Primary angiosarcoma of aorta: A systematic review

Abstract

Purpose:

To elucidate the epidemiology, anatomical, presentation, classification, pathology, investigative modalities, management and prognosis of primary angiosarcoma of the aorta.

Material and Methods:

A systematic review of literature from the database inception to January 2021 in PubMed and Embase, CINAHL and Cochrane Library in accordance to PRISMA was conducted. Retrieval and extraction was performed by two independent reviewers. The hierarchy of the evidence was assessed through the National Institute for Health and Care Excellence Checklist. Data were subjected to pooled prevalence analysis, Kaplan–Meier survival and test of probability using log-rank analysis. This review is registered with International Prospective Register of Systematic Reviews: RD42021231314.

Results:

82 studies with n = 123 cases met the inclusion criterion. Abdominal (45%) aorta was the commonest anatomical site with female predominance in ascending aorta (4:1) and aortic arch (2:1). The longest survival was in the ascending aorta and the shortest in the abdominal aorta [540 (interquartile range [IQR], 7–1560 days vs. 180 (IQR, 1–5730 days)], respectively. The overall median survival was 210 days (IQR, 1–5730 days) or 7 months. Lack of metastasis (47%) was a marker of longer survival (p < 0.03) irrespective of other attributes.

Conclusion:

The pathophysiology appears to be a trend of increasing fatigue, fever and weight loss associated with segmental dysfunction of the aorta projecting occlusive or destructive phenotypes. Computed tomography angiography features of volume-occupying, bulky, polypoid (intraluminal), protrusive vegetation, hyper vascular without atherosclerotic lesions are extremely suggestive of PA of the aorta at 5th and 6th decades of life.

Keywords

angiosarcoma primary angiosarcoma hemangiosarcoma: aorta systematic review

Introduction

Primary malignant tumours of the aorta (PMTAs) are rare but aggressive tumours that are sub-type of soft tissue sarcoma of endothelial nature arising from vascular or lymphatic origin.¹ The first report dates back to 1873 by Browdoski.^2,3 It is estimated that 2% of soft tissue and 5.4% of cutaneous soft tissue sarcomas are angiosarcomas. Primary angiosarcoma (PA) arising from endothelial cell of the aorta or cardiac accounts for 4.7% of all angiosarcomas.⁴ Their presentation is non-specific and commonly misdiagnosed and upon diagnosis, most patients have distant metastatic disease with poor long-term survival.⁵ Their management is currently based on anecdotal experience ranging from biopsy to surgical resection with or without adjuvant chemo- and/or radiotherapy. This is primarily due to paucity of reported cases and lack of collated clinical knowledge and consensus. In addition, there has been multiple theorem and hypothesis regarding their incidence in the clinical practice.⁴ However, to date, no consensus on their management and treatment has been formulated. Therefore, the primary aim of this systematic review is to collate and elucidate the epidemiology, anatomical incidence, clinical presentation, differential diagnosis, classification, pathology, investigative modalities, management and prognosis of PA of the aorta in the clinical practice.

Materials and methods

Search strategy

A systematic review of literature from the database inception to 14 January 2021 in PubMed, Embase, CINAHL and Cochrane Library in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was conducted.⁶ Medical Subject Headings (MeSH) terms or keywords included (“haemangiosarcoma”[All Fields] OR “hemangiosarcoma”[MeSH Terms] OR “hemangiosarcoma”[All Fields] OR “haemangiosarcomas”[All Fields] OR “angiosarcoma”[All Fields] OR “angiosarcomas”[All Fields] OR “hemangiosarcomas”[All Fields]) AND (“aorta”[MeSH Terms] OR “aorta”[All Fields] OR ("ascending”[All Fields] AND “aorta”[All Fields]) OR “ascending aorta”[All Fields]). (“haemangiosarcoma”[All Fields] OR “hemangiosarcoma”[MeSH Terms] OR “hemangiosarcoma”[All Fields] OR “haemangiosarcomas”[All Fields] OR “angiosarcoma”[All Fields] OR “angiosarcomas”[All Fields] OR “hemangiosarcomas”[All Fields]) AND (“aorta, thoracic”[MeSH Terms] OR (“aorta”[All Fields] AND “thoracic”[All Fields]) OR “thoracic aorta”[All Fields] OR (“aortic”[All Fields] AND “arch”[All Fields]) OR “aortic arch”[All Fields]). (“haemangiosarcoma”[All Fields] OR “hemangiosarcoma”[MeSH Terms] OR “hemangiosarcoma”[All Fields] OR “haemangiosarcomas”[All Fields] OR “angiosarcoma”[All Fields] OR “angiosarcomas”[All Fields] OR “hemangiosarcomas”[All Fields]) AND (“aorta, thoracic”[MeSH Terms] OR (“aorta”[All Fields] AND “thoracic”[All Fields]) OR “thoracic aorta”[All Fields] OR (“descending”[All Fields] AND “aorta”[All Fields]) OR “descending aorta”[All Fields]). (“haemangiosarcoma”[All Fields] OR “hemangiosarcoma”[MeSH Terms] OR “hemangiosarcoma”[All Fields] OR “haemangiosarcomas”[All Fields] OR “angiosarcoma”[All Fields] OR “angiosarcomas”[All Fields] OR “hemangiosarcomas”[All Fields]) AND (“aorta, thoracic”[MeSH Terms] OR (“aorta”[All Fields] AND “thoracic”[All Fields]) OR “thoracic aorta”[All Fields] OR (“thoracic”[All Fields] AND “aorta”[All Fields])). (“haemangiosarcoma”[All Fields] OR “hemangiosarcoma”[MeSH Terms] OR “hemangiosarcoma”[All Fields] OR “haemangiosarcomas”[All Fields] OR “angiosarcoma”[All Fields] OR “angiosarcomas”[All Fields] OR “hemangiosarcomas”[All Fields]) AND (“aorta”[MeSH Terms] OR “aorta”[All Fields] OR “aortas”[All Fields] OR “aortae”[All Fields]). ("haemangiosarcoma”[All Fields] OR “hemangiosarcoma”[MeSH Terms] OR “hemangiosarcoma”[All Fields] OR “haemangiosarcomas”[All Fields] OR “angiosarcoma”[All Fields] OR “angiosarcomas”[All Fields] OR “hemangiosarcomas”[All Fields]) AND (“iliacal”[All Fields] OR “iliacs”[All Fields] OR “ilium”[MeSH Terms] OR “ilium”[All Fields] OR “iliac”[All Fields]).

Bibliographies of the retrieved articles were also manually evaluated for any additional literature not identified in the primary search. All abstracts were retrieved and reviewed by two separate investigators. Studies that appeared to fulfil the eligibility criteria but had insufficient information in the abstracts were also retrieved and examined in full. The data extraction was also performed by two separate investigators, and inter-rater reliability [Cohen’s kappa coefficient was (k)] was calculated. This systematic review was also registered with International Prospective Register of Systematic Reviews (PROSPERO) National Institute for Health Research, UK, with registration (NIHR) number RD42021231314.

Selection criteria

All studies involving humans, pertained to sarcomas of the aorta and published in the English language were selected for inclusion. Published material that were experimental studies and angiosarcomas involving other organs and not primarily aortic in nature (i.e. lymphatic, bone, head and neck, visceral, cardiac and breast angiosarcomas) were excluded.

Statistical analysis

To achieve an informed conclusion and evidence-based approach, the included articles were evaluated for their validity, bias, applicability and inference using a critical appraisal tool provided by Oxford Critical Appraisal Skills Programme (CASP).⁸ Due to a lack of consistency, uniformity and comparative groups in the recruited population, meta-analysis was not plausible. However, a pooled analysis was conducted by calculation of the median value along with their interquartile range (IQR). The data output was calculated and presented with percentile of each category. Sub-group analyses were also performed using survival analysis (Kaplan–Meier) and test of probability (p-value) using log-rank test. This analysis was conducted to ascertain the impact of gender, anatomical site, surgical intervention, chemotherapy, radiotherapy and presence of metastatic disease on the survival within each category. In addition, inter-related reliability (Cohen’s kappa coefficient was (k) was assessed between the independent reviewers using a two-way random effect model. The strength of the evidence and their recommendation for future practice was also assessed through the National Institute for Health and Care Excellence (NICE) Checklist.⁹ In addition, recommendation for future research was formulated based on the current systematic review outcomes.

Current classification

The first morphological classification of the aortic angiosarcoma was established in 1972, by Salm.⁷ In this classification, there are three distinguished subtypes of tumour: (1) polypoid and intraluminal, (2) intimal and (3) adventitial. However, in 1985, Wright et al.¹ modified this classification into two distinct types of intimal (also referred to as luminal arising from intima) and mural angiosarcoma (originating from media and adventitia) with further division of the intimal type into obstructive and non-obstructive type. Thalheimer et al., based on immunohistochemistry, classified intimal subtype further into angiosarcoma (endothelial cell–specific antigens) and myofibroblastic sarcoma (mesenchymal cell–specific antigens) with mural ones demonstrating mesenchymal cell–specific antigens.⁸

WHO classification

The current suggested nomenclature by aforementioned authors remains controversial as there is currently no consensus on primary aortic angiosarcoma classifications and its subtypes. Whilst the World Health Organization⁹ highlights ‘vascular tumours’ as a separate entity in the tumours of soft tissue, their subtype such as intimal or mural remains unrecognised.¹⁰ However, Dewaele et al. demonstrated that all ‘intimal sarcomas’ demonstrate amplification of platelet-derived growth factor receptor alpha (PDGFRA) and epidermal growth factor receptor (EGFR) due to over expression of MDM2 (murine double minute 2) oncogene, a p53 target gene.^11,12 Therefore, it appears, such tumours despite their lack of recognition and adequate classification pose a shared genetic alteration. ¹²

Results

A total of n = 396 articles were retrieved (n = 122 aorta, n = 36 thoracic aorta, n = 122 ascending aorta, n = 39 descending aorta, n = 40 aortic arch and n = 37 iliac artery/aortic bifurcation) with no systematic or comprehensive review on this topic. All articles were found to be a case reports or cohort case series (class III/IIb, level C/D). The overall rate of missing data was 6%; of which, 3% were in presenting symptoms, 2% on modality of investigations and 1% on mode of treatment (1%). After application of the inclusion criteria, a total of n = 82 articles were found eligible. The PRISMA flow chart is highlighted in Figure 1. Inter-rater reliability was 0.87 for study retrieval and 0.85 for data extraction.

Figure 1.

PRISMA flow chart. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Across these n = 82 studies, there were n = 123 cases of PA with an accumulative median age of 64 years (IQR, 23–86 years) and male predominance (n = 71/123, 57%). The most common site of PA in order of prevalence was abdominal aorta (45%), thoracic aorta (37%), aortic arch (13%) and ascending (4%) and iliac aortic bifurcation (1%). The most common overall presenting symptom irrespective of the anatomical site was lower limb claudication (25%), abdominal pain or back pain (22%), weight loss (10%), renovascular hypertension (8%) and acute upper or lower limb ischaemia (6%).The investigative modality of the choice was computed tomography with or without contrast (CT/CTA) in the majority of the cases (62%). Platelet endothelial cell adhesion molecule or CD31 was the most positive immunohistochemistry assay (47%) on histopathological examination followed by anti-haemophilic factor (Factor VIII) (16%). Aortic replacement was performed in 52% of the cases with Dacron being the most common prosthetic material (47%) followed up by endarterectomy (12%) and biopsy (10%), respectively. Chemotherapy was undertaken in 28% of the cases and 16% had radiotherapy. The overall rate of distant metastases was 53% (n = 66) of which visceral organs (mainly, the spleen, kidney, adrenal, pancreas and liver) were most commonly affected (34%) followed by long bones and vertebrae (23%). The overall median survival was 210 days (IQR, 1–5730 days) or 7 months (Table 1).

Table 1.

The overall outcome of n = 123 cases of PA of the aorta with median survival of 210 days (IQR, 1–5730 days).

Categories	%	Categories	%
Anatomical site		Procedures
Ascending aorta	4%	Aortic replacement	52%
Aortic arch	13%	No intervention	16%
Thoracic aorta	37%	Endarterectomy	12%
Abdominal aorta	45%	Biopsy	10%
Aortic bifurcation/iliac	1%	Embolectomy/thrombectomy	5%
		Endovascular (stent)	4%
Presentation		Adjuvant therapies
Lower limb claudication	25%	Chemotherapy	28%
Abdominal/back pain	22%	Radiotherapy	16%
Weight loss	11%	Chemotherapy and radiotherapy	8.5%
Renovascular hypertension	8%	Surgery and/or chemotherapy and radiotherapy	47%
Acute limb ischemia (upper or lower)	8%	Metastatic sites
Fever	6%	Visceral	34%
Fatigue	6%	Bone	23%
Upper limb claudication	5%	Skin	17%
Dyspnoea	4%	Lung	14%
Stroke	4%	Brain	6%
Others (headache/anaemia/per rectal bleed)	2%	Lymph node	4%
		Expanding aneurysm or endoleak	2%
Investigative modality		Immunohistology assay
CT/CTA	62%	CD31	47%
MRI/MRA	21%	Factor VIII	16%
PET	10%	Fil-1	13%
TEE	4%	Vimentin	12%
Biopsy	3%	CD 34	5%
		Desmin	4%
		Keratin	3%

PA: primary angiosarcoma; IQR: interquartile range; CT/CTA: computed tomography with or without contrast; MRI/MRA: magnetic resonance imaging with or without contrast; PET: positron emission tomography; TEE: transoesophageal echocardiogram.

Ascending aorta

The median age of this group was 60 years (IQR, 47–85), with female predominance (4:1). The most common presenting symptom was dyspnoea and acute limb ischaemia of the upper limb (80%) followed by stroke (20%). CTA and transoesophageal echocardiogram (TEE) were the investigative modalities of choice, and metastasis disease was commonly noted in viscera and brain (60%). This group demonstrated the longest survival at the median of 540 days (IQR, 7–1560) with the highest adjuvant chemotherapy regimen (Table 2).^5,13-26

Table 2.

Comparative presentation of various categories of primary angiosarcoma based on anatomical sites.

Anatomical site	Age (years)	Gender F:M	Presentation	Diagnosis	Tumour marker
Ascending aorta	60 (IQR, 47–85)	4:1	Dyspnoea and ALI* (80%)	CTA 100%	CD31/Factor VIII/vimentin
Ascending aorta	60 (IQR, 47–85)	4:1	Stroke (20%)	Adjuvant MRI/TEE (100%)	CD31/Factor VIII/vimentin
Aortic arch	56 (IQR, 32–85)	2:1	CLI (38%)	CTA (87%)	CD31/Factor VIII/vimentin/CD34
			Hypertension (25%)	Adjuvant MRI/TEE (56%)
			Stroke (19%)
			Dyspnoea (12%)
Thoracic aorta	64 (IQR, 23–82)	1:1	Back/abdominal pain and CLI (71%)	CTA 90%	CD31/Factor VIII/vimentin/Fil-1/desmin
			Weight loss (16%)	Adjuvant MRI/PET/TEE (59%)
			ALI** (16%)
			Hypertension (16%)
Abdominal aorta	67 (IQR, 42–86)	1:1	Back/abdominal pain and CLI (70%)	CTA (84%)	CD31/Factor VII/vimentin/Fil-1/desmin
			Fever and fatigue and weight loss (34%)	Adjuvant MRI/PET (42%)
			ALI** (4%)
Aortic bifurcation/iliac	63 (IQR, 31–82)	3:1	Chronic/ALI** (100%)	CTA (100%)	CD31/Factor VIII/Fil-1
Aortic bifurcation/iliac	63 (IQR, 31–82)	M:F	Fever/fatigue/weight loss/abdominal pain (63%)	Adjuvant MRI/PET (10%)	CD31/Factor VIII/Fil-1

Anatomical site	Mets	Treatment	Chemotherapy/radiotherapy	Survival in days
Ascending aorta^1,2	Visceral and brain (60%)	Aortic replacement (60%)	40%/none	540 (IQR, 7–1560) (18 months)
Ascending aorta^1,2	Skin (20%)	Biopsy (40%)	40%/none	540 (IQR, 7–1560) (18 months)
Aortic arch	Visceral and brain (68%)	Aortic replacement (68%)	6%/6%	195 (IQR, 1–1620) (6.5 months)
	Brain and skin (24%)	None (12%)
	Lung (18%)	Biopsy (6%)
		EDA* (6%)
Thoracic aorta	Visceral and bone (71%)	Aortic replacement (45%)	22%/9.5%	195 (IQR, 1–1800) (6.5 months)
	Skin (19%)	EDA* (19%)
	Lung (14%)	No procedure (16%)
	Lymph node (7%)	Biopsy (11%)
		Embolectomy/stent (14%)
Abdominal aorta	Visceral and bone (61%)	Aortic replacement (52%)	34%/22%	180 (IQR, 1–5730 (6 months)
	Skin (22%)	None (19%)
	Lung (17%)	EDA (12%)
	Lymph node (7%)	Stent (4%)
Aortic bifurcation/iliac	Visceral and bone (61%)	Aortic replacement (72%)	27%/18%	240 (IQR, 30–1590) (8 months)
	Skin (18%)	EDA (9%)
	Skin (9%)	Biopsy (9%)

CTA: computed tomography angiography; EDA: endarterectomy; IQR: interquartile range; MRI: magnetic resonance imaging; PET: positron emission tomography; TEE: transoesophageal echocardiogram.

*Acute limb ischaemia of the upper limb. ** Acute limb ischaemia of the lower limb.

Aortic arch

The median age of this group was 56 years (IQR, 32–85), with female predominance (2:1). The most common presenting symptom was chronic upper limb ischaemia (CLI) (38%), hypertension (25%) and stroke (19%). CTA and MRI/A were the investigative modalities of choice, and metastasis disease was commonly noted in viscera and brain (68%). Aortic replacement was conducted in 68% of cases with median survival of 195 days (IQR, 1–1620 days) (Table 2).^{4,14-21,23-25}

Thoracic aorta

The median age of this group was 64 years (IQR, 23–82), with equal gender distribution. The most common presenting symptom was back pain and/or abdominal pain associated with lower limb claudication (Leriche syndrome) (71%). CTA and MRI were the investigative modalities of choice, and metastasis disease was commonly noted in viscera and bones (vertebral and long bones) (71%). Aortic replacement, endarterectomy and embolectomy were the main procedures with median survival of 195 days (IQR, 1–1800) (Table 2).^{4,15,18,19,27-38,39-44.}

Abdominal aorta

The median age of this group was 67 years (IQR, 42–86) with equal gender distribution. The most common presentation was back pain and/or abdominal pain associated with lower limb claudication (Leriche syndrome) (61%). CTA was the investigative modalities of choice, and metastasis disease was commonly noted in viscera and brain (60%). Adjuvant chemotherapy and radiotherapy (56%) with aortic replacement and endarterectomy resulted in the median survival of 180 (IQR, 1–5730) (Table 2).^{3,5,8,14,15,23,30-32,34,38,45-76}

Aortic bifurcation/iliac

The median age of this group was 63 years (IQR, 31–82) with male predominance (3:1). The most common presentation was lower limb claudication (Leriche syndrome) and acute lower limb ischaemia (100%). CTA was the investigative modalities of choice, and metastasis disease was commonly noted in viscera and brain (61%). Adjuvant chemotherapy and radiotherapy (45%) with aortic replacement resulted in the median survival of 240 days (IQR, 1–1590) (Table 2).^{19,23,31,35,77-80}

Sub-group analysis

A survival analysis was performed based on hypothesis that independent variables of anatomical site, gender, surgical approach, adjuvant chemotherapy, radiotherapy and metastatic disease have no impact on survival (days) (Kaplan–Meier and log-rank test). The test of probability did not reach any statistical significance for an objective inference on anatomical site, gender, surgical approach, adjuvant chemotherapy and radiotherapy (p > 0.05) (for supplementary information, see Figures 3 to 5). However, the lack of metastatic disease was statistically significant for longer survival at the time of presentation (p < 0.03) (Figure 2).

Figure 2.

Comparative analysis of presence versus lack of distant metastatic disease at the time of presentation (Kaplan–Meier survival analysis rank test) (p < 0.03) (median value of 210 vs. 430 days).

Discussion

The outcome of this systematic review highlights that PA of the aorta is much rarer than previously expected, and the aortic arch is affected in 5th decade of life and at 6th decade for the rest of the aorta. Contrary to prior inference about male predominance,³ it appears that PA of ascending aorta and aortic arch is more common in females, whilst such is more apparent in males at aortic bifurcation with rest exhibiting equal gender distribution (thoracic and abdominal aorta) (Table 2). Anatomical distribution of the aortic PA is more common in the abdominal aorta (45%) followed by the thoracic aorta (37%) conflicting prior report suggesting the thoracic aorta to be the predominant anatomical site.⁵

The presentation appears to be non-specific mimicking signs and symptom of acute and chronic vascular pathologies ranging from Leriche syndrome to stroke and renovascular hypertension. However, apart from the ascending aorta, there appears to be a pattern of weight loss, fatigue, fever and pain (abdominal or back) associated with aforementioned cardinal symptoms. This trend is more profound in the distal aorta (aortic bifurcation: 63% vs. thoracic aorta: 16%) compared to proximal sites (Table 2).

The investigative modality of the choice appears to be computed tomography angiography (CTA) and prior to CTA availability, conventional digital subtraction angiography (DSA). Depending on the anatomical site, adjuvant TEE and/or magnetic resonance imaging with or without contrast (MRI/MRA) was also used. Qualitative information gathered from MRI/MRA as an adjuvant investigation is vital as such, and it could discriminate atherosclerotic plaque from intraluminal lesion, enhance vessel wall and delineate extravascular spread and immediate soft tissue.^18,81 In addition, few features and patterns were commonly noted in majority of CTAs in this systematic review. Firstly, these tumours appear volume-occupying and bulky limiting the luminal diameter. Secondly, they appear polypoid (intraluminal) and are attached with a stalk to the aortic wall. Thirdly, they appear hyper enhanced on arterial phase due to their vascularity that makes them separable from atherosclerotic plaques. Fourthly, they sometimes mimic protrusive vegetation or nodular soft tissue component. Finally, peri-aortic infiltration of the mass suggests tumour rather than thrombus or atherosclerotic disease on CTA. The use of positron emission tomography (PET) scan as a stand-alone modality remains controversial as the uptake or so called hot spots could be mistaken for inflammatory or infective disease resulting in an incorrect diagnosis of aortitis.⁵³

Upon diagnosis, the surgical dictum mandates surgical resection of the tumour, and unsurprisingly, survival appears to be longer in those without metastatic disease at the time of presentation (p < 0.03). The feasibility of such approach is embedded in the patient’s physical, physiological and extent of the disease. Distant metastasis occurs in viscera from all anatomical sites, but the brain is predominant second site in the aortic arch and ascending aorta and bones (vertebral and long bones) from the thoracic aorta. Surgical excision of the tumour was not possible in almost 31% of cases in whom initial presentation led to diagnosis of acute limb ischaemia (ALI) and/or chronic limb ischaemia (CLI) instead of PA of aorta resulting in endarterectomy, thrombectomy, embolectomy and stenting. The subsequent impact of this misdiagnosis resulted in no intervention in 16% of cases. This highlights the vital role of specimen examination obtained from thrombectomy and embolectomy along with suspicious looking vegetation from endarterectomies. Overall, 52% of cohort had an aortic replacement with majority of them using Dacron as the prosthetic conduit of the choice.

The capillaries and venules within tumour stained positive for platelet endothelial cell adhesion molecule (CD31) (47%) and anti-haemophilic factor (Factor VIII) antigen (16%). The endothelial markers outlined cellular ‘ghosts’ and chicken wire–like patterns with areas of central necrosis. Some of the tumours with atypical eosinophilic cells with low mitotic index were positive for vimentin, desmin, Fli-1 and CD34^{23, 82} (Table 1).

The role of adjuvant chemotherapy and/or radiotherapy remains unclear.²² A large meta-analysis based on individual patient data demonstrated doxorubicin-containing agents statistically lower the probability of disease relapse (p = 0.003) and result in longer survival (p = 0.001). However, this only translates to 4% survival rate after 10 years in clinical practice that appears negligible for a disease with overall cumulative survival of 7 months or at best 18 months (ascending aorta).⁸³ Furthermore, the Italian Sarcoma Group demonstrated only 17.6% improvement over 48 months’ period.⁸⁴ Radiotherapy appears to have minimal impact, and overall, it appears that adjuvant therapy (chemo-radiotherapy) might be justified when local resection of the tumour is not complete. This could also be applicable to palliative disease as well.⁸⁵ According to the Cochrane Library, the role of paclitaxel is currently being evaluated and results are pending.

The aetiology for PA of aorta remains elusive to this date. The earliest recorded hypothesis suggests that the use of prosthetic material (grafts) could result in malignancy (angiosarcoma) within a month of its use. However, such theorem was only evaluated in rats, and since 1958, there has been significant advancement in production of prosthetic conduits.⁸⁶ To date, various factors such as radiotherapy and exposure to chemicals such as arsenic, vinyl chloride and thorium dioxide have been considered as a cause but direct association or causal link is still pending. The Li–Fraumeni syndrome (LFS), first reported in 1969 as hereditary cancer predisposition syndrome with over expression of MDM2 (murine double minute 2) oncogene, a p53 target gene appears to have common genetic pathway with that of PA of the aorta.²¹ Furthermore, there are suggestions that Stewart–Treves syndrome could also contribute to PA of the aorta; however, they are mainly limited to lymphatics or cutaneous angiosarcomas.⁸⁷

Patient presentation (signs and symptoms) are not conclusive or objective for diagnosis of PA of the aorta. However, there appears to be a trend of increasing fatigue, fever and weight loss associated with ALI and/or CLI once the disease is more distal. This usually increases the suspicion of aortitis and vasculitis. Therefore, PA of the aorta should be included in the differential diagnosis at 5th or 6th decade of life. CTA features of volume-occupying, bulky, polypoid (intraluminal), protrusive vegetation, hyper vascular without atherosclerotic lesions are extremely suggestive of PA of the aorta. In addition, any aforementioned features on retracted specimens (embolectomy, thrombectomy and endarterectomy) should be sent for histological evaluation. Full resection in view of patient functional, physiological and metastatic disease is highly advocated (class III/IIb, level C), and use of adjuvant modalities (chemotherapy and radiotherapy) requires further evaluation.

Conclusion

PA is a rare but devastating aortic pathology that mainly affects the population at their 5th and 6th decades of life. The aetiology is poorly understood; further, it has non-specific clinical presentation. The pathophysiology of the disease is primarily limited to segmental dysfunction of the aorta and iliac systems and is projected by either occlusive or destructive phenotypes. These phenotypes correlate with initial presentation of either symptomatic aneurysmal degeneration or end organ ischaemia.

This review emphasises the importance of the early diagnosis to provide a window of opportunity for acceptable surgical excision, in order to excel the survivals. The overall aim of this review was to collate all the available descriptive data and reach an informed approach. This has created a platform for future work to develop a prognostic tool that can help with the management of these complex and rare presentations. Furthermore, development of an international registry for PA of aorta will be of high value for a comprehensive approach to this disease.

Supplemental Material

sj-pdf-1-std-10.1177_09564624211007260 – Supplemental Material for Primary angiosarcoma of aorta: A systematic review

Supplemental Material, sj-pdf-1-std-10.1177_09564624211007260 for Primary angiosarcoma of aorta: A systematic review by Ali Kordzadeh, Alan Askari, Ali Navi, Sandeep Patel, Ali D Parsa and Alexandros Charalabopoulos in Vascular

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Ali Kordzadeh

Supplemental material

Supplemental material for this article is available online.

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