Breast cancer management has changed significantly, with radical surgery being replaced by breast-conserving treatment followed by chemotherapy and radiotherapy. This has resulted in an improved quality for life of the patient but with an increased incidence of radiotherapy-associated angiosarcoma, which carries a poor prognosis.
The incidence of angiosarcoma of the breast is 1% of breast tumors; it may be primary or secondary. The risk of secondary angiosarcoma following radiation therapy is between 0.05% and 0.3%. The clinical presentation is subtle and is often confused with telangiectasia.
Patients who receive radiation therapy for breast cancer have a 26-fold increased risk of developing angiosarcoma. The prognosis is poor, with a 5-year overall survival between 27% and 48%. Here we report the case of a patient who presented with breast angiosarcoma 7 years after receiving radiotherapy for infiltrating breast carcinoma-no special type (NST).
A 62-year-old woman was diagnosed with grade 2 invasive ductal carcinoma (NST) with estrogen receptor (ER) positivity and HER2 negativity. She underwent wide local excision with lymphadenectomy followed by 50 Gy of Cobalt-60 adjuvant radiotherapy. Seven years following radiotherapy, the patient noticed a purplish spot in the region of the irradiated skin of size 4 × 3 cm with induration and skin erosion. Ultrasonography revealed a hypoechoic lesion involving the right breast. With her informed consent, a core needle biopsy was performed, which showed few thrombosed vessels undergoing recanalization with luminal, mildly atypical papillary endothelial tufts, confirmed on immunohistochemistry. This morphology was consistent with an atypical vascular lesion favoring angiosarcoma. A computed tomography scan showed no evidence of metastases to other organs. Subsequently, a right mastectomy with wide skin excision was performed.
Macroscopically, the resected mastectomy specimen was 9 × 6 cm in size and showed an irregular, hemorrhagic lesion, of size 4.3 × 3.2 cm with surface ulceration. Microscopic examination revealed that the predominant morphology comprised numerous anastomosing vascular spaces, many with recanalizing thrombi and several with intraluminal, papillary and tufted proliferation of markedly atypical cells with pleomorphic, hyperchromatic nuclei and a moderate amount of eosinophilic cytoplasm. The lesional configuration eminently resembled a malignant endovascular papillary angioendothelioma or Dabska tumor [Figures 1a and b]. On immunohistochemistry, strong diffuse cytoplasmic and membranous positivity for Factor VIII related antigen [Figure 1c] and CD31 [Figure 1d] was noted – confirming the endothelial phenotype of the neoplastic cells. Thus, a diagnosis of a post radiation mammary angiosarcoma, with Dabska tumor-like morphology, was established.
As the lesion was less than 5 cm and the surgical resection margins were negative, no adjuvant therapy was administered. It is prudent to consider adjuvant radiation therapy in tumors larger than 5 cm, with deep invasion, and positive surgical margins to prevent a recurrence. It is also important to conduct a general physical examination, and a positron emission tomography scan during the follow-up period, especially in the first 2 years. Our patient is doing well at 6 months of follow-up. The timeline of the clinical events is depicted in Figure 2.
The first case of radiation-induced secondary angiosarcoma was reported by Peng et al. in 1987. The diagnostic criteria for radiogenic angiosarcoma of the breast include a history of radiation therapy approximately 5 to 6 years prior, the development of sarcoma in the irradiated field, and confirmation by histopathology. Radiogenic angiosarcoma of the breast is an aggressive high-grade tumor. It has a poor prognosis with a 70% risk of recurrence following mastectomy. Although surgery is the mainstay of treatment, the use of hyperfractionated and accelerated radiotherapy has been found to lead to better outcomes after surgery and in patients presenting with disease at an advanced stage. Chemotherapy may also be considered as a treatment option. A good clinical examination and radiologic imaging with a positron emission tomography scan during the follow-up period are recommended, especially in the first 2 years.
Primary angiosarcoma affects young women, while radiogenic angiosarcoma of the breast is seen in older women with a mean age of onset of 70 years. Our patient was in the seventh decade of life and presented with a purple skin patch, with induration and skin ulceration, and no significant breast lump. The differential diagnoses of radiation-induced angiosarcoma include benign angiomas, small hematomas, and atypical telangiectasias. It presents as a painless cutaneous or subcutaneous flat or nodular lesion, with bluish or purplish discoloration.[3,12] The latency period for developing radiogenic angiosarcoma of the breast after radiation treatment for breast cancer is variable, ranging from 6 months to 20 years.
Imaging in cases of angiosarcoma shows non-specific findings and the diagnosis is difficult to establish on mammography. It may rarely present as an ill-defined mass with calcifications. A histopathological examination is needed to arrive at a conclusive diagnosis. Furthermore, both primary angiosarcoma and radiation-induced angiosarcoma share the same histological features, except that cutaneous involvement are more commonly encountered in radiation-induced angiosarcoma.
Angiosarcomas shows immunoreactivity for vascular markers like CD31, CD34, Factor VIII related antigen, Podoplanin, and ERG1.[10,11] Laé et al. have reported c-myc gene amplification in radiation-induced angiosarcomas, which may be helpful in planning targeted therapy. Almost exclusive malignant endovascular papillary angioendothelioma or Dabska tumor-like morphology in an angiosarcoma is distinctly rare and finding this in a post-irradiation milieu is singular, but this was the distinctive morphology in our patient. To contextualize - a malignant endovascular papillary angioendothelioma or Dabska tumor is a neoplasm having a stark predilection for infancy and childhood.
Radiation-induced angiosarcoma is treated by a wide surgical resection. Morgan had proposed complete excision of all radiation-exposed tissue in order to lower the risk of recurrence. Angiosarcomas are resistant to radiotherapy and chemotherapy.[14,15] Angiosarcomas overexpress vascular endothelial growth factor (VEGF); therefore, targeted therapies such as VEGF inhibitors can be novel treatment options.
To conclude, radiation-induced angiosarcoma is an aggressive disease, often missed on mammography and usually presenting as a non-specific skin lesion. It poses great diagnostic and therapeutic challenges. It usually occurs years after radiotherapy, so the surgeon should be aware of the deceptively subtle appearance of the disease and keep the patient under close follow-up. The pathologist should also be watchful for unexpected morphologies, as illustrated by this case.
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The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
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Conflicts of interest
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