Diagnosis: Angiosarcoma Angiosarcoma is a rare malignant neoplasm of the skin and soft tissues, the cells of which variably recapitulate the morphological and functional features of normal endothelium.1 Angiosarcomas represent fewer than 1% of all sarcomas, and up to half of angiosarcomas involve the head and neck.2 They typically present as bruiselike violaceous macules or plaques that are almost always found on the face or scalp of elderly white men; sometimes, however, they appear simply as nondescript nodules. They are typically asymptomatic, although bleeding, ulceration, and pain can occur late in the disease progression. The diagnosis is often missed or delayed owing to the asymptomatic nature and polymorphous appearance of these lesions, which may mimic a wide range of more common dermatologic conditions, including allergic reactions, cellulitis, rosacea, or granuloma pyogenicum. As a result, up to 30% of patients may have distant metastasis at the time of presentation. Definitive diagnosis is made by biopsy, which often reveals a vascular neoplasm with anastomosing channels lined by atypical endothelium. Low-grade tumors may retain the characteristics of normal endothelium, while high-grade lesions typically show histologic features such as marked cellular atypia, including angulated, hyperchromatic nuclei with frequent and bizarre mitoses and sheets of pleomorphic cells.3 In the skin, these tumors usually infiltrate the dermis, with variably vasoformative areas and anastomosing vascular spaces dissecting through collagen bundles.4 Although there are frequently areas of discernible endothelial appearance, even in high-grade lesions, there is often extensive hemorrhage into these spaces, and the lesion may be mistaken for an irregular hematoma. The primary immunohistochemical markers for angiosarcoma are CD31 and CD34, as well as the less specific endothelial marker D2-40 and, occasionally, factor VIII–related antigen. Factor VIII–related antigen is often negative in higher-grade lesions, and von Willebrand factor (monoclonal) has been found to have a level of positivity similar to that of CD31.4 These immunomarkers are vessel specific, but the diagnosis of malignancy is based solely on the histologic features. The prognosis for angiosarcoma is almost universally poor as a result of late presentation and diagnosis as well as aggressive biologic behavior. Histologic grading plays virtually no role in the prognosis of these tumors other than to describe the morphologic appearance (C. D. M. Fletcher, MD, e-mail communication, November 20, 2009). Five-year survival rates in the face, neck, and scalp vary between 12% and 33%.4-6 As angiosarcoma tends to spread subcutaneously over large areas, it is often difficult to achieve true negative margins on initial resection. Penel et al7 showed that the quality of surgical resection is an independent prognostic factor in the outcome of patients with a variety of head and neck sarcomas, including angiosarcoma; accordingly, preoperative and perioperative suspicion of a malignant process, which often influences the extent of initial resection, is similarly paramount. Currently, surgery is typically combined with radiation therapy and/or chemotherapy to achieve higher rates of local control. Angiosarcoma has a higher likelihood of lymphatic metastatic spread than other sarcomas, and isolated lymph node metastasis does not appear to adversely affect survival.8 Mark et al3 demonstrated a survival advantage for surgery plus radiation therapy over surgery alone in angiosarcoma. A recent study by Lahat et al8 studied the outcomes of locally recurrent and metastatic angiosarcoma treated with surgical resection, chemotherapy, and/or radiation therapy. Patients with local recurrence were typically more easily treated, especially if complete surgical resection could be accomplished; such patients had a median disease-specific survival of 50 months. In Lahat and colleagues' study, 70% of patients with local recurrence were able to undergo subsequent surgical resection. Patients with distant metastatic disease, excluding isolated lymphatic metastasis, however, had a worse prognosis, as they were more unlikely to have any definitive surgical options. Lahat and coauthors hypothesized that systemic angiosarcoma metastasis indicates more aggressive tumor behavior than either local recurrence or isolated lymphatic metastasis; therefore, the currently available therapies are more likely to fail in such cases. Death in patients with angiosarcomas of the face, head, and neck is usually a result of extensive local disease or widespread metastasis, especially to the lungs.4 Research efforts have focused on chemotherapeutic options in the treatment of metastatic angiosarcoma. Taxanes such as paclitaxel have shown promise,9 and a phase 2 study of sorafenib, a vascular endothelial growth factor inhibitor, was recently completed.10 A cohort of 145 patients with recurrent or metastatic angiosarcoma were treated with sorafenib and exhibited a median progression-free survival of 3.2 months and a median overall survival of 14.3 months. Sorafenib appears to be biologically active against angiosarcoma, but only a subset of tumors were responsive to therapy. Additional studies of the molecular biologic makeup of these susceptible tumors may shed further light on the mechanisms of tumor sensitivity to emergent chemotherapeutic drugs and advance the development of additional molecular-targeted therapies for the treatment of angiosarcoma. The case reported herein highlights the importance of clinical suspicion for the diagnosis of angiosarcoma, as the delay in diagnosis for our patient was 8 months despite close monitoring for skin cancer of the auricle. He was treated with wide local excision that was preceded by numerous dermatologic punch biopsies around the perimeter of the lesion, the specimens of which were sent for frozen-section analysis to define the limits of the resection. If nonvisible subcutaneous spread of the angiosarcoma was found to extend to functionally or cosmetically sensitive areas of the head and neck that would require extensive resection and complex reconstruction to achieve clear margins, the procedure would have been aborted to avoid subjecting the patient to highly morbid surgery that might be functionally, socially, and psychologically devastating. In this particular case, the results of the punch biopsies were negative; therefore, definitive excision was performed and followed by an anterolateral thigh free tissue transfer to reconstruct the large defect that was left after resection of the infiltrative lesion. Return to Quiz Case 1. References 1. Weiss SWLasota JMiettinen MM Angiosarcoma of soft tissue. Fletcher CDMUnni KKMertens F World Health Organization Classification of Tumours Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon France IARC Press2002;175- 177Google Scholar 2. Fedok FGLevin RJMaloney METipirneni K Angiosarcoma: current review. Am J Otolaryngol 1999;20 (4) 223- 231PubMedGoogle ScholarCrossref 3. Mark RJPoen JCTran LMFu YSJuillard GF Angiosarcoma: a report of 67 patients and a review of the literature. Cancer 1996;77 (11) 2400- 2406PubMedGoogle ScholarCrossref 4. Calone EFletcher CDM Vascular tumors. Fletcher CDM Diagnostic Histopathology of Tumors. 3rd ed. Philadelphia, PA Elsevier Publishing2007;63- 67Google Scholar 5. Holden CASpittle MFJones EW Angiosarcoma of the face and scalp, prognosis and treatment. Cancer 1987;59 (5) 1046- 1057PubMedGoogle ScholarCrossref 6. Lydiatt WMShaha ARShah JP Angiosarcoma of the head and neck. Am J Surg 1994;168 (5) 451- 454PubMedGoogle ScholarCrossref 7. Penel NMallet YRobin Y-M et al. Prognostic factors for adult sarcomas of head and neck. Int J Oral Maxillofac Surg 2008;37 (5) 428- 432PubMedGoogle ScholarCrossref 8. Lahat GDhuka ARLahat S et al. Outcome of locally recurrent and metastatic angiosarcoma. Ann Surg Oncol 2009;16 (9) 2502- 2509PubMedGoogle ScholarCrossref 9. Penel NBui BNBay JO et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clin Oncol 2008;26 (32) 5269- 5274PubMedGoogle ScholarCrossref 10. Maki RGD’Adamo DRKeohan ML et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol 2009;27 (19) 3133- 3140PubMedGoogle ScholarCrossref
Archives of Otolaryngology - Head & Neck Surgery – American Medical Association
Published: Feb 21, 2011
Keywords: hemangiosarcoma,neoplasms,excision,surgical procedures, operative,biopsy
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