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Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation
Annals of Diagnostic Pathology 9 (2005) 209 – 214
Radiologic-pathologic correlation
Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation Lei Huo, MD, PhDa, Syeling Lai, MDa, Gregory Gladish, MDb, Bogdan A. Czerniak, MD, PhDa, Cesar A. Moran, MDa,T a
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA Department of Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA
b
Abstract
A 69-year-old man presented with cough, shortness of breath, and fatigue. He was initially treated for allergies and then for pulmonary embolism. Radiologically, a tumor mass was found to occlude the right pulmonary artery and involve the pulmonary trunk. A right pneumonectomy was performed. Histologically, a cellular malignant spindle and epithelioid tumor with areas of necrosis and brisk mitotic activity was seen. In some areas, the tumor appeared to form vascular channels. Focal osteosarcomatous differentiation was present. Immunohistochemical studies were performed including vimentin, smooth muscle actin, desmin, CD31, CD34, S100, and pan-cytokeratin. The tumor cells were positive for CD31 and vimentin and negative for pan-cytokeratin, CD34, and S100. Two months after surgery, the patient was alive and well. D 2005 Elsevier Inc. All rights reserved.
Keywords:
Pulmonary artery; Intimal sarcoma; Angiosarcoma
1. Introduction Primary pulmonary artery sarcomas are uncommon. They are believed to originate from pluripotent intimal cells and hence given the name intimal sarcomas [1,2]. Occasionally, pulmonary artery sarcomas exhibit distinct histological differentiation and are classified as osteosarcomas, rhabdomyosarcomas, and angiosarcomas among others [3,4]. We report a case of pulmonary artery angiosarcoma. 2. Clinical and radiological findings A 69-year-old man with a past medical history significant for type 2 diabetes mellitus, hypertension, and hypercholesterolemia was evaluated for a dry, chronic cough and was initially treated for allergies. He had progressive shortness of breath and fatigue in the next 2 months and was admitted to the intensive care unit for the treatment of pulmonary embolism with anticoagulants. Physical examination revealed clear lungs to auscultation with no rales or wheezes.
T Corresponding author. Tel.: +1 713 792 8134; fax: +1 713 745 0789. E-mail address: [email protected] (C.A. Moran). 1092-9134/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2005.04.012
Heart sounds were regular with S1 and S2 without murmurs or gallops. No cervical, subclavicular, axillary, or inguinal lymphadenopathy was noted. Bronchoscopy showed no evidence of endobronchial disease. A ventilation perfusion scan revealed approximately 11% perfusion to the right lung and 89% to the left. A 2-dimensional transthoracic echocardiogram detected an elevated right ventricular systolic pressure greater than 60 mm Hg, mild tricuspid regurgitation, and a normal right ventricular size. Cardiac-gated magnetic resonance imaging (MRI; Fig. 1A-E) of the heart demonstrated an intermediate single-intensity mass filling the distal portion of the main pulmonary artery, most of the right pulmonary artery, and extending into the left pulmonary artery. The tumor extended to the pulmonic root, but valve involvement was not demonstrated. Valve leaflet motion was normal on fast imaging employing steady-state acquisition cine images. Gadolinium contrast media administration demonstrated enhancement of the tumor. Cardiac-gated computed tomography of the heart likewise demonstrated a tumor filling the main and right pulmonary arteries and extending into the left pulmonary artery. Both MRI and computed tomography demonstrated a mobile polypoid component of the tumor. No pulmonary metastatic lesions were demonstrated.
210
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
Fig. 1. Cardiac-gated MRI images of pulmonary artery angiosarcoma. Oblique axial (A, B) and oblique sagittal (C) double-inversion recovery images through the pulmonary artery demonstrate a lobulated mass (*) filling the main and right pulmonary arteries and extending into the left pulmonary artery. The tumor extends to the root of the pulmonary artery but appears separate from the pulmonary valve (arrows). The tumor enhances after gadolinium contrast media administration (B). Fast imaging employing steady-state acquisition cine images in diastole (D) and end systole (E) demonstrate a polypoid mobile tumor component (arrowheads) and normal valve motion. Ao indicates aorta; RV, right ventricle.
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
211
A biopsy of the mass revealed a sarcoma. The patient underwent right pneumonectomy, en bloc resection of right pulmonary artery, and resection of pulmonary trunk and pulmonary valve. Intraoperative findings indicated that the tumor completely occluded the right pulmonary artery and extended down to the pulmonary valve. It invaginated into the left pulmonary artery without involvement of the vascular wall. 3. Pathologic findings 3.1. Gross features The right lung measured 18 15 5 cm, with 7 cm of the right pulmonary artery completely obstructed by a yellow friable intraluminal mass measuring 7 2.8 2.5 cm (Fig. 2A and B). The tumor mainly involved the posterior wall of the artery without reaching the adventitia. It also extended to the right upper lobe and middle lobe pulmonary artery branches. No gross masses were identified in the lung parenchyma. In addition, a 3.5-cm proximal portion of the pulmonary trunk with pulmonary valve and an attached rim of right ventricle measuring 9 0.3 0.3 cm (Fig. 2C) was received. In the lumen of the pulmonary trunk was an irregular tumor mass measuring 2.5 2.2 1.5 cm adherent to the wall. The resection margins on the specimens were grossly free of tumor. Multiple mediastinal and hilar lymph nodes, which were grossly unremarkable, were taken. 3.2. Histological features Microscopic sections showed an intraluminal tumor adherent and focally infiltrative to the vascular wall. The medial elastic fibers were largely intact, consistent with the intimal origin of the tumor (Fig. 3A and B). The tumor cells were arranged in hypercellular sheets or nests separated by bands of collagen and a few myxoid areas. The cells were highly pleomorphic. Most were spindle cells with a hyperchromatic nucleus and an inconspicuous cytoplasm (Fig. 3C). There were areas of round cells with more distinct cell borders, abundant cytoplasm, and vesicular nucleus containing clumpy chromatin, giving an epithelioid appearance (Fig. 3D). Multiple bizarre tumor giant cells were present among the spindle and epithelioid cells. Mitotic figures were brisk with up to 13 mitoses per 10 high-power fields, including atypical forms. Large areas of necrosis were present. Focally, slit-like vascular channels were present, lined by pleomorphic tumor cells (Fig. 3E). Careful examination revealed more areas where tumor cells formed vague vascular spaces. A microscopic focus of osteosarcomatous differentiation was noted (Fig. 3F). Immunohistochemical studies demonstrated that the tumor cells were diffusely positive for vimentin and CD31 (Fig. 3G). Pan-cytokeratin (AE1/AE3) was negative in tumor cells, including the epithelioid cells. In addition, CD34, S100, and epithelial membrane antigen were negative. Smooth muscle actin and desmin showed scattered positive cells.
Fig. 2. Gross appearance of pulmonary artery angiosarcoma. A and B, Pneumonectomy and en bloc resection of the right pulmonary artery. The right pulmonary artery is filled with a tumor mass. A, Adventitial surface. B, Cut surface. C, Pulmonary trunk with tumor adherent to the wall.
A few tumor nodules were identified in the perihilar lung parenchyma. The resection margins were microscopically negative. All lymph nodes were negative for tumor. 4. Discussion Angiosarcoma is one of the rarest types of pulmonary artery sarcomas. In 1988, Nonomura et al [3] reviewed 110 cases of pulmonary artery sarcomas that included only
212
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
Fig. 3. Intraluminal pulmonary artery angiosarcoma. A and B, Tumor adherent to the artery wall with focal infiltration to the media. A, Hematoxylin and eosin section. B, Verhoeff’s elastic stain highlighting the elastic fibers in the media. C, Spindle cell area. D, Epithelioid area. E, Vascular channels formed by tumor cells. F, Osteosarcomatous differentiation. G, Diffuse positive CD31 staining in tumor cells.
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
4 angiosarcomas. Since then, fewer than a dozen of cases have been reported in the English literature (Table 1). Cases 4 to 7 in Table 1 were reported in a study of dynamic contrast-enhanced MRI characteristics of pulmonary artery angiosarcomas. Detailed information regarding patient sex, distal metastasis, treatment, and follow-up was not provided. Based on the published literature (Table 1) of pulmonary artery angiosarcomas, the mean age of the 11 patients at the time of diagnosis was 55 years (range, 38-69 years). Of the 7 patients of known sex, 5 were men and 2 were women. The most common presenting symptoms were nonspecific, including cough and dyspnea. Because clinical findings usually could not distinguish a tumor from acute or chronic embolic disease, 5 of the 7 patients, including the current case patient, were initially treated for pulmonary emboli with anticoagulants [2,5,8,9]. (In addition, for cases 4 to 7, it was mentioned that the patients were referred for suspected recurrent chronic pulmonary embolism or mediastinal tumor although more information was not available.) Lung involvement was seen in 5 of 11 patients. These features are in keeping with those of pulmonary artery sarcomas in general [2,4]. Pulmonary artery sarcomas have poor
213
prognosis, with more than half of patients not surviving during the first year and a dismal 5-year survival [4]. Of 6 patients with a maximal follow-up of 12 months, 4 were alive and well at the time of the report (Table 1). Long-term follow-up is necessary to determine whether the prognosis of pulmonary artery angiosarcomas is different from that of pulmonary artery sarcomas as a whole. Some pulmonary artery sarcomas (16%; [4]) have been shown to metastasize distantly (extrathoracic metastasis). This was not observed for the angiosarcomas, possibly because of the small number of the cases and lack of long-term follow-up. The current case is a high-grade spindle cell malignancy with histological and immunohistochemical features of angiosarcomas. The tumor also showed a focal area of osteosarcomatous differentiation, an unusual feature for angiosarcomas. Interestingly, osteosarcomatous differentiation was also seen in 2 other reported pulmonary artery angiosarcomas (cases 8 and 9 in Table 1). The occurrence of osteosarcomas and undifferentiated (intimal) sarcomas with osteosarcomatous areas has been reported arising from the pulmonary artery [2,4]. It has been suggested that although the intimal sarcomas, including the rare osteosarcomas,
Table 1 Clinical and pathologic characteristics of pulmonary artery angiosarcomas No.
Age
Sex
Presentation
Site
Additional involvement
Histology
Treatment
Follow-up
Source
1 2
57 69
F M
PT, RPA RPA
None Lung
F
PV to both PAs
Lung
Died at 2 wk Died at day 22 of hospitalization Alive and well at 12 mo
Ref. [2] Ref. [5]
49
Angiosarcoma Epithelioid angiosarcoma Hemangiosarcoma
Resection Resection
3
Pulmonary emboli Dyspnea on exertion Dyspnea on exertion
4
59
NA
NA
Ref. [7]
42
NA
Resection
NA
Ref. [7]
6
38
NA
PT to branches PT to branches PT to branches
Lunga
5
Dyspnea on exertion Dyspnea on exertion Dyspnea on exertion
Resection
NA
Ref. [7]
7
43
NA
PAsb
Nonea
Resection
NA
Ref. [7]
8
57
M
Dyspnea on exertion Cough, chest pain, dyspnea
PT, RPA
None
Resection
Alive and well at 9 mo
Ref. [8]
9
59
M
Progressive dyspnea and cough
PT to RPA
Lung
Tumor debulking
NA
Ref. [9]
10
67
M
Anterior mediastinal mass
PT
Endovascular stent, chemoradiation
Alive and well at 6 mo
Ref. [10]
11
69
M
Cough, dyspnea
PT, RPA
Left atrium left pulmonary veins (by computed tomography) Lung
Resection
Alive and well at 2 mo
Current
Nonea Nonea
Angiosarcoma (low differentiation) Angiosarcoma (low differentiation) Angiosarcoma (intermediate differentiation) Angiosarcoma (high differentiation) Angiosarcomatous (2/3) and osteosarcomatous (1/3) areas Angiosarcoma with osteosarcomatous foci Angiosarcoma
Angiosarcoma with focal osteosarcomatous differentiation
Neoadjuvant chemotherapy, resection Resection
PT indicates pulmonary trunk; RPA, right pulmonary artery; PV, pulmonary valve; PA, pulmonary artery; NA, not available. a Information on lung involvement but not on distal metastasis was available. b The site was not specified.
Ref. [6]
214
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
derive from the intimal mesenchymal cells, angiosarcomas may be of endothelial origin [2]. Considering the rarity of angiosarcomas in this location, the proportion of cases showing osteosarcomatous differentiation seems to be surprisingly high. Perhaps this is a reflection of the pluripotent nature of the intimal cells capable of giving rise to all these sarcomas, including angiosarcoma. Surgical resection remains the therapy of choice for pulmonary artery sarcomas and is thought to give the best chance for survival. However, even with surgical resection, the mean survival is only approximately 12 months [11]. Information on adjuvant therapy is still limited. Some believe that postoperation chemoradiation has no effect on long-term survival [4], whereas others have suggested that adjuvant therapy can benefit patients by relieving symptoms and prolonging survival [6,11,12]. Neoadjuvant chemotherapy has also been shown to be effective [6]. Nowadays, systemic therapy for soft tissue sarcomas is improving with more specific chemotherapy regimens, including those for rare entities such as angiosarcomas [13]. Conceivably, these new developments can be used for sarcomas occurring in uncommon locations such as the pulmonary artery. Thus, subclassification of these sarcomas will allow the application of potentially more effective adjuvant therapies. References [1] Altman NH, Shelley WM. Primary intimal sarcoma of the pulmonary artery. Johns Hopkins Med J 1973;133:214 - 22.
[2] Burke AP, Virmani R. Sarcomas of the great vessels. A clinicopathologic study. Cancer 1993;71:1761 - 73. [3] Nonomura A, Kurumaya H, Kono N, et al. Primary pulmonary artery sarcoma. Report of two autopsy cases studied by immunohistochemistry and electron microscopy, and review of 110 cases reported in the literature. Acta Pathol Jpn 1988;38:883 - 96. [4] Cox JE, Chiles C, Aquino SL, et al. Pulmonary artery sarcomas: a review of clinical and radiological features. J Comput Assist Tomogr 1997;21:750 - 5. [5] Goldblum JR, Rice TW. Epithelioid angiosarcoma of the pulmonary artery. Hum Pathol 1995;26:1275 - 7. [6] Zerkowski HR, Hofmann HS, Gybels I, et al. Primary sarcoma of pulmonary artery and valve: multimodality treatment by chemotherapy and homograft replacement. J Thorac Cardiovasc Surg 1996;112:1122 - 4. [7] Kacl GM, Bruder E, Pfammatter T, et al. Primary angiosarcoma of the pulmonary arteries: dynamic contrast-enhanced MRI. J Comput Assist Tomogr 1998;22:687 - 91. [8] Govender D, Pillay S. Right pulmonary artery sarcoma. Pathology 2001;33:243 - 5. [9] Tschirch FT, Del Grande F, Marincek B, et al. Angiosarcoma of the pulmonary trunk mimicking pulmonary thromboembolic disease. A case report. Acta Radiol 2003;44:504 - 7. [10] Totaro M, Miraldi F, Ghiribelli C, et al. Cardiac angiosarcoma arising from pulmonary artery: endovascular treatment. Ann Thorac Surg 2004;78:1468 - 70. [11] Anderson MB, Kriett JM, Kapelanski DP, et al. Primary pulmonary artery sarcoma: a report of six cases. Ann Thorac Surg 1995;59: 1487 - 90. [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] Vogt T, Hafner C, Bross K, et al. Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors. Cancer 2003;98:2251 - 6.
Radiologic-pathologic correlation
Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation Lei Huo, MD, PhDa, Syeling Lai, MDa, Gregory Gladish, MDb, Bogdan A. Czerniak, MD, PhDa, Cesar A. Moran, MDa,T a
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA Department of Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030-4009, USA
b
Abstract
A 69-year-old man presented with cough, shortness of breath, and fatigue. He was initially treated for allergies and then for pulmonary embolism. Radiologically, a tumor mass was found to occlude the right pulmonary artery and involve the pulmonary trunk. A right pneumonectomy was performed. Histologically, a cellular malignant spindle and epithelioid tumor with areas of necrosis and brisk mitotic activity was seen. In some areas, the tumor appeared to form vascular channels. Focal osteosarcomatous differentiation was present. Immunohistochemical studies were performed including vimentin, smooth muscle actin, desmin, CD31, CD34, S100, and pan-cytokeratin. The tumor cells were positive for CD31 and vimentin and negative for pan-cytokeratin, CD34, and S100. Two months after surgery, the patient was alive and well. D 2005 Elsevier Inc. All rights reserved.
Keywords:
Pulmonary artery; Intimal sarcoma; Angiosarcoma
1. Introduction Primary pulmonary artery sarcomas are uncommon. They are believed to originate from pluripotent intimal cells and hence given the name intimal sarcomas [1,2]. Occasionally, pulmonary artery sarcomas exhibit distinct histological differentiation and are classified as osteosarcomas, rhabdomyosarcomas, and angiosarcomas among others [3,4]. We report a case of pulmonary artery angiosarcoma. 2. Clinical and radiological findings A 69-year-old man with a past medical history significant for type 2 diabetes mellitus, hypertension, and hypercholesterolemia was evaluated for a dry, chronic cough and was initially treated for allergies. He had progressive shortness of breath and fatigue in the next 2 months and was admitted to the intensive care unit for the treatment of pulmonary embolism with anticoagulants. Physical examination revealed clear lungs to auscultation with no rales or wheezes.
T Corresponding author. Tel.: +1 713 792 8134; fax: +1 713 745 0789. E-mail address: [email protected] (C.A. Moran). 1092-9134/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2005.04.012
Heart sounds were regular with S1 and S2 without murmurs or gallops. No cervical, subclavicular, axillary, or inguinal lymphadenopathy was noted. Bronchoscopy showed no evidence of endobronchial disease. A ventilation perfusion scan revealed approximately 11% perfusion to the right lung and 89% to the left. A 2-dimensional transthoracic echocardiogram detected an elevated right ventricular systolic pressure greater than 60 mm Hg, mild tricuspid regurgitation, and a normal right ventricular size. Cardiac-gated magnetic resonance imaging (MRI; Fig. 1A-E) of the heart demonstrated an intermediate single-intensity mass filling the distal portion of the main pulmonary artery, most of the right pulmonary artery, and extending into the left pulmonary artery. The tumor extended to the pulmonic root, but valve involvement was not demonstrated. Valve leaflet motion was normal on fast imaging employing steady-state acquisition cine images. Gadolinium contrast media administration demonstrated enhancement of the tumor. Cardiac-gated computed tomography of the heart likewise demonstrated a tumor filling the main and right pulmonary arteries and extending into the left pulmonary artery. Both MRI and computed tomography demonstrated a mobile polypoid component of the tumor. No pulmonary metastatic lesions were demonstrated.
210
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
Fig. 1. Cardiac-gated MRI images of pulmonary artery angiosarcoma. Oblique axial (A, B) and oblique sagittal (C) double-inversion recovery images through the pulmonary artery demonstrate a lobulated mass (*) filling the main and right pulmonary arteries and extending into the left pulmonary artery. The tumor extends to the root of the pulmonary artery but appears separate from the pulmonary valve (arrows). The tumor enhances after gadolinium contrast media administration (B). Fast imaging employing steady-state acquisition cine images in diastole (D) and end systole (E) demonstrate a polypoid mobile tumor component (arrowheads) and normal valve motion. Ao indicates aorta; RV, right ventricle.
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
211
A biopsy of the mass revealed a sarcoma. The patient underwent right pneumonectomy, en bloc resection of right pulmonary artery, and resection of pulmonary trunk and pulmonary valve. Intraoperative findings indicated that the tumor completely occluded the right pulmonary artery and extended down to the pulmonary valve. It invaginated into the left pulmonary artery without involvement of the vascular wall. 3. Pathologic findings 3.1. Gross features The right lung measured 18 15 5 cm, with 7 cm of the right pulmonary artery completely obstructed by a yellow friable intraluminal mass measuring 7 2.8 2.5 cm (Fig. 2A and B). The tumor mainly involved the posterior wall of the artery without reaching the adventitia. It also extended to the right upper lobe and middle lobe pulmonary artery branches. No gross masses were identified in the lung parenchyma. In addition, a 3.5-cm proximal portion of the pulmonary trunk with pulmonary valve and an attached rim of right ventricle measuring 9 0.3 0.3 cm (Fig. 2C) was received. In the lumen of the pulmonary trunk was an irregular tumor mass measuring 2.5 2.2 1.5 cm adherent to the wall. The resection margins on the specimens were grossly free of tumor. Multiple mediastinal and hilar lymph nodes, which were grossly unremarkable, were taken. 3.2. Histological features Microscopic sections showed an intraluminal tumor adherent and focally infiltrative to the vascular wall. The medial elastic fibers were largely intact, consistent with the intimal origin of the tumor (Fig. 3A and B). The tumor cells were arranged in hypercellular sheets or nests separated by bands of collagen and a few myxoid areas. The cells were highly pleomorphic. Most were spindle cells with a hyperchromatic nucleus and an inconspicuous cytoplasm (Fig. 3C). There were areas of round cells with more distinct cell borders, abundant cytoplasm, and vesicular nucleus containing clumpy chromatin, giving an epithelioid appearance (Fig. 3D). Multiple bizarre tumor giant cells were present among the spindle and epithelioid cells. Mitotic figures were brisk with up to 13 mitoses per 10 high-power fields, including atypical forms. Large areas of necrosis were present. Focally, slit-like vascular channels were present, lined by pleomorphic tumor cells (Fig. 3E). Careful examination revealed more areas where tumor cells formed vague vascular spaces. A microscopic focus of osteosarcomatous differentiation was noted (Fig. 3F). Immunohistochemical studies demonstrated that the tumor cells were diffusely positive for vimentin and CD31 (Fig. 3G). Pan-cytokeratin (AE1/AE3) was negative in tumor cells, including the epithelioid cells. In addition, CD34, S100, and epithelial membrane antigen were negative. Smooth muscle actin and desmin showed scattered positive cells.
Fig. 2. Gross appearance of pulmonary artery angiosarcoma. A and B, Pneumonectomy and en bloc resection of the right pulmonary artery. The right pulmonary artery is filled with a tumor mass. A, Adventitial surface. B, Cut surface. C, Pulmonary trunk with tumor adherent to the wall.
A few tumor nodules were identified in the perihilar lung parenchyma. The resection margins were microscopically negative. All lymph nodes were negative for tumor. 4. Discussion Angiosarcoma is one of the rarest types of pulmonary artery sarcomas. In 1988, Nonomura et al [3] reviewed 110 cases of pulmonary artery sarcomas that included only
212
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
Fig. 3. Intraluminal pulmonary artery angiosarcoma. A and B, Tumor adherent to the artery wall with focal infiltration to the media. A, Hematoxylin and eosin section. B, Verhoeff’s elastic stain highlighting the elastic fibers in the media. C, Spindle cell area. D, Epithelioid area. E, Vascular channels formed by tumor cells. F, Osteosarcomatous differentiation. G, Diffuse positive CD31 staining in tumor cells.
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
4 angiosarcomas. Since then, fewer than a dozen of cases have been reported in the English literature (Table 1). Cases 4 to 7 in Table 1 were reported in a study of dynamic contrast-enhanced MRI characteristics of pulmonary artery angiosarcomas. Detailed information regarding patient sex, distal metastasis, treatment, and follow-up was not provided. Based on the published literature (Table 1) of pulmonary artery angiosarcomas, the mean age of the 11 patients at the time of diagnosis was 55 years (range, 38-69 years). Of the 7 patients of known sex, 5 were men and 2 were women. The most common presenting symptoms were nonspecific, including cough and dyspnea. Because clinical findings usually could not distinguish a tumor from acute or chronic embolic disease, 5 of the 7 patients, including the current case patient, were initially treated for pulmonary emboli with anticoagulants [2,5,8,9]. (In addition, for cases 4 to 7, it was mentioned that the patients were referred for suspected recurrent chronic pulmonary embolism or mediastinal tumor although more information was not available.) Lung involvement was seen in 5 of 11 patients. These features are in keeping with those of pulmonary artery sarcomas in general [2,4]. Pulmonary artery sarcomas have poor
213
prognosis, with more than half of patients not surviving during the first year and a dismal 5-year survival [4]. Of 6 patients with a maximal follow-up of 12 months, 4 were alive and well at the time of the report (Table 1). Long-term follow-up is necessary to determine whether the prognosis of pulmonary artery angiosarcomas is different from that of pulmonary artery sarcomas as a whole. Some pulmonary artery sarcomas (16%; [4]) have been shown to metastasize distantly (extrathoracic metastasis). This was not observed for the angiosarcomas, possibly because of the small number of the cases and lack of long-term follow-up. The current case is a high-grade spindle cell malignancy with histological and immunohistochemical features of angiosarcomas. The tumor also showed a focal area of osteosarcomatous differentiation, an unusual feature for angiosarcomas. Interestingly, osteosarcomatous differentiation was also seen in 2 other reported pulmonary artery angiosarcomas (cases 8 and 9 in Table 1). The occurrence of osteosarcomas and undifferentiated (intimal) sarcomas with osteosarcomatous areas has been reported arising from the pulmonary artery [2,4]. It has been suggested that although the intimal sarcomas, including the rare osteosarcomas,
Table 1 Clinical and pathologic characteristics of pulmonary artery angiosarcomas No.
Age
Sex
Presentation
Site
Additional involvement
Histology
Treatment
Follow-up
Source
1 2
57 69
F M
PT, RPA RPA
None Lung
F
PV to both PAs
Lung
Died at 2 wk Died at day 22 of hospitalization Alive and well at 12 mo
Ref. [2] Ref. [5]
49
Angiosarcoma Epithelioid angiosarcoma Hemangiosarcoma
Resection Resection
3
Pulmonary emboli Dyspnea on exertion Dyspnea on exertion
4
59
NA
NA
Ref. [7]
42
NA
Resection
NA
Ref. [7]
6
38
NA
PT to branches PT to branches PT to branches
Lunga
5
Dyspnea on exertion Dyspnea on exertion Dyspnea on exertion
Resection
NA
Ref. [7]
7
43
NA
PAsb
Nonea
Resection
NA
Ref. [7]
8
57
M
Dyspnea on exertion Cough, chest pain, dyspnea
PT, RPA
None
Resection
Alive and well at 9 mo
Ref. [8]
9
59
M
Progressive dyspnea and cough
PT to RPA
Lung
Tumor debulking
NA
Ref. [9]
10
67
M
Anterior mediastinal mass
PT
Endovascular stent, chemoradiation
Alive and well at 6 mo
Ref. [10]
11
69
M
Cough, dyspnea
PT, RPA
Left atrium left pulmonary veins (by computed tomography) Lung
Resection
Alive and well at 2 mo
Current
Nonea Nonea
Angiosarcoma (low differentiation) Angiosarcoma (low differentiation) Angiosarcoma (intermediate differentiation) Angiosarcoma (high differentiation) Angiosarcomatous (2/3) and osteosarcomatous (1/3) areas Angiosarcoma with osteosarcomatous foci Angiosarcoma
Angiosarcoma with focal osteosarcomatous differentiation
Neoadjuvant chemotherapy, resection Resection
PT indicates pulmonary trunk; RPA, right pulmonary artery; PV, pulmonary valve; PA, pulmonary artery; NA, not available. a Information on lung involvement but not on distal metastasis was available. b The site was not specified.
Ref. [6]
214
L. Huo et al. / Annals of Diagnostic Pathology 9 (2005) 209 –214
derive from the intimal mesenchymal cells, angiosarcomas may be of endothelial origin [2]. Considering the rarity of angiosarcomas in this location, the proportion of cases showing osteosarcomatous differentiation seems to be surprisingly high. Perhaps this is a reflection of the pluripotent nature of the intimal cells capable of giving rise to all these sarcomas, including angiosarcoma. Surgical resection remains the therapy of choice for pulmonary artery sarcomas and is thought to give the best chance for survival. However, even with surgical resection, the mean survival is only approximately 12 months [11]. Information on adjuvant therapy is still limited. Some believe that postoperation chemoradiation has no effect on long-term survival [4], whereas others have suggested that adjuvant therapy can benefit patients by relieving symptoms and prolonging survival [6,11,12]. Neoadjuvant chemotherapy has also been shown to be effective [6]. Nowadays, systemic therapy for soft tissue sarcomas is improving with more specific chemotherapy regimens, including those for rare entities such as angiosarcomas [13]. Conceivably, these new developments can be used for sarcomas occurring in uncommon locations such as the pulmonary artery. Thus, subclassification of these sarcomas will allow the application of potentially more effective adjuvant therapies. References [1] Altman NH, Shelley WM. Primary intimal sarcoma of the pulmonary artery. Johns Hopkins Med J 1973;133:214 - 22.
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