Primary pulmonary artery sarcoma: A report of six cases

Primary Pulmonary Artery Sarcoma: A Report of Six Cases Mark B. Anderson, MD, Jolene M. Kriett, MD, David P. Kapelanski, MD, Riyad Tarazi, MD, and Stuart W. Jamieson, FRCS Division of Cardiothoracic Surgery, University of California at San Diego Medical Center, San Diego, California

Pulmonary artery tumors are rare and a frequently overlooked cause of pulmonary artery occlusion. The presentation is one of progressive pulmonary dysfunction and right ventricular failure. The diagnosis s e l d o m is made preoperatively. We report 6 cases of primary sarcoma of the pulmonary artery identified at operation, which were

treated surgically. Resection with or without adjuvant therapy currently offers the only chance for survival. Emphasis must be placed on earlier identification of these tumors.

p

ules. All patients h a d abnormalities identified on ventilation-perfusion scintiscan, as well as on p u l m o n a r y a n g i o g r a p h y (Fig 1). A single patient h a d aspiration biopsies during p u l m o n a r y angioscopy, which were suggestive b u t not diagnostic of malignancy. At operation in all 6 cases there was evidence of bilateral disease. O p e r ative p r o c e d u r e s consisted of excision of all gross t u m o r (endarterectomy of vessel) in 4 patients, limited t u m o r resection (partial e n d a r t e r e c t o m y leaving residual tumor) in the fifth, a n d right ventricular outflow reconstruction and distal b y p a s s into the right p u l m o n a r y artery with a valved aortic homograft (secondary to unresectable locally invasive disease) in the r e m a i n i n g patient. A single patient in w h o m it was thought the t u m o r h a d b e e n resected u n d e r w e n t left p n e u m o n e c t o m y for isolated p u l m o n a r y metastases at an outside institution 2 m o n t h s after the initial operation.

r i m a r y tumors of the p u l m o n a r y arteries are rare. The clinical presentation closely r e s e m b l e s several more c o m m o n conditions, so they seldom are d i a g n o s e d preoperatively. The etiology of these tumors r e m a i n s obscure. N e w e r diagnostic techniques have h e l p e d in est a b l i s h i n g earlier identification. The h i s t o p a t h o l o g i c characteristics are variable a n d precise identification is often difficult. Treatment is primarily surgical with the role of adjuvant t h e r a p y as yet not clearly defined. The prognosis r e m a i n s poor. O u r institution has b e e n e n g a g e d in a p r o g r a m for surgical correction of chronic p u l m o n a r y t h r o m b o e m bolic disease since 1970, and recently has r e p o r t e d the experience and results with 150 p u l m o n a r y t h r o m b o e n d arterectomy operations [1]. Patients are referred from all areas for evaluation of their progressive p u l m o n a r y dysfunction associated with p u l m o n a r y hypertension. In this p u r s u i t we have e n c o u n t e r e d 6 cases of p r i m a r y sarcoma of the p u l m o n a r y artery within the last 6 years. W e p r e s e n t these cases, as well as their diagnosis a n d m a n agement, and review the literature. M a t e r i a l and M e t h o d s This series includes 4 m e n and 2 w o m e n ranging from 37 to 73 years of age who were identified over a 6-year period. All patients p r e s e n t e d with progressive dyspnea; 1 with associated cough, another with associated cough a n d pleuritic pain, a n d 1 with associated chest pain a n d pleural effusion. The average duration of s y m p t o m s was 17 months. All patients u n d e r w e n t evaluation for chronic t h r o m b o e m b o l i c disease, with only 2 patients having strong evidence suggesting previous p u l m o n a r y e m b o lism. Each patient h a d a preoperative chest radiologic examination, with abnormalities b e i n g identified in 2 patients, which consisted of scattered p u l m o n a r y nodAccepted for publication Feb. 16, 1995. Address reprint requests to Mr Jamieson, Division of Cardiothoracic Surgery, University of California Medical Center, 225 Dickinson St, San Diego, CA 92103-1990. © 1995 by The Society of Thoracic Surgeons

(Ann Thorac Surg 1995;59:1487-90)

Results The p a t h o l o g y consisted of malignant fibrous histiocytoma in 4 patients, e m b r y o n a l r h a b d o s a r c o m a in the fifth, a n d m y x o s a r c o m a with liposarcoma a n d fibrosarcoma characteristics in the last patient. Each patient was evalu a t e d routinely with r e g a r d to p u l m o n a r y function postoperatively. All patients d e m o n s t r a t e d i m p r o v e m e n t in exercise tolerance a n d h a d d e c r e a s e d resting oxygen requirements. In addition, all patients h a d i m p r o v e d h e m o d y n a m i c s . There were no postoperative complications. Three patients received postoperative c h e m o t h e r a p y after gross excision of all tumor; in 2 of these patients c h e m o t h e r a p y was c o m b i n e d with radiotherapy. The patients who received combination t h e r a p y d i e d at 7 a n d 8 m o n t h s postoperatively. The patient receiving only c h e m o t h e r a p y d i e d 11 months after the operation. O n e patient who u n d e r w e n t p n e u m o n e c t o m y a n d chemot h e r a p y after excision of all t u m o r died 19 m o n t h s after t u m o r resection and 17 months after p n e u m o n e c t o m y . The fifth patient died 5 m o n t h s after limited resection without adjuvant therapy. The r e m a i n i n g patient is alive 0003-4975195/$9.50 0003-4975(95)00149-F

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Ann Thorac Surg 1995;59:1487-90

Fig 1. Pulmonary anfiogram showing complete occlusion of left main pulmonary artery. Tumor also was Jbund in the right pulmonary artery at operation.

6 months after the operation and is receiving chemotherapy with limited t u m o r response (Table 1).

Comments Arterial t u m o r s r e p r e s e n t less than 20% of all vascular tumors. Most occur in the large veins, c o m m o n l y in the inferior vena cava. Involvement of the aorta, pulmonary, iliac, femoral, splenic, internal m a m m a r y , and inferior mesenteric arteries has been r e p o r t e d [2]. The majority of these tumors are malignant, being sarcomatous neoplasms. Similarly, p r i m a r y t u m o r s of the p u l m o n a r y artery are of the same histology. The differential diagnosis includes p u l m o n a r y arteritis, congenital p u l m o n a r y stenosis, tumors of the lung and m e d i a s t i n u m , p u l m o -

nary infections, fibrosing mediastinitis, a n d chronic pulm o n a r y t h r o m b o e m b o l i c disease. The first case of p u l m o n a r y artery sarcoma was rep o r t e d by M a n d e l s t a m m in 1923, and since then, there have been few reports in the literature [3-5], with the total n u m b e r of cases r e p o r t e d only a p p r o a c h i n g 100. Although rare, the true incidence is u n k n o w n and p r o b ably understated. In our experience of p u l m o n a r y h y p e r tension due to t h r o m b o e m b o l i c disease, patients generally do not p r e s e n t until well over half the p u l m o n a r y vasculature has b e e n occluded, a n d even in the late stages of the disease the diagnosis is often missed. It is therefore likely that there are patients in w h o m p u l m o nary h y p e r t e n s i o n due to t u m o r is u n d i a g n o s e d . O u r interest in the surgical t r e a t m e n t of chronic t h r o m b o e m bolic disease has led to our encountering 6 of these patients in a 6-year period. The clinical picture in our patients varied from mild d y s p n e a on exertion to respiratory distress a n d florid right heart failure. The usual history of patients with p u l m o n a r y artery tumors is one of progressive dyspnea, often with associated cough a n d chest pain. There m a y be coexisting signs of increasing right ventricular dysfunction. The presence of flow bruits over the p u l m o n a r y arteries is also suggestive. This clinical history is strikingly similar to that of patients with chronic t h r o m b o e m bolic disease. A l t h o u g h there was no strong history of previous deep venous t h r o m b o s i s or p u l m o n a r y e m b o lism in 4 of our 6 patients, only 50% of our p u l m o n a r y t h r o m b o e n d a r t e r e c t o m y patients here have no prior history of t h r o m b o e m b o l i s m or d e e p venous thrombosis [1]. Once the diagnosis is entertained, an extensive workup m a y be required. The evaluation of our patients included chest radiologic examination, ventilationperfusion scintiscan, echocardiogram, right heart catheterization, bilateral p u h n o n a r y angiography, a n d often p u l m o n a r y angioscopy. Chest radiologic examination is usually nonspecific. However, hilar p u l m o n a r y artery dilatation, increased heart size, and a c h a n g e d pulmo-

Table l. Patient Characteristics Patient Age No. (y) Sex 1

73

M

2

37

M

3

38

F

4

68

M

5

44

M

6

43

F

Symptoms

Duration

Progressive dyspnea Progressive dyspnea Chest pain, dyspnea, pleural effusion Cough, dyspnea

30 mo

Cough, chest pain, dyspnea Progressive dyspnea

MFH - malignant fibrous histiocytoma;

24 mo 5 mo 4 mo 14 mo 24 mo

Procedure Gross excision of tumor Limited resection Gross excision of tumor

Pathology

Adjuvant Therapy

Outcome

Myxosarcoma (lipofibroma) MFH

None

MFH

Chemotherapy, radiotherapy Died 8 mo

Chemotherapy, radiotherapy Died 7 mo

Gross excision MFH Left pneumonectomy, of tumor chemotherapy Gross excision Embryonal Chemotherapy of tumor rhabdosarcoma Homograft MFH Chemotherapy reconstruction RVOT

RVOT~ right ventricular outflow tract.

Died 5 mo

Died 19 mo Died 11 mo Alive 6 mo

A n n Thorac S u r g 1995;59:1487-90

Fig 2. Specimensfrom right and left pulmonary arteries.

nary vascular pattern, as well as secondary lesions, may arouse suspicion of a pulmonary artery tumor. Atypical patterns for pulmonary embolism seen on ventilationperfusion scans, as well as pedunculated or lobulated lesions with "to and fro" motion, or smooth tapering and distal pruning of pulmonary vessels seen on pulmonary angiography is also characteristic. Echocardiography, computed tomography, and magnetic resonance imaging scanning can allow for direct imaging of the tumor. Computed tomographic scanning cannot differentiate between thrombus and tumor; however, it can visualize secondary lesions. Gadolinium-diethylene triamene pentaacetic acid-enhanced magnetic resonance imaging may differentiate between vascularized tumor and intraluminal thrombus. Smith and colleagues [6] described magnetic and CT findings in pulmonary artery sarcoma, and they concluded that the tumor distribution of these lesions is highly distinctive and can be suggestive of the diagnosis. Preoperative histologic verification is generally not possible for vascular tumors; however, aspiration biopsy specimens may be obtained via pulmonary angioscopy, which allows direct visualization of the tumor. The etiology of these tumors remains obscure. They have been related to the malignant degeneration of thrombus and the neoplastic transformation of primitive mesenchymal cells [7-9]. Grossly, these tumors are typically large and mucoid, and line or completely fill the pulmonary vessels but do not resemble thrombus (Fig 2). Morphologic descriptions of tumor growth patterns include intimal, intraluminal, and adventitial. The World Health Organization has set criteria for histologic classification of vascular sarcomas based on stained sections [10]. Immunohistochemical studies using smooth muscle actin, desmin, and $100 protein can assist in identifying the tumors. Positive staining for factor VII-related antigen and QBend/CD34 can suggest primary endothelial origin. Finally, Burke and Virmani [11] recently presented a clinicopathologic study of sarcomas of the great vessels and reported a wide variety of histologic findings. Treatment of these tumors remains primarily surgical. There are reports of patients surviving extended lengths of time after surgical resection [12]. Historically, the surgical approach was thoracotomy and pneumonectomy. As these tumors arise from the intima, rarely extend through the adventitia, and invade surrounding

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structures, resection via a sternotomy and cardiopulmonary bypass are being used increasingly. For early lesions endarterectomy (removing the intima and most of the media) may result in complete tumor removal. Frozen section analysis to determine vessel wall involvement may be helpful in this regard. For advanced but resectable lesions, total excision of the pulmonary trunk and artery using one of the several reconstructive techniques described may be the best procedure [13]. However, because microscopic distal embolization is common in these patients, endarterectomy is perhaps a more simple approach. Heart and lung transplantation also has been performed in a patient with a known diagnosis of pulmonary artery sarcoma. Finally, in patients with extensive or metastatic disease, limited tumor resection or a bypass procedure can result in excellent palliation. Because all our patients had evidence of bilateral disease at operation, pneumonectomy, even if practical, was not a consideration. There were no cases of reperfusion edema after operation in this series. This is consistent with our experience in pulmonary thromboendarterectomy patients, in whom the incidence of clinically significant edema is now less than 10%. The prognosis of these tumors depends largely on local recurrence. Length of survival of patients with primary pulmonary artery sarcomas is intermediate between that of patients with aortic and inferior vena caval sarcomas. Median length of survival without surgical resection is approximately 1.5 months, which is not affected by the addition of adjuvant therapy. Surgical resection has lengthened survival time to approximately 1 year. The addition of adjuvant radiotherapy and chemotherapy has extended this somewhat further. The survival times of our patients are consistent with these findings. The most beneficial protocols for this tumor, however, are yet to be described. Pulmonary metastases are present in up to 60% of patients, but extrathoracic disease is unusual. Thus, in the absence of distal disease, resection of pulmonary metastases after obtaining local control may provide a survival benefit. Distal microembolization is common; therefore, adjuvant chemotherapy, even in the absence of pulmonary nodules, would seem appropriate. Our institution is involved actively in the evaluation and surgical therapy of patients with progressive pulmonary dysfunction related to chronic pulmonary thromboembolic disease, and we undoubtedly will continue to encounter primary pulmonary artery sarcomas in this endeavor. The extensive preoperative work-up currently used, perhaps with the addition of computed tomography and magnetic resonance imaging, should allow for earlier preoperative diagnosis. When clinicians encounter patients with advancing pulmonary failure who have an atypical history with findings suggestive of pulmonary artery occlusion, the diagnosis of pulmonary artery tumor must be considered. Emphasis should be placed on early identification of these lesions. As evidenced by our patients with an average duration of symptoms of 17 months, diagnosis is often delayed and the tumor is incurable. Total surgical resection with the addition of

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chemotherapy, radiotherapy, or both, or excision of all gross t u m o r in combination with adjuvant t r e a t m e n t should offer these patients significant palliation a n d an o p p o r t u n i t y for increased length of survival.

References 1. Jamieson SW, Auger WR, Fedullo PF, et al. Experience and results with 150 pulmonary thromboendarterectomy operations over a 29-month period. J Thorac Cardiovasc Surg 1993;106:116-26. 2. Becquemin ]P, Lebbe C, Saada F, et al. Sarcoma of the aorta: report of a case and review of the literature. Ann Vasc Surg 1988;2:225-30. 3. Delany SG, Doyle TCA, Bunton RW. Pulmonary artery sarcoma mimicking puhnonary embolism. Chest 1993;103:1631-3. 4. Eng J, Murday AJ. Leiomyosarcoma of the pulmonary artery. Ann Thorac Surg 1992;53:905-6. 5. Mandelstamm M. Uber primare Neubildugen des Herzens. Virchows Arch [Pathol Anat] 1923;245:43-54.

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6. Smith WS, Lesar MS, Travis WD, et al. MR and CT findings in pulmonary artery sarcoma. J Comput Assist Tomogr 1989;13:906-9. 7. Kattus AA, Longmire WP, Cannon JA, et al. Primary intraluminal tumor of the aorta producing malignant hypertension. N Engl J Med 1960;262:694-700. 8. Iwasaki H, Isayama T, Johzaki H, et al. Malignant fibrous histiocytoma. Am J Pathol 1987;128:528-37. 9. Bleisch VR, Kraus FT. Polypoid sarcoma of the pulmonary trunk. Cancer 1980;46:314-24. 10. Enzinger FM, Lattes R, Torloni R. Histological typing of soft tissue tumors: international classification of tumors. No 3. Geneva: WHO, 1969:19-25. 11. Burke AP, Virmani R. Sarcomas of the great vessels. A clinicopathologic study. Cancer 1993;71:1761-73. 12. Head HD, Flam MS, John MJ, et al. Long-term palliation of pulmonary artery sarcoma by radical excision and adjuvant therapy. Ann Thorac Surg 1992;53:332-4. 13. Okada K, Okada M, Yamamoto S, et al. Successful resection of a recurrent leiomyosarcoma of the pulmonary trunk. Ann Thorac Surg 1993;55:1009-12.

INVITED COMMENTARY With one of the w o r l d ' s most extensive experiences with the evaluation and surgical t r e a t m e n t of patients with t h r o m b o e m b o l i c p u l m o n a r y artery occlusive disease, A n d e r s o n a n d associates now have r e p o r t e d w h a t is p e r h a p s the largest single experience with the operative t h e r a p y of p u l m o n a r y artery sarcomas. On the basis of the data presented, however, it is difficult to accept the conclusion of the article that "total surgical resection [of p u l m o n a r y artery sarcomas] with the addition of chemotherapy, radiotherapy, or both, or excision of all gross t u m o r in combination with adjuvant t r e a t m e n t should offer these patients significant palliation a n d an o p p o r tunity for increased length of survival." The dismal survival of their patients (five deaths at 5, 7, 8, 11, a n d 19 months, and only 1 patient alive after 6 m o n t h s of follow-up) w o u l d suggest that p u l m o n a r y artery sarcomas are almost invariably incurable. As p o i n t e d out by A n d e r s o n and associates, the clinical history (dyspnea, respiratory distress, a n d right ventricular dysfunction) of patients with p u l m o n a r y artery t u m o r s is not significantly different from that of patients with chronic thromboembolic disease. A l t h o u g h two thirds (416) of their patients with tumors h a d no prior history of t h r o m b o e m bolism or deep venous thrombosis, 50% of their p u l m o nary t h r o m b o e n d a r t e r e c t o m y patients similarly h a d a negative history for prior t h r o m b o e m b o l i c disease, so this is not a true differentiating feature b e t w e e n these groups. The reality is that very few patients p r e s e n t i n g with a clinical history consistent with p u l m o n a r y thromboembolic disease and requiring a pulmonary thromb o e n d a r t e r e c t o m y (4% in A n d e r s o n a n d a s s o c i a t e s ' extensive experience) will be f o u n d on frozen section evaluation of the resected clot to have a p u l m o n a r y artery sarcoma. There is generally little reason to consider this diagnosis preoperatively, except in the occasional patient with an atypical pattern for p u l m o n a r y e m b o l i s m on

ventilation-perfusion scan or p e d u n c u l a t e d lesions with "to a n d fro" motion on p u l m o n a r y angiography. N e w biologic scanning techniques such as the G d - D T P A e n h a n c e d magnetic resonance i m a g i n g scan m a y differentiate a vascular t u m o r from intraluminal thrombus. Unfortunately, it is easily concluded from this article that the incidental finding of sarcomatous elements in the t h r o m b o e n d a r t e r e c t o m y specimen of patients u n d e r going surgical t r e a t m e n t for p r e s u m e d chronic p u l m o nary t h r o m b o e m b o l i c disease signifies a virtually fatal t u m o r for which current t h e r a p y seems totally inadequate. W o u l d it not provide a better margin of resection in these patients if the involved p u l m o n a r y artery were resected a n d r e p l a c e d with a homograft rather than "shelling o u t " a p r i m a r y m a l i g n a n c y of the arterial wall using traditional techniques of t h r o m b o e n d a r t e r e c t o m y ? At the p r e s e n t time, a p l a n n e d surgical a p p r o a c h to patients with p r i m a r y p u l m o n a r y artery malignancies rarely will occur b e c a u s e few are d i a g n o s e d p r e o p e r a tively, a n d most of these t u m o r s will be " s t u m b l e d across" during p e r f o r m a n c e of a t h r o m b o e n d a r t e r e c t o m y for p r e s u m e d chronic t h r o m b o e m b o l i c disease. Routine p e r f o r m a n c e of a frozen section on the thromb o e n d a r t e r e c t o m y s p e c i m e n will establish the diagnosis, a n d it r e m a i n s to be seen if traditional principles of full-thickness resection of the involved blood vessel a n d reconstruction have a meaningful role in the t r e a t m e n t of p u l m o n a r y artery sarcomas.

Mark B. Orringer, MD Section of Thoracic Surgery The University of Michigan Taubman Health Care Center 1500 E Medical Center Dr, Rm 2110 Ann Arbor, MI 48109