Giant Breast Angiosarcoma in a 20-Year-Old Young Adult Female: A Case Report and Review of Literature

Abstract

Introduction

Primary breast angiosarcoma (PAS) is an extremely rare vascular malignancy that typically presents as a breast mass or cutaneous changes. Given its highly aggressive nature, rapid progression, and early metastasis that result in a poor prognosis, coupled with a lack of standardized treatment guidelines, there is an urgent need to develop novel, effective therapeutic strategies.

Case presentation

This report focused on a 20-year-old Uyghur woman presenting with a painless, rapidly enlarging mass in the left breast. Staging evaluation with breast MRI, whole-body contrast-enhanced CT, and bone scintigraphy revealed a large (10 × 7 cm) primary tumor and bilateral axillary lymphadenopathy suspicious for metastasis, with no evidence of distant disease (cT3N1M0, stage III). The high-grade angiosarcoma was confirmed through a core needle biopsy of the breast mass. With no remarkable medical or family history of breast cancer, the patient underwent complete surgical resection of the breast angiosarcoma, which provided a definitive pathological diagnosis. Given negative lymph node biopsy results, axillary lymph node dissection was not performed. Postoperatively, the patient received adjuvant chemotherapy with paclitaxel and bevacizumab. The regimen was well tolerated, and no disease recurrence was observed during follow-up. This case exemplified a practical management strategy for PAS, emphasizing the key role of clinical presentation and conventional imaging in guiding surgical decisions, particularly in resource-limited settings.

Conclusions

As a rare, highly malignant tumor, PAS requires early diagnosis and multidisciplinary management, including thorough metastasis evaluation and personalized therapy, to optimize survival and quality of life.

Introduction

Breast angiosarcoma (BA) is a rare malignant tumor, typically classified into primary and secondary subtypes. Primary breast angiosarcoma (PAS), primarily originating from the endothelial cells of blood vessels within the breast tissue, is exceedingly rare, comprising less than 0.05% of all primary malignant breast tumors [1]. This rarity and distinct origin not only distinguish PAS from other malignant breast tumors but also further complicates the diagnosis [2]. Clinically, PAS manifests with heterogeneous symptoms that complicate diagnosis and has a relatively low incidence of approximately 17 new cases per million women annually, according to epidemiological data [3, 4]. While PAS predominantly affects older adults, its incidence in adolescents remains poorly defined owing to limited literature [5]. Clinical presentations of BA are generally nonspecific, including palpable breast masses, skin erythema, localized pain, and changes in breast morphology [6]. Due to its highly malignant potential, PAS may grow rapidly and metastasize early, which severely affects overall prognosis [7] and yields a 5-year survival rate of approximately 40%–46%, underscoring the importance of personalized treatment plans [8]. Although imaging techniques, including mammography, ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT), play a crucial role in the preliminary assessment of the disease, pathological and immunohistochemical studies are required to make a definitive diagnosis [9]. The accurate diagnosis of PAS, which is challenged by clinical symptom overlap with other breast diseases, hinges on the integration of clinical presentations, imaging, and histological data [10]. To date, most available studies have reported that surgical resection remains the mainstay of treatment for PAS and that prognosis is closely associated with early diagnosis [11]. This case report described a 20-year-old female with PAS, aiming to enhance disease recognition and minimize diagnostic errors, including misdiagnosis and missed diagnosis.

Case Presentation

Clinical Data

Clinical History and Initial Examination

In May 2024, a 20-year-old Uyghur woman sought medical attention due to a painless left breast mass that she had first noticed 20 days earlier. Following an initial visit to a local county hospital, she was referred to a higher-level institution, a local grade A tertiary hospital, for comprehensive evaluation and treatment on May 7, 2024, due to limited medical resources.

There was no family history of breast cancer, sarcoma, or other hereditary cancer syndromes. The patient had no previous surgical history. She was unmarried and had no history of pregnancy or childbirth. The patient had no history of radiation exposure at any time, with no relevant radiation exposure history throughout her lifetime, not limited to the past 6 months. Given her young age, genetic testing and fertility preservation counseling were recommended. However, for personal reasons, the patient and her guardian ultimately declined these interventions, opting instead to prioritize immediate surgical intervention. The CARE Checklist for this case report has been completed and provided as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000553620).

Physical examination revealed marked bilateral breast asymmetry: the right breast was normally developed, whereas the left breast appeared significantly enlarged and swollen due to the massive tumor burden (online suppl. Fig. 1a, b). Marked breast asymmetry was caused by the large, space-occupying lesion and secondary skin edema. A total of two distinct palpable masses were identified in the upper hemisphere of the left breast (online suppl. Fig. 1a, b), which are described below in descending order of size. Tumor 1 was a large, irregular mass measuring 10 × 7 cm that occupied the upper half of the left breast (online suppl. Fig. 1a, b). The overlying skin presented with edema, and the lesion exhibited mild fixation without significant tenderness (online suppl. Fig. 1a, b). Tumor 2 was a relatively smaller dual-component lesion, including a 4.0 × 4.5 cm cystic, firm, painless mass at the 12 o’clock position and another firm, irregular mass of 4.0 × 4.5 cm with ill-defined margins and slight immobility at the 3 o’clock position (online suppl. Fig. 1a, b). In addition, firm and enlarged lymph nodes were palpable in the ipsilateral axilla and supraclavicular fossa (online suppl. Fig. 1a, b).

Breast ultrasound: a total of two lesions were detected in the left breast, which were described below in descending order of size and defined as tumor 1 and tumor 2 consistently throughout the manuscript. Breast ultrasound examination revealed a hypoechoic lesion in the left breast at the 12 o’clock position, measuring 4.7 cm × 3.8 cm × 6.1 cm (tumor 1) with clear boundaries, heterogeneous internal echoes, irregular morphology, and both internal and peripheral blood flow signals on color Doppler (online suppl. Fig. 2a). At the 3 o’clock position, another hypoechoic lesion measuring 4.3 cm × 3.3 cm × 3.3 cm (tumor 2) was detected, with relatively clear boundaries, heterogeneous internal echoes, irregular morphology, and blood flow signals on color Doppler within and surrounding the lesion (online suppl. Fig. 2b). The subcutaneous soft tissue layer of the left breast was thickened, with increased echogenicity and fissure-like change. Bilateral axillary scanning revealed no obvious abnormal enlarged lymph nodes in the right axilla. In the left axilla, several hypoechoic nodes were demonstrated with well-defined borders, oval shape, no significant cortical thickening, preserved hilar structure, no fusion, necrosis or abnormal vascular signals, and the largest one measured 27 mm × 13 mm with internal vascularity (lymph node, online suppl. Fig. 2c). Ultrasound diagnosis demonstrated a solid mass in the left breast (the lesion was initially suspected to be phyllodes like based on its large size, rapid growth, heterogeneous internal echo, irregular border, and abundant blood flow on ultrasound, which overlapped with typical imaging features of phyllodes tumor) (BI-RADS-US classification: left breast, category 4a), with left axillary lymphadenopathy.

Preoperative staging, including contrast-enhanced CT scans of the head, chest, and abdomen and a whole-body bone scan, confirmed the absence of distant metastasis (M0). Enhanced chest CT revealed a 10 × 7 cm oval-shaped mass in the medial region of the left breast. The mass presented heterogeneous enhancement, predominantly at the periphery, with visible internal strip-like blood vessels (online suppl. Fig. 3a–c). Crucially, the CT scans identified multiple enlarged lymph nodes in both axillae, with some nodes exhibiting central necrosis, a feature highly suggestive of regional metastasis.

Breast MRI (plain scan and contrast-enhanced MRI): during the plain scan phase, multiple abnormal signal mass shadows were observed in the upper and lower quadrants of the left breast, including an irregular, slightly hyperintense mass of 6.7 cm × 5.0 cm, with unclear boundary (Fig. 1a–c). Figure 1d–f represented the enhancement phase, where the dynamically enhancing mass was lobulated, the left breast skin was widely thickened, the near thoracic major muscle was rough, the multiple bilateral lymph nodes were enlarged, and the left side measured 3.3 cm × 1.3 cm, with mild post-contrast enhancement. MRI findings indicated (1) multiple occupying lesions in the left breast, suspicious for malignancy (BI-RADS-MRI class 5); (2) widely thickened skin of the left breast, cloudy subcutaneous fat layer, and rough adjacent pectoralis major muscle; (3) multiple nodules in the right breast, considered as cystic lesions (BI-RADS-MRI class 0); (4) multiple enlarged lymph nodes in bilateral axillae.

Fig. 1.

Preoperative MRI examination images. a–c MRI plain scan. d–f MRI enhanced.

Laboratory tests: routine laboratory investigations, comprising a complete blood count, metabolic panel, and liver function tests, were all within normal limits. However, hormonal assays revealed a significantly elevated prolactin level of 1,596.0 mIU/L and an increased testosterone level of 2.40 nmol/L. Notably, this marked hyperprolactinemia reflects a reactive hormonal imbalance associated with the large tumor burden and systemic stress, serving as a potential auxiliary clinical indicator to support the diagnosis of PAS in this case.

To further establish the diagnosis, biopsies of the supraclavicular lymph nodes, axillary lymph nodes, and the left breast mass were performed. Histopathological examination of the supraclavicular and axillary lymph nodes revealed reactive lymphoid hyperplasia with no definitive evidence of malignancy. However, core needle biopsy of the left breast mass confirmed a high-grade angiosarcoma (core needle biopsy histopathology, Fig. 2a). Tumor cells were immunohistochemically verified to be positive for CD31 (core needle biopsy histopathology, Fig. 2b), ERG (core needle biopsy histopathology, Fig. 2c), FLI-1 (core needle biopsy histopathology, Fig. 2d), and CD99, yet negative for CK, Myogenin, MyoD1, Desmin, ER, PR, and GATA-3, alongside a high Ki-67 proliferation index (>80%).

Fig. 2.

Pathological images of specimens obtained via core needle biopsy. a Conventional pathological image (SP, ×100). b Positive CD31 immunohistochemical staining (SP, ×200). c Positive ERG immunohistochemical staining (SP, ×200). d Positive FLI-1 immunohistochemical staining (SP, ×200).

Surgery and pathology: under general anesthesia, a left unilateral mastectomy with ipsilateral axillary lymph node biopsy was performed. With the left breast tumor as the center, a spindle-shaped incision was made around the breast, approximately 5 cm from the tumor margin. After resection of breast tissue, resection margins were sampled from all directions (Fig. 3a–b). Frozen section analysis of the upper, lower, inner, and outer margins showed no tumor involvement, confirming negative resection margin. Despite imaging findings suggestive of lymphadenopathy, the multidisciplinary team (MDT) decided against performing a comprehensive level I-III axillary lymph node dissection, given negative lymph node biopsy results and the specific characteristics of this disease. Gross examination showed that the resected left breast specimen measured 25 cm × 18 cm × 11 cm, containing a mass of 14 cm × 8 cm × 7.5 cm (Fig. 3a, b). The cut surface was grayish-yellow and grayish-red with a soft, fish-like texture, accompanied by extensive hemorrhage and necrotic areas (Fig. 3a, b). Microscopically, the tumor showed infiltrative growth composed of atypical vascular endothelial cells. Irregular, anastomotic vascular luminal structures were observed, with partial solid sheet-like and spindle cell proliferation, and red blood cells were visible within the lumens (postoperative histopathology, online suppl. Fig. 4a–e). Tumor cells were predominantly spindle to epithelioid with faintly eosinophilic cytoplasm, hyperchromatic and varied-sized nuclei, visible nucleoli, obvious nuclear atypia, and frequent mitotic figures (postoperative histopathology, online suppl. Fig. 4a–e). Large areas of hemorrhage and necrosis were noted within the tumor. No definite perineural or vascular invasion was identified (postoperative histopathology, online suppl. Fig. 4a–e). The superior, inferior, medial, lateral, and basal resection margins were free of tumor involvement; the skin, nipple, and areola were uninvolved, and no metastatic tumor was found in axillary lymph nodes (postoperative histopathology, online suppl. Fig. 4a–e).

Fig. 3.

Gross pathological images of the tumor. a, b Macroscopic images of tumor specimens under naked eye and postoperative tumors.

The patient recovered well after surgery with the postoperative recovery course illustrated in online supplementary Figure 5a–c, and adjuvant chemotherapy was commenced on the tenth postoperative day. The regimen consisted of paclitaxel (270 mg) and bevacizumab (300 mg), which were administered every 21 days, and all six planned cycles were completed. The patient tolerated the therapy reasonably well. The primary adverse events were dermatological, manifesting as a facial acneiform eruption and a pruritic rash on the back. The facial lesions were managed with topical clindamycin gel, while the back rash was treated by a combination of oral loratadine and topical mometasone furoate cream. Upon completion of chemotherapy, postoperative radiotherapy was initiated on October 21, 2024, with a total dose of 50 Gy delivered in 25 fractions (2 Gy per fraction). As of September 21, 2025, follow-up examinations after all treatment modalities revealed no evidence of disease recurrence or metastasis. Following radiotherapy, the patient entered a structured follow-up program, with tri-monthly examinations. This protocol included ultrasound of the breast, axillary, and supraclavicular lymph nodes, hepatobiliary-pancreatic-splenic region, and gynecological organs, along with complete blood count (CBC), biochemical tests, and tumor marker assays. An annual chest CT scan was also carried out. From year 3 onward, the follow-up frequency was adjusted to once every 6 months, and after 5 years, annual comprehensive examinations were conducted. The pre-radiotherapy follow-up, encompassing ultrasonography of the breast, hepatobiliary-pancreatic-splenic region, and gynecological organs, as well as chest CT, revealed no definitive evidence of recurrence or metastasis. Routine blood tests, biochemical panels, and cardiac enzymes were within normal limits. Sex hormone analysis data showed prolactin at 1,106.0 mIU/L and elevated testosterone at 2.20 nmol/L. After active treatment and tumor resection, the serum prolactin level was significantly decreased compared with that before treatment, which further supported that the preoperative hyperprolactinemia was reactive and related to the physical stress and tumor burden. Tumor markers included CA72-4 at 7.56 U/mL and squamous cell carcinoma antigen (SCC-Ag) at 2.35 U/mL, with other tumor markers within normal limits. Currently, the patient was clinically stable, with no definitive signs of tumor recurrence or metastasis.

Discussion

PAS is a rare vascular endothelial malignant tumor with extremely low incidence in young patients. We reported a 20-year-old PAS case, consistent with the decreasing onset age and rising incidence in adolescents and young adults reported in Asia and sub-Saharan Africa [12, 13]. For instance, a multicenter study in China by Zhu et al. [13] reported that a substantial proportion of PAS patients were younger than 25, while another cohort study confirmed a progressive increase in PAS incidence among females aged 15–25 over the past 2 decades [14]. However, diagnosis in young patients is often delayed due to nonspecific clinical and radiological features [15]. This case showed highly aggressive features consistent with PAS. Using the American Joint Committee on Cancer (AJCC) staging system for soft tissue sarcomas, the patient was classified as stage IIIB (T3N0M0, G3) based on the >10 cm tumor size, absence of nodal/distant metastasis, and high-grade histology. The Ki-67 index of ∼80% further confirmed its highly proliferative nature. These features collectively place the patient in the subgroup with the poorest prognosis [16, 17].

PAS is notoriously difficult to diagnose as it often mimics benign conditions [18], typically presenting as a rapidly growing mass with skin discoloration and often misdiagnosed [4]. To distinguish benign breast lesions from early BA, clinicians should focus on key clinical and imaging features: rapid tumor growth, unclear boundaries, abundant blood flow on ultrasound, heterogeneous enhancement on MRI, and skin edema or discoloration. Core needle biopsy with immunohistochemical markers (CD31, ERG, FLI-1) is essential for definitive diagnosis. This patient had a rapidly enlarging painless mass initially suspected as phyllodes tumor. No history of radiotherapy excluded radiation-associated angiosarcoma, confirming primary PAS [19].

Conventional imaging lacks specificity for PAS, whereas MRI is essential for diagnosis [20]. In our case, MRI findings were highly suggestive of a high-grade angiosarcoma, revealing marked T2 signal hyperintensity, a rapid “fast-in, fast-out” enhancement pattern, and signs of internal hemorrhage and necrosis [21], and histopathology with CD31/ERG positivity confirmed PAS. High Ki-67 (80%) indicated aggressive behavior, distinguishing it from less aggressive malignancies like breast carcinoma [19, 22]. This case illustrates the PAS diagnostic triad: atypical clinical presentation, characteristic MRI, and pathological verification. Multidisciplinary care is required to improve outcomes [23]. Notably, the patient presented with elevated serum prolactin preoperatively. This hyperprolactinemia was considered a transient reactive change induced by physical stress, local tissue compression, and anxiety associated with the rapidly enlarging giant BA. No pituitary lesions or primary endocrine disorders were identified. Following tumor resection and comprehensive treatment, the prolactin level decreased significantly, consistent with a stress- and tumor burden-related reactive elevation rather than a primary endocrine disease.

PAS lacks standardized treatment; surgery with adequate margins is the mainstay to lower recurrence risk and improve survival. Mastectomy is preferred, while axillary dissection is unnecessary since PAS mainly spreads hematogenously [24]. Rosen et al. found only 1 case of metastasis among 35 patients who underwent axillary lymph node dissection [25]. Positive margins predict poor prognosis [26], and wide negative skin margins are critical given its infiltrative growth [27]. PAS recurs frequently in the tumor bed [28], requiring margins ≥3 cm for extensive disease, often needing total mastectomy [29]. Despite imaging-suspected lymphadenopathy, negative biopsies and limited resources led MDT to perform modified radical mastectomy. Given the patient’s young age, the team initially discussed breast reconstruction and fertility preservation (e.g., ovarian function suppression and oocyte cryopreservation). However, reconstruction and fertility preservation were declined by the patient for personal and financial reasons.

Postoperatively, MDT recommended adjuvant chemotherapy for high-risk PAS patients with large or high-grade tumors. Given the patient’s high-risk features – including large tumor size, high histological grade, and a Ki-67 index of 80%, the MDT consensus recommended adjuvant chemotherapy tailored to tumor characteristics and individual conditions. For this patient, paclitaxel plus bevacizumab was selected for its anti-angiogenic and anti-proliferative effects [30]. Angiosarcoma is sensitive to taxanes [31], and the ANGIOTAX study showed better survival with paclitaxel [26]. Additionally, anti-angiogenic, targeted, and immune therapies show potential, particularly targeting the vascular endothelial growth factor (VEGF) pathway [32]. Vascular-targeted agents including sunitinib, sorafenib, and bevacizumab can inhibit VEGF/VEGF receptors (VEGFR)-mediated angiogenesis in angiosarcoma. Bevacizumab has been applied in locally advanced and metastatic angiosarcoma, with efficacy yet to be fully validated [33]. Activating KDR (VEGFR-2) mutations in about 10% of angiosarcomas support the use of VEGFR-targeted treatment. A phase I trial of bevacizumab demonstrated clinical activity in angiosarcoma [34]. This strategy remains valuable for selected patients [35]. This patient received 6 cycles of paclitaxel plus bevacizumab, with no recurrence observed. This regimen provides a useful reference for clinical practice.

Postoperative radiotherapy improves local control and reduces recurrence, especially for large or high-grade tumors. Adjuvant radiotherapy is recommended for tumors >5 cm or positive margins [36]. Dutch researchers performed a retrospective analysis of 222 secondary breast angiosarcoma (SBA) patients treated with radiotherapy from 74 articles and proved that 17% of patients receiving re-radiotherapy display an improved 5-year local recurrence rate [31]. In our case, the large (>10 cm), stage IIIB, highly malignant tumor indicated the need for radiotherapy. A total dose of 50–60 Gy was delivered to the breast with a tumor bed boost. PAS has a poor 5-year survival rate (<40%) associated with grade, margin, and stage [37, 38], so intensive follow-up with imaging and clinical evaluation was performed in the first two postoperative years.

In summary, PAS is a rare tumor with considerable diagnostic challenges, requiring pathological confirmation. This case was initially misdiagnosed as phyllodes tumor and finally confirmed by biopsy and expert consultation. Multi-site sampling and multiple sections are essential for pathological diagnosis. Difficult cases should be referred to a higher-level medical institution to avoid misdiagnosis and inappropriate treatment.

Conclusion

This case underscores key points in PAS management. Early suspicion is critical for young women with rapidly growing breast masses; diagnosis relies on pathological examination, multi-site sampling, and expert consultation. Multidisciplinary treatment should balance oncologic control and quality of life. Future research should focus on early diagnosis, personalized therapy, and molecular mechanisms. Multi-center studies are needed to clarify heterogeneity and develop precision medicine. Genomic and proteomic advances may identify biomarkers and targets. Multidisciplinary care involving surgical oncologists, pathologists, radiologists, medical oncologists, and radiation therapists ensures accurate diagnosis, individualized surgical planning, and optimized systemic therapy and radiotherapy. International collaboration facilitates multicenter data sharing to establish standardized diagnostic criteria and treatment guidelines for rare BA. Emerging technologies such as artificial intelligence-assisted imaging and histological diagnosis can improve early recognition and differential diagnostic accuracy, thereby reducing misdiagnosis and delaying intervention and ultimately improving survival and quality of life for patients.

Acknowledgments

The authors thank the patients and their family for their interest and cooperation.

Statement of Ethics

This study was approved by the Institutional Review Board and Ethics Committee of The First People’s Hospital of Aksu Prefecture, Xinjiang (Approval No: KY2024073). The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Written informed consent was obtained from the patient for the publication of this case report and related images. The patient’s anonymity has been fully preserved.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was supported by Zhejiang Science and Technology Plan for Medical and Health (Grant No.: 2023KY588); Open Project of Xinjiang Key Laboratory of Artificial Intelligence Assisted Imaging Diagnosis (Grant No.: XJRGZN202423); and the Provincial-level Project of The First People’s Hospital of Aksu Prefecture, Xinjiang (Grant No.: YJKT 2024-10). The funder had no role in the design, data collection, data analysis, and reporting of this study.

Author Contributions

Haojun Xuan contributed to all the work, especially to the revision of the manuscript. Contributor Jingkun Wang wrote the manuscript and followed this BA patient for related research and developed the treatment plan with the help of breast experts. Xinhai Wang and Jingbo Yang provided reliable analysis of pathological results. Zhiquan Chen and Yufeng Wang informed the patient of informed consent and signed the consent form under the supervision of Haojun Xuan.

Funding Statement

This study was supported by Zhejiang Science and Technology Plan for Medical and Health (Grant No.: 2023KY588); Open Project of Xinjiang Key Laboratory of Artificial Intelligence Assisted Imaging Diagnosis (Grant No.: XJRGZN202423); and the Provincial-level Project of The First People’s Hospital of Aksu Prefecture, Xinjiang (Grant No.: YJKT 2024-10). The funder had no role in the design, data collection, data analysis, and reporting of this study.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.