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Background

This is a rare sarcoma that arises from the endothelial lining cells of major vessels or from the smooth muscle lining. The overall prognosis is poor but there is definite paucity of cases that preclude well-controlled studies to determine the most efficacious treatment.

OUTLINE

Pathogenesis  
Laboratory/Radiologic/
Other Diagnostic Testing
 
Gross Appearance
and Clinical Variants
 
Histopathological Features
and Variants
 
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

 

PATHOGENESIS CHARACTERIZATION
GENETIC ALTERATIONS  
Combined comparative genomic hybridization and genomic microarray for detection of gene amplifications in pulmonary artery intimal sarcomas and adrenocortical tumors.

Zhao J, Roth J, Bode-Lesniewska B, Pfaltz M, Heitz PU, Komminoth P.

Department of Pathology, University of Zurich, Zurich, Switzerland.
Genes Chromosomes Cancer. 2002 May;34(1):48-57. Abstract quote  

Identification of gene amplifications in human tumors is important for the understanding of tumorigenesis and may lead to discovery of diagnostic and prognostic markers. In this study, we used a microarray-based comparative genomic hybridization (CGH) technique, combined with conventional CGH, to identify gene amplifications in 43 tumors including eight pulmonary artery intimal sarcomas and 35 adrenocortical tumors.

Conventional CGH revealed gains or amplifications of 12q13-q15 in six sarcomas and in two adrenocortical carcinomas. Using microarrays, we demonstrated that, among genes located on 12q13-q15, SAS/CDK4 were amplified in six sarcomas, and MDM2 and GLI in five and four sarcomas, respectively. The two adrenocortical tumors showed coamplifications of SAS/CDK4 and MDM2. Furthermore, PDGFRA (located on 4q12) amplification was identified in five sarcomas.

Our data demonstrate: (1) amplifications of SAS/CDK4, MDM2, GLI, and PDGFRA are strongly associated with the tumorigenesis of pulmonary artery intimal sarcomas, whereas SAS/CDK4 and MDM2 coamplification may contribute to the progression of adrenocortical tumors; (2) microarray-based CGH is a useful tool for simultaneous detection of multiple gene amplifications, with a high sensitivity and resolution compared to that of conventional CGH.
Gains of 12q13-14 and overexpression of mdm2 are frequent findings in intimal sarcomas of the pulmonary artery.

Bode-Lesniewska B, Zhao J, Speel EJ, Biraima AM, Turina M, Komminoth P, Heitz PU.

Department of Pathology, University Hospital, Zurich, Switzerland.
Virchows Arch. 2001 Jan;438(1):57-65. Abstract quote  

The characterization of clinical, histopathological, immunohistochemical, and genetic features of intimal sarcomas arising in the pulmonary artery is presented in this study. Four resected lungs, one endarterectomy specimen and three biopsies from eight patients (four males and four females; median age 41 years) suffering from intimal sarcomas of the pulmonary artery using conventional stains, immunohistochemistry, and comparative genomic hybridization (CGH) were analyzed.

The predominant clinical presentation was dyspnea (all eight patients) and febrile pulmonary disease (six of eight). Signs of embolic lung disease were present in all patients. One patient died postoperatively, six patients died of disease 8-35 months after presentation, and one patient was alive 6 months after surgery.

Histopathological examination of the submitted material showed spindle cell, partially myxoid and pleomorphic sarcomas. Metastases were histologically confirmed in three patients (lung, pleura, and skull). Immunohistochemically, vimentin was strongly expressed in all tumors. Focal positivity was observed for alpha smooth muscle actin, CD117, CD68, p53, and bcl2. No reaction could be obtained for endothelial markers. The proliferation index Ki-67 was between 5% and 80%. Six examined tumors were positive for mdm2. In the CGH analysis, gains and amplifications in the 12q13-14 region were found in six of eight tumors (75%). Other, less consistent alterations, were losses on 3p, 3q, 4q, 9p, 11q, 13q, Xp, and Xq, gains on 7p, 17p, and 17q, and amplifications on 4q, 5p, 6p, and 11q.

Intimal sarcomas of the pulmonary artery are tumors with an unfavorable prognosis and poorly differentiated morphology. A majority of tumors show a consistent genetic alteration (gains and amplifications in the 12q13-14 region) and overexpression of mdm2, implicating the mdm2/p53 pathway as a possible mechanism in the tumor pathogenesis.
OSTEOPONTIN  
Osteopontin expression in primary sarcomas of the pulmonary artery.

Gaumann A, Petrow P, Mentzel T, Mayer E, Dahm M, Otto M, Kirkpatrick CJ, Kriegsmann J.

MPI fur Physiologische und Klinische Forschung, W.G. Kerckhoff Institut, Abt fur Molekulare Zellbiologie, Bad Nauheim, Germany.
Virchows Arch. 2001 Nov;439(5):668-74. Abstract quote  

Primary tumors of the great vessels (aorta, pulmonal artery, and inferior vena cava) are rare and represent in most cases vascular leiomyosarcomas. Furthermore, there also exists a group of sarcomas arising from the intima, known as intimal sarcomas, associated with early metastasis and a very poor prognosis. Osteopontin (OPN) is an extracellular matrix protein that binds to alphav integrins, thereby promoting cell attachment, chemotaxis, and signal transduction.

The reported association of OPN with malignancy and metastasis prompted us to examine the expression of this protein in seven sarcomas of the pulmonary artery. Strong OPN-specific staining could be detected in tumor cells and the adjacent extracellular matrix. Using a double labeling procedure, proliferating cells showed a strong positive reaction with antibodies against OPN. In addition, this protein could be demonstrated in the cytoplasm of macrophages. CD44, a putative receptor of OPN, was expressed on the cellular surface of tumor-associated lymphocytes. The expression of OPN in macrophages and tumor cells indicates that this molecule could possibly mediate cellular adhesion of both cell types in pulmonary sarcomas. The detection in the extracellular matrix shows that OPN is actively secreted and may interact with the corresponding receptor, CD44, on the surface of lymphocytes.

Although the function of OPN is not yet fully understood, our data indicate that strong expression of this molecule in poorly differentiated sarcomas could play a role in the progression of malignancy and metastasis as described previously for carcinomas.

 

LABORATORY/
RADIOLOGIC/
OTHER TESTS

CHARACTERIZATION
RADIOLOGIC  
A case of pulmonary artery intimal sarcoma diagnosed with multislice CT scan with 3D reconstruction.

Choi EY, Yoon YW, Kwon HM, Kim D, Park BE, Hong YS, Koo JS, Kim TH, Kim HS.

Division of Cardiology, Internal Medicine, Yongdong Severance Hospital, Yonsei University College of Medicine, 146-92 Dogok-dong, Kangnam-gu, Seoul 135-720, Korea.

Yonsei Med J. 2004 Jun 30;45(3):547-51. Abstract quote  

Pulmonary artery intimal sarcoma is a rare highly lethal disease, with additional retrograde extension to pulmonic valve and right ventricle being an extremely rare condition. It is frequently mistaken for pulmonary thromboembolism.

We report a case of 64-year-old woman with progressive dyspnea initially suspected and treated for pulmonary thromboembolism. Her helical chest CT scan with 3 dimensional (3D) reconstruction combined with echocardiography revealed a compacting main pulmonary artery mass extending to the right ventricular outflow tract and the right pulmonary artery. After excision of the mass, the patient's condition improved dramatically, and the pathologic findings revealed pulmonary intimal sarcoma.

This report emphasizes that helical chest CT with 3D reconstruction can be an important tool to differentiate the characteristics of pulmonary artery lesions, such as intimal sarcoma and thromboembolism.
Primary sarcoma of the distal abdominal aorta: CT angiography findings.

Hagspiel KD, Hunter YR, Ahmed HK, Lu P, Spinosa DJ, Angle JF, Leung DA, Matsumoto AH, Kern JA.

Department of Radiology, University of Virginia Health System, Charlottesville, VA 22908, USA.
Abdom Imaging. 2004 Jul-Aug;29(4):507-10. Epub 2004 May 12. Abstract quote  

Primary aortic angiosarcomas are extremely rare. Clinically and radiographically, they mimic atherosclerosis and atheroembolic disease.

For a definitive diagnosis, histologic evaluation of the tumor or of peripheral emboli is required. The imaging findings are frequently nonspecific and in most published cases did not allow a definitive preoperative diagnosis.

This is the first report of the computed tomographic angiographic findings of a primary intimal abdominal aortic sarcoma and a review of previously described imaging findings in these tumors.

 

GROSS APPEARANCE/
CLINICAL
VARIANTS
CHARACTERIZATION
GENERAL  
VARIANTS  
AORTA  
Intimal angiosarcoma of the aorta: report of a case and review of the literature.

Thalheimer A, Fein M, Geissinger E, Franke S.

Department of Vascular Surgery, University of Wuerzburg, Germany.
J Vasc Surg. 2004 Sep;40(3):548-53. Abstract quote

Although extremely rare, the group of primary malignant tumors of the aorta (PMTA) exhibits enormous histologic heterogeneity. In most cases, diagnosis is established late in the course of the disease; the median survival time is only a few months.

We present the case of a 75-year-old patient with an intimal angiosarcoma of the infrarenal abdominal aorta and discuss the clinical presentation, histopathologic diagnosis, and classification of primary aortic sarcomas. A critical review of the diagnostic and therapeutic management in this case revealed that the atypical aortic thrombus should have prompted a comprehensive preoperative diagnostic work-up, specifically with magnetic resonance tomography of the aorta and bone scintigraphy.
Primary endothelial sarcoma of the thoracic aorta.

Ruckert RI, Rudolph B, Rogalla P, Walter M.

Department of Surgery, Humboldt University Medical School, Campus Charite Mitte, Berlin, Germany.
Vascular. 2004 Mar;12(2):140-4. Abstract quote  

Primary malignant tumors of the aorta are extremely rare. The case of a 64-year-old woman who presented with peripheral embolism to both femoropopliteal arteries is reported. The search for a source revealed a polypoid lesion severely narrowing the lumen of the distal thoracic aorta. Differential diagnosis included thrombus and primary aortic tumor. Extirpation of the tumorous lesion was performed.

Histologic examination revealed intimal aortic sarcoma of endothelial cell origin. Although the liver was the only site of suspected metastases at the time of operation, during the 18-month follow-up until the patient's death, generalized metastatic spread had developed.

This case report thus demonstrates the generally poor prognosis of this rare variety of aortic sarcoma, in particular when symptoms have already occurred.

 

HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL  
Histopathological characterization of aortic intimal sarcoma with multiple tumor emboli.

Nishida N, Yutani C, Ishibashi-Ueda H, Tsukamoto Y, Ikeda Y, Nakamura Y.

Department of Pathology, National Cardiovascular Center, Suita, Osaka, Japan.
Pathol Int. 2000 Nov;50(11):923-7. Abstract quote  


A case of aortic intimal sarcoma with multiple tumor emboli and distal metastasis is reported. All metastasis (adrenal, spleen) were via the arteries. This case also had independent lung cancer.

Macroscopically, the aortic tumor did not form a bulged mass, but had linear ulceration with abundant mural thrombi. Poorly cohesive large atypical cells were seen in the intima of the abdominal aorta without invasion into the media. Tumor cells were disseminated into the mural thrombi on the aorta and embolized its branches. In the metastatic tumor or tumor emboli of the distal artery, there were not only large atypical cells, but also the foci of spindle-shaped cells or epithelioid differentiation.

Tumor cells in the aorta were immunohistochemically positive for only vimentin. Muscle-specific actin was positive focally for spindle-shaped cells of tumor emboli and metastatic tumors. Furthermore, cytokeratin-positive cells were scatteredly seen. All tumor cells were negative for factor VIII and did not have a histologic or phenotypic analogy with lung cancer.

The primary intimal sarcoma in the present case was of undifferentiated non-endothelial intimal stromal cell origin, and may have had multipotential for differentiation. Investigation of the metastatic site was useful for recognizing the features of this tumor.
RHABDOMYOSARCOMA  

Intimal-type primary sarcoma of the aorta. Report of a case with evidence of rhabdomyosarcomatous differentiation.

Miracco C, Laurini L, Santopietro R, De Santi MM, Sassi C, Neri E, Pepi F, Luzi P.

Institute of Pathological Anatomy and Histology, University of Siena, Italy.
Virchows Arch. 1999 Jul;435(1):62-6. Abstract quote  

We report an intimal sarcoma presenting as an aortic aneurysm. A 68-year-old man suffered from chest pain and speech disturbance. Computed tomography showed a sacciform aneurysm of the aorta, which was resected, revealing a polypoid tumour measuring 1.5x2x2.5 cm projecting into the lumen.

This proved to be a poorly differentiated high-grade sarcoma having morphological, immunophenotypic and ultrastructural features consistent with rhabdomyosarcomatous differentiation. Primary sarcomas of the aorta are extremely rare. Many cases have been diagnosed as "intimal" on the basis of their site of origin, and they are not easy to classify from their histological pattern.

Electron microscopy and the use of a more comprehensive panel of immunohistochemical markers should be applied in the histological classification of"intimal" sarcoma.

 

SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHER
CHARACTERIZATION
SPECIAL STAINS  
IMMUNOPEROXIDASE  
CD31  
Intimal angiosarcoma of the aorta with tumour embolisation causing mesenteric ischaemia. Report of a case diagnosed using CD31 immunohistochemistry in an intestinal resection specimen.

Santonja C, Martin-Hita AM, Dotor A, Costa-Subias J.

Department of Pathology, Hospital Universitario de Getafe, Carretera de Toledo, km. 12.5. Getafe E-28905, Madrid, Spain.
Virchows Arch. 2001 Apr;438(4):404-7. Abstract quote  

Primary intimal angiosarcomas of the aorta (i.e. mostly intraluminal sarcomas with evidence of endothelial differentiation) are extraordinarily rare.

We report a case in which the diagnosis was accurately made using immunohistochemistry in an intestinal resection specimen and confirmed during autopsy. The patient was a 64-year-old woman with mesenteric ischaemia and a "thrombus" in the abdominal aorta. Two segments of the ileum and the right colon were surgically removed. Histological examination showed multiple tumour emboli in small arteries of the submucosa, serosa and mesentery. The highly atypical cells comprising these emboli were positive immunohistochemically with antibodies to Ulex Europaeus, von Willebrand factor and CD31 and negative for CD34. During post-mortem examination, the intraaortic mass was located around the orifices of the coeliac and the superior mesenteric arteries, and gross tumour thrombi were found in the left renal and splenic arteries.

This case emphasises the need for a wide panel of immunohistochemical antibodies when tumour emboli of unknown origin are under study.
ELECTRON MICROSCOPY  

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
SARCOMA  
Primary pulmonary sarcoma: a clinicopathologic study of 26 cases.

Keel SB, Bacha E, Mark EJ, Nielsen GP, Rosenberg AE.

James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Mod Pathol. 1999 Dec;12(12):1124-31. Abstract quote  

The clinical and pathologic features of 26 primary pulmonary sarcomas were analyzed. Fourteen patients were male and 12 were female; ranging in age from 18 to 75 years (mean, 48 yr). The tumors measured from 0.9 cm in greatest diameter to filling the entire hemithorax. Thirteen tumors were in the left lung and nine in the right lung; one was bilateral, two were in the pulmonary artery, and the location of one tumor was not available.

The histologic diagnoses were malignant fibrous histiocytoma (7), synovial sarcoma (6), malignant peripheral-nerve sheath tumor (3), leiomyosarcoma (3), angiosarcoma (2), intimal sarcoma (2), fibrosarcoma (2), and one case of epithelioid hemangioendothelioma. Immunohistochemical and ultrastructural examination supported these diagnoses. Morphologically, the differential diagnosis often included sarcomatoid carcinoma or desmoplastic malignant mesothelioma Patients were treated with surgery, chemotherapy, radiation therapy, or a combination of these. Follow-up was available for 22 patients and ranged from 2 to 183 months (mean, 45 mo). Fourteen patients are free of disease, four died of disease, three are alive with disease, and one died of surgical complications. A variety of sarcomas, especially malignant fibrous histiocytoma and synovial sarcoma, arise within the pulmonary parenchyma.

These tumors have the potential to behave aggressively but can be cured by resection, with or without adjuvant therapy. Immunohistochemistry and electron microscopy can be helpful in distinguishing primary pulmonary sarcoma from other tumors in the differential diagnosis.

 

PROGNOSIS CHARACTERIZATION
Abdominal aortic sarcoma: report of a case with long-term survival and review of the literature.

Shuster TA, Dall'Olmo CA, Spadone D, Silver D.

Division of Vascular Surgery, University of Missouri, Columbia, MO, USA.
Ann Vasc Surg. 2002 Sep;16(5):545-9. Epub 2002 Aug 19. Abstract quote  

We present a case of an intimal epitheliod aortic sarcoma. Diagnosis was established after an aortic endarterectomy.

The tumor was subsequently resected and an aortic graft was inserted. The patient underwent adjuvant chemotherapy. The patient is alive and free of metastatic disease at 48 months. Aortic tumors are rare, with an extremely poor prognosis and 1-year survival of 0-13%. The diagnosis is usually established postmortem, with metastatic disease being a common finding. The diagnosis should be suspected in patients with symptoms of nonatherosclerotic-related aortic occlusive disease or distal embolic events.

Resection followed by adjuvant therapy and close follow-up can offer a prolonged survival for the patient with an extremely lethal aortic sarcoma.
Primary aortic intimal sarcoma of the endothelial cell type with long-term survival.

Majeski J, Crawford ES, Majeski EI, Duttenhaver JR.

Department of Surgery, Medical University of South Carolina, Charleston, USA.
J Vasc Surg. 1998 Mar;27(3):555-8 Abstract quote.  

Primary tumors of the aorta are rare and are difficult to diagnose preoperatively. These tumors are malignant and ultimately fatal.

A patient had initial evidence of aortoiliac obstructive disease. Aortic endarterectomy produced an excellent postoperative clinical result until the pathology report from the endarterectomy specimen revealed aortic sarcoma. The patient refused a second operation for en bloc aortic resection. One year later with recurrent symptoms, the patient underwent en bloc resection of the aorta and common iliac vessels until clear margins were obtained. The tumor was found to be intimal aortic sarcoma of endothelial cell origin. The only metastasis was to bone, and it was controlled with radiation and chemotherapy. The patient lived a total of 8 years from the time of initial diagnosis. Abdominal aortic intimal sarcoma of the endothelial cell type is a rare variety of aortic sarcoma that can be managed successfully if diagnosed early.

This specific type of tumor has a longer survival period and better prognosis than other types of aortic sarcoma when managed with aggressive surgical resection, radiation, and chemotherapy.

 

TREATMENT CHARACTERIZATION
GENERAL  
SURGERY  
Primary tumors of the thoracoabdominal aorta: surgical treatment of 5 patients and review of the literature.

Chiche L, Mongredien B, Brocheriou I, Kieffer E.

Services de Chirurgie Vasculaire et d'Anatomie Pathologique, CHU Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, Paris, France.
Ann Vasc Surg. 2003 Jul;17(4):354-64. Abstract quote

The objectives of this study were to describe five cases involving primary tumors of the thoracoabdominal aorta and to review the pertinent literature. Between April 1990 and April 2000, we performed surgery on five patients with primary tumors of the aorta (PTA). There were three men and two women ranging in age from 37 to 65 years (mean, 49.8 years). The presenting manifestations were renovascular hypertension in four cases, including three associated with abdominal angina and lower extremity embolism in one case. In all patients aortograms identified atherosclerotic-like occlusive lesions in the thoracoabdominal aorta extending to the descending thoracic aorta in three cases, visceral arteries in four cases, and infrarenal aorta in one case.

Preoperative histological diagnosis of PTA was achieved in two patients following open repair with placement of an aortoaortic graft in one case and peripheral embolectomy in one case. In two cases, diagnosis of PTA was strongly suspected before or during the procedure. In the remaining case, diagnosis was not achieved until the definitive histological report. In two patients surgical treatment was carried out with curative intent (aortic resection with graft replacement). In two cases surgical treatment was incomplete (endarterectomy of the aorta and visceral arteries). In the remaining case surgical treatment was purely palliative (aortic and superior mesenteric artery bypass).

Histological findings demonstrated intimal-type sarcoma in two cases, leiomyosarcoma in one case, and angiosarcoma in one case. In the remaining case, histological analysis was unfeasible for technical reasons. One patient died due to massive cerebral embolism 2 days after surgical treatment involving revascularization of the aortic arch carried out with hypothermic circulatory arrest. One patient developed secondary paraplegia. All four patients who survived the immediate postoperative period died of tumor-related complications and cachexia at 5, 7, 16, and 24 months after the initial surgical procedure. The results of this small series as well as those of 130 previously reported cases confirm the extremely dismal prognosis of PTA. Mean overall survival for patients presenting PTA was less than 16 months. Survival at 5 years was 8%.

Survival rates appear to be higher after surgical treatment and were significantly improved by adjuvant chemotherapy. The main factors correlated with poor prognosis were intimal type, involvement of the ascending aorta, aortic arch, or visceral aorta, and incomplete resection.

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Last Updated November 18, 2004

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