Primary Angiosarcoma of the Breast Clinicopathologic Analysis of 49 Cases, Suggesting That Grade is not Prognostic

Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 09/2008; 32(12):1896-904. DOI: 10.1097/PAS.0b013e318176dbc7
Source: PubMed


Mammary angiosarcoma is a rare neoplasm, accounting for about 0.05% of all primary malignancies of the breast. It is currently believed that histologic grading of mammary angiosarcomas plays an important role in prognostication. Forty-nine cases of primary angiosarcoma of the breast were retrieved from our files. Clinical details and follow-up information were obtained from referring pathologists and clinicians, and by chart review. All statistics were performed using Fisher exact test and only P<0.05 was considered significant. Recurrence-free survival and overall survival curves were established using Statistica software version 5.5 (StatSoft Inc). All patients were female with ages ranging from 15 to 74 years (mean 41.5, median 40). Peak incidence was between the ages of 30 and 50 years. All tumors examined were located within breast parenchyma with or without minor cutaneous involvement. The right side was more commonly affected than the left side (66% vs. 29.5%). Tumor was bilateral at presentation in 2 cases (4.5%). Tumor size varied from 0.7 to 25 cm (mean 6.7, median 5). Most patients presented with a palpable, painless mass. Two patients had a history of prior radiation treatment for breast carcinoma. Histologically, primary tumors were graded using Rosen's 3-tier system: 17 tumors (35.4%) as low grade, 17 (35.4%) as intermediate grade, and 14 (29.2%) as high grade. Forty-six patients were treated surgically, 11 underwent chemotherapy, and 12 patients received radiotherapy. Follow-up was available in 41 patients (83.7%, median duration 29 mo). Ten patients (24.4%) showed evidence of local recurrence within 11 to 60 months (median 36) after diagnosis. Twenty-four patients (58.5%) thus far have developed metastases, which were most commonly to lung, liver, skin, and bone. Time interval between diagnosis and metastasis ranged from 2 to 144 months (median 34). Eighteen patients (44%) so far have died of disease and 1 died of presumably disseminated breast carcinoma. Five patients (12.2%) are alive with disease and 15 patients (36.6%) are alive with no evidence of disease. Statistical analysis evaluating correlation between tumor grade and size, and rate of local recurrence, metastasis, and death owing to disease showed no significant difference among tumors of different grades. The median recurrence-free and overall survival rates for the entire cohort were 2.8 and 5.7 years, respectively. In conclusion, mammary angiosarcoma is a rare disease that affects relatively younger patients. This tumor seems to have an overall similar clinical course as other types of angiosarcoma arising in skin or soft tissue; it carries a moderate risk of local recurrence, and a high risk of metastasis and death. In this large series, there is no correlation between histologic grade and patient outcome, more in line with angiosarcomas at other sites.

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    • "Angiosarcomas represent a rare and highly aggressive soft tissue sarcoma subtype with a high risk for local recurrences and distant metastases (Nascimento et al, 2008; Antonescu et al, 2009; Neuhaus et al, 2009; Manner et al, 2010; Styring et al, 2010; Guo et al, 2011; Seinen et al, 2012). Angiosarcomas are broadly divided into primary and secondary tumours in relation to whether a predisposing factor, for example, radiotherapy, long-standing lymphedema or chemical exposure can be identified in which case the tumours are classified as secondary angiosarcoma (Stewart and Treves, 1948; Mark et al, 1976; Popper et al, 1978; Body et al, 1987; Karlsson et al, 1998; Lipshutz et al, 2002; Styring et al, 2010; Shon et al, 2011). "
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    ABSTRACT: Background: Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas. Methods: Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT–qPCR, immunohistochemistry and validation of the gene signature to an external data set. Results: In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of MYC, KIT and RET and downregulation of CDKN2C. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT–qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas. Conclusions: Upregulation of MYC, KIT and RET and downregulation of CDKN2C characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours.
    British Journal of Cancer 07/2014; 111(2). DOI:10.1038/bjc.2014.359 · 4.84 Impact Factor
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    • "Approximately 8% of ASs arise in the breast [3]. Primary breast angiosarcomas (BAs) most commonly affect women aged 20 to 40 years without a recognized associated factor [4]. Secondary BAs are usually found in older women at the site of radiotherapy (RT) for breast cancer (BC). "
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    ABSTRACT: Breast angiosarcomas (BAs) are rare but serious events that may arise after radiation exposure. Disease outcome is poor, with high risk of local and distant failure. Recurrences are frequent also after resection with negative margins. The spectrum of vascular proliferations associated with radiotherapy in the setting of breast cancer has expanded, including radiation-associated atypical vascular lesions (AVLs) of the breast skin as a rare, but well-recognized, entity. Although pursuing a benign behavior, AVLs have been regarded as possible precursors of postradiation BAs. We report an unusual case of a 71-year-old woman affected by well-differentiated bilateral cutaneous BA, diagnosed 1.9 years after adjuvant RT for synchronous bilateral breast cancer. Whole-life clinical followup is of crucial importance in breast cancer patients.
    Case Reports in Oncological Medicine 03/2014; 2014(4):413030. DOI:10.1155/2014/413030
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    • "Grading angiosarcoma is not considered useful, as grade is not associated with prognosis [10]. Large series of angiosarcomas of the breast appear to show similar patterns of spread, regardless of whether tumor is a primary neoplasm or occurs secondary to radiotherapy [4] [6] [7]. The commonest sites of spread, apart from locoregional recurrences, are lung, bone, and liver. "
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    ABSTRACT: Primary de novo angiosarcoma of the breast is an uncommon, aggressive neoplasm. Here, we present a case of a young woman who initially developed primary angiosarcoma of the breast, and subsequently angiosarcoma of the ovary during pregnancy two years later. Only two confirmed primary angiosarcomas of the breast metastasizing specifically to the ovary have been described in the literature. However, all previous cases had ovarian metastases at presentation or shortly after initial diagnosis. This case is unusual as it occurred after a relatively long interval, and apparently developed during pregnancy. We discuss this rare phenomenon, as well as the possible factors contributing to the recurrence.
    Case Reports in Oncological Medicine 12/2013; 2013:209610. DOI:10.1155/2013/209610
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