Abstract and Introduction
Postradiation cutaneous vascular lesions after treatment of breast carcinoma comprise a heterogeneous group of benign, atypical, and malignant lesions and are best regarded as points along a morphological spectrum. We analyzed a series of cutaneous angiosarcomas after treatment of breast cancer in comparison with control cases and cases of atypical vascular lesions with special emphasis on the expression and amplification of MYC. The 66 cases were divided into control cases (5), cases in which a slight vascular proliferation was seen after radiotherapy of breast cancer (12), cases of atypical vascular lesions after radiotherapy (16), cases of postradiation cutaneous angiosarcomas (25), and cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (8). None of the control cases (2 M, 3 F, 20–76 years), of cases showing slight vascular proliferation, dermal fibrosis and inflammation after radiotherapy of breast cancer (12 F, 48–79 years), of cases of atypical vascular lesions after radiotherapy (16 F, 29–81 years), and of cases of angiosarcomas of skin and soft tissues unrelated to radiotherapy (3 M, 5 F, 25–92 years) showed an amplification of MYC by FISH analysis. In striking contrast, in all cases of postradiation cutaneous angiosarcomas (25 F, 46-95 years), MYC amplification was found by FISH analysis in a variable number of counted nuclei. Immunohistochemically, strong positive nuclear staining for MYC and prox-1 was seen in cases of postradiation cutaneous angiosarcoma, whereas control cases and cases of atypical vascular proliferation after radiotherapy were negative for MYC, and stained only focally positive for prox-1 in a number of cases. In conclusion, the presence of MYC amplification represents an important additional diagnostic tool in the distinction of postradiation cutaneous angiosarcomas from atypical vascular lesions after radiotherapy. Immunohistochemical stainings for MYC are useful for mapping of these lesions and for careful tumor margin control.
Cutaneous angiosarcomas occur in three main clinical settings: so-called idiopathic angiosarcoma arising most frequently in sun-damaged skin of the face in elderly patients, rare lymphedematous angiosarcoma arising in patients with chronic lymphedema, and postradiation cutaneous angiosarcoma, usually occurring in patients with a history of radiation therapy for breast cancer. In addition to postradiation angiosarcoma, benign and atypical vascular proliferations after radiotherapy have been described. Benign lymphangiomatous papule usually presents as a solitary, well-circumscribed, and superficially located dermal neoplasm that is composed of dilated, lymphangioma-like vascular spaces lined by slightly enlarged but uniform endothelial cells without increased atypia and proliferative activity, and endothelial multilayering is usually not present.[1,2] Atypical vascular lesions following radiotherapy for breast cancer are solitary or multicentric vascular lesions composed of either superfially located, lymphangioma-like vascular lesions or of narrow and dissecting vascular proliferations that may show focally anastomosing spaces. The lining endothelial tumor cells may contain hyperchromatic nuclei, but significant cytologic atypia, an increased mitotic rate and infiltration of subcutaneous tissue are not seen. During the last 15 years it has been shown that there is significant clinical and morphological overlap between benign, atypical, and malignant vascular proliferations after radiotherapy, neoplasms that are best regarded as points along a morphological spectrum, and that exact classification especially on a small biopsy may cause significant diagnostic problems. In addition, shared mutations of the p53 tumor suppressor gene emphasize that atypical and malignant radiation-induced vascular changes are closely related. Most recently it has been reported, that so-called secondary cutaneous angiosarcomas (postradiation angiosarcomas and lymphedema-associated angiosarcomas) show high-level amplifications of MYC at locus 8q24.21 in contrast to primary cutaneous angiosarcomas. We decided to study benign, atypical, and malignant vascular proliferations after radiotherapy in order to compare immunohistochemical expression of MYC and the presence or absence of MYC amplifications in these lesions.
Mod Pathol. 2012;25(1):75-85. © 2012 Nature Publishing Group