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Prolonged Survival of Pulmonary Artery Sarcoma After Aggressive Surgical Resection
Prolonged Survival of Pulmonary Artery Sarcoma After Aggressive Surgical Resection Samuel P. Morreau, and David A. Haydock, MBChB, FRACS Cardiothoracic Surgery, Auckland City Hospital, Auckland, New Zealand
Pulmonary artery sarcomas are rare tumors with a poor prognosis. Presentation is usually with symptoms of cardiorespiratory dysfunction, and although preoperative diagnosis was unusual historically, modern imaging techniques allow a high degree of confidence, and transvenous catheter biopsy can give confirmation of the diagnosis. This patient survived 6 years after surgical resection of the tumor and left lung with pulmonary artery reconstruction followed by postoperative adjuvant chemotherapy. The prolonged survival supports an aggressive approach in suitable cases. (Ann Thorac Surg 2017;103:e21–3) Ó 2017 by The Society of Thoracic Surgeons
P
rimary intimal sarcomas arising from the pulmonary arteries are rare and typically have a poor prognosis [1]. The true incidence is unknown because these tumors are thought to be difficult to distinguish from chronic thromboembolic disease and are often diagnosed during operation or autopsy [2]. We describe a patient with a pulmonary artery angiosarcoma who survived for 6 years after presentation. A 47-year-old man presented with a 10-month history of increasing dyspnea on exertion without any history of angina, palpitations, syncope, or orthopnea. He had previously been fit and well, with no significant medical history except for excision of a cholesteatoma several years earlier. Of interest, his mother had undergone excision of a left atrial myxoma when she was 65. He was slim, with normal blood pressure and jugular venous pressure. His apex beat was normal, with no parasternal heave. A grade 2/6 midsystolic murmur was noted, best heard in the left parasternal second intercostal space. The results of the rest of the examination were normal; his lungs were clear to percussion and auscultation. The patient had never smoked, and his respiratory function was normal preoperatively. An electrocardiogram was abnormal, with evidence of right ventricular strain in the inversion of T waves in V1 through V4. An echocardiogram revealed severe pulmonary stenosis with moderate right ventricular
dilatation but preserved right ventricular systolic function. There was also a suggestion of filling defects within the pulmonary arteries on the echocardiogram. Further computed tomography (CT) and magnetic resonance imaging (MRI) showed an irregular wall thickening of the main, left, and right pulmonary arteries stenosed to a minimum diameter of 6 mm in the right pulmonary artery and 4 mm in the left pulmonary artery (Figs 1–3). It was unclear whether or not the tumor involved the extramural soft tissue, but there was no evidence of distant metastasis. The tumor did involve a left upper lobe pulmonary artery branch. The branches of the right pulmonary artery and the sinotubular junction of the pulmonary trunk appeared clear of tumor. These images were thought to be consistent with a primary pulmonary artery sarcoma. Examination of a right heart catheter biopsy specimen confirmed this diagnosis. After an informed discussion about his options and likely prognosis, the patient elected to proceed to operation followed by postoperative chemotherapy. A clamshell thoracotomy was made after femoral cannulation. Cardiopulmonary bypass was initiated, the aorta was cross-clamped, and antegrade cardioplegia was given. A left pneumonectomy was performed, with sacrifice of the left recurrent laryngeal nerve. The right pulmonary artery was divided, in continuity with the main specimen, at its division into upper, middle, and lower lobe branches, and the confluence between these branches was retained. Although there was no macroscopic evidence of disease at the resection margins, examination of an intraoperative frozen section revealed tumor involvement of the distal right pulmonary artery margin. No further resection was attempted because resection was already as far distal as could be achieved without disconnecting the lobar branches from their confluence. A 20-mm Gore-Tex graft was used to reconstruct the pulmonary artery from just above the pulmonary valve to the confluence of the lobar arteries on the right. The pericardial defect on the left was
Accepted for publication May 30, 2016. Address correspondence to Dr Haydock, Cardiothoracic Surgery, Auckland City Hospital, 2 Park Rd, Grafton, Auckland, New Zealand; email: [email protected].
Ó 2017 by The Society of Thoracic Surgeons Published by Elsevier
Fig 1. Left pulmonary artery. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2016.05.119
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CASE REPORT MORREAU AND HAYDOCK PULMONARY ARTERY SARCOMA
Fig 2. Right pulmonary artery.
repaired with bovine pericardium. Right ventricular function appeared to improve significantly with the resolution of outflow stenosis, and the patient was closed and transferred to the intensive care unit (ICU) postoperatively. The patient experienced widespread capillary leakage. He was discharged home 1 month later after prolonged weaning from respiratory support. Pathologic review demonstrated that the tumor involved the main, left, and right pulmonary arteries, with macroscopic extension into the left lung. Histologic analyses of the specimens revealed spindle-shaped tumor cells arising from the intima, which were pleomorphic and hyperchromatic, with frequent mitoses. There were also acellular collagenous areas within the tumor. Immunostaining of the tumor cells showed positivity for CD31, CD34, and factor VIII; hence, this tumor was thought to be an angiosarcoma. There were a few atypical cells within the media but no direct extension of the tumor cells into the media and no local invasion outside the vessel wall. None of the mediastinal nodes sampled during the operation contained any tumor cells. Distal arteries randomly sampled within the left lower lobe
Fig 3. Right pulmonary artery stenosed by the tumor to a nadir of 6 mm.
Ann Thorac Surg 2017;103:e21–3
were also found to contain tumor deposits. Although the distal right pulmonary artery and pulmonary trunk resection margins were positive for tumor microscopically, there was no recurrence in these regions in the long term. Two months after the operation, the patient began chemotherapy with doxorubicin, although this regimen was altered to ifosfamide and pegylated doxorubicin after one cycle. Although six cycles of chemotherapy were planned, the patient experienced Fournier’s gangrene and was neutropenic during the third cycle, and he spent a week in the ICU receiving support by inotropic agents. After he recovered, his chemotherapy was abandoned. A CT – positron emission tomography scan at this time showed no evidence of active disease. and this clinical and radiographic remission was maintained for nearly 5 years. Ultimately, the patient represented with pain in his right chest wall, and CT revealed bone metastasis to his ribs and vertebrae and a metastasis within the right lung. He received further chemotherapy with etoposide and ifosfamide for six cycles as planned, with clinical and radiographic improvement but significant neutropenia and fatigue. He had a course of radiotherapy to manage pain from metastases in his ribs and hip. He survived a further year after discontinuation of this chemotherapy, giving a total of 6 years of survival after initial treatment.
Comment Pulmonary artery intimal sarcomas are rare and are thought to arise from pluripotent mesenchymal cells from the bulbus cordis [1]. Patients normally present with nonspecific symptoms of cardiopulmonary disease such as cough, exertional dyspnea, or pain; as such, making a clinical diagnosis can be difficult [2, 3]. However, radiographic images produced with modern techniques (echocardiography, cardiac-gated CT, and gadolinium-enhanced MRI) are often sufficiently distinct from those of thromboembolism [1, 4, 5], and it appears to be the rarity of this tumor that makes early diagnosis difficult once these imaging techniques are used. Biopsy through a right heart catheter approach is possible and was successfully performed in this case. Therapy for pulmonary artery sarcomas revolves around surgical resection where possible, whereas chemotherapy and radiotherapy are thought to have a lesser role, although some now advocate for neoadjuvant chemotherapy with ifosfamide and doxorubicin [1]. Endovascular stenting can also be considered as a palliative procedure to relieve the right heart; right heart failure is the main cause of mortality for these patients. Other palliative options previously described in the literature include tumor debulking and endarterectomy [3]. This patient’s tumor was also treated with two chemotherapy regimens, with significant side effects. Pegylated doxorubicin has been shown to have less impact on cardiac function than standard doxorubicin
Ann Thorac Surg 2017;103:e21–3
CASE REPORT MORREAU AND HAYDOCK PULMONARY ARTERY SARCOMA
and was chosen because of existing and future concerns for this patient’s cardiorespiratory function [6]. The median survival time has historically been reported between 1.5 and 12 months, although more recent case series have shown the benefit of earlier diagnosis and improved management, with longer survival times reported [2, 3, 7, 8]. This case supports approaching suitable patients with aggressive surgical resection and adjuvant chemotherapy. This treatment can be associated with prolonged survival in patients with pulmonary artery sarcomas.
4.
References
7.
1. Blackmon SH, Rice DC, Correa AM, et al. Management of primary pulmonary artery sarcomas. Ann Thorac Surg 2009;87:977–84. 2. Nonomura A, Kurumaya H, Kono N, et al. Primary pulmonary artery sarcoma: report of two autopsy cases studied by
3.
5.
6.
8.
e23
immunohistochemistry and electron microscopy, and review of 110 cases reported in the literature. Pathol Int 1988;38: 883–96. Huo L, Lai S, Gladish G, Czerniak BA, Moran CA. Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation. Ann Diagn Pathol 2005;9:209–14. Restrepo CS, Betancourt SL, Martinez-Jimenez S, Gutierrez FR. Tumors of the pulmonary artery and veins. Semin Ultrasound CT MR 2012;33:580–90. Chin AY, Lee KS, Choe YH, Han D, Kwon OJ, Kim S. Computed tomography in pulmonary artery sarcoma: distinguishing features from pulmonary embolic disease. J Comput Assist Tomogr 2004;28:34–9. Duggan ST, Keating GM. Pegylated liposomal doxorubicin. Drugs 2011;71:2531–58. Mayer E, Kriegsmann J, Gaumann A, et al. Surgical treatment of pulmonary artery sarcoma. J Thorac Cardiovasc Surg 2001;121:77–82. Huo L, Moran CA, Fuller GN, Gladish G, Suster S. Pulmonary artery sarcoma: a clinicopathologic and immunohistochemical study of 12 cases. Am J Clin Pathol 2006;125: 419–24.
Pulmonary artery sarcomas are rare tumors with a poor prognosis. Presentation is usually with symptoms of cardiorespiratory dysfunction, and although preoperative diagnosis was unusual historically, modern imaging techniques allow a high degree of confidence, and transvenous catheter biopsy can give confirmation of the diagnosis. This patient survived 6 years after surgical resection of the tumor and left lung with pulmonary artery reconstruction followed by postoperative adjuvant chemotherapy. The prolonged survival supports an aggressive approach in suitable cases. (Ann Thorac Surg 2017;103:e21–3) Ó 2017 by The Society of Thoracic Surgeons
P
rimary intimal sarcomas arising from the pulmonary arteries are rare and typically have a poor prognosis [1]. The true incidence is unknown because these tumors are thought to be difficult to distinguish from chronic thromboembolic disease and are often diagnosed during operation or autopsy [2]. We describe a patient with a pulmonary artery angiosarcoma who survived for 6 years after presentation. A 47-year-old man presented with a 10-month history of increasing dyspnea on exertion without any history of angina, palpitations, syncope, or orthopnea. He had previously been fit and well, with no significant medical history except for excision of a cholesteatoma several years earlier. Of interest, his mother had undergone excision of a left atrial myxoma when she was 65. He was slim, with normal blood pressure and jugular venous pressure. His apex beat was normal, with no parasternal heave. A grade 2/6 midsystolic murmur was noted, best heard in the left parasternal second intercostal space. The results of the rest of the examination were normal; his lungs were clear to percussion and auscultation. The patient had never smoked, and his respiratory function was normal preoperatively. An electrocardiogram was abnormal, with evidence of right ventricular strain in the inversion of T waves in V1 through V4. An echocardiogram revealed severe pulmonary stenosis with moderate right ventricular
dilatation but preserved right ventricular systolic function. There was also a suggestion of filling defects within the pulmonary arteries on the echocardiogram. Further computed tomography (CT) and magnetic resonance imaging (MRI) showed an irregular wall thickening of the main, left, and right pulmonary arteries stenosed to a minimum diameter of 6 mm in the right pulmonary artery and 4 mm in the left pulmonary artery (Figs 1–3). It was unclear whether or not the tumor involved the extramural soft tissue, but there was no evidence of distant metastasis. The tumor did involve a left upper lobe pulmonary artery branch. The branches of the right pulmonary artery and the sinotubular junction of the pulmonary trunk appeared clear of tumor. These images were thought to be consistent with a primary pulmonary artery sarcoma. Examination of a right heart catheter biopsy specimen confirmed this diagnosis. After an informed discussion about his options and likely prognosis, the patient elected to proceed to operation followed by postoperative chemotherapy. A clamshell thoracotomy was made after femoral cannulation. Cardiopulmonary bypass was initiated, the aorta was cross-clamped, and antegrade cardioplegia was given. A left pneumonectomy was performed, with sacrifice of the left recurrent laryngeal nerve. The right pulmonary artery was divided, in continuity with the main specimen, at its division into upper, middle, and lower lobe branches, and the confluence between these branches was retained. Although there was no macroscopic evidence of disease at the resection margins, examination of an intraoperative frozen section revealed tumor involvement of the distal right pulmonary artery margin. No further resection was attempted because resection was already as far distal as could be achieved without disconnecting the lobar branches from their confluence. A 20-mm Gore-Tex graft was used to reconstruct the pulmonary artery from just above the pulmonary valve to the confluence of the lobar arteries on the right. The pericardial defect on the left was
Accepted for publication May 30, 2016. Address correspondence to Dr Haydock, Cardiothoracic Surgery, Auckland City Hospital, 2 Park Rd, Grafton, Auckland, New Zealand; email: [email protected].
Ó 2017 by The Society of Thoracic Surgeons Published by Elsevier
Fig 1. Left pulmonary artery. 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2016.05.119
e22
CASE REPORT MORREAU AND HAYDOCK PULMONARY ARTERY SARCOMA
Fig 2. Right pulmonary artery.
repaired with bovine pericardium. Right ventricular function appeared to improve significantly with the resolution of outflow stenosis, and the patient was closed and transferred to the intensive care unit (ICU) postoperatively. The patient experienced widespread capillary leakage. He was discharged home 1 month later after prolonged weaning from respiratory support. Pathologic review demonstrated that the tumor involved the main, left, and right pulmonary arteries, with macroscopic extension into the left lung. Histologic analyses of the specimens revealed spindle-shaped tumor cells arising from the intima, which were pleomorphic and hyperchromatic, with frequent mitoses. There were also acellular collagenous areas within the tumor. Immunostaining of the tumor cells showed positivity for CD31, CD34, and factor VIII; hence, this tumor was thought to be an angiosarcoma. There were a few atypical cells within the media but no direct extension of the tumor cells into the media and no local invasion outside the vessel wall. None of the mediastinal nodes sampled during the operation contained any tumor cells. Distal arteries randomly sampled within the left lower lobe
Fig 3. Right pulmonary artery stenosed by the tumor to a nadir of 6 mm.
Ann Thorac Surg 2017;103:e21–3
were also found to contain tumor deposits. Although the distal right pulmonary artery and pulmonary trunk resection margins were positive for tumor microscopically, there was no recurrence in these regions in the long term. Two months after the operation, the patient began chemotherapy with doxorubicin, although this regimen was altered to ifosfamide and pegylated doxorubicin after one cycle. Although six cycles of chemotherapy were planned, the patient experienced Fournier’s gangrene and was neutropenic during the third cycle, and he spent a week in the ICU receiving support by inotropic agents. After he recovered, his chemotherapy was abandoned. A CT – positron emission tomography scan at this time showed no evidence of active disease. and this clinical and radiographic remission was maintained for nearly 5 years. Ultimately, the patient represented with pain in his right chest wall, and CT revealed bone metastasis to his ribs and vertebrae and a metastasis within the right lung. He received further chemotherapy with etoposide and ifosfamide for six cycles as planned, with clinical and radiographic improvement but significant neutropenia and fatigue. He had a course of radiotherapy to manage pain from metastases in his ribs and hip. He survived a further year after discontinuation of this chemotherapy, giving a total of 6 years of survival after initial treatment.
Comment Pulmonary artery intimal sarcomas are rare and are thought to arise from pluripotent mesenchymal cells from the bulbus cordis [1]. Patients normally present with nonspecific symptoms of cardiopulmonary disease such as cough, exertional dyspnea, or pain; as such, making a clinical diagnosis can be difficult [2, 3]. However, radiographic images produced with modern techniques (echocardiography, cardiac-gated CT, and gadolinium-enhanced MRI) are often sufficiently distinct from those of thromboembolism [1, 4, 5], and it appears to be the rarity of this tumor that makes early diagnosis difficult once these imaging techniques are used. Biopsy through a right heart catheter approach is possible and was successfully performed in this case. Therapy for pulmonary artery sarcomas revolves around surgical resection where possible, whereas chemotherapy and radiotherapy are thought to have a lesser role, although some now advocate for neoadjuvant chemotherapy with ifosfamide and doxorubicin [1]. Endovascular stenting can also be considered as a palliative procedure to relieve the right heart; right heart failure is the main cause of mortality for these patients. Other palliative options previously described in the literature include tumor debulking and endarterectomy [3]. This patient’s tumor was also treated with two chemotherapy regimens, with significant side effects. Pegylated doxorubicin has been shown to have less impact on cardiac function than standard doxorubicin
Ann Thorac Surg 2017;103:e21–3
CASE REPORT MORREAU AND HAYDOCK PULMONARY ARTERY SARCOMA
and was chosen because of existing and future concerns for this patient’s cardiorespiratory function [6]. The median survival time has historically been reported between 1.5 and 12 months, although more recent case series have shown the benefit of earlier diagnosis and improved management, with longer survival times reported [2, 3, 7, 8]. This case supports approaching suitable patients with aggressive surgical resection and adjuvant chemotherapy. This treatment can be associated with prolonged survival in patients with pulmonary artery sarcomas.
4.
References
7.
1. Blackmon SH, Rice DC, Correa AM, et al. Management of primary pulmonary artery sarcomas. Ann Thorac Surg 2009;87:977–84. 2. Nonomura A, Kurumaya H, Kono N, et al. Primary pulmonary artery sarcoma: report of two autopsy cases studied by
3.
5.
6.
8.
e23
immunohistochemistry and electron microscopy, and review of 110 cases reported in the literature. Pathol Int 1988;38: 883–96. Huo L, Lai S, Gladish G, Czerniak BA, Moran CA. Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation. Ann Diagn Pathol 2005;9:209–14. Restrepo CS, Betancourt SL, Martinez-Jimenez S, Gutierrez FR. Tumors of the pulmonary artery and veins. Semin Ultrasound CT MR 2012;33:580–90. Chin AY, Lee KS, Choe YH, Han D, Kwon OJ, Kim S. Computed tomography in pulmonary artery sarcoma: distinguishing features from pulmonary embolic disease. J Comput Assist Tomogr 2004;28:34–9. Duggan ST, Keating GM. Pegylated liposomal doxorubicin. Drugs 2011;71:2531–58. Mayer E, Kriegsmann J, Gaumann A, et al. Surgical treatment of pulmonary artery sarcoma. J Thorac Cardiovasc Surg 2001;121:77–82. Huo L, Moran CA, Fuller GN, Gladish G, Suster S. Pulmonary artery sarcoma: a clinicopathologic and immunohistochemical study of 12 cases. Am J Clin Pathol 2006;125: 419–24.