RESUMEN
MYC amplification has been reported as a prominent feature of secondary angiosarcomas (SAS). The differential diagnosis between atypical vascular lesion (AVL) and low-grade angiosarcoma (AS) can be occasionally very difficult or even impossible, and MYC amplification status has been pointed as an important diagnostic tool to distinguish cutaneous vascular lesions of the breast. We assessed MYC amplification and protein expression status by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC), respectively, in 49 patients diagnosed with breast AS, and 30 patients diagnosed with post-radiation AVL of the breast. Clinical and pathological features, and follow-up data were collected, and survival analyses were performed. Among 37 patients with SAS, twenty patients had tumors with high-level MYC amplification and protein overexpression (54 %). None of primary angiosarcomas (PAS) or AVL cases showed MYC amplification or protein expression. Concordance between MYC amplification (FISH) and protein expression (IHC) was 100 % in AVL, PAS, and SAS. Survival analysis of the SAS patients demonstrates that those with MYC amplification had a significantly worse overall survival compared to cases without MYC amplification (P = 0.035). There was a non-significant trend toward a poor disease-free survival between cases with and without MYC amplification (P = 0.155). Our findings show that MYC amplification is a highly specific but poorly sensitive marker for SAS and, therefore, a negative result does not exclude the diagnosis of angiosarcoma. MYC amplification was associated with adverse prognosis, suggesting a prognostic role of MYC amplification status on SAS of the breast.
Asunto(s)
Neoplasias de la Mama/genética , Hemangiosarcoma/genética , Neoplasias Inducidas por Radiación/genética , Proteínas Proto-Oncogénicas c-myc/genética , Neoplasias Cutáneas/genética , Malformaciones Vasculares/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Diagnóstico Diferencial , Supervivencia sin Enfermedad , Femenino , Amplificación de Genes , Regulación Neoplásica de la Expresión Génica , Heterogeneidad Genética , Hemangiosarcoma/diagnóstico , Hemangiosarcoma/patología , Humanos , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/diagnóstico , Neoplasias Inducidas por Radiación/patología , Pronóstico , Proteínas Proto-Oncogénicas c-myc/biosíntesis , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Malformaciones Vasculares/diagnóstico , Malformaciones Vasculares/patologíaRESUMEN
Atypical vascular lesions (AVL) that occur in the field of prior radiation therapy for breast carcinoma are placed within the differential diagnosis with low grade angiosarcoma and other benign vascular lesions. Although considered a benign entity, the exact biological behavior of AVLs is not fully established because of the small number of cases reported in the literature. We aim to further characterize these lesions clinically and histopathologically, and to study their behavior. We report a series of 30 patients with AVL of the breast occurring after radiation exposure, diagnosed and treated at the European Institute of Oncology, Italy. Immunohistochemical study was performed in all cases, using CD31, D2-40, CD105, and Ki-67 antibodies. Twenty-seven patients were treated with standard doses of conventional adjuvant radiation therapy for the prior breast carcinoma. Three patients were treated with intraoperative radiotherapy with electrons. The post-radiation latency interval from breast carcinoma to AVL was 48.5 months (ranged from 1 to 146 months). Most of the lesions were classified as lymphatic type (78.6 %) based on D2-40 positivity. No extension into subcutaneous tissue or significant atypia was noted in all cases. Despite the fact that the AVL of our series have shown benign behavior in 93.3 %, one patient developed local recurrence of AVL, and two cases progressed to angiosarcoma at the previous AVL site. Further studies should be conducted to better understand the clinical behavior and to propose additional histopathologic diagnostic criteria to distinguish AVL from low grade angiosarcoma and those AVL with increased risk for malignant progression. Concerning current treatments of AVL, we recommend complete excision with free surgical margins and close follow up.