Introduction
Angiosarcoma is a rare and highly aggressive malignant tumour of endothelial origin, accounting for less than 2 per cent of all soft tissue sarcomas.Reference Houpe, Seger, Neill, Kang, Hocker and Alam1 It predominantly arises in the skin and soft tissues of the head and neck region, particularly in the scalp and face of elderly individuals. However, its presence in the nasal cavity and paranasal sinuses is exceedingly rare, with only a few cases documented worldwide.
Among reported sinonasal angiosarcomas, primary involvement of the nasal septum is particularly uncommon. Previous cases have primarily described angiosarcomas originating from the nasal cavity, maxillary sinus and ethmoid sinus, often exhibiting extensive local invasion and poor prognosis.Reference Kimura, Tanaka and Furukawa2–Reference Kou and Cheng4 The management of sinonasal angiosarcoma is complicated by the lack of diagnostic criteria and standardised treatment guidelines. This report reviews previously documented cases to understand their clinical presentation, imaging characteristics, histopathological features, treatment approaches and patient outcomes. The analysis highlights the unique aspects of the case, emphasising its distinct clinical course and limited local involvement.
Due to its non-specific symptoms, including recurrent epistaxis and nasal obstruction, nasal septal angiosarcoma is frequently misdiagnosed as a benign vascular lesion such as haemangioma, pyogenic granuloma or inverted papilloma, leading to delayed diagnosis and suboptimal treatment outcomes.Reference Gravvanis, Lagogiannis, Kyriakopoulos, Keramidas, Kakiopoulos and Tsoutsos5, Reference Chai, Feng, Li, Yan, Tan and Weng6 Histopathological confirmation is essential, as angiosarcoma is characterised by marked endothelial proliferation, irregular vascular channels and high mitotic activity. Immunohistochemical markers such as CD34 and CD31 can aid in distinguishing angiosarcoma from other vascular tumours.Reference Cao, Wang, He and Fang7 Given its high recurrence rate and metastatic potential, a multimodal treatment approach incorporating surgery, radiotherapy and emerging targeted therapies is typically required for optimal disease control.Reference Weidema, Versleijen-Jonkers, Flucke, Desar and van der Graaf8
This case report highlights diagnostic and therapeutic challenges associated with primary nasal septal angiosarcoma, underscores the necessity for early suspicion and histopathological confirmation and contributes to the ongoing literature review of sinonasal angiosarcoma cases, providing a broader perspective on this rare malignancy.
Case presentation
A 46-year-old female with no significant medical history presented with intermittent left-sided epistaxis and nasal congestion that persisted for several months. She denied any history of nasal trauma, previous nasal surgery or smoking. Using a nasal endoscope, a 1.0 × 0.5 cm protruding lesion was identified on the left anterior nasal septum (Figure 1).
(A) Pre- and (B) post-operative endoscopic photograph of the mass on the left anterior nasal septum.
Routine laboratory investigations including complete blood count and coagulation profile, and inflammatory markers were unremarkable. Pre-operative imaging was not performed because the lesion was small and the patient declined additional imaging. Given the clinical findings, an excisional biopsy was performed under local anaesthesia with 1:100,000 epinephrine infiltration. Intra-operatively, a well-demarcated haemangioma-like mass was identified, without ulceration or necrosis. The septal cartilage and surrounding mucosa appeared intact. The lesion was excised completely on gross inspection and bleeding was successfully controlled.
In Figure 2, histopathological examination revealed proliferating atypical endothelial cells forming irregular vascular channels, with moderate nuclear pleomorphism and a high mitotic rate (24 mitoses per 10 high-power fields). Focal necrosis was observed, accounting for approximately 15 per cent of the tumour area. Although the lesion appeared completely excised macroscopically, histopathology demonstrated diffusely infiltrative margins with residual tumour at the resection edges. Lymphatic, vascular and perineural invasion were absent.
Histopathological features of angiosarcoma. (A) The tumour demonstrates high cellularity with markedly atypical, pleomorphic endothelial cells arranged in solid sheets and irregular vascular channels. (B) Extensive areas of geographic necrosis are observed, indicating aggressive tumour behaviour. (C) Immunohistochemical staining reveals diffuse and strong positivity for CD34, supporting endothelial differentiation. (D) Ki-67 immunostaining highlights a high proliferative index in tumour cells, consistent with the highly proliferative nature of the neoplasm.
Figure 2 Long description
The image A showing a purple and pink stained tissue section with many small dark-purple nuclei, multiple irregular pale spaces and several red areas. A white scale bar is present at the lower right. The image B showing a purple and pink stained tissue section with a large pale region on the right and denser purple tissue on the left. Several red areas are scattered. A white scale bar is present at the lower right. The image C showing a pale gray background with a light brown branching network pattern across the field. A white scale bar is present at the lower right. The image D showing a pale background with numerous small brown stained dots distributed across the field, with lighter open spaces between clusters. A white scale bar is present at the lower right.
Immunohistochemical staining demonstrated strong CD34 positivity, confirming an endothelial origin of the tumour. The Ki-67 proliferation index was approximately 60 per cent, suggesting high proliferative activity. Desmin and actin were negative, ruling out myogenic differentiation. Based on these findings, the patient was referred to an oncology centre at the outside hospital. Post-operative staging with PET-CT performed at an outside hospital showed no regional lymph node or distant metastasis. Given the positive margins and high proliferative index, adjuvant radiotherapy was administered. At 12 months’ follow-up, there was no evidence of local recurrence.
This case report presented the findings derived retrospectively from the patient’s medical records. Therefore, this study did not require an Informed Consent statement, and ethical approval was waived by the Institutional Review Board (exempt number SC25ZISE0029).
Discussion
Primary angiosarcoma of the nasal septum is an exceptionally rare malignancy, with few cases documented in the literature. Most previously reported cases of sinonasal angiosarcoma involved extensive local invasion, affecting the paranasal sinuses.Reference Chai, Feng, Li, Yan, Tan and Weng6 Our case was rare in that the angiosarcoma was confined solely to the nasal septum without bony destruction or spread to adjacent tissues, distinguishing it from previously reported sinonasal angiosarcomas.Reference Chai, Feng, Li, Yan, Tan and Weng6, Reference Cao, Wang, He and Fang7
A review of previously reported sinonasal angiosarcoma cases revealed significant heterogeneity in clinical presentation and prognosis (Table 1). While some patients, such as those reported by Kimura et al. and Kurien et al., achieved long-term survival following surgical resection.Reference Kimura, Tanaka and Furukawa2, Reference Kurien, Nair and Thomas3 Others, such as the case reported by Chai et al., demonstrated lymphatic metastasis despite no initial distant spread.Reference Chai, Feng, Li, Yan, Tan and Weng6 These findings emphasise the need for early diagnosis and close follow-up.
Previously reported sinonasal angiosarcoma
Table 1 Long description
The table summarizes 10 published cases plus a current case of sinonasal angiosarcoma, listing patient sex and age, tumour site, imaging findings, pathology, treatment, follow-up, recurrence, and mortality. Ages range from 8 to 70 years, with most patients male; the current case is a 46-year-old female with a nasal septum tumour. Tumours most often involve the maxillary sinus, nasal cavity, turbinates, or middle meatus, with imaging commonly describing a mass and, in several cases, bone erosion or destruction. Pathology descriptions frequently note irregular or anastomosing vascular channels with pleomorphic, hyperchromatic endothelial cells, and several reports include endothelial markers such as CD31, CD34, ERG, or Factor VIII; reported proliferation indices vary, including about 30 to 40 percent and 60 percent in the current case. Treatment is usually surgery alone or surgery with post-operative radiotherapy; one case received multiple surgeries plus combined chemo-radiotherapy and radiosurgery. Follow-up ranges from 8 months to 7 years when reported, and most cases report no recurrence. Notable exceptions include one patient with a fifth recurrence who died, and another with lymphatic metastasis at 3 years; several recent reports have missing outcome data, limiting comparisons.
CT = computed tomography; MRI = magnetic resonance imaging; NA = not available
Given its nonspecific clinical presentation, nasal septal angiosarcoma is frequently misdiagnosed as a benign vascular lesion, particularly haemangioma, pyogenic granuloma or inverted papilloma. The papillomatous appearance of the lesion in our case raised the possibility of a lobular capillary haemangioma, one of the most common benign vascular tumours in the nasal cavity. However, haemangiomas typically exhibit well-circumscribed margins and lack infiltrative behaviour with a lower mitotic index, which can distinguish them from angiosarcoma.Reference Cao, Wang, He and Fang7
Due to a high recurrence rate and metastatic potential of nasal septal angiosarcoma, surgical resection alone is often insufficient. While radiotherapy and chemotherapy remain standard adjuvant therapies, recent advances in targeted therapy and immunotherapy offer promising alternatives.Reference Weidema, Versleijen-Jonkers, Flucke, Desar and van der Graaf8
Angiosarcomas are highly vascular tumours, making angiogenesis-related pathways a key therapeutic target. Vascular endothelial growth factor receptor (VEGFR) inhibitors such as bevacizumab have shown limited efficacy as monotherapy. They might provide benefits when combined with paclitaxel. Similarly, pazopanib, a multi-targeted tyrosine kinase inhibitor targeting VEGFR1, VEGFR2 and VEGFR3, has demonstrated moderate clinical benefit, with a response rate of 20 per cent and median progression-free survival of 3 months.Reference Kollár, Jones, Stacchiotti, Gelderblom, Guida and Grignani9
In addition to VEGF-targeted therapies, immune checkpoint inhibitors such as pembrolizumab and ipilimumab have been investigated in angiogenic tumours. One study showed that 30–40 per cent of angiosarcomas expressed PD-L1, suggesting that checkpoint inhibitors could be a viable therapeutic approach for a subset of patients.Reference D’Angelo, Mahoney, Van Tine, Atkins, Milhem and Jahagirdar10 While data on angiosarcoma are limited, preliminary studies suggest that ICIs may provide durable responses in tumours with high PD-L1 expression.Reference D’Angelo, Mahoney, Van Tine, Atkins, Milhem and Jahagirdar10 A phase II clinical trial is currently investigating avelumab combined with paclitaxel for locally advanced and metastatic angiosarcoma.Reference D’Angelo, Mahoney, Van Tine, Atkins, Milhem and Jahagirdar10
Another emerging target is the PI3K/AKT/mTOR signalling pathway, which plays a crucial role in tumour proliferation and angiogenesis. mTOR inhibitors such as everolimus and temsirolimus have demonstrated an ability to inhibit tumour growth in preclinical models, although their clinical efficacy remains under investigation.Reference Weidema, Versleijen-Jonkers, Flucke, Desar and van der Graaf8 Combination therapy using mTOR and MEK inhibitors has shown promising results, significantly reducing tumour growth in angiosarcoma cell models.Reference Weidema, Versleijen-Jonkers, Flucke, Desar and van der Graaf8 In addition, recent genomic studies have identified recurrent mutations in PIK3CA and PLCG1, suggesting that PI3K pathway inhibitors could be a potential therapeutic approach.Reference Huang, Zhang, Sung, Chen, Kao and Agaram11 Some angiosarcomas also exhibit RAS/RAF/MEK pathway alterations, making MEK inhibitors another possible treatment strategy.Reference Huang, Zhang, Sung, Chen, Kao and Agaram11 However, clinical responses to these inhibitors have been variable, highlighting the need for biomarker-driven treatment selection.Reference Huang, Zhang, Sung, Chen, Kao and Agaram11
Despite these promising developments, angiosarcoma remains a challenging malignancy to treat, showing variable response rates to targeted therapies. Further research is needed to identify biomarkers that can predict treatment response and to develop more effective therapeutic strategies.Reference Huang, Zhang, Sung, Chen, Kao and Agaram11
A key limitation of this case report is the lack of pre-operative cross-sectional imaging (computed tomography [CT] and/or magnetic resonance imaging [MRI]), which is widely regarded as standard practice prior to biopsy or excision of sinonasal vascular lesions. In this case, imaging was not obtained because the lesion was small and the patient declined additional investigations. To mitigate this limitation, post-operative staging with positron emission tomography (PET)-CT demonstrated no regional lymph node or distant metastasis, and the patient received adjuvant radiotherapy owing to positive margins. She remains disease-free at 12 months.
Conclusion
We present an exceptionally rare case of primary angiosarcoma confined to the nasal septum with no evidence of adjacent tissue invasion or identifiable predisposing factors. This report highlights the importance of maintaining a high index of suspicion for patients presenting with recurrent epistaxis and nasal congestion, given the potential for misdiagnosis as a benign vascular lesion. Due to the aggressive nature of angiosarcoma, a multidisciplinary approach incorporating surgery and radiotherapy is often required, with systemic therapies considered for optimising patient outcomes. Prospective data remain limited in sinonasal angiosarcoma, and collaborative registries may help define optimal multimodal strategies.
Competing interests
There are no potential conflicts of interest to report.
Acknowledgements
None
Author contributions
Y.J.K.: Conceptualisation, Data curation, Formal analysis, Writing – original draft, Writing – review & editing. M.S.K.: Data curation, Formal analysis. Y.S.P.: Data curation, Formal analysis. J.H.C.: Conceptualisation, Methodology, Project administration, Visualisation, Writing – original draft, Writing – review & editing. All authors have read and agreed to the published version of the manuscript.
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