery, University of Southern California, Keck School of Medicine, Los Angeles, California
Pericardial constriction is extremely rare after lung transplantation. We present a case and review the potential contributing factors for pericardial constriction after lung transplantation. Treatment for this condition, irrespective of the cause, remains pericardiectomy. (Ann Thorac Surg 2010;90:1361–3) © 2010 by The Society of Thoracic Surgeons Accepted for publication March 17, 2010. Address correspondence to Dr Afshar, University of Southern California, Keck School of Medicine, Division of Pulmonary and Critical Care Medicine, 1200 N State St, GH 11900, Los Angeles, CA 90033; e-mail: [email protected].
© 2010 by The Society of Thoracic Surgeons Published by Elsevier Inc
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P
ericardial constriction is a consequence of progressive fibrosis of the pericardium. The resulting loss of pericardial compliance impairs cardiac diastolic filling and diminishes cardiac output. Mortality from pericardial constriction depends on the underlying cause, such as infection, malignancy, pericarditis, rheumatic disorders, or previous cardiac surgery [1]. Pericardial constriction is extremely rare after lung transplantation. Despite 26,000 lung transplants performed worldwide since 1989, only a single case has been reported. We report a second case of pericardial constriction after bilateral sequential lung transplantation, and we review the potential causes after lung transplantation.
A 43-year-old woman presented with dyspnea, orthopnea, and lower extremity edema 4 years after cadaveric bilateral sequential lung transplantation for bronchiectasis. Triple-drug immunosuppression was adequately maintained with tacrolimus (1 mg twice a day), mycophenolate mofetil (250 mg twice a day), and prednisone (10 mg daily). Her medical history included moderately well-controlled post-transplant diabetes mellitus and hypertension. Heparin-induced, left lower extremity, deep vein thrombus resulted in a nonfatal pulmonary embolism. Subsequent anticoagulation resulted in nonlifethreatening bleeding requiring inferior vena cava filter placement. A single A2 acute cellular rejection episode occurring 3 years after lung transplantation was successfully reversed. The physical examination of the patient demonstrated muted heart sounds and jugular venous distention with a hepatojugular reflux. Diminished breath sounds and percussion dullness were appreciated over the left lower hemithorax. Her forced expiratory volume in 1 second was 1.44 L (61% predicted, which was a 25% reduction from her best post-transplant value); her laboratory studies were only significant for acute uremia (blood urea nitrogen, 94; creatinine, 2.6 mg/dL). The leucocyte count was 5,700 cells/cm3 and the serum tacrolimus level was 8.9 ng/mL, which was in the acceptable range. A chest roentgenogram demonstrated cardiomegaly and moderate left-sided pleural effusion (Fig 1). A thoracentesis revealed exudative pleural effusion. The echocardiogram showed pericardial effusion with respiratory variance, suggestive for tamponade physiology. Pulmonary hemodynamic measurements showed equalization of pressures with a mean right arterial pressure of 24 mm Hg, a diastolic pulmonary artery pressure of 24 mm Hg, and a pulmonary artery wedge pressure of 26 mm Hg. The cardiac index was severely impaired to 1.4 L/min/m2. After removal of 150 cc of pericardial fluid, her hemodynamic profile normalized, and her respiratory symptoms significantly improved, as did the renal function. Again, the pericardial fluid was consistent with an exudative process of unclear cause. Serum rheumatoid factor, antinuclear antibody and double stranded DNA serologies were negative. Complement C3 and C4 levels were normal at 97 mg/dL and 33 mg/dL, respectively. Inflammatory markers C-reactive protein (0.21 mg/dL) and 0003-4975/$36.00 doi:10.1016/j.athoracsur.2010.03.027
FEATURE ARTICLES
Ann Thorac Surg 2010;90:1361–3
CASE REPORT HAYAMA AND MAEDA MEDIASTINAL MALIGNANT MESOTHELIOMA
Ann Thorac Surg 2010;90:1358 – 61
surgery. If our hypothesis is true that MBL deficiency may affect the outcomes of patients undergoing open heart surgery with aortic cross clamping, preoperative screening for MBL deficiency will become important, and necessary perioperative management should be implemented. Further investigations are needed to delineate the correlation and possible predictive value of MBLmediated inflammatory response with clinical outcomes.
Fig 1. Perioperative mannan-binding-lectin (MBL) changes in patients who had MBL deficiency and who were undergoing cardiac surgery. Plasma samples were collected at 7 time points preoperatively, intraoperatively, and postoperatively: (1) preoperatively before skin incision, (2) after skin incision and prior to the sternotomy, (3) 5 minutes after cardiopulmonary bypass (CPB) started, (4) 5 minutes after stopping aortic cross clamping, (5) 5 minutes after CPB cessation, (6) postoperatively on day 1, and (7) postoperatively on day 2. The MBL enzyme-linked immunosorbent assay (ELISA) was performed using a human MBL ELISA kit according to the instructions by the manufacturer (Cell Sciences, Caton, MA).
FEATURE ARTICLES
MBL deficiency and who underwent cardiac surgery with CPB. Two of these patients expired with similar postoperative changes of MBL. Taken together, our results indicated the postoperative pattern of abrupt increase followed by decrease of MBL may be related with an unfavorable outcome after cardiac surgery. One possible mechanism to explain our findings is that the sudden influx of exogenous MBL into these MBL deficient patients activates a complement cascade, thus leading to systemic inflammation. The MBL may target certain patterns of carbohydrate structures or natural immunoglobulin-M ischemic antigen complex [4], which are likely exposed during the global heart ischemia through aortic cross clamping. This hypothesis is supported by a recent report that reperfusion of regionally ischemic hearts had a favorable clinical outcome in MBL-deficient patients [5]. It is interesting to note that reperfusions in these patients were achieved without blood transfusion; thus no exogenous MBL were infused. In our study, the patient who had favorable recovery had a sustained postoperative MBL level, indicating that infused exogenous MBL was not consumed and activated as with the other patients. A possible explanation is that in this patient the target(s) for MBL was not fully exposed in cardiac surgery. Supporting this hypothesis is that this patient had the shortest aortic clamping duration and CPB time. Therefore, the patient had the least global heart ischemia in comparison with the others. Although this study is descriptive, it cannot claim causality, as our interpretation of findings merely supports previous experimental models and justifies the need for future studies. The MBL deficiency is not uncommon and occurs in about 5% of normal human population [6, 7]. However, MBL deficiency is not routinely tested before open heart © 2010 by The Society of Thoracic Surgeons Published by Elsevier Inc
The authors would like to thank Dr James Cottrell for his continued support through Brooklyn Anesthesia Research, Inc, and Lawrence Lai, Michael Lee, Amy Gleed, Hsiao-ying Chin, Donna Newman, Chris Johnson, and Downstate CT-ICU staffs for their valuable assistance. The research was funded in part by the National Institutes of Health, Grant No. 1R21HL088527 (MZ) and the Empire Clinical Research Investigator Program (ECRIP) Award of New York State Department of Health (KS and MZ). Yunfang Joan Hou is an ECRIP fellow.
References 1. Carroll MC. The role of complement and complement receptors in induction and regulation of immunity. Annu Rev Immunol 1997;16:545– 68. 2. Lai LT, Lee DC, Ko W, Shevde K, Zhang M. Deficiency of complement factor MBL in a patient required cardiac surgery after an acute myocardial infarction with underlining chronic lymphocytic leukemia. Int J Cardiol 2010;139:e24 – 6. 3. Bilgin YM, Brand A, Berger SP, Daha MR, Roos A. Mannosebinding lectin is involved in multiple organ dysfunction syndrome after cardiac surgery: effects of blood transfusions. Transfusion 2008;48:601– 8. 4. Zhang M, Takahashi K, Alicot EM, et al. Activation of the Lectin Pathway by Natural IgM in a Model of Ischemia/ Reperfusion Injury. J Immunol 2006;177:4727–34. 5. Trendelenburg M, Theroux P, Stebbins A, Granger C, Armstrong P, Pfisterer M. Influence of functional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Eur Heart J 2010;31:1181–7. 6. Sorensen GL, Petersen I, Thiel S, et al. Genetic influences on mannan-binding lectin (MBL) and mannan-binding lectin associated serine protease-2 (MASP-2) activity. Genet Epidemiol 2007;31:31– 41. 7. Presanis JS, Kojima M, Sim RB. Biochemistry and genetics of mannan-binding lectin (MBL). Biochem Soc Trans 2003;31: 748 –52.
A Rare Cause of Dysphagia: Malignant Pleural Mesothelioma in the Posterior Mediastinum Makio Hayama, MD, and Hiroya Maeda, MD Department of Thoracic Surgery, Mitoyo General Hospital, Kagawa, Japan
A 69-year-old man presented to the emergency room with dysphagia and vomiting. A computed tomographic scan Accepted for publication March 22, 2010. Address correspondence to Dr Hayama, Department of Thoracic Surgery, Mitoyo General Hospital, 708 Himehama, Toyohama-cho, Kanonji-City, Kagawa, 769-1695, Japan; e-mail: [email protected].
0003-4975/$36.00 doi:10.1016/j.athoracsur.2010.03.082
revealed a posterior mediastinal mass surrounding the lower portion of the esophagus. Endoscopic examination demonstrated narrowing of the lower esophagus without malignant mucosal lesions. Thoracoscopic biopsies of the mediastinal mass failed to yield a pathologic diagnosis. The hyaluronic acid concentration in the left pleural effusion was remarkably high (755 mg/L), which is a finding strongly suggestive of malignant mesothelioma. Four months after the initial admission, a subcutaneous nodule was found in the left chest wall and a biopsy was taken. The histopathologic and immunohistochemical findings of the biopsy were consistent with the diagnosis of pleural malignant mesothelioma. (Ann Thorac Surg 2010;90:1358 – 61) © 2010 by The Society of Thoracic Surgeons
M
alignant pleural mesothelioma usually develops diffusely along the parietal and visceral pleura. This report describes a relatively rare case of malignant pleural mesothelioma in which the patient presented with dysphagia as the initial symptom. In this case, the
CASE REPORT HAYAMA AND MAEDA MEDIASTINAL MALIGNANT MESOTHELIOMA
1359
tumor had formed a mass in the lower posterior mediastinum and had surrounded the esophagus, resulting in the development of dysphagia. A 69-year-old man visited our emergency room complaining of dysphagia and vomiting. He had experienced these symptoms for several months. He was currently a heavy smoker, but had no history of occupational asbestosis exposure. A chest roentgenogram showed a moderate amount of pleural effusion with pneumothorax. The patient was admitted into our hospital for further evaluation and treatment. The results of routine laboratory tests were within normal limits, although the serum level of cytokeratin 19 fragment was high at a concentration of 6.0 ng/mL (normal range ⬍ 3.5). A computed tomographic scan of his chest and abdomen revealed a posterior mediastinal mass surrounding the lower portion of the esophagus, which was causing esophageal stenosis (Fig 1A). In the same computed tomographic scan, no pleural thickening (as in cases of diffuse malignant pleural mesothelioma) was observed in either pleural cavity, Fig 1. (A) A chest computed tomographic scan shows a posterior mediastinal mass surrounding the lower portion of the esophagus. (B) Thoracoscopic examination revealed that the surface of the posterior mediastinal mass (arrow) was smooth. (C) A positron emission tomographic and computed tomographic scan shows that the standardized uptake value of the mediastinal mass is high at 5.2 (arrow).
FEATURE ARTICLES
Ann Thorac Surg 2010;90:1358 – 61
1360
CASE REPORT HAYAMA AND MAEDA MEDIASTINAL MALIGNANT MESOTHELIOMA
Ann Thorac Surg 2010;90:1358 – 61
cutaneous nodule were consistent with the diagnosis of malignant pleural mesothelioma (epithelioid type). To relieve his symptoms, a self-expanding esophageal metal stent (Ultraflex; Boston Scientific Japan Corporation, Tokyo, Japan) was deployed endoscopically. After this procedure there was a marked improvement in the patient’s dysphagia. The patient received cisplatin and pemetrexed combination chemotherapy, but this did not result in any symptomatic or radiographic improvement. The patient died 6 months after the first admission.
Comment
Fig 2. Microscopic findings indicate a diffuse epithelial tumor cell proliferation with a condensed or palisading pattern in the fibrous tissue. (Hematoxylin and eosin stain; ⫻40.)
FEATURE ARTICLES
even though there were small to moderate amounts of pleural effusion on both sides and the pneumothorax on the right side. Endoscopic examination revealed narrowing of the entire lower portion of the esophagus. There were no malignant mucosal lesions in the esophagus or stomach. At this point, he underwent thoracoscopic surgery to treat the right pneumothorax, and a surgical biopsy was taken from the mediastinal mass. Thoracoscopic examination revealed no obvious mass formation in the visceral and parietal pleura. Furthermore, no bullae or blebs were observed. The surface of the mediastinal mass was smooth (Fig 1B). We performed surgical biopsies of the mass, but failed to reach a pathologic diagnosis. A positron emission tomographic and computed tomographic scan showed that the standardized uptake value of the mediastinal mass was high (5.2) and that the tumor had invaded the diaphragm and extended to the peritoneal cavity at the level of the abdominal aorta (Fig 1C). A repeated cytological examination of both pleural effusions was negative; however, the hyaluronic acid concentration in the patient’s left pleural effusion was remarkably high at 755 mg/L. We made a tentative diagnosis of malignant pleural mesothelioma. However, the patient refused to undergo another surgical biopsy of the mediastinal mass. Therefore, he was discharged from the hospital without a determined diagnosis, even though he could only consume liquid food. Two and a half months later, he began to experience difficulty in swallowing any type of food. On his second admission, we noticed that he had a subcutaneous nodule in his left chest wall, in a location where a pleural drainage tube had been previously placed. Immediately a pathologic examination was performed on the surgical biopsy of the nodule. Hematoxylin and eosin staining of the specimen (Fig 2) revealed diffuse epithelial tumor cell proliferation with a condensed or palisading pattern in the fibrous tissue. Immunohistochemistry was positive for calretinin, vimentin, epithelial membrane antigen, and cytokeratin. These histopathologic findings from the implanted sub-
Malignant mesothelioma, which usually originates from the pleura and peritoneum, was once rare. However, currently the incidence of this type of tumor is increasing worldwide [1], which is probably a result of occupational or environmental exposure to asbestos, as first described by Wagner and colleagues [2]. The largest series [3] of malignant mesothelioma cases revealed that dyspnea, chest pain, or a combination of these were usually the initial symptoms of the malignant pleural mesothelioma, which accounted for 90% of all patients. Dysphagia only occurs in 1.4% of pleural malignant mesotheliomas and is very rare as the initial symptom [3]. Johnson and colleagues [4] reported the first case of malignant pleural mesothelioma presenting as dysphagia in 1983. According to a previous report, pleural mesothelioma is a rare cause of malignant pseudoachalasia, which accounts for 7.6% of all diagnoses [5]. The pathogenesis of pseudoachalasia continues to remain unclear; however, as the most common mechanism, it is believed that the tumor might directly infiltrate the nerves within the myenteric plexus of the esophagus [5]. In this case, pseudoachalasia (as previously described) might have occurred as the initial event, or the mass in the posterior mediastinum itself may have simply obstructed the free passage of the esophagus. Mesothelioma usually develops diffusely along the parietal and visceral pleura. In our case, the tumor formed a mass in the lower posterior mediastinum and surrounded the esophagus concentrically without mucosal invasion. Mesothelioma has a propensity to spread within tissue planes [4]. This aspect might explain the tumor growth and clinical presentation of our case. Malignant mesothelioma with pleural or abdominal effusion is diagnosed cytologically in 33% to 84% of cases [6]. However, in our case, even repeated cytologic examinations of the pleural effusions failed to yield a diagnosis of malignant pleural mesothelioma. An extremely high concentration (⬎100 mg/L) of hyaluronic acid in the pleural effusions makes the diagnosis of malignant mesothelioma very likely, even though cytologic inspections might be negative [7]. At this point, we were highly suspicious of malignant mesothelioma in our case, even before pathologic confirmation was obtained from the subcutaneous tumor implanted in the left chest wall. Although it is extremely difficult to treat malignant mesothelioma, there has been significant progress during the last few years [1]. We administered pemetrexed plus
CASE REPORT AFSHAR ET AL PERICARDIAL CONSTRICTION AFTER LUNG TRANSPLANTATION
cisplatin chemotherapy after esophageal stent placement. In a multicenter phase 3 study, those patients treated with pemetrexed plus cisplatin had a longer overall median survival (12.1 months) than those treated with cisplatin only (9.3 months) [8]. This report describes a relatively rare case of malignant pleural mesothelioma presenting as dysphagia as the initial symptom. This type of mesothelioma is extremely difficult to treat at an advanced stage. Therefore it is critical to reach a confirmative diagnosis at an early stage.
References 1. Robinson BWS, Lake RA. Advances in Malignant Mesothelioma. N Engl J Med 2005;353:1591–1603. 2. Wagner JC, Sleggs CA, Marchand P. Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province. Br J Ind Med 1960;17:260 –271. 3. Ruffie P, Feld R, Minkin S, et al. Diffuse Malignant Mesothelioma of the Pleura in Ontario and Quebec: A Retrospective Study of 332 Patients. J Clin Oncol 1989;7:1157–1168. 4. Johnson CE, Wardman AG, McMahon MJ, Cooke NJ. Dysphagia complicating malignant mesothelioma. Thorax 1983; 38:635– 636. 5. Liu W, Fackler W, Rice TW, Richter JE, Achkar E, Goldblum JR. The Pathogenesis of Pseudoachalasia A Clinicopathologic Study of 13 Cases of a Rare Entity. Am J Surg Pathol 2002;26:784 –788. 6. Whitaker D. The cytology of malignant mesothelioma. Cytopathology 2000;11:139 –151. 7. Welker L, Müller M, Holz O, Vollmer E, Magnussen H, Jörres RA. Cytological diagnosis of malignant mesothelioma— improvement by additional analysis of hyaluronic acid in pleural effusions. Virchows Arch 2007;450:455– 461. 8. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21:2636 –2644.
Pericardial Constriction After Lung Transplantation Kamyar Afshar, DO, Mark J. Cunningham, MD, Richard G. Barbers, MD, and Paul Michael McFadden, MD Divisions of Pulmonary and Critical Care Medicine and Cardiothoracic Surgery, University of Southern California, Keck School of Medicine, Los Angeles, California
Pericardial constriction is extremely rare after lung transplantation. We present a case and review the potential contributing factors for pericardial constriction after lung transplantation. Treatment for this condition, irrespective of the cause, remains pericardiectomy. (Ann Thorac Surg 2010;90:1361–3) © 2010 by The Society of Thoracic Surgeons Accepted for publication March 17, 2010. Address correspondence to Dr Afshar, University of Southern California, Keck School of Medicine, Division of Pulmonary and Critical Care Medicine, 1200 N State St, GH 11900, Los Angeles, CA 90033; e-mail: [email protected].
© 2010 by The Society of Thoracic Surgeons Published by Elsevier Inc
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ericardial constriction is a consequence of progressive fibrosis of the pericardium. The resulting loss of pericardial compliance impairs cardiac diastolic filling and diminishes cardiac output. Mortality from pericardial constriction depends on the underlying cause, such as infection, malignancy, pericarditis, rheumatic disorders, or previous cardiac surgery [1]. Pericardial constriction is extremely rare after lung transplantation. Despite 26,000 lung transplants performed worldwide since 1989, only a single case has been reported. We report a second case of pericardial constriction after bilateral sequential lung transplantation, and we review the potential causes after lung transplantation.
A 43-year-old woman presented with dyspnea, orthopnea, and lower extremity edema 4 years after cadaveric bilateral sequential lung transplantation for bronchiectasis. Triple-drug immunosuppression was adequately maintained with tacrolimus (1 mg twice a day), mycophenolate mofetil (250 mg twice a day), and prednisone (10 mg daily). Her medical history included moderately well-controlled post-transplant diabetes mellitus and hypertension. Heparin-induced, left lower extremity, deep vein thrombus resulted in a nonfatal pulmonary embolism. Subsequent anticoagulation resulted in nonlifethreatening bleeding requiring inferior vena cava filter placement. A single A2 acute cellular rejection episode occurring 3 years after lung transplantation was successfully reversed. The physical examination of the patient demonstrated muted heart sounds and jugular venous distention with a hepatojugular reflux. Diminished breath sounds and percussion dullness were appreciated over the left lower hemithorax. Her forced expiratory volume in 1 second was 1.44 L (61% predicted, which was a 25% reduction from her best post-transplant value); her laboratory studies were only significant for acute uremia (blood urea nitrogen, 94; creatinine, 2.6 mg/dL). The leucocyte count was 5,700 cells/cm3 and the serum tacrolimus level was 8.9 ng/mL, which was in the acceptable range. A chest roentgenogram demonstrated cardiomegaly and moderate left-sided pleural effusion (Fig 1). A thoracentesis revealed exudative pleural effusion. The echocardiogram showed pericardial effusion with respiratory variance, suggestive for tamponade physiology. Pulmonary hemodynamic measurements showed equalization of pressures with a mean right arterial pressure of 24 mm Hg, a diastolic pulmonary artery pressure of 24 mm Hg, and a pulmonary artery wedge pressure of 26 mm Hg. The cardiac index was severely impaired to 1.4 L/min/m2. After removal of 150 cc of pericardial fluid, her hemodynamic profile normalized, and her respiratory symptoms significantly improved, as did the renal function. Again, the pericardial fluid was consistent with an exudative process of unclear cause. Serum rheumatoid factor, antinuclear antibody and double stranded DNA serologies were negative. Complement C3 and C4 levels were normal at 97 mg/dL and 33 mg/dL, respectively. Inflammatory markers C-reactive protein (0.21 mg/dL) and 0003-4975/$36.00 doi:10.1016/j.athoracsur.2010.03.027
FEATURE ARTICLES
Ann Thorac Surg 2010;90:1361–3