Pulmonary artery sarcoma with angiosarcoma phenotype mimicking pleomorphic malignant fibrous histiocytoma: a case report
© Bohn et al.; licensee BioMed Central Ltd. 2012
Received: 14 July 2012
Accepted: 31 October 2012
Published: 7 November 2012
Primary sarcomas of the major blood vessels can be classified based on location in relationship to the wall or by histologic type. Angiosarcomas are malignant neoplasms that arise from the endothelial lining of the blood vessels; those arising in the intimal compartment of pulmonary artery are rare. We report a case of pulmonary artery angiosarcoma in a 36-year old female with pulmonary masses. The patient had no other primary malignant neoplasm, thus excluding a metastatic lesion. Gross examination revealed a thickened right pulmonary artery and a necrotic and hemorrhagic tumor, filling and occluding the vascular lumen. The mass extended distally, within the pulmonary vasculature of the right lung. Microscopically, an intravascular undifferentiated tumor was identified. The tumor cells showed expression for vascular markers VEGFR, VEGFR3, PDGFRa, FGF, Ulex europaeus, FVIII, FLI-1, CD31 and CD34; p53 was overexpressed and Ki67 proliferative rate was increased. Intravascular angiosarcomas are aggressive neoplasms, often associated with poor outcome.
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Primary sarcomas of the major blood vessels can be classified based on location in relationship to the wall (mural or intraluminal (also known as “intimal”) or by histologic type. Angiosarcomas are malignant tumors that arise from the endothelial lining of the blood vessels. Pulmonary artery sarcomas (PAS) include two types: intimal sarcomas, presenting as intraluminal growing excrescences, and mural sarcomas, involving the pulmonary artery wall. PAS are rare tumors, with unknown and probably, underestimated incidence, which may show myofibroblastic, leiomyosarcomatous, osteosarcomatous, rhabdomyosarcomatous or angiosarcomatous differentiation. Angiosarcoma of the pulmonary artery is a distinctive tumor and few cases have been reported to the date[2, 3].
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Based on clinical, radiological and histopathological findings, the tumor was diagnosed as angiosarcoma arising on the pulmonary artery.
The patient received four cycles of ifosfamide-based chemotherapy with tolerable toxicity. Eighteen months after diagnosis an extensive radiological examination showed no other primary neoplasm or metastatic lesion. The patient was disease free 18 months and then the tumor recurred (additional biopsies were taken showing similar histopathological findings). She developed metastatic disease to liver and contralateral lung and died 29 months after the recurrence. No autopsy was performed.
Primary sarcomas arising from major blood vessels (aorta, pulmonary artery, inferior vena cava) are exceedingly rare[4–8], and some of the cases presented in the literature have been autopsy reports[5, 9, 10]. Most patients are adults, however, a few cases have been found in children. Burke et al. found that intimal sarcomas affect males more frequently than females and arise predominatly in the right pulmonary vessels, with intraluminal involvement rather than intraparenchymal infiltration.
Clinically, primary sarcomas of the major blood vessels, are usually associated to embolic phenomena[6, 12, 13]; therefore, their true incidence is probably underestimated because of misdiagnosis with thromboembolism, especially when located at aorta. The radiographic distinction of pulmonary thromboembolic disease and pulmonary artery sarcoma (PAS) is challenging, because both conditions appear as intraluminal filling defects in the pulmonary artery system on contrast-enhanced CT scans[14, 15]. Some authors have reported that the diagnosis may be suspected by magnetic resonance imaging (MRI)[4, 6] and positron emission tomography (PET). However, findings that favor a diagnosis of a PAS include the heterogeneous soft tissue density and the enhancement of the gadolinium contrast[11, 16]. Therefore, PAS should always be considered as a possibility, as a misdiagnosis with thromboembolic disease will result in delaying appropriate therapy and increased morbi-mortality[15, 17].
Grossly, a careful examination of the specimen, the pulmonary vasculature and its branches is essential to achieve the correct diagnosis. PAS may spread and grow as intraluminal masses along the endothelium and an organizing thromboemboli needs to be ruled out. In addition, direct lung parenchyma involvement is a common event, as direct extension through the pulmonary vasculature can occur due to the prominent intravascular growth along the arterial intima. On the other hand, mural sarcomas with a solid growth can also be confused with other entities including metastatic extension from primary malignancies of the lung or tumors from the mediastinum, such as lymphoma and sarcomas. In our case, an extensive work-up that included clinical and radiological evaluation was a key determinant for the appropriate conclusion of the case.
Pulmonary artery sarcomas of the lung are malignant tumors of indeterminate cause, usually presenting heterogenous histology that most likely reflect a pluripotential or mesenchymal cell origin. Some examples that have been reviewed in the literature represent undifferentiated sarcomas that may display a myofibroblastic or leiomyosarcomatous component[5, 18]; nevertheless, osteosarcomatous, chondrosarcomatous, rhabdomyosarcomatous, liposarcomatous and angiosarcomatous elements have also been described[5, 6, 8–10, 21–23]. The present case displays an undifferentiated sarcoma that mimics pleomorphic malignant fibrous histiocytoma; however, the tumor expresses the majority of vascular-specific markers. It is important to highlight that the final diagnosis could not have been achieved without a high level of suspicion. Interestingly, one of the most significant features helpful for identification of angiosarcoma was the intimal origin of the tumor. Furthermore, undifferentiated tumors as primary pulmonary angiosarcomas have been confused with malignant neoplasms (primary or metastatic malignancies) with dedifferentiated component, such as carcinomas, sarcomas and lymphomas[24–27]. Differential diagnoses in this specific case include high grade sarcomas with leiomyosarcomatous, fibro or myofibroblastic differentiation. For that reason, an appropriate and consecutive utilization of a broad panel of antibodies, and occasionally, electron microscopy (not used in this case) are often necessary to distinguish the origin[8, 13, 28]. We found in this case, that co-expression of endothelial markers such as VEGF, PDGFR, Ulex europaeus, FLI1, CD31 and CD34 is useful in classifying the neoplasm, representing an unusual presentation of a true angiosarcoma similar to those observed in soft tissues.
Although in this case it was not possible to identify specific exposure, angiosarcomas have been reported associated to previous irradiation fields or arteriovenous fistulas. Comparative genomic hybridization (CGH) analysis of intimal pulmonary sarcomas have shown gains and amplifications in the 12q13–14 region, with other less consistent findings including 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. Currently, no prognostic markers have been extensively studied; however, in one study, Gaumann et al. found that osteopontin expression may contribute to metastasis due to its role in cell attachment and therefore to poor prognosis. In addition, Bode-Lesniewska et al. reported that dysregulation of the cell cycle proteins in p53 pathway and overexpression of mdm2 might be implicated in the pathogenesis. At this point, further gene profiling studies, including a larger group of this specific type of vascular malignancy can be used to identify predictive and prognostic markers for intravascular angiosarcoma of the pulmonary vessels.
Overall, PAS are considered aggressive neoplasms, often associated to poor outcome irrespective of treatment[9, 10, 32, 33], and with no exception for pulmonary artery angiosarcomas. Only few patients have survived more than 12 months[5, 34]; surgery and complete resection of the tumor provide local control. Adjuvant chemotherapy and radiotherapy have a controversial role in the management of this disease[5, 33]. The role of chemotherapy is unclear, but a 50% response rate has been found to palliative chemotherapy with anthracyclines and ifosfamide in patients with advanced PAS[11, 35].
In summary, we report an unusual case of pulmonary artery sarcoma with angiosarcoma phenotype that mimics pleomorphic malignant fibrous histiocytoma. A high level of suspicion and identification of the intimal location of the tumor, in addition to the use of a broad panel of immunohistochemical markers were helpful for the identification of the vascular origin. A multidisciplinary clinical and radiological approach and an extensive work-up were key determinant for the appropriate conclusion of the case.
Written informed consent was obtained from the patient’s family members for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor-in Chief of this journal.
- Rosai and Ackerman's Surgical Pathology, 10th edition. Edited by: Rosai J. 2011, Philadelphia: Mosby ElservierGoogle Scholar
- 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: 419-424.View ArticlePubMedGoogle Scholar
- Huo L, Lai S, Gladish G, Czerniak BA, Moran CA: Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation. Ann Diagn Pathol. 2005, 9: 209-214. 10.1016/j.anndiagpath.2005.04.012.View ArticlePubMedGoogle Scholar
- Seelig MH, Klingler PJ, Oldenburg WA, Blackshear JL: Angiosarcoma of the aorta: report of a case and review of the literature. J Vasc Surg. 1998, 28: 732-737. 10.1016/S0741-5214(98)70104-1.View ArticlePubMedGoogle Scholar
- Burke AP, Virmani R: Sarcomas of the great vessels. A clinicopathologic study. Cancer. 1993, 71: 1761-1773. 10.1002/1097-0142(19930301)71:5<1761::AID-CNCR2820710510>3.0.CO;2-7.View ArticlePubMedGoogle Scholar
- Santonja C, Costa-Subias J, Martin-Hita AM, Dotor A: Intimal angiosarcoma of the aorta with tumour embolisation causing mesenteric ischaemia. Report of a case diagnosed using CD31 immunohistochemistry in an intestinal resection specimen. Virchows Arch. 2001, 438: 404-407. 10.1007/s004280000344.View ArticlePubMedGoogle Scholar
- Hottenrott G, Mentzel T, Peters A, Schroder A, Katenkamp D: Intravascular ("intimal") epithelioid angiosarcoma: clinicopathological and immunohistochemical analysis of three cases. Virchows Arch. 1999, 435: 473-478. 10.1007/s004280050430.View ArticlePubMedGoogle Scholar
- Miracco C, Laurini L, Santopietro R, De Santi MM, Sassi C, Neri E, Pepi F, Luzi P: Intimal-type primary sarcoma of the aorta. Report of a case with evidence of rhabdomyosarcomatous differentiation. Virchows Arch. 1999, 435: 62-66. 10.1007/s004280050396.View ArticlePubMedGoogle Scholar
- Nonomura A, Kurumaya H, Kono N, Nakanuma Y, Ohta G, Terahata S, Matsubara F, Matsuda T, Asaka T, Nishino T: 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: 883-896.PubMedGoogle Scholar
- Gaumann A, Tews DS, Mayer E, Dahm M, Petrow PK, Otto M, Kirkpatrick CJ, Kriegsmann J: Expression of apoptosis-related proteins, p53, and DNA fragmentation in sarcomas of the pulmonary artery. Cancer. 2001, 92: 1237-1244. 10.1002/1097-0142(20010901)92:5<1237::AID-CNCR1443>3.0.CO;2-E.View ArticlePubMedGoogle Scholar
- Chappell T, Creech CB, Parra D, Strauss A, Scholl F, Whitney G: Presentation of pulmonary artery intimal sarcoma in an infant with a history of neonatal valvular pulmonic stenosis. Ann Thorac Surg. 2008, 85: 1092-1094. 10.1016/j.athoracsur.2007.08.072.View ArticlePubMedGoogle Scholar
- Nishida N, Yutani C, Ishibashi-Ueda H, Tsukamoto Y, Ikeda Y, Nakamura Y: Histopathological characterization of aortic intimal sarcoma with multiple tumor emboli. Pathol Int. 2000, 50: 923-927. 10.1046/j.1440-1827.2000.01144.x.View ArticlePubMedGoogle Scholar
- Goldblum JR, Rice TW: Epithelioid angiosarcoma of the pulmonary artery. Hum Pathol. 1995, 26: 1275-1277. 10.1016/0046-8177(95)90205-8.View ArticlePubMedGoogle Scholar
- Scheffel H, Stolzmann P, Plass A, Weber A, Pretre R, Marincek B, Alkadhi H: Primary intimal pulmonary artery sarcoma: a diagnostic challenge. J Thorac Cardiovasc Surg. 2008, 135: 949-950. 10.1016/j.jtcvs.2007.11.041.View ArticlePubMedGoogle Scholar
- Thurer RL, Thorsen A, Parker JA, Karp DD: FDG imaging of a pulmonary artery sarcoma. Ann Thorac Surg. 2000, 70: 1414-1415. 10.1016/S0003-4975(00)01963-9.View ArticlePubMedGoogle Scholar
- Yi ES: Tumors of the pulmonary vasculature. Cardiol Clin. 2004, 22: 431-440. 10.1016/j.ccl.2004.05.001. vi-viiView ArticlePubMedGoogle Scholar
- Scheidl S, Taghavi S, Reiter U, Troster N, Kovacs G, Rienmuller R, Lang S, Klepetko W, Olschewski H: Intimal sarcoma of the pulmonary valve. Ann Thorac Surg. 2010, 89: e25-e27. 10.1016/j.athoracsur.2010.01.053.View ArticlePubMedGoogle Scholar
- Bode-Lesniewska B, Zhao J, Speel EJ, Biraima AM, Turina M, Komminoth P, Heitz PU: Gains of 12q13-14 and overexpression of mdm2 are frequent findings in intimal sarcomas of the pulmonary artery. Virchows Arch. 2001, 438: 57-65. 10.1007/s004280000313.View ArticlePubMedGoogle Scholar
- Sebenik M, Ricci A, DiPasquale B, Mody K, Pytel P, Jee KJ, Knuutila S, Scholes J: Undifferentiated intimal sarcoma of large systemic blood vessels: report of 14 cases with immunohistochemical profile and review of the literature. Am J Surg Pathol. 2005, 29: 1184-1193. 10.1097/01.pas.0000159774.70288.7d.View ArticlePubMedGoogle Scholar
- McGlennen RC, Manivel JC, Stanley SJ, Slater DL, Wick MR, Dehner LP: Pulmonary artery trunk sarcoma: a clinicopathologic, ultrastructural, and immunohistochemical study of four cases. Mod Pathol. 1989, 2: 486-494.PubMedGoogle Scholar
- Johansson L, Carlen B: Sarcoma of the pulmonary artery: report of four cases with electron microscopic and immunohistochemical examinations, and review of the literature. Virchows Arch. 1994, 424: 217-224.View ArticlePubMedGoogle Scholar
- Baker PB, Goodwin RA: Pulmonary artery sarcomas. A review and report of a case. Arch Pathol Lab Med. 1985, 109: 35-39.PubMedGoogle Scholar
- Tavora F, Miettinen M, Fanburg-Smith J, Franks TJ, Burke A: Pulmonary artery sarcoma: a histologic and follow-up study with emphasis on a subset of low-grade myofibroblastic sarcomas with a good long-term follow-up. Am J Surg Pathol. 2008, 32: 1751-1761. 10.1097/PAS.0b013e31817d7fd0.View ArticlePubMedGoogle Scholar
- Hisaoka M, Tsuji S, Hashimoto H, Aoki T, Uriu K: Dedifferentiated liposarcoma with an inflammatory malignant fibrous histiocytoma-like component presenting a leukemoid reaction. Pathol Int. 1997, 47: 642-646. 10.1111/j.1440-1827.1997.tb04556.x.View ArticlePubMedGoogle Scholar
- Hollowood K, Holley MP, Fletcher CD: Plexiform fibrohistiocytic tumour: clinicopathological, immunohistochemical and ultrastructural analysis in favour of a myofibroblastic lesion. Histopathology. 1991, 19: 503-513. 10.1111/j.1365-2559.1991.tb01498.x.View ArticlePubMedGoogle Scholar
- Kao YC, Chow JM, Wang KM, Fang CL, Chu JS, Chen CL: Primary pleural angiosarcoma as a mimicker of mesothelioma: a case report **VS**. Diagn Pathol. 2011, 6: 130-10.1186/1746-1596-6-130.PubMed CentralView ArticlePubMedGoogle Scholar
- Jinghong X, Lirong C: Pulmonary epithelioid hemangioendothelioma accompanied by bilateral multiple calcified nodules in lung. Diagn Pathol. 2011, 6: 21-10.1186/1746-1596-6-21.PubMed CentralView ArticlePubMedGoogle Scholar
- Emmert-Buck MR, Stay EJ, Tsokos M, Travis WD: Pleomorphic rhabdomyosarcoma arising in association with the right pulmonary artery. Arch Pathol Lab Med. 1994, 118: 1220-1222.PubMedGoogle Scholar
- Davies JD, Rees GJ, Mera SL: Angiosarcoma in irradiated post-mastectomy chest wall. Histopathology. 1983, 7: 947-956. 10.1111/j.1365-2559.1983.tb02309.x.View ArticlePubMedGoogle Scholar
- Byers RJ, McMahon RF, Freemont AJ, Parrott NR, Newstead CG: Epithelioid angiosarcoma arising in an arteriovenous fistula. Histopathology. 1992, 21: 87-89.View ArticlePubMedGoogle Scholar
- Gaumann A, Petrow P, Mentzel T, Mayer E, Dahm M, Otto M, Kirkpatrick CJ, Kriegsmann J: Osteopontin expression in primary sarcomas of the pulmonary artery. Virchows Arch. 2001, 439: 668-674.View ArticlePubMedGoogle Scholar
- Anderson MB, Kriett JM, Kapelanski DP, Tarazi R, Jamieson SW: Primary pulmonary artery sarcoma: a report of six cases. Ann Thorac Surg. 1995, 59: 1487-1490. 10.1016/0003-4975(95)00149-F.View ArticlePubMedGoogle Scholar
- Gaumann A, Bode-Lesniewska B, Zimmermann DR, Fanburg-Smith JC, Kirkpatrick CJ, Hofstadter F, Woenckhaus M, Stoehr R, Obermann EC, Dietmaier W, Hartmann A: Exploration of the APC/beta-catenin (WNT) pathway and a histologic classification system for pulmonary artery intimal sarcoma. A study of 18 cases. Virchows Arch. 2008, 453: 473-484. 10.1007/s00428-008-0671-0.View ArticlePubMedGoogle Scholar
- Mayer E, Kriegsmann J, Gaumann A, Kauczor HU, Dahm M, Hake U, Schmid FX, Oelert H: Surgical treatment of pulmonary artery sarcoma. J Thorac Cardiovasc Surg. 2001, 121: 77-82. 10.1067/mtc.2001.111423.View ArticlePubMedGoogle Scholar
- Manso L, Alvarez E, Quintela M, Cortes-Funes H, Hitt R: Primary pulmonary artery sarcoma: report of three cases and review of the literature. Clin Lung Cancer. 2007, 8: 277-281. 10.3816/CLC.2007.n.007.View ArticlePubMedGoogle Scholar
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