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Primary Cardiac Angiosarcoma: Morphologically Deceptive Benign Appearance and Potential Pitfalls in Diagnosis
CLINICAL SPOTLIGHT
Clinical Spotlight
Primary Cardiac Angiosarcoma: Morphologically Deceptive Benign Appearance and Potential Pitfalls in Diagnosis Chi Wing Wong ∗ , Seif El-Jack, Colin Edwards and Hitesh Patel Cardiovascular Division, North Shore Hospital, Auckland, New Zealand
Cardiac angiosarcoma is the most common malignant primary cardiac tumour. We report a case of cardiac angiosarcoma with recurrent complex pericardial effusion. Histological diagnosis was elusive underscoring the potential difficulty in differentiating this tumour from normal vascular endothelium. (Heart, Lung and Circulation 2010;19:473–475) © 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved. Keywords. Cardiac tumour; Sarcoma; Pericardial effusion
Introduction
C
ardiac angiosarcoma is the most common malignant primary cardiac tumour. We report a case of cardiac angiosarcoma with recurrent complex pericardial effusion. Histological diagnosis was elusive underscoring the potential difficulty in differentiating this tumour from regenerative endothelial proliferation.
Case Report A previously well 49-year-old woman was admitted with a two-day history of shortness of breath and syncope. On admission she was in sinus rhythm with a blood pressure of 93/75 mm Hg. Her neck veins were distended bilaterally and there was no pulsus paradoxus. No heart murmurs or rub were noted. Echocardiography showed a relatively small pericardial effusion with a depth of 0.7 cm anteriorly and 1.5 cm posteriorly. An urgent non-ECG gated computerised tomogram (CT) scan excluded aortic dissection and intramural haematoma. Two days later a repeat echocardiogram revealed increase in size of the pericardial effusion which features of tamponade physiology. Pericardiocentesis was performed using the subcostal approach with echo guidance. A total of 300 ml of haemorrhagic pericardial fluid was drained and it was felt that inadvertent puncture of the right ventricle may have occurred. Microscopy and culture of the pericardial fluid was negative and there was no evidence of Received 10 June 2009; received in revised form 7 January 2010; accepted 28 February 2010; available online 24 April 2010 ∗
Corresponding author. Tel.: +64 21 2608923; fax: +64 9 3074950. E-mail address: [email protected] (C.W. Wong).
malignancy on cytological examination. Polymerase chain reaction (PCR) for tuberculosis was also negative. There was no clinical evidence of breast, thyroid or pulmonary malignancy By a process of elimination, it was concluded that she had had an episode of viral pericarditis with inadvertent right ventricular puncture causing a haemorrhagic effusion. Alternatively, viral pericarditis alone can very occasionally result in a haemorrhagic pericardial effusion. Six weeks later she was readmitted to hospital with breathlessness and near syncope. She was noted to have engorged jugular veins and a pulsus paradoxus of 20 mm Hg. An echocardiogram show layered pericardial thrombus with overlying echolucent fluid. Repeat pericardiocentesis once again yielded 300 ml of haemorrhagic fluid; her jugular veins remained markedly engorged. CT had revealed the presence of a mass adjacent to the right atrial free wall with Hounsfield units consistent with a haematoma. Cardiac magnetic resonance (CMR) imaging confirmed a large 11 cm × 8 cm well circumscribed mass compressing the anterior right ventricular free wall and right atrium, extending superiorly to also compress the superior vena cava (SVC). There was no gadolinium contrast enhancement on both first pass perfusion, nor on delayed imaging (Fig. 1A). Pre-operative coronary angiography revealed no significant coronary artery disease, with the mass displacing the right coronary artery without significant compression. She proceeded to cardiac surgery and the pericardium was found to be distended with old clot. The description was of residual haematoma densely adhering to the right atrium and this could be only partially removed.
© 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved.
1443-9506/04/$36.00 doi:10.1016/j.hlc.2010.02.027
CLINICAL SPOTLIGHT
474
Wong et al. Deceptive appearance and potential pitfalls of cardiac angiosarcoma diagnosis
Fig. 1. Cardiac MRI (four chamber view) T1 inversion recovery on delayed enhancement: (A) Initial CMR demonstrating a mass compressing on RV free wall with no contrast retention by mass (arrow). (B) There is now contrast retention on repeated CMR 3 months later.
Haematoma surrounding the SVC, aorta and the right ventricle was fully evacuated. There was no obvious cardiac injury from previous pericardiocentesis. Histological examination of evacuated tissue was consistent with organising haematoma. She represented 7 weeks later with breathlessness and distension of her neck veins. An echocardiogram and nonECG gated chest CT found appearances consistent with a haematoma overlying the right atrium and extending to the mediastinum surrounding the aorta and pulmonary arteries and compressing the SVC. She required repeat surgical evacuation of the mediastinal clot. There was difficulty distinguishing haematoma from the right atrial free wall. Histological examination reported organising haematoma with no significant cytologic atypia or malignancy. Within a few weeks she represented with signs and symptoms consistent with SVC obstruction. CMR imaging confirmed expansion of the pericardial mass with posterior mediastinal extension. Furthermore, unlike on the previous scan, there was now gadolinium uptake and retention which is obviously not consistent with haematoma (Fig. 1B). A 3rd mediastinal exploration was performed. There was no obvious tissue plane between the haemorrhagic mass and the right heart, indicative of localised infiltration.
Heart, Lung and Circulation 2010;19:473–475
Fig. 2. Histological findings on tissues from the final operation. (A) Fibrous pericardium with high-grade angiosarcoma (H&E, original magnification ×10). (B) High power view showing anastomosing vascular spaces and marked endothelial atypical (H&E, original magnification ×400).
She died the following day after the operation.
Post-mortem Examination There was a haemorrhagic, friable mass of tissue involving the anterior mediastinum and extending around the base of the heart. Histology of this and the material from the final operation showed high-grade angiosarcoma (Fig. 2A and B). The origin of the angiosarcoma was obscure although it might have arisen in the pericardium. The previous histology was then re-examined and with the benefit of hindsight, small foci consistent with angiosarcoma were also identified.
Discussion Primary pericardial tumours not involving the rest of the heart are rare and most would have right atrial involvement. Cardiac angiosarcoma is the commonest primary malignant cardiac tumour and recurrent pericardial effusion is a common manifestation thereof [1]. Pericardiocentesis usually yields bloody fluid that often does not
Wong et al. Deceptive appearance and potential pitfalls of cardiac angiosarcoma diagnosis
contain malignant cells even when the tumour has invaded the pericardium [2,3]. CMR imaging is a useful tool in the evaluation of cardiac tumours. Use of gadolinium contrast can furthermore aid in differentiating thrombus from tumour tissue, though the signal intensity of a thrombus depends on its age. “Sunray” appearances of gadolinium uptake have been described in cases with diffuse pericardial malignant infiltration [5]. The initial CMR of our case was consistent with pericardial haematoma. There were probably very few tumour cells present initially and hence absence perfusion and enhancement following administration of gadolinium. In the space of a couple of months there was extensive tumour growth and the repeat CMR demonstrated extension of tumour with more heterogeneous imaging characteristics. Evidence of tumour perfusion and retention of gadolinium became apparent. Cardiac angiosarcomas are malignant endothelial tumours and the histological features can be difficult to distinguish from the endothelial hyperplasia seen in organising haematoma. Immunohistochemistry is of no help in this differential diagnosis. They have a tendency for rapid growth and dissemination and patients almost always have poor prognosis; there are case reports though of favourable outcome up to 4 years [4]. The mean reported survival reported is 4–10 months from the onset of symptoms [1]. Because of initial histological findings and the suspicion of inadvertent puncture of the right atrium, the diagnosis of the current case was ambiguous for 6 months from the initial presentation. In retrospect, the haematoma indistinguishable from right atrial free wall provides us
475
a clue of the diagnosis. Moreover, the similar histological features between angiosarcoma and hyperplastic endothelium created a pitfall in the diagnosis. Unexplained bloody pericardial effusion in the presence of negative cytology should prompt the search for primary or secondary malignancy, as was undertaken in our case. Failing to document that, close monitoring and follow up for recurrence or change of the clinical scenario is warranted. Cardiologist and clinicians should be aware of these limitations when interpreting histological results of pericardial fluid or tissue.
Acknowledgements We thank Dr. Mike Watson (Pathologist at Auckland City Hospital) for providing the histological images and helpful comments.
References [1] Janigan D, Husain A, Robinson N. Cardiac angiosarcomas: a review and a case report. Cancer 1986;57:852–9. [2] Tremaine LA, Gaetner EM. Persistent hemopericardial effusion in a 54-year-old man. Arch Pathol Lab Med 2005;129:117–8. [3] Oshima K, Ohtaki A, Kano M, Tange S, Hasegawa Y, Ikeda F, Ishikawa S, Morishita Y. Primary cardiac angiosarcoma associated with cardiac tamponade. Jpn Circ J 1999;63:822–4. [4] Centella T, Oliva E, Andrade I, Lamas M, Epeldegui A. A patient with cardiac angiosarcoma who survived for four years; Case report and literature review. Rev Esp Cardiol 2005;58(3):310–2. [5] Yahata S, Endo T, Honma H, Ino T, Hayakawa H, Ogawa M, Hayashi H, Kumazaki T. Sunray appearance on enhanced magnetic resonance image of cardiac angiosarcoma with pericardial obliteration. Am Heart J 1994;127(February (2)):468–71.
CLINICAL SPOTLIGHT
Heart, Lung and Circulation 2010;19:473–475
Clinical Spotlight
Primary Cardiac Angiosarcoma: Morphologically Deceptive Benign Appearance and Potential Pitfalls in Diagnosis Chi Wing Wong ∗ , Seif El-Jack, Colin Edwards and Hitesh Patel Cardiovascular Division, North Shore Hospital, Auckland, New Zealand
Cardiac angiosarcoma is the most common malignant primary cardiac tumour. We report a case of cardiac angiosarcoma with recurrent complex pericardial effusion. Histological diagnosis was elusive underscoring the potential difficulty in differentiating this tumour from normal vascular endothelium. (Heart, Lung and Circulation 2010;19:473–475) © 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved. Keywords. Cardiac tumour; Sarcoma; Pericardial effusion
Introduction
C
ardiac angiosarcoma is the most common malignant primary cardiac tumour. We report a case of cardiac angiosarcoma with recurrent complex pericardial effusion. Histological diagnosis was elusive underscoring the potential difficulty in differentiating this tumour from regenerative endothelial proliferation.
Case Report A previously well 49-year-old woman was admitted with a two-day history of shortness of breath and syncope. On admission she was in sinus rhythm with a blood pressure of 93/75 mm Hg. Her neck veins were distended bilaterally and there was no pulsus paradoxus. No heart murmurs or rub were noted. Echocardiography showed a relatively small pericardial effusion with a depth of 0.7 cm anteriorly and 1.5 cm posteriorly. An urgent non-ECG gated computerised tomogram (CT) scan excluded aortic dissection and intramural haematoma. Two days later a repeat echocardiogram revealed increase in size of the pericardial effusion which features of tamponade physiology. Pericardiocentesis was performed using the subcostal approach with echo guidance. A total of 300 ml of haemorrhagic pericardial fluid was drained and it was felt that inadvertent puncture of the right ventricle may have occurred. Microscopy and culture of the pericardial fluid was negative and there was no evidence of Received 10 June 2009; received in revised form 7 January 2010; accepted 28 February 2010; available online 24 April 2010 ∗
Corresponding author. Tel.: +64 21 2608923; fax: +64 9 3074950. E-mail address: [email protected] (C.W. Wong).
malignancy on cytological examination. Polymerase chain reaction (PCR) for tuberculosis was also negative. There was no clinical evidence of breast, thyroid or pulmonary malignancy By a process of elimination, it was concluded that she had had an episode of viral pericarditis with inadvertent right ventricular puncture causing a haemorrhagic effusion. Alternatively, viral pericarditis alone can very occasionally result in a haemorrhagic pericardial effusion. Six weeks later she was readmitted to hospital with breathlessness and near syncope. She was noted to have engorged jugular veins and a pulsus paradoxus of 20 mm Hg. An echocardiogram show layered pericardial thrombus with overlying echolucent fluid. Repeat pericardiocentesis once again yielded 300 ml of haemorrhagic fluid; her jugular veins remained markedly engorged. CT had revealed the presence of a mass adjacent to the right atrial free wall with Hounsfield units consistent with a haematoma. Cardiac magnetic resonance (CMR) imaging confirmed a large 11 cm × 8 cm well circumscribed mass compressing the anterior right ventricular free wall and right atrium, extending superiorly to also compress the superior vena cava (SVC). There was no gadolinium contrast enhancement on both first pass perfusion, nor on delayed imaging (Fig. 1A). Pre-operative coronary angiography revealed no significant coronary artery disease, with the mass displacing the right coronary artery without significant compression. She proceeded to cardiac surgery and the pericardium was found to be distended with old clot. The description was of residual haematoma densely adhering to the right atrium and this could be only partially removed.
© 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved.
1443-9506/04/$36.00 doi:10.1016/j.hlc.2010.02.027
CLINICAL SPOTLIGHT
474
Wong et al. Deceptive appearance and potential pitfalls of cardiac angiosarcoma diagnosis
Fig. 1. Cardiac MRI (four chamber view) T1 inversion recovery on delayed enhancement: (A) Initial CMR demonstrating a mass compressing on RV free wall with no contrast retention by mass (arrow). (B) There is now contrast retention on repeated CMR 3 months later.
Haematoma surrounding the SVC, aorta and the right ventricle was fully evacuated. There was no obvious cardiac injury from previous pericardiocentesis. Histological examination of evacuated tissue was consistent with organising haematoma. She represented 7 weeks later with breathlessness and distension of her neck veins. An echocardiogram and nonECG gated chest CT found appearances consistent with a haematoma overlying the right atrium and extending to the mediastinum surrounding the aorta and pulmonary arteries and compressing the SVC. She required repeat surgical evacuation of the mediastinal clot. There was difficulty distinguishing haematoma from the right atrial free wall. Histological examination reported organising haematoma with no significant cytologic atypia or malignancy. Within a few weeks she represented with signs and symptoms consistent with SVC obstruction. CMR imaging confirmed expansion of the pericardial mass with posterior mediastinal extension. Furthermore, unlike on the previous scan, there was now gadolinium uptake and retention which is obviously not consistent with haematoma (Fig. 1B). A 3rd mediastinal exploration was performed. There was no obvious tissue plane between the haemorrhagic mass and the right heart, indicative of localised infiltration.
Heart, Lung and Circulation 2010;19:473–475
Fig. 2. Histological findings on tissues from the final operation. (A) Fibrous pericardium with high-grade angiosarcoma (H&E, original magnification ×10). (B) High power view showing anastomosing vascular spaces and marked endothelial atypical (H&E, original magnification ×400).
She died the following day after the operation.
Post-mortem Examination There was a haemorrhagic, friable mass of tissue involving the anterior mediastinum and extending around the base of the heart. Histology of this and the material from the final operation showed high-grade angiosarcoma (Fig. 2A and B). The origin of the angiosarcoma was obscure although it might have arisen in the pericardium. The previous histology was then re-examined and with the benefit of hindsight, small foci consistent with angiosarcoma were also identified.
Discussion Primary pericardial tumours not involving the rest of the heart are rare and most would have right atrial involvement. Cardiac angiosarcoma is the commonest primary malignant cardiac tumour and recurrent pericardial effusion is a common manifestation thereof [1]. Pericardiocentesis usually yields bloody fluid that often does not
Wong et al. Deceptive appearance and potential pitfalls of cardiac angiosarcoma diagnosis
contain malignant cells even when the tumour has invaded the pericardium [2,3]. CMR imaging is a useful tool in the evaluation of cardiac tumours. Use of gadolinium contrast can furthermore aid in differentiating thrombus from tumour tissue, though the signal intensity of a thrombus depends on its age. “Sunray” appearances of gadolinium uptake have been described in cases with diffuse pericardial malignant infiltration [5]. The initial CMR of our case was consistent with pericardial haematoma. There were probably very few tumour cells present initially and hence absence perfusion and enhancement following administration of gadolinium. In the space of a couple of months there was extensive tumour growth and the repeat CMR demonstrated extension of tumour with more heterogeneous imaging characteristics. Evidence of tumour perfusion and retention of gadolinium became apparent. Cardiac angiosarcomas are malignant endothelial tumours and the histological features can be difficult to distinguish from the endothelial hyperplasia seen in organising haematoma. Immunohistochemistry is of no help in this differential diagnosis. They have a tendency for rapid growth and dissemination and patients almost always have poor prognosis; there are case reports though of favourable outcome up to 4 years [4]. The mean reported survival reported is 4–10 months from the onset of symptoms [1]. Because of initial histological findings and the suspicion of inadvertent puncture of the right atrium, the diagnosis of the current case was ambiguous for 6 months from the initial presentation. In retrospect, the haematoma indistinguishable from right atrial free wall provides us
475
a clue of the diagnosis. Moreover, the similar histological features between angiosarcoma and hyperplastic endothelium created a pitfall in the diagnosis. Unexplained bloody pericardial effusion in the presence of negative cytology should prompt the search for primary or secondary malignancy, as was undertaken in our case. Failing to document that, close monitoring and follow up for recurrence or change of the clinical scenario is warranted. Cardiologist and clinicians should be aware of these limitations when interpreting histological results of pericardial fluid or tissue.
Acknowledgements We thank Dr. Mike Watson (Pathologist at Auckland City Hospital) for providing the histological images and helpful comments.
References [1] Janigan D, Husain A, Robinson N. Cardiac angiosarcomas: a review and a case report. Cancer 1986;57:852–9. [2] Tremaine LA, Gaetner EM. Persistent hemopericardial effusion in a 54-year-old man. Arch Pathol Lab Med 2005;129:117–8. [3] Oshima K, Ohtaki A, Kano M, Tange S, Hasegawa Y, Ikeda F, Ishikawa S, Morishita Y. Primary cardiac angiosarcoma associated with cardiac tamponade. Jpn Circ J 1999;63:822–4. [4] Centella T, Oliva E, Andrade I, Lamas M, Epeldegui A. A patient with cardiac angiosarcoma who survived for four years; Case report and literature review. Rev Esp Cardiol 2005;58(3):310–2. [5] Yahata S, Endo T, Honma H, Ino T, Hayakawa H, Ogawa M, Hayashi H, Kumazaki T. Sunray appearance on enhanced magnetic resonance image of cardiac angiosarcoma with pericardial obliteration. Am Heart J 1994;127(February (2)):468–71.
CLINICAL SPOTLIGHT
Heart, Lung and Circulation 2010;19:473–475