Cutaneous angiosarcomas are aggressive tumors that arise in either the blood or lymphatic vessels, and account for ~15% of all head and neck sarcomas and 1% of all soft tissue sarcomas (1). Cutaneous angiosarcoma has a reported 5-year overall survival (OS) rate between 9 and 30% (2–4). The scalp and face are the most common sites of cutaneous angiosarcoma (4). Previous studies investigated the survival outcomes for cutaneous angiosarcoma of the scalp vs. face, and the results have indicated that scalp angiosarcoma has a worse survival rate compared with facial angiosarcomas (2,4). However, the present study focused on the outcomes of scalp angiosarcoma; therefore, patients with facial angiosarcomas were excluded.

Scalp angiosarcoma has an innocuous presentation (5,6). Complete surgical resection with wide margins is preferred for loco-regional disease (7). Chemotherapy is widely used in patients with lesions that cannot be entirely resected, or who have distant metastatic disease (7). However, the optimal treatment for patients with scalp angiosarcoma has not yet been defined.

Due to its low incidence, the available literature on scalp angiosarcoma primarily consists of case reports, and few large single institution series on scalp angiosarcoma have been published (5,6,8). In the present analysis, a relatively large cohort study was performed, where 42 patients with scalp angiosarcoma were diagnosed and treated at a monocenter (Zhongshan Hospital, Fudan University) over a period of 12 years. The present study analyzed patient and tumor characteristics, as well as treatment algorithms. The potential associations between these parameters and patient outcomes were investigated.

Scalp angiosarcoma is a malignant aggressive head soft tissue neoplasm often with an innocuous presentation (5,6). Despite ongoing researches, the treatment options for angiosarcoma are limited, and even following aggressive therapy, patient survival is very poor (2,7). Therefore, timely and accurate diagnosis of this disease is critical in order to ensure an optimal patient outcome. However, initial diagnosis is often difficult due to a lack of definitive symptoms (8).

In the present study, the 5-year OS rate was 19%, and the 5-year RFS rate was 10%, with these demographic results being similar to previous reports (4,9–11). A total of 23 (55%) patients experienced disease recurrence, and this result was consistent with a previously reported case (12). In our surgical practice, it was noted that patients with nodular tumor presentation usually had definitive local resection, while patients with diffuse presentation usually had uncertain margins that may be associated with recurrence. Other institutional reviews of angiosarcoma revealed that there was no significant difference in rates of loco-regional recurrence among the different tumor presentations or treatment modalities (7,13). Guadagnolo et al (9) reported that tumor size >5 cm was significantly indicative of a worse prognosis for OS rate; however, the present study did not observe a statistically significant association between these two parameters.

In the present study, only two (5%) patients developed distant metastasis. This low distant metastatic rate was inconsistent with previously reported cases (10,11). This inconsistency may be due to the fact that an autopsy was not performed in the majority of cases, therefore some metastases may have been neglected.

It has been previously reported that angiosarcoma can be caused by therapeutic radiation or chronic lymphedema; therefore, secondary breast angiosarcomas are an important subgroup of angiosarcomas (14). However, in the present study, no patients presented with a history of radiotherapy or chronic lymphedema. In the department of Plastic and Reconstructive Surgery, Zhongshan Hospital (Shanghai, China), the most commonly observed presentation of angiosarcoma was on the scalp.

Morgan et al (15) demonstrated that a positive surgical margin was associated with poor OS in 44 patients with angiosarcoma of the face and scalp. However, in the current literature, the implication of surgical margins on the outcome of scalp angiosarcoma is still debated, and multiple studies did not identify such correlation (4,7,9). In the present study, surgical resection margin for visible tumor was at ≥3 cm. This extended resection aimed to obtain negative surgical margin status, which coincided with literature that supported the role of curative-intent surgery, irrespective of the histological surgical margin status (16). Reconstructive options involve skin grafting, local pedicled and axial flaps, and microsurgery for complex and extensive wound reconstruction (13). If bone invasion was not present, the skull periosteum and graft skin were retained (12).

Current treatment for angiosarcomas of the scalp, face and neck typically involves surgery and neoadjuvant/adjuvant chemotherapy (4,7). In this study, it was noted that no patients survived without chemotherapy treatment, suggesting that chemotherapy played an important part in angiosarcoma research. The study by Chow et al (17) reported that monotherapy with the β-blocker propranolol was capable of reducing the proliferative index of a cutaneous angiosarcoma. In the study conducted by Singla et al (18), patients received paclitaxel-based regimens. Similarly, Schlemmer et al (19) reported that patients with advanced angiosarcoma who were treated with paclitaxel had a significantly improved survival. However, no assumptions can be made pertaining to the OS from these studies. Gebhardt et al (20) reported that complete remission of treatment-refractory advanced scalp angiosarcoma occurred following protracted intralesional interleukin-2 therapy. Young et al (21) investigated vascular-targeted agents, including bevacizumab [an anti-vascular endothelial growth factor (VEGF) antibody], axitinib [a VEGF receptor (VEGFR) tyrosine kinase inhibitor], everolimus (an mTOR inhibitor), selumetinib (a mitogen-activated protein kinase kinase inhibitor) and vadimezan (a vascular-disrupting agent) on cutaneous angiosarcoma cell lines, showing positive responses. However, a subsequent clinical study indicated that patients did not benefit from VEGF/VEGFR targeted treatment (22). Additional studies with expanded patient populations are necessary to fully examine the adjuvant natures of these agents in the setting of other therapeutic regimens. In the present study, three patients received apatinib, a tyrosine kinase inhibitor that selectively inhibits VEGFR2; however, it did not significantly improve the outcome of the patients.

The complete pathogenesis of angiosarcoma remains unknown, and it is still a matter of debate whether angiosarcomas are derived from blood or lymph vessels or their progenitors (23). In recent years, multiple studies have sought to establish the molecular pathogeneses of angiosarcomas and identify specific targets for its treatment: Wada et al (24) investigated the effect of inhibitors of the PI3K/AKT/mTOR pathway using ISOS-1 and ISO-HAS angiosarcoma cell lines, and demonstrated that the phosphoinositide-dependent kinase 1 (PDK1) inhibitor was a promising therapeutic agent. In addition, Tsuneki et al (25) identified an agent named survivin as a promising biomarker and critical regulator of cellular proliferation for angiosarcoma using human angiosarcoma specimens, and also suggested that YM155 may function as a potential therapeutic agent.

However, there are limitations to the present study, as it was retrospective regarding data collection, and could be influenced by the inherent bias of study design. The present study spanned over a period of 12 years, and has been accompanied by rapid advances in the treatment modalities. Therefore, selection bias may be involved due to the heterogeneous treatment. In conclusion, the present study indicates that scalp angiosarcoma is an aggressive malignancy with a high mortality rate and poor prognosis. Despite the fact that the exact mechanisms underlying angiosarcoma remain unclear, the research on cutaneous angiosarcoma genomics is preliminary but consistent (26).