Atypical Vascular Lesions of the Breast: Clinicopathological and Immunohistochemical Study of 24 Cases from a Single Institution

Abstract

INTRODUCTION: Atypical Vascular Lesions (AVL) of the breast after radiation exposure show heterogeneous clinical and histopathologic features. Most data on outcomes reported previously favored a benign process, but some studies have challenged this concept, suggesting that AVL and post-radiation angiosarcoma represent a morphologic continuum, implying AVL as a precursor to angiosarcoma. However, the risk of malignancy is still undefined due to small number of reported cases with follow-up information. OBJECTIVES: To characterize AVL of the breast clinically and histopathologically, and to study their behavior, trying to establish whether they are a true benign process or a risk factor for developing angiosarcoma. MATERIAL AND METHODS: All cases of AVL of the breast diagnosed at the Department of Anatomic Pathology at the European Institute of Oncology (EIO), Milan, from 1999 to 2009 were selected. Histo-pathologic review and immunohistochemical studies for podoplanin (D2-40), CD31, Ki67 and endoglin (CD105) were performed. RESULTS: Twenty-four female patients treated at the EIO were diagnosed with AVL of the breast after radiotherapy for breast carcinoma. The median age was 58 years old (range: 36-81 years), and AVL size ranged from 0.3cm to 1.1cm (median, 0.5cm). The latency interval between radiotherapy and AVL diagnosis was 49 months (range: 17-124 months). The most common clinical presentation of AVL was an erythematous or violet unique papule in the irradiation field (62.5% of the cases). Microscopically, AVL did not infiltrate the subcutaneous tissue and did not have endothelial multilayering, prominent nucleoli, mitoses or lakes of blood. A patchy chronic inflammatory infiltrate accompanied all AVL to varying degrees. Thirteen cases were classified as lymphatic type (LT) AVL and 11 cases as vascular type (VT) AVL, according to positive staining for D2-40. The endothelial cells stained for CD31 (18 cases), Ki-67 (5 cases), and CD105 (12 cases). One patient with VT-AVL with positive margin developed local recurrence. Two patients, one with VT-AVL, and the other with LT-AVL with compromised margin, developed high grade angiosarcoma in the previous biopsy site, 19 and 89 months later, respectively. Both cases showed overexpression of Ki-67 in the endothelial cells of the AVL. Margin involvement was associated to unfavorable outcome. DISCUSSION: Our data indicate that post-radiation angiosarcoma and AVL may represent a morphologic continuum. AVL cases of both types, VT and LT-AVL, showed similar risk of progressing to angiosarcoma, as well as AVL with high Ki-67 expression. CONCLUSION: Although our data are not conclusive, the development of local recurrence and subsequent angiosarcoma indicate that AVL must be completely excised, with free surgical margins, and patients must be accompanied by clinical exams and imaging until the natural history of the AVL is better explained.