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which was formed by a proliferation of vascular structures alternating with undifferentiated solid areas &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The vascular structures were covered by endothelial cells with atypia&#44; whereas the solid areas contained highly proliferative pleomorphic epithelioid cells &#40;6 mitoses per 10 high-power fields&#41; and interstitial hemorrhaging&#46; The tumor cells proved to be immunoreactive to vascular markers &#40;CD31 and CD34&#41; and negative to epithelial markers &#40;epithelial membrane antigen and pancytokeratin&#41;&#46; Immunostaining for herpes simplex virus type 8 was negative&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">These findings confirmed the diagnosis of angiosarcoma&#44; and the patient underwent simple mastectomy&#46; Pathological examination of the surgical specimen showed the presence of several dermal nodules &#40;the largest measuring 4<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>cm&#41; and foci in the breast parenchyma &#40;2-5<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; Histopathology confirmed the diagnosis of high-grade angiosarcoma&#44; with disease-free margins&#46; The results of the staging study &#40;computed tomography of the thorax&#44; abdomen&#44; and pelvis and positron emission tomography&#41; were negative&#46; After a 9-month follow-up period&#44; the patient remains disease-free&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Angiosarcoma is a very uncommon endothelial cell tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It accounts for less than 1&#37; of cases of sarcoma and most frequently affects the skin&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> Cutaneous angiosarcoma can be divided into 3 main types&#58; the classic or idiopathic type&#44; the chronic lymphedema&#8211;associated type&#44; and the radiation-induced type&#46; Classic idiopathic angiosarcoma affects the skin of the head and neck in elderly patients<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> and is the most frequent variety &#40;50&#37;-60&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Chronic lymphedema&#8211;associated angiosarcoma appears after a period ranging from 4 to 27 years<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and almost always &#40;&#62;<span class="elsevierStyleHsp" style=""></span>90&#37; of cases&#41; develops in a limb with chronic lymphedema following radical mastectomy with axillary lymph node dissection &#40;Stewart-Treves syndrome&#41;&#46; Radiation-induced angiosarcoma appears in an irradiated field after a latency period&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In previous decades&#44; this variety mostly affected the abdomen after radiotherapy for abdominopelvic tumors&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> Today&#44; however&#44; angiosarcoma is detected mainly on the skin of the breast in women aged more than 60 years who have undergone adjuvant radiotherapy after conservative surgery for breast cancer&#46; The latency period is 3 to 5 years in most cases&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In any case&#44; angiosarcoma remains a very uncommon complication &#40;0&#46;05&#37;-0&#46;16&#37; of patients<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;6</span></a>&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Clinically&#44; angiosarcoma is characterized by the onset of erythematous-violaceous nodules or plaques that are typically multifocal&#46; Histopathology findings correspond to those reported in our case&#46; Growth is explosive in high-grade tumors and more insidious in low-grade tumors&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Its appearance may be similar to that of cutaneous metastases and of erysipelatoid carcinoma &#40;cutaneous metastasis whose symptoms are similar to those of erysipelas&#41;&#46; The differential diagnosis should include atypical vascular lesions &#40;AVLs&#41;&#44; which are cutaneous vascular proliferations that appear after radiotherapy for breast cancer with a latency period of 3 to 6 years&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Unlike angiosarcoma&#44; AVLs are not characterized by multiple layers of endothelial cells&#44; prominent nucleoli&#44; mitosis&#44; atypia&#44; destruction of skin appendages&#44; areas of solid growth&#44; invasion of the subcutis&#44; or hemorrhage&#46; Furthermore&#44; AVLs are circumscribed lesions with frequent chronic inflammation and stromal projections in the lumen&#44; which are not found in angiosarcoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7</span></a> Radiation-induced angiosarcoma was recently shown to involve an amplification of the v-myc myelocytomatosis viral oncogene homolog &#40;avian&#41; gene &#40;<span class="elsevierStyleItalic">MYC</span>&#41;&#44; which is not found in AVLs&#46; The presence of this gene could be used to confirm a diagnosis in complex cases or when the available tissue is limited&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> It is therefore important to remember that sufficient sample material must be obtained&#44; since punch biopsy findings can lead to an erroneous diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Treatment involves aggressive surgical excision&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Hyperfractionated accelerated adjuvant radiotherapy has been reported to achieve better control of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Prognosis is poor&#44; with high recurrence rates and a strong tendency to metastasize&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Overall survival at 5 years is 12&#37; to 20&#37;&#44; and mean survival is 18 to 28 months&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Some data suggest that radiation-induced angiosarcoma could have a poorer prognosis than sporadic angiosarcoma&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion&#44; we present a case of multifocal angiosarcoma of the skin of the breast&#46; This condition is a very uncommon yet very aggressive complication of radiotherapy that should be suspected in patients with erythematous-violaceous nodules on a previously irradiated breast&#46; Given the recent trend towards conservative management of breast cancer&#44; we should be on the alert for possible increases in the incidence of this tumor&#46;</p></span>"
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Case and Research Letters
Angiosarcoma of the Skin After Breast Cancer Radiotherapy
Angiosarcoma cutáneo tras radioterapia por cáncer de mama
M. Armengot-Carbóa,
Autor para correspondencia
miquelarmengot@gmail.com

Corresponding author.
, M.J. Roca-Estellésb, E. Quecedo-Estébaneza, E. Gimeno-Carpioa
a Servicio de Dermatología, Hospital Arnau de Vilanova, Valencia, Spain
b Servicio de Anatomía Patológica, Hospital Arnau de Vilanova, Valencia, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In recent years&#44; there has been a trend towards conservative management of breast cancer&#44; which involves the use of adjuvant radiotherapy&#46; This approach carries a risk of radiation-induced secondary malignancy&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 70-year-old woman who underwent quadrantectomy combined with adjuvant radiotherapy to treat invasive ductal carcinoma in her right breast in 2007&#46; She was referred to our center 3 years later with a 1-month history of skin lesions&#46; Examination revealed several red-violaceous nodules and papules&#44; with multifocal involvement of the treated breast &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Histopathology of 1 of the nodules revealed a poorly defined dermal tumor infiltrating the subcutaneous layer&#44; which was formed by a proliferation of vascular structures alternating with undifferentiated solid areas &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; The vascular structures were covered by endothelial cells with atypia&#44; whereas the solid areas contained highly proliferative pleomorphic epithelioid cells &#40;6 mitoses per 10 high-power fields&#41; and interstitial hemorrhaging&#46; The tumor cells proved to be immunoreactive to vascular markers &#40;CD31 and CD34&#41; and negative to epithelial markers &#40;epithelial membrane antigen and pancytokeratin&#41;&#46; Immunostaining for herpes simplex virus type 8 was negative&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">These findings confirmed the diagnosis of angiosarcoma&#44; and the patient underwent simple mastectomy&#46; Pathological examination of the surgical specimen showed the presence of several dermal nodules &#40;the largest measuring 4<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>cm&#41; and foci in the breast parenchyma &#40;2-5<span class="elsevierStyleHsp" style=""></span>mm&#41;&#46; Histopathology confirmed the diagnosis of high-grade angiosarcoma&#44; with disease-free margins&#46; The results of the staging study &#40;computed tomography of the thorax&#44; abdomen&#44; and pelvis and positron emission tomography&#41; were negative&#46; After a 9-month follow-up period&#44; the patient remains disease-free&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Angiosarcoma is a very uncommon endothelial cell tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It accounts for less than 1&#37; of cases of sarcoma and most frequently affects the skin&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> Cutaneous angiosarcoma can be divided into 3 main types&#58; the classic or idiopathic type&#44; the chronic lymphedema&#8211;associated type&#44; and the radiation-induced type&#46; Classic idiopathic angiosarcoma affects the skin of the head and neck in elderly patients<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> and is the most frequent variety &#40;50&#37;-60&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Chronic lymphedema&#8211;associated angiosarcoma appears after a period ranging from 4 to 27 years<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and almost always &#40;&#62;<span class="elsevierStyleHsp" style=""></span>90&#37; of cases&#41; develops in a limb with chronic lymphedema following radical mastectomy with axillary lymph node dissection &#40;Stewart-Treves syndrome&#41;&#46; Radiation-induced angiosarcoma appears in an irradiated field after a latency period&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In previous decades&#44; this variety mostly affected the abdomen after radiotherapy for abdominopelvic tumors&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> Today&#44; however&#44; angiosarcoma is detected mainly on the skin of the breast in women aged more than 60 years who have undergone adjuvant radiotherapy after conservative surgery for breast cancer&#46; The latency period is 3 to 5 years in most cases&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In any case&#44; angiosarcoma remains a very uncommon complication &#40;0&#46;05&#37;-0&#46;16&#37; of patients<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;6</span></a>&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Clinically&#44; angiosarcoma is characterized by the onset of erythematous-violaceous nodules or plaques that are typically multifocal&#46; Histopathology findings correspond to those reported in our case&#46; Growth is explosive in high-grade tumors and more insidious in low-grade tumors&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Its appearance may be similar to that of cutaneous metastases and of erysipelatoid carcinoma &#40;cutaneous metastasis whose symptoms are similar to those of erysipelas&#41;&#46; The differential diagnosis should include atypical vascular lesions &#40;AVLs&#41;&#44; which are cutaneous vascular proliferations that appear after radiotherapy for breast cancer with a latency period of 3 to 6 years&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Unlike angiosarcoma&#44; AVLs are not characterized by multiple layers of endothelial cells&#44; prominent nucleoli&#44; mitosis&#44; atypia&#44; destruction of skin appendages&#44; areas of solid growth&#44; invasion of the subcutis&#44; or hemorrhage&#46; Furthermore&#44; AVLs are circumscribed lesions with frequent chronic inflammation and stromal projections in the lumen&#44; which are not found in angiosarcoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7</span></a> Radiation-induced angiosarcoma was recently shown to involve an amplification of the v-myc myelocytomatosis viral oncogene homolog &#40;avian&#41; gene &#40;<span class="elsevierStyleItalic">MYC</span>&#41;&#44; which is not found in AVLs&#46; The presence of this gene could be used to confirm a diagnosis in complex cases or when the available tissue is limited&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> It is therefore important to remember that sufficient sample material must be obtained&#44; since punch biopsy findings can lead to an erroneous diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Treatment involves aggressive surgical excision&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Hyperfractionated accelerated adjuvant radiotherapy has been reported to achieve better control of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Prognosis is poor&#44; with high recurrence rates and a strong tendency to metastasize&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Overall survival at 5 years is 12&#37; to 20&#37;&#44; and mean survival is 18 to 28 months&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Some data suggest that radiation-induced angiosarcoma could have a poorer prognosis than sporadic angiosarcoma&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion&#44; we present a case of multifocal angiosarcoma of the skin of the breast&#46; This condition is a very uncommon yet very aggressive complication of radiotherapy that should be suspected in patients with erythematous-violaceous nodules on a previously irradiated breast&#46; Given the recent trend towards conservative management of breast cancer&#44; we should be on the alert for possible increases in the incidence of this tumor&#46;</p></span>"
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