Radiation-Associated Secondary Angiosarcoma of the Breast: Case Report and Literature Review

Case report

A 5A 7-year-old woman, with a prior history of bilateral breast carcinoma, treated with breast-conserving surgery and adjuvant radiotherapy eight years earlier, presented for routine follow-up. She reported progressive skin changes of the right breast. Clinical examination revealed extensive erythematous-violaceous plaques, with multiple raised nodules, involving approximately 2/3 of the breast surface, extending toward the sternal region. No palpable intraparenchymal mass or axillary lymphadenopathy was detected.

A pA biopsy demonstrated atypical vascular proliferation with endothelial atypia, consistent with angiosarcoma. Immunohistochemistry confirmed vascular differentiation (CD31/CD34 positive).

Sta. Positron emission tomography showed no distant metastases.

Following a multidisciplinary discussion, mastectomy was recommended. The patient opted for unilateral surgery, and a right-sided mastectomy was performed. Initially, postoperative recovery was uneventful.

However, three months later, multiple nodular lesions appeared in the surgical field. Histological reassessment confirmed local recurrence. Given the aggressive course, systemic chemotherapy with weekly taxane therapy was initiated.

Discussion

RAAS is a distinct clinic-pathological entity, arising from radiation-induced endothelial damage. Molecular alterations such as MYC amplification have been implicated in its pathogenesis [5,6].

MYC amplification is a common genetic aberration where the MYC gene (often c-MYC at 8q24) is duplicated multiple times, leading to overproduction of the MYC protein. This acts as a powerful oncogenic driver, fueling cancer progression by promoting rapid cell proliferation, inhibiting cell death, and increasing genomic instability, often indicating a poor prognosis [12,13].

Detailed information regarding prior radiotherapy is essential for understanding the pathogenesis of radiation-associated angiosarcoma. In the present case, the patient underwent adjuvant radiotherapy following initial breast-conserving surgery for left-sided breast carcinoma. The total delivered dose was 50 Gy in 25 fractions, followed by a boost dose of 10–16 Gy to the tumor bed, consistent with standard protocols.

The radiation energy employed was within the megavoltage range (typically 6–10 MV photons), ensuring adequate tissue penetration while minimizing superficial toxicity. The field arrangement consisted of tangential opposed fields encompassing the whole breast, with careful sparing of adjacent organs such as the heart and lungs.

Importantly, no intentional overlap existed between irradiation fields of the two breasts, as the contralateral (right) breast had not been irradiated at the time of the initial treatment. However, it must be acknowledged that scatter radiation and low-dose peripheral exposure may occur, albeit at clinically negligible levels. From a pathogenic standpoint, radiation-associated angiosarcomas are typically confined to the previously irradiated field, supporting the causal relationship between high-dose exposure and sarcomagenesis.

In cases where bilateral irradiation or field overlap occurs, there is a theoretical increase in cumulative radiation dose to shared tissues, potentially amplifying the risk of secondary malignancies, including angiosarcoma. However, in this patient, the absence of field overlap reinforces the classical model of radiation-induced sarcoma, localized strictly within the high-dose region.

Typical clinical presentation includes: violaceous or erythematous patches, rapidly evolving nodules, and absence of a deep palpable mass in early stages. These features were consistent with our case.

Diagnosis relies on histopathology and immunohistochemistry. Imaging is primarily used for staging, with PET/CT useful for detecting metastatic disease [18] (Figures 1,2).

Figure 1: Histopathology of secondary angiosarcoma of the breast. A) H&E: Irregular, anastomosing vascular channels lined by atypical endothelial cells with hyperchromatic nuclei and mitotic figures (arrows). B) Immunohistochemistry: Strong diffuse positivity for CD31 highlighting vascular endothelial proliferation.

Figure 2: PET/CT (FDG) – Staging. A) Axial fused PET/CT: Intense hypermetabolic activity in the skin and subcutaneous tissue of the right breast (arrow), corresponding to angiosarcoma. B) Whole-body PET (MIP): Increased uptake limited to the right breast region (arrow); no distant metastases detected.

Following the right mastectomy, postoperative radiotherapy (PMRT) was carefully evaluated but ultimately not indicated. The decision was based on: absence of high-risk pathological features (e.g., large tumor size, positive margins, extensive nodal involvement); lack of chest wall invasion; favorable surgical margins (R₀ resection). Given these findings, the anticipated benefit of PMRT in reducing locoregional recurrence was outweighed by the potential risks, particularly in a patient with a prior history of radiation exposure and a documented radiation-induced malignancy. Thus, omission of PMRT was considered clinically justified and aligned with current oncological guidelines (Figure 3 and Table 1).

Figure 3: Clinical presentation of radiation-associated angiosarcoma of the breast: extensive cutaneous involvement of the right breast showing erythematous to violaceous discoloration with multiple raised nodules and indurated plaques. The lesions occupy approximately 2/3 of the breast surface and extend toward the sternal region. No obvious underlying mass is visible.

Treatment: wide surgical excision remains the mainstay of treatment. However, margin-negative resection is often difficult, and recurrence rates are high. Chemotherapy (e.g., taxanes) may provide disease control. Emerging strategies, such as reirradiation and targeted therapies, are under investigation but lack consensus [7,8].

The selection of therapeutic strategies in breast cancer is inherently multifactorial and individualized. The following parameters are central to clinical decision-making: tumor-related factors - size, histological subtype, grade, lymphovascular invasion; biological profile - hormone receptor status (ER/PR), HER2 expression, Ki-67 index; disease extent - nodal involvement, metastatic spread; patient-related factors - age, comorbidities, performance status; previous treatments - prior irradiation or systemic therapy; patient preference (particularly regarding breast conservation). In this context, multidisciplinary evaluation remains the cornerstone of optimal care.

Mastectomy continues to play a crucial role in breast cancer treatment; however, it is not universally superior to breast-conserving therapy (BCT). Multiple landmark trials have demonstrated equivalent overall survival between mastectomy and BCT (lumpectomy followed by radiotherapy) in early-stage breast cancer. Therefore, mastectomy is generally reserved for: large tumors relative to breast size; multifocal or multicentric disease; contraindications to radiotherapy; persistent positive margins after re-excision; and patient preference. In contrast, breast-conserving approaches are preferred when oncologically safe, due to better cosmetic outcomes and comparable survival rates.

In the specific context of radiation-associated angiosarcoma, however, mastectomy becomes the treatment of choice, as wide surgical excision with negative margins is critical for local control, and further irradiation is generally contraindicated.

While breast-conserving therapy remains standard for many patients, prior radiation exposure and secondary malignancy risk fundamentally alter management strategies, necessitating a more radical surgical approach [14-17].

Prognosis remains poor, with frequent early recurrence, as observed in this case. Survival outcomes depend on tumor size, margin status, and early detection.

Conclusions

Radiation-associated angiosarcoma of the breast is an aggressive malignancy with increasing incidence due to modern breast cancer treatment strategies [18].

This case highlights:

- The importance of early biopsy of suspicious skin lesions;

- The critical importance of detailed radiotherapy documentation, individualized therapeutic decision-making, and the nuanced role of mastectomy;

- The high recurrence rate despite surgery

- The need for individualized, multidisciplinary treatment

Future research should focus on molecular profiling and targeted therapies to improve outcomes in this rare but devastating disease [19].

Ethical approval statement

This study was conducted in accordance with the ethical standards of the institutional research committee and with the Declaration of Helsinki. Ethical approval was obtained from the Institutional Ethics Committee of County Emergency Clinical Hospital Brăila, under approval number [protocol number. 826 from 2024, August 26].

Informed consent statement

Written informed consent was obtained from the patient for participation in this study and for the publication of clinical data and images. A copy of the consent is available upon request.

Conflict of interest declaration

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Funding Statement: This research received no external funding.

Author contributions

Conceptualization: D.C.V, M.A.D; Methodology: C.P, D.M.; Data Collection: D.S, P.Z. S.A.L.; Analysis: D.C.V, M.A.D.; Writing – Original draft: M.A.D.; Writing – Review & Editing: D.C.V.; Supervision: D.C.V. All authors have read and approved the final manuscript.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request.