Recurrent radiogenic angiosarcoma of the breast: a rare case report

Abstract

Introduction:

Post-radiation angiosarcoma of the breast is a rare but aggressive vascular malignancy that can develop as a late complication of radiotherapy for breast cancer. It is associated with a risk of local recurrence and a poor prognosis.

Case presentation:

Herein, we describe a case of an 80-year-old postmenopausal woman with a prior history of stage IIIC left breast invasive ductal carcinoma, treated with lumpectomy, axillary dissection, radiotherapy, and endocrine therapy. Several years after treatment, she presented with a painless, superficial brown skin lesion over the irradiated breast. Histopathological examination and immunohistochemical analysis confirmed high-grade angiosarcoma with epithelioid features. Staging investigations showed no distant metastatic disease, and the patient underwent a left simple mastectomy. During follow-up, she developed recurrent disease, presenting as cutaneous and chest wall lesions, both confirmed histologically as recurrent angiosarcoma. The patient subsequently underwent wide local excision with rotational flap reconstruction for local recurrence. The patient is currently under regular follow-up with no further recurrence or active complaints.

Discussion:

Radiogenic breast angiosarcoma is an uncommon cancer, and while various studies have documented its clinical features and treatment, few have specifically addressed recurrent instances. Our case demonstrates the clinical course of recurrent post-radiation angiosarcoma and the difficulty in achieving local disease control following several surgical treatments.

Conclusions:

This report highlights the prognosis, treatment, and clinical presentation of recurrent breast radiogenic angiosarcoma. Clinicians should maintain a high index of suspicion in previously irradiated patients presenting with new or progressive skin changes.

Introduction

Breast angiosarcoma is a rare and aggressive vascular malignancy that accounts for less than 1% of all soft tissue tumors and represents the most common histologic subtype of breast sarcomas^[1^]. It may occur as a primary tumor or develop secondary to prior radiation therapy. Primary angiosarcoma is more commonly reported among younger women without a history of breast cancer, particularly during the third to fifth decades of life. It usually develops within the breast parenchyma. On the other hand, post-radiation angiosarcoma typically appears in women between the ages of 60 and 70, originates in the skin, and then spreads to the breast parenchyma^[2,3^]. Post-radiation angiosarcoma is an uncommon but serious late complication of breast irradiation and is associated with poor clinical outcomes due to its aggressive nature and high risk of local recurrence. Histopathological confirmation remains essential for diagnosis. Cahan et al proposed diagnostic criteria for radiation-induced sarcoma, including prior radiation exposure, development of the tumor within the irradiated field after a latency period, and histological confirmation of sarcoma^[4^]. Although several reports have described post-radiation breast angiosarcoma, recurrent cases remain rarely documented in the literature. Reporting such cases is important because recurrence after surgical management poses significant therapeutic challenges and highlights the aggressive biological behavior of this malignancy. Herein, we report a rare case of recurrent radiogenic angiosarcoma of the breast in an elderly woman previously treated with lumpectomy and radiotherapy for invasive ductal carcinoma. This case report has been prepared in line with the SCARE criteria^[5^].

HIGHLIGHTS

• Recurrent radiogenic breast angiosarcoma is rare, with few reported studies.

• Skin changes post-radiation should prompt an early biopsy for angiosarcoma.

• Local disease control is difficult after multiple surgical interventions.

• Surgery with complete excision remains the mainstay of treatment.

• Imaging has limitations; biopsy remains the gold standard for diagnosis.

Case presentation

We describe a case of an 80-year-old postmenopausal woman with a history of left breast carcinoma who presented with a superficial swelling over the left breast skin that had been progressively increasing for 1 month. The lesion was painless and not associated with bleeding or nipple discharge. Her past oncologic history was significant for infiltrating ductal carcinoma with lobular cancerization of the left breast. Histopathological examination at the time of initial diagnosis demonstrated a grade 3 tumor measuring T2 (2 cm), N3a (15/24), M0–STAGE III. Immunohistochemistry showed estrogen receptor (ER)-positive and progesterone receptor (PR)-positive status, with human epidermal growth factor receptor 2 (HER2)-negative.

The patient underwent a left-sided lumpectomy with axillary lymph node dissection, followed by adjuvant radiotherapy. Chemotherapy was advised; however, the patient declined systemic treatment after discussion with her family. She subsequently received endocrine therapy with letrozole 2.5 mg daily for 5 years. At presentation with the new skin lesion, physical examination revealed a superficial brown-colored swelling measuring approximately 1 × 2 cm, located away from the previous surgical scar (Fig. 1). No palpable axillary lymphadenopathy was identified. Breast ultrasonography demonstrated normal breast parenchymal echogenicity without suspicious focal solid or cystic lesions in either breast. Mammography revealed postsurgical changes in the upper outer quadrant of the left breast, with mild skin and subcutaneous soft tissue thickening that remained stable compared to prior imaging. No suspicious soft tissue masses, pleomorphic microcalcifications, or significant lymphadenopathy were noted.

Figure 1.

Blue blackish para-areolar skin nodule, developed in the scar of a mastectomy.

Given the persistence of the cutaneous lesion, a punch biopsy was performed. Histopathological examination revealed a malignant vascular neoplasm, most consistent with angiosarcoma with partial epithelioid features. Kaposi sarcoma was considered in the differential diagnosis. Microscopic examination demonstrated a highly proliferative tumor with a mitotic rate of 27 mitoses per 10 high-power fields. Immunohistochemical staining showed strong, diffuse positivity for vimentin, CD31, CD34, and factor VIII, confirming vascular differentiation (Fig. 2). Tumor cells were negative for ER, PR, HER2, cytokeratin (AE1/AE3), S100, and HMB45. The lesion was classified as FNCLCC grade 3 angiosarcoma.

Figure 2.

(A–C) H&E staining x40, 40., X 100. X 400: Tumoral cell proliferation infiltrating the skin with ulceration. The tumoral cells are spindle or epithelioid in shape, showing severe nuclear atypia with numerous mitoses, lining vascular spaces. (E–G) The tumor cells express CD34 (E), factor VIII (F), and CD31 (g).

The case was discussed at a multidisciplinary tumor board meeting, where the lesion was considered most likely secondary to prior radiation therapy. On subsequent clinical evaluation, the lesion had progressed to approximately 2 × 2 cm with black discoloration of the overlying skin, but there was still no bleeding or palpable lymphadenopathy. Computed tomography (CT) demonstrated no evidence of distant metastatic disease. The patient subsequently underwent a left simple mastectomy.

Following surgery, the patient remained under surveillance until she developed recurrent swelling over the left chest wall, which was associated with skin redness. The lesion was not accompanied by pain or nipple discharge. On examination, there was a small bluish skin lesion on the left breast, which was completely excised with a rotational flap and revealed recurrence of cutaneous angiosarcoma (Fig. 3). Imaging was performed and excluded any possibility of metastasis.

Figure 3.

(A) A bluish-blackish nodule of the skin appeared in the scar of the mastectomy. (B) Multiple small similar nodules are seen in the subcutaneous tissue.

Currently, the patient is under regular follow-up, with no evidence of further recurrence or complaints.

Discussion

Post-radiation breast angiosarcoma is an uncommon late complication after lumpectomy with adjuvant radiotherapy. It commonly presents with nonspecific cutaneous findings, including painless enlarging masses, superficial skin lesions, bruising, erythematous rash-like changes, or skin discoloration, which may delay diagnosis because they can mimic benign post-radiation skin changes^[6,7^]. In the present case, the patient initially developed a painless brownish-black cutaneous lesion away from the previous surgical scar following treatment for infiltrating ductal carcinoma with lobular cancerization. Subsequent recurrence presented as a bluish skin lesion associated with surrounding erythema over the chest wall. Several studies have discussed the clinical characteristics and treatment, but there are few reports focusing specifically on recurrent radiogenic angiosarcoma^[7,8^]. Our case demonstrates the aggressive clinical behavior of recurrent post-radiation angiosarcoma and highlights challenges in achieving durable local disease control despite repeated surgical interventions.

According to Cohen-Hallaleh et al, the median age at diagnosis of radiation-induced angiosarcoma is 72 years (51–92), with a median latency period of 7.5 years (1–26) following radiotherapy^[9^]. Our patient developed breast angiosarcoma at 80 years of age, with a latency period of approximately 4 years after radiotherapy. Breast angiosarcoma is associated with a poor prognosis, with reported 5-year overall survival rates of approximately 44.9%^[10,11^]. More than half of cases occur in locoregional locations; distant metastasis usually involves the liver (13.6%), lung (10.5%), and bone (10.5%). Recurrence has been reported as early as 37 months following radiation^[10,11^]. In the current case, recurrence occurred approximately 3 years after initial surgical management of the radiation-associated angiosarcoma.

Breast angiosarcomas appear on mammography as ill-defined masses without spiculations or calcifications, with no specific radiographic features, and up to one-third of patients may show normal mammograms^[12^]. Ultrasonographic findings are also nonspecific and may demonstrate heterogeneous, hyperechoic, or hypoechoic lesions without posterior acoustic shadowing, often mimicking benign breast abnormalities. Breast angiosarcoma can be diagnosed using MRI data, which often reveal high signal intensities on T1- and T2-weighted imaging^[13–15^]. Given the limitations of imaging modalities in detecting post-radiation angiosarcoma, maintaining a high index of clinical suspicion is essential, particularly in previously irradiated patients presenting with new or progressive cutaneous changes. Histopathological examination remains the gold standard for diagnosis^[8^].

In our case, mammography showed slight thickening of the epidermis and subcutaneous tissues of the left breast without suspicious masses or microcalcifications. On ultrasound, there were no suspicious lesions or notable axillary lymphadenopathy. These findings are consistent with previous reports describing the limited sensitivity of conventional imaging in detecting post-radiation breast angiosarcoma^[13–15^]. Definitive diagnosis in our patient was established through biopsy and immunohistochemical analysis. The tumor showed strong positivity for vimentin, CD31, CD34, and factor VIII, supporting endothelial differentiation and confirming the diagnosis of angiosarcoma. Histology revealed that cells with spindle and epithelioid shapes were occupying vascular spaces. They also had multiple mitoses and distinct nuclei. The differential diagnosis also includes other vascular tumors, such as hemangiomas and atypical vascular lesions, which usually do not show the strong cellular atypia and mitotic activity of angiosarcoma but may share some histological features.

Percutaneous biopsy for breast angiosarcoma has been reported to carry a false-negative rate of up to 37%, which may contribute to delayed diagnosis^[12,16^]. Therefore, in clinically suspicious cases, particularly in the setting of recurrent disease or progressive post-radiation skin changes, excisional biopsy may be required to establish a definitive diagnosis. Due to the rarity of radiation-associated angiosarcoma, there is no universally established treatment protocol. National Comprehensive Cancer Network guidelines suggest total surgical excision with clear margins as the mainstay of therapy^[17^]. While surgery is the main treatment for localized illness, systemic chemotherapy and re-irradiation may be considered for individuals with disseminated or recurrent radiation-associated angiosarcoma of the breast. In research that examined 377 cases of post-radiation angiosarcoma, 83% of patients underwent mastectomy. In 58% of cases, chemotherapy was the main treatment for recurrence; adjuvant radiation and chemotherapy were applied in just 6% and 4% of cases, respectively. In 30% and 33% of patients, respectively, recurrent surgery and radiotherapy were used^[8^].

Similarly, another retrospective series reported mastectomy as the principal treatment approach in all included patients with post-radiation angiosarcoma^[18^]. Management strategies are largely based on expert opinion and retrospective studies because of the rarity of the disease^[19^]. In our case, the patient initially underwent a left simple mastectomy for the primary radiation-associated angiosarcoma, followed by wide local excision with rotational flap reconstruction after local recurrence. Axillary lymph node dissection is generally not recommended because angiosarcoma most commonly metastasizes through hematogenous spread rather than lymphatic dissemination^[20^]. Achieving complete tumor excision appears to be one of the most important prognostic factors. Strobbe et al, for example, found that 21 Dutch women with post-radiation angiosarcoma had an overall 2-year survival rate of 86% after complete surgical excision, as opposed to 0% after partial excision^[21^]. The D’Angelo et al study showed that 78 out of 79 patients underwent local surgery, and 23 patients needed adjuvant therapy, as they showed no improvement or metastasis and received chemotherapy^[8,22^]. Re-irradiation for the breast may be helpful to enhance survival and long-term results for patients with secondary angiosarcoma. Smith et al reported prolonged survival outcomes in patients treated with hyperfractionated accelerated re-irradiation, either alone or combined with surgery^[23^].

The management of recurrent radiation-associated angiosarcoma remains challenging, and improving patient outcomes requires early detection and targeted surgical procedures.

Conclusion

Recurrent post-radiation angiosarcoma is a rare and usually aggressive cancer that should be diagnosed, particularly in women who develop skin abnormalities after radiation therapy, in order to confirm the final diagnosis. We advise all patients to undergo a biopsy because imaging cannot detect breast angiosarcoma, and to continue with close follow-up and individualized surgical management for recurrent cases. Further reports and research are needed in the future to establish a treatment protocol for post-radiation angiosarcoma, especially recurrent cases, which are a rare entity.

Ethical approval

Not applicable.

Consent

Written informed consent was obtained from the son for publication of this case report and accompanying images.

Sources of funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author contributions

H.A. is the corresponding author, collected the clinical data, drafted the manuscript, and revised the text. T.Y. provided the pathological diagnosis, contributed to the pathology section, added pathological comments, and revised the text. Afnan Alshayeb assisted in manuscript writing, prepared the references, conducted the literature review, and revised the text. J.A. assisted in manuscript writing, prepared the references, conducted the literature review, and revised the text. T.A. was the senior consultant who performed the surgery, supervised the study, and provided the final revision of the manuscript.

Conflicts of interest disclosure

The authors declare that there is no conflict of interest.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Hussain Alessa.

Provenance and peer review

Not commissioned, externally peer reviewed.

Data availability statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.