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Primary central nervous system angiosarcoma: two case reports
© Hackney et al.; licensee BioMed Central Ltd. 2012
Received: 10 August 2011
Accepted: 2 March 2012
Published: 21 August 2012
Primary angiosarcoma of the brain is extremely rare; only 15 cases have been reported in adults over the last 25 years.
We describe two cases of primary angiosarcoma of the brain that are well characterized by imaging, histopathology, and immunohistochemistry. Case 1: our first patient was a 35-year-old woman who developed exophthalmos. Subtotal resection of a left extra-axial retro-orbital mass was performed. Case 2: our second patient was a 47-year-old man who presented to our facility with acute visual loss, word-finding difficulty and subtle memory loss. A heterogeneously-enhancing left sphenoid wing mass was removed. We also review the literature aiming at developing a rational approach to diagnosis and treatment, given the rarity of this entity.
Gross total resection is the standard of care for primary angiosarcoma of the brain. Adjuvant radiation and chemotherapy are playing increasingly recognized roles in the therapy of these rare tumors.
Angiosarcoma of the brain in adults: case reports and series
Charman et al. 
Paulus et al. 
Mena et al. 
M (5), F (3)
2 weeks to 72 years (mean 38 years)
Hemisphere (6), meninges (1), unknown (1)
Four months (4), 30 months (1), alive 39 months (1), alive 102 months (1), unknown (1)
Cookston et al. 
Surgery + RT
Alive three-and-a-half years
Fuse et al. 
Surgery + RT
Antoniadis et al. 
Surgery + RT + chemotherapy
Alive 41 months
Lach and Benoit 
Merimsky et al. 
Radiation only; surgery
Two-and-a-half months; five months
Charman et al.  described the first case of primary CNS angiosarcoma in an adult; a 65-year-old man, treated by surgical resection followed by radiation therapy, who survived for 13 months. Since this initial report, the hallmarks of CNS angiosarcoma are recognized as highly vascular malignant tumors with aggressive local recurrence and only modest response to chemotherapy or radiation treatment .
We report two cases of primary CNS angiosarcoma well characterized by imaging, histopathology, and immunohistochemistry. We discuss these cases in the context of similar cases reported within the last 35 years in an attempt to develop a rational approach to diagnosis and treatment, given the rarity of this entity.
Accurate diagnosis of primary CNS angiosarcoma is greatly enhanced by the recognition of characteristic, though not always specific, features of clinical presentation, imaging characteristics, and histopathology. Usually there is rapid onset of neurological symptoms that relate to the tumor’s location and rapidity of growth . Imaging studies characteristically show a well-demarcated lesion of the cerebral hemisphere with avid enhancement following administration of intravenous contrast material such as gadolinium [5, 6]. Although significant vasogenic edema has been reported in prior cases, neither of our patient’s cases were associated with any cerebral edema. Histological examination demonstrates a malignant tumor with a range of differentiation that often includes vascular channels lined by tufted or papillary aggregates of malignant endothelial cells, as well as poorly-differentiated solid areas with malignant spindle cells residing within a collagenous or myxoid stroma . Immunohistochemical staining with CD31, a sensitive and specific endothelial marker, is characteristically positive in both the well-differentiated vasoformative regions and in the less-differentiated solid areas of tumor.
Chemotherapy for primary CNS angiosarcoma, as for virtually all soft tissue sarcomas, is problematic. Combination chemotherapy has not been shown to be any more effective than single agent therapy in most instances . Temozolomide has shown promising activity against sarcomas in general ; it is an option for CNS disease because it crosses the blood brain barrier. For most histological types of sarcoma, single agent therapy with doxorubicin is favored because of its beneficial profile of progression-free survival and relatively tolerable toxicity . Regardless, its use is palliative rather than curative. Paclitaxel has been shown to produce favorable progression-free survival rates at three and six months in both chemonaive and previously-treated patients with the diagnosis of soft tissue angiosarcoma in Phase II clinical trials . Schlemmer et al. report a response rate of 62% for paclitaxel in the setting of advanced angiosarcoma of soft tissue. However, the use of paclitaxel or other chemotherapeutic agents has not yet been reported in primary CNS angiosarcoma.
Bevacizumab, a vascular endothelium growth factor (VEGF) inhibitor, has been used with some success in recurrent glioblastoma, a primary CNS tumor that is known to produce VEGF . The use of bevacizumab for primary CNS angiosarcoma has not been reported, although a phase II trial looking at bevacizumab in patients with unresectable soft tissue angiosarcoma is ongoing (NCT00288015). Preliminary results from the first 27 patients in this trial have been briefly reported by Park et al.. Median progression-free survival was 12 weeks. These authors also discuss data suggesting that combining temozolomide with bevacizumab may result in a potentiation of the latter’s anti-angiogenic effect.
In addition, two multicenter phase II clinical trials are currently in recruitment to look at paclitaxel and bevacizumab in the treatment of metastatic or unresectable visceral or soft tissue angiosarcoma (NCT01055028 and NCT01303497). These studies do not address primary CNS angiosarcoma; in fact, known CNS disease is an exclusion criterion.
The rarity of primary angiosarcoma of the brain and the resulting paucity of relevant studies and case reports precludes a definitive judgment concerning optimal therapy. Regardless, suggestions derived from the few published cases, along with the short follow-up from our two more recent cases, may allow the preliminary formulation of a potentially effective treatment plan using modern, multimodality therapy. Surgery with or without tumor embolization, with the goal of gross total resection, remains the standard of care. Post-operative adjuvant radiation therapy may provide a benefit, particularly in cases where gross total resection is not possible. There may be a rationale for using anti-angiogenesis agents such as bevacizumab, perhaps in combination with temozolomide for synergistic anti-angiogenic effect. Finally, treatment results for paclitaxel in soft tissue angiosarcoma suggest that there may also be a role for this chemotherapeutic agent in primary CNS angiosarcoma.
Written informed consent was obtained from both patients for publication of this manuscript and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
An abbreviated form of this manuscript was presented at the 16th Annual Society for NeuroOncology Meeting in Orange County, California, November 2011.
- Mena H, Ribas JL, Enzinger FM, Parisi JE: Primary angiosarcoma of the central nervous system. J Neurosurg. 1991, 75: 73-76. 10.3171/jns.1991.75.1.0073.View ArticlePubMedGoogle Scholar
- Merimsky O, Lepechous C, Terrier P, Vanel D, Delord JP, LeCesne A: Primary sarcomas of the central nervous system. Oncology. 2000, 58: 210-214. 10.1159/000012102.View ArticlePubMedGoogle Scholar
- Paulus W, Slowik F, Jellinger K: Primary intracranial sarcomas: Histopathological features of 19 cases. Histopathol. 1991, 18: 395-402. 10.1111/j.1365-2559.1991.tb00869.x.View ArticleGoogle Scholar
- Antoniadis C, Selviaridis P, Zaramboukas T, Fountzilas G: Primary angiosarcoma of the brain: case report. Neurosurg. 1996, 38: 583-586.Google Scholar
- Charman HP, Lowenstein DH, Cho KG, DeArmond SJ, Wilson CB: Primary cerebral angiosarcoma. J Neurosurg. 1988, 68: 806-810. 10.3171/jns.1988.68.5.0806.View ArticlePubMedGoogle Scholar
- Cookston M, Cotter GW, Schlitt M, Bastian FD: Primary angiosarcoma of the brain. South Med J. 1991, 84: 517-520. 10.1097/00007611-199104000-00031.View ArticlePubMedGoogle Scholar
- Fuse T, Takagi T, Hirose M: Primary intracranial epithelioid angiosarcoma. Neurol Med Chir (Tokyo). 1995, 35: 364-368. 10.2176/nmc.35.364.View ArticleGoogle Scholar
- Muhlau M, Schlegel J, von Einsiedel HG, Conrad B, Sander D: Multiple progressive intracerebral hemorrhages due to an angiosarcoma: a case report. Eur J Neurol. 2003, 10: 741-742. 10.1046/j.1468-1331.2003.00680.x.View ArticlePubMedGoogle Scholar
- Lach B, Benoit BG: Primary composite angiogenic leiomyosarcoma-epitheloid angiosarcoma of the brain. Ultrastruct Pathol. 2000, 24: 339-346.View ArticlePubMedGoogle Scholar
- Grimer R, Judson I, Peake D, Seddon B: Guidelines for the management of soft tissue sarcomas. Sarcoma. 2010, 2010: 1-15.Google Scholar
- Penel N, Van Glabbeke M, Marreaud S, Ouali M, Blay JY, Hohenberger P: Testing new regimens in patients with advanced soft tissue sarcoma: analysis of publications from the last 10 years. Ann Oncol. 2011, 22: 1266-1272. 10.1093/annonc/mdq608.View ArticlePubMedGoogle Scholar
- Penel N, Bui BN, Bay JO, Cupissol D, Ray-Coquard I, Piperno-Neumann S, Kerbrat P, Fournier C, Taieb S, Jimenez M, Isambert N, Peyrade F, Chevreau C, Bompas E, Brain EG, Blay JY: Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX study. J Clin Oncol. 2008, 26: 5269-5274. 10.1200/JCO.2008.17.3146.View ArticlePubMedGoogle Scholar
- Schlemmer M, Reichardt P, Verweij J, Hartmann JT, Judson I, Thyss A, Hogendoorn PC, Marreaud S, Van Glabbeke M, Blay JY: Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group. Eur J Cancer. 2008, 44: 2346-2433.View ArticleGoogle Scholar
- Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T: Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009, 27: 4733-4740. 10.1200/JCO.2008.19.8721.View ArticlePubMedGoogle Scholar
- Park MS, Ravi V, Araujo DM: Inhibiting the VEGF-VEGFR pathway in angiosarcoma, epithelioid hemangioendothelioma, and hemangiopericytoma/solitary fibrous tumor. Curr Opin Oncol. 2010, 22: 351-355. 10.1097/CCO.0b013e32833aaad4.View ArticlePubMedGoogle Scholar
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