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Primary malignant mesothelioma of the pericardium
Cardiovascular Pathology 20 (2011) 107 – 109
Original Article
Primary malignant mesothelioma of the pericardium Junaid Patel⁎, Mary N. Sheppard CRY Centre for Cardiac Pathology, National Heart and Lung Institute, Imperial College, London, UK Received 31 August 2009; received in revised form 24 November 2009; accepted 5 January 2010
Abstract Primary malignant pericardial mesothelioma is an extremely rare tumor. One of the largest autopsy series gave an incidence of primary pericardial tumors of 0.0022%, of which mesothelioma is the most common type. A male predominance of the disease has been described, and the majority of cases occur in the fourth to seventh decades of life. Unlike peritoneal and pleural mesothelioma, there has been no definite correlation between asbestos exposure and pericardial disease. Malignant pericardial mesothelioma carries a poor prognosis with few successful treatment strategies and little benefit from radiation and chemotherapy. We report a case of a 66year-old man who presented with shortness of breath, right shoulder pain, and peripheral edema of the lower limbs. A large pericardial effusion was seen on echocardiography, which was drained but the patient died the following day. A malignant tumor was found on autopsy and a final diagnosis of primary malignant pericardial mesothelioma was made following histopathological examination. © 2011 Elsevier Inc. All rights reserved. Keywords: Pericardial effusion; Echocardiogram, Tumor; Pericardium; Mesothelioma
1. Introduction Primary malignant pericardial mesothelioma is an extremely rare tumor with about 150 cases described in the literature to date. It arises from mesothelial cells or possibly a more primitive precursor cell situated submesothelially. The definition of primary pericardial mesothelioma stipulates that there is no tumor present outside the pericardium, with the exception of lymph node metastases [1]. Here we present a case of malignant pericardial mesothelioma in a 66-year-old man who was diagnosed at autopsy. 2. Case A 66-year-old man was admitted with a 3-week history of shortness of breath and right shoulder pain. Over the ⁎ Corresponding author. Department of Histopathology, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. Tel.: +44 2073518424; fax: + 44 2073518293. E-mail address: [email protected] (J. Patel). 1054-8807/10/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2010.01.005
same period he developed oliguria and pitting leg edema. His past medical history included right carotid endarterectomy and glaucoma (1998). He also had atrial fibrillation and had been treated with warfarin. He suffered a spinal hematoma (2001) which left him with paralysis and urinary incontinence. His medication included digoxin, enalapril, allopurinol, aspirin, and oxybutinin. He was a nonsmoker and had no apparent history of occupational or incidental exposure to asbestos. On examination, the patient appeared distressed with a respiratory rate of 20 breaths per minute. He had an irregularly irregular pulse of 110 beats per minute and his blood pressure was 100/70. His jugular venous pressure was elevated and he had severe peripheral edema of his lower limbs. An echocardiogram showed a large pericardial effusion and he was transferred on the same day to the National Heart and Lung Institute for treatment. The pericardial effusion was drained (1200 ml straw-colored fluid), and fluid and tissue were sent for cytological, histological, and microbiological investigation. One thousand milliliters of left pleural effusion was drained at the same time. The following day, the patient was found not breathing and was declared dead following unsuccessful resuscitation.
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J. Patel, M.N. Sheppard / Cardiovascular Pathology 20 (2011) 107–109
On autopsy, the pericardial sac was noted to be markedly thickened and expanded and a malignant tumor was seen encasing the heart on both visceral and parietal aspects (Fig. 1A). In the pericardial space, necrotic fragments of the tumor were found. The tumor had a variegated white and hemorrhagic cut surface (Fig. 1B). Both right and left ventricles were compressed by the tumor. The thickness of the parietal pericardium was 12 mm and the visceral 10 mm. The heart was otherwise normal with no intramuscular tumor. There were no pulmonary emboli but the left pleural cavity contained 700 ml of serous effusion. The parietal and visceral pleura of the lungs were smooth. However, a nodular area was present in the right middle lobe beneath the pleura (2×1×1 cm) close to a subsegmental bronchus which also contained a pale plug of tissue which was blocking it. Microscopic examination of the tumor surrounding the heart showed a spindle cell tumor with hyperchromatic, pleomorphic nuclei (Fig. 2A). Mitoses and hemorrhages were present. Immunohistochemistry showed the tumor to stain positively for calretinin (Fig. 2B) and thrombomodulin. The nodule in the right middle lobe of the lung stained positively for calretinin. These findings were consistent with a primary spindle cell pericardial malignant mesothelioma with metastasis in the right middle lobe of the lung.
Fig. 2. (A) Microscopic examination showing a spindle cell tumor with hyperchromatic, pleomorphic nuclei. (Hematoxylin and eosin stain; magnification ×200.) (B) Immunohistochemistry showing the tumor to stain positively for calretinin.
3. Discussion
Fig. 1. (A) Malignant tumor encasing the heart on both visceral and parietal aspects. (B) The tumor has a variegated white and hemorrhagic cut surface.
Primary malignant pericardial mesothelioma is an exceptionally rare tumor. One of the largest autopsy series gave an incidence of primary pericardial tumors of 0.0022%, of which mesothelioma was the most common type [2]. They account for about 2–3% of all cardiac and pericardial primary tumors and about 1% of all mesotheliomas [3]. Of 240 thoracic mesotheliomas in the Armed Forces of Institute of Pathology (AFIP) files from 1970 to 1995, only eight were limited to the heart and pericardium [1]. A male predominance of the disease has been described, and the majority of cases occur in the fourth to seventh decades of life [1]. A review of 59 cases of pericardial mesothelioma by AFIP found the mean age of patients at presentation to be 46 years with an age range of 2 to 78 years. Of these patients, 39 were men and 20 were women. The male-to-female ratio of nearly 2:1 is lower than the ratio of approximately 3.5:1 for mesotheliomas of the pleura. The higher proportion of women suggests that the link with asbestos exposure is weaker for pericardial than for pleural mesothelioma, or that some pericardial mesotheliomas are pathogenetically distinct from their pleural counterparts [1]. The etiology of primary malignant mesothelioma of the pericardium remains unclear. Unlike peritoneal and pleural
J. Patel, M.N. Sheppard / Cardiovascular Pathology 20 (2011) 107–109
mesothelioma, there has been no definite correlation between asbestos exposure and pericardial disease, as in our case [2]. In most reported cases of pericardial mesotheliomas no history of asbestos exposure is mentioned. However, many of these reports appeared before the link was established. The association between malignant mesothelioma of the pleura and asbestosis was first described in 1954 and subsequently established in 1960 [1]. Due to the relative rarity of pericardial mesotheliomas, it has been difficult to establish a link between them and asbestos exposure. Thomason et al. [4] described 28 cases of primary pericardial mesothelioma from 1972 through 1992 and noted that, unlike in the case of pleural mesothelioma, asbestos exposure as a causative factor in the development of pericardial mesothelioma is not certain, although in their series asbestos exposure had been documented in a few patients. In the AFIP series, four of the eight patients diagnosed with pericardial mesothelioma had a history of asbestos exposure [1]. There have been increasing reports of pericardial mesothelioma arising in patients with known exposure to asbestos. It is currently believed that, like pleural mesotheliomas, at least some mesotheliomas of the pericardium are caused by asbestosis. One patient developed a pericardial mesothelioma 15 years after pericardial dusting with asbestos and fiber glass as a treatment for angina pectoris [1]. Clinical presentation of these tumors can be quite varied and patients can present with chest pain, dyspnea, cough, and palpitations. Nearly 75% of patients are dyspneic at the time of presentation and radiographically demonstrate cardiac enlargement. Pericardial effusions, which are often asymptomatic, or solid tumor infiltrates are the cause of cardiomegaly as in our case. Cardiac tamponade is a known complication, but is rarely the first manifestation [1]. On microscopy, malignant mesotheliomas of the pericardium resemble pleural mesotheliomas. Mesotheliomas are divided into epithelial, mixed (biphasic), and
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sarcomatoid (as in our case) types on the basis of histologic growth patterns with over 75% of the biphasic variety. Immunohistochemically, almost 100% of pleural mesotheliomas express cytokeratin in epitheloid areas. Sarcomatoid cells express cytokeratin in about 75% of cases, vimentin is preferentially expressed in the spindle cell areas, and epithelial membrane antigen (EMA) is frequently present in the epitheloid areas. With pericardial mesotheliomas, EMA and vimentin are present in fewer than 50% of pericardial cases [1]. Malignant mesothelioma carries a poor prognosis with few successful treatment strategies and little benefit from radiation and chemotherapy. Even with therapy, the medial survival from the onset of symptoms is approximately 6 months [3]. The course of disease includes thromboembolism, structural heart disease (valvular distress, dilatation), rhythm disturbances, and metastases. Surgical management of these patients may therefore require various approaches to myocardiotomy with potentially increased risks of complications with conduction and contraction pathways. If significant valvular or structural distress is present, then a treatment option can include prosthetic replacement or even transplantation in cases of significant disease infiltration [5]. References [1] Burke AP, Virmani R. Malignant mesothelioma of the pericardium. In: Rosai J, Sobin LH, editors. Tumors of the Heart and Great Vessels. Washington DC: Atlas of Tumor Pathology, 1995. p. 181–94. [2] Lagrotteria DD, Tsang B, Elavathil LJ, et al. A case of primary malignant pericardial mesothelioma. Can J Cardiol 2005:185–7. [3] Kaul TK, Fields BL, Kahn DR. Primary malignant pericardial mesothelioma: a case report and review. J Cardiovasc Surg 1994;35: 261–7. [4] Thomason R, Schlegel W, Lucca M, et al. Primary malignant mesothelioma of the pericardium. Tex Heart Inst J 1994:170–4. [5] Vigneswaran WT, Stefanacci PR. Pericardial mesothelioma. Curr Treat Options Oncol 2000:299.
Original Article
Primary malignant mesothelioma of the pericardium Junaid Patel⁎, Mary N. Sheppard CRY Centre for Cardiac Pathology, National Heart and Lung Institute, Imperial College, London, UK Received 31 August 2009; received in revised form 24 November 2009; accepted 5 January 2010
Abstract Primary malignant pericardial mesothelioma is an extremely rare tumor. One of the largest autopsy series gave an incidence of primary pericardial tumors of 0.0022%, of which mesothelioma is the most common type. A male predominance of the disease has been described, and the majority of cases occur in the fourth to seventh decades of life. Unlike peritoneal and pleural mesothelioma, there has been no definite correlation between asbestos exposure and pericardial disease. Malignant pericardial mesothelioma carries a poor prognosis with few successful treatment strategies and little benefit from radiation and chemotherapy. We report a case of a 66year-old man who presented with shortness of breath, right shoulder pain, and peripheral edema of the lower limbs. A large pericardial effusion was seen on echocardiography, which was drained but the patient died the following day. A malignant tumor was found on autopsy and a final diagnosis of primary malignant pericardial mesothelioma was made following histopathological examination. © 2011 Elsevier Inc. All rights reserved. Keywords: Pericardial effusion; Echocardiogram, Tumor; Pericardium; Mesothelioma
1. Introduction Primary malignant pericardial mesothelioma is an extremely rare tumor with about 150 cases described in the literature to date. It arises from mesothelial cells or possibly a more primitive precursor cell situated submesothelially. The definition of primary pericardial mesothelioma stipulates that there is no tumor present outside the pericardium, with the exception of lymph node metastases [1]. Here we present a case of malignant pericardial mesothelioma in a 66-year-old man who was diagnosed at autopsy. 2. Case A 66-year-old man was admitted with a 3-week history of shortness of breath and right shoulder pain. Over the ⁎ Corresponding author. Department of Histopathology, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. Tel.: +44 2073518424; fax: + 44 2073518293. E-mail address: [email protected] (J. Patel). 1054-8807/10/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2010.01.005
same period he developed oliguria and pitting leg edema. His past medical history included right carotid endarterectomy and glaucoma (1998). He also had atrial fibrillation and had been treated with warfarin. He suffered a spinal hematoma (2001) which left him with paralysis and urinary incontinence. His medication included digoxin, enalapril, allopurinol, aspirin, and oxybutinin. He was a nonsmoker and had no apparent history of occupational or incidental exposure to asbestos. On examination, the patient appeared distressed with a respiratory rate of 20 breaths per minute. He had an irregularly irregular pulse of 110 beats per minute and his blood pressure was 100/70. His jugular venous pressure was elevated and he had severe peripheral edema of his lower limbs. An echocardiogram showed a large pericardial effusion and he was transferred on the same day to the National Heart and Lung Institute for treatment. The pericardial effusion was drained (1200 ml straw-colored fluid), and fluid and tissue were sent for cytological, histological, and microbiological investigation. One thousand milliliters of left pleural effusion was drained at the same time. The following day, the patient was found not breathing and was declared dead following unsuccessful resuscitation.
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J. Patel, M.N. Sheppard / Cardiovascular Pathology 20 (2011) 107–109
On autopsy, the pericardial sac was noted to be markedly thickened and expanded and a malignant tumor was seen encasing the heart on both visceral and parietal aspects (Fig. 1A). In the pericardial space, necrotic fragments of the tumor were found. The tumor had a variegated white and hemorrhagic cut surface (Fig. 1B). Both right and left ventricles were compressed by the tumor. The thickness of the parietal pericardium was 12 mm and the visceral 10 mm. The heart was otherwise normal with no intramuscular tumor. There were no pulmonary emboli but the left pleural cavity contained 700 ml of serous effusion. The parietal and visceral pleura of the lungs were smooth. However, a nodular area was present in the right middle lobe beneath the pleura (2×1×1 cm) close to a subsegmental bronchus which also contained a pale plug of tissue which was blocking it. Microscopic examination of the tumor surrounding the heart showed a spindle cell tumor with hyperchromatic, pleomorphic nuclei (Fig. 2A). Mitoses and hemorrhages were present. Immunohistochemistry showed the tumor to stain positively for calretinin (Fig. 2B) and thrombomodulin. The nodule in the right middle lobe of the lung stained positively for calretinin. These findings were consistent with a primary spindle cell pericardial malignant mesothelioma with metastasis in the right middle lobe of the lung.
Fig. 2. (A) Microscopic examination showing a spindle cell tumor with hyperchromatic, pleomorphic nuclei. (Hematoxylin and eosin stain; magnification ×200.) (B) Immunohistochemistry showing the tumor to stain positively for calretinin.
3. Discussion
Fig. 1. (A) Malignant tumor encasing the heart on both visceral and parietal aspects. (B) The tumor has a variegated white and hemorrhagic cut surface.
Primary malignant pericardial mesothelioma is an exceptionally rare tumor. One of the largest autopsy series gave an incidence of primary pericardial tumors of 0.0022%, of which mesothelioma was the most common type [2]. They account for about 2–3% of all cardiac and pericardial primary tumors and about 1% of all mesotheliomas [3]. Of 240 thoracic mesotheliomas in the Armed Forces of Institute of Pathology (AFIP) files from 1970 to 1995, only eight were limited to the heart and pericardium [1]. A male predominance of the disease has been described, and the majority of cases occur in the fourth to seventh decades of life [1]. A review of 59 cases of pericardial mesothelioma by AFIP found the mean age of patients at presentation to be 46 years with an age range of 2 to 78 years. Of these patients, 39 were men and 20 were women. The male-to-female ratio of nearly 2:1 is lower than the ratio of approximately 3.5:1 for mesotheliomas of the pleura. The higher proportion of women suggests that the link with asbestos exposure is weaker for pericardial than for pleural mesothelioma, or that some pericardial mesotheliomas are pathogenetically distinct from their pleural counterparts [1]. The etiology of primary malignant mesothelioma of the pericardium remains unclear. Unlike peritoneal and pleural
J. Patel, M.N. Sheppard / Cardiovascular Pathology 20 (2011) 107–109
mesothelioma, there has been no definite correlation between asbestos exposure and pericardial disease, as in our case [2]. In most reported cases of pericardial mesotheliomas no history of asbestos exposure is mentioned. However, many of these reports appeared before the link was established. The association between malignant mesothelioma of the pleura and asbestosis was first described in 1954 and subsequently established in 1960 [1]. Due to the relative rarity of pericardial mesotheliomas, it has been difficult to establish a link between them and asbestos exposure. Thomason et al. [4] described 28 cases of primary pericardial mesothelioma from 1972 through 1992 and noted that, unlike in the case of pleural mesothelioma, asbestos exposure as a causative factor in the development of pericardial mesothelioma is not certain, although in their series asbestos exposure had been documented in a few patients. In the AFIP series, four of the eight patients diagnosed with pericardial mesothelioma had a history of asbestos exposure [1]. There have been increasing reports of pericardial mesothelioma arising in patients with known exposure to asbestos. It is currently believed that, like pleural mesotheliomas, at least some mesotheliomas of the pericardium are caused by asbestosis. One patient developed a pericardial mesothelioma 15 years after pericardial dusting with asbestos and fiber glass as a treatment for angina pectoris [1]. Clinical presentation of these tumors can be quite varied and patients can present with chest pain, dyspnea, cough, and palpitations. Nearly 75% of patients are dyspneic at the time of presentation and radiographically demonstrate cardiac enlargement. Pericardial effusions, which are often asymptomatic, or solid tumor infiltrates are the cause of cardiomegaly as in our case. Cardiac tamponade is a known complication, but is rarely the first manifestation [1]. On microscopy, malignant mesotheliomas of the pericardium resemble pleural mesotheliomas. Mesotheliomas are divided into epithelial, mixed (biphasic), and
109
sarcomatoid (as in our case) types on the basis of histologic growth patterns with over 75% of the biphasic variety. Immunohistochemically, almost 100% of pleural mesotheliomas express cytokeratin in epitheloid areas. Sarcomatoid cells express cytokeratin in about 75% of cases, vimentin is preferentially expressed in the spindle cell areas, and epithelial membrane antigen (EMA) is frequently present in the epitheloid areas. With pericardial mesotheliomas, EMA and vimentin are present in fewer than 50% of pericardial cases [1]. Malignant mesothelioma carries a poor prognosis with few successful treatment strategies and little benefit from radiation and chemotherapy. Even with therapy, the medial survival from the onset of symptoms is approximately 6 months [3]. The course of disease includes thromboembolism, structural heart disease (valvular distress, dilatation), rhythm disturbances, and metastases. Surgical management of these patients may therefore require various approaches to myocardiotomy with potentially increased risks of complications with conduction and contraction pathways. If significant valvular or structural distress is present, then a treatment option can include prosthetic replacement or even transplantation in cases of significant disease infiltration [5]. References [1] Burke AP, Virmani R. Malignant mesothelioma of the pericardium. In: Rosai J, Sobin LH, editors. Tumors of the Heart and Great Vessels. Washington DC: Atlas of Tumor Pathology, 1995. p. 181–94. [2] Lagrotteria DD, Tsang B, Elavathil LJ, et al. A case of primary malignant pericardial mesothelioma. Can J Cardiol 2005:185–7. [3] Kaul TK, Fields BL, Kahn DR. Primary malignant pericardial mesothelioma: a case report and review. J Cardiovasc Surg 1994;35: 261–7. [4] Thomason R, Schlegel W, Lucca M, et al. Primary malignant mesothelioma of the pericardium. Tex Heart Inst J 1994:170–4. [5] Vigneswaran WT, Stefanacci PR. Pericardial mesothelioma. Curr Treat Options Oncol 2000:299.