Primary angiosarcoma of superior vena cava: an unexpected diagnosis after an oncological emergency

Abstract

Angiosarcoma (AS) is a rare malignant tumour representing 1%–2% of all sarcomas. Primary AS of superior vena cava (SVC) was reported in two cases worldwide. We report a 69-year-old woman with neck discomfort, headache and dyspnoea for 3 months. CT angiography showed thrombosis in SVC and brachiocephalic veins resulting in an SVC syndrome. The patient began anticoagulant therapy and underwent balloon angioplasty with clinical improvement. Additionally, a positron emission tomography scan confirmed the presence of a mediastinal mass involving the SVC locally. The tumour was excised and a prosthesis was placed on the SVC. Histology revealed a heterogeneous tumour matrix, either myxoid and composed by fusiform cells with vimentin, homogeneous CD31 and a 30% Ki67 immunoexpression, supporting the diagnosis of an AS. Due to multiple complications, the patient never started chemotherapy, and after tumour recurrence, she died within 5 months after diagnosis.

Background

Angiosarcoma (AS) is a rare and aggressive tumour of endothelial origin, lymphatic or vascular endothelial cell, counting for less than 2% of all human tissue sarcomas. AS can occur in any location of the body, being the cutaneous lesions the more common.^{1 2} Its extension to the superior vena cava (SVC) is mostly related to a primary site in the right atrium with the involvement of the adjacent vascular structure, sometimes manifesting as an SVC syndrome either by invasion or compression of the vascular structures and prothrombotic state associated with the tumour.^{3 4} The primary AS of SVC is very rare, with only two cases reported in the literature.^{5 6}

The diagnosis is usually postponed due to its rarity and the fact that the signs and symptoms are nonspecific. In addition, AS has a high rate of recurrence and local metastasis, making its prognosis poor. From a therapeutic point of view, depending on the site, size, resectability, histological type and degree of dissemination, options include surgery, radiotherapy and chemotherapy, in all cases with wide response variability.^{7 8}

Here, we describe a case of a rare tumour in an unusual location, more specifically in a vein subject to high flow and blood pressure that rarely develops any neoplastic process. We briefly discuss the AS treatment model and its application to the standard and current case.

Case presentation

The patient is a 69-year-old Caucasian woman, independent for daily activities, who presented to the emergency department with neck discomfort, headache and dyspnoea for the past 3 months. On the medical observation, she was a sensitive and non pulsatile bilateral swelling of the neck with a heart rate of 93 beats per minute, blood pressure of 145/85 mm Hg and respiratory rate of 25/min. No significant changes were found in the laboratory examination. In its turns, chest X-ray revealed an elevation of right haemidiaphragm and cervical ultrasound described an increase in the number of ganglionic formations along the jugular-carotid and cervical chains in a probable inflammatory association. CT angiography showed thrombosis in the proximal third of the SVC, extending to the right brachiocephalic venous trunk. The examination also allowed the visualisation of an ovoid area with soft-tissue densities, with about 27×20 mm of larger axial axes, without cleavage planes with the SVC that could represent a thrombus (figure 1). There was also a partial thrombosis of the distal third of the right internal jugular vein, just before the confluence with the subclavian vein and a small right pleural effusion and pulmonary nodules. The SVC syndrome was diagnosed; she started therapeutic doses of enoxaparin and admitted for further aetiological studies. The patient had a medical history of myocardial infarction 18 years ago and dyslipidaemia, there was no family or personal history of cancer.

Figure 1.

Homogeneous conglomerate adhered to the proximal third of the SVC, suggesting it is a thrombus with 27×20 mm (red circle). SVC, superior vena cava.

Considering that the patient remained symptomatic after 4 days with anticoagulation, it was decided to perform a balloon angioplasty that went without any complications and with good clinical response. A body CT was performed 4 days after the angioplasty revealed densification of the right lower lung, small nodules (<1 cm) in the medial lobe and lingula and right pleural effusion. The cytological evaluation of pleural fluid did not, reveal the presence of neoplastic cells. The study involved breast and thyroid ultrasound, as well as fiberoptic bronchoscopy in order to exclude any pathology, namely oncology, all results were normal.

All laboratory serologies and thrombophilia studies were negative, as well as protein electrophoresis and immunofixation electrophoresis. Due to the known correlation between gastric tumours and hypercoagulability syndromes, an upper endoscopy was also performed, which showed no changes.

Proceeding with the study, the patient developed a sudden back pain that preceded the loss of motor and sensory function in the four limbs, with distal predominance. An urgent MRI of the cervicothoracic vertebral column was performed, which showed vertebral subdural haematoma, with irregular and asymmetric distribution, bulkier between C7 and C3 in the anterior level and left posterolateral between D3 and D6, causing marked spinal compression, with more defined medullary oedema between C5 and C7. She underwent emerging decompression surgery. Postoperative MRI showed regression of the vertebral subdural collection previously present, but with the persistence of intramedullary hyper signal from C5 to D4.

The MRI imaging findings, not previously detected on CT, were the thickening of the SVC wall in contiguity with the thrombotic finding point (figure 2).

Figure 2.

MRI detected thickening of the superior vena cava (SVC) wall (red arrow), as found after a vertebral study of a probable subdural haematoma.

After clinical stabilisation, a positron emission tomography (PET) scan was requested, showing a hypermetabolic lesion in the SVC suggestive of malignant neoplastic and adenopathy in the right lower parasternal region (figure 3). The case was discussed in a multidisciplinary team and made an intravascular approach guided by CT with the intention of biopsy of the lesion. Four millimetric fragments were obtained for histological study, revealed diffuse involvement by neoplasia composed of spindle cells, rounded dissociated from the fibromuscular wall of the vein and with areas of fibrinoid necrosis. Immunohistochemistry showed neoplastic cells with diffuse expression of Cam 5.2, vimentin, a focal expression for AE1/3 with no expression for calretinin, CK5/6, p63, CK7, TTF1, caldesmon or desmin. The smooth muscle actin label was focal and interpreted as positive in myofibroblasts. The most likely diagnosis by histology was carcinoma of the thymus. On revaluation of the case with the surgical team, it was considered that using mediastinoscopy would involve some risks, with low potential benefit. Furthermore, taking into consideration that the lesion seemed to be circumscribed to the SVC and possibly to an adjacent ganglion, it was assumed the surgical approach as potentially curative.

Figure 3.

PET scan revealed a hypermetabolic lesion in the superior vena cava, bringing together imaging features suggestive of a high-metabolic malignant neoplastic lesion (maximum standardized uptake value of 6.3) and hypermetabolic adenopathy of the right lower parasternal (SUVmax. 4.3). PET, positron emission tomography.

The mediastinal mass and the adjacent mediastinal ganglion were excised, and a Gore-Tex tube prosthesis replaced the SVC. The postoperative pathological study revealed malignant mesenchymal neoplasia, with involvement and invasion of the vascular structure of the SVC, of the surrounding adipose tissue, as well as the location on the margin of circumferential resection. The neoplasm had a vaguely storiform pattern, composed of spindle cells, eosinophilic cytoplasm with indistinct limits and oval or elongated nuclei, with granular chromatin and evident nucleolus. Presence of three mitoses per 10 high power fields (HPF). Absence of lymphovascular invasion. Hyaline stromal bundles involving neoplastic cells were observed. The immunohistochemical study revealed positivity of neoplastic cells for vimentin, CD31, CD34, smooth muscle actin, S100 and Cam5.1 (focal), with Ki67 of 30% and negativity for CKAE1/AE3, CK7, CK5.6, CD56, caldesmon, desmin, Wt1, calretinin, PD-L1 and TTF1 (figure 4). From the surrounding adipose tissue, 22 lymph nodes without metastatic disease were isolated, preserving the architecture. The mediastinal ganglion did not present metastatic disease. The final diagnosis demonstrated that it was an AS of the SVC.

Figure 4.

Angiosarcoma developed on a venous vessel wall. Tumourous cells are large with eosinophilicor clear cytoplasm and anisocariosis with 10 mitosis /10 HPF, together with 30% Ki67 immunoexpression; tumourous matrix was heterogeneous, either myxoid and composed by fusiform cells. Homogeneous CD31 was verified in tumourous cells. (A) venous vessel wall with angiosarcoma invasion, HE×40; (B) tumourous cells with clear and eosinophilic cytoplasm in fibro—myxoid matrix; (C) tumouruous cells expressing CD31×400. HPF, high power fields.

Differential diagnosis

The SVC syndrome tends to present neoplasms between 60% and 85%, namely, non-small cell lung carcinoma (50%), small cell lung carcinoma (25%), non-Hodgkin’s lymphoma (10%) or thymoma. Among the non-oncological causes, postradiation fibrosis, fibrosing mediastinitis, vascular diseases, infection (histoplasmosis, syphilis, tuberculosis) or thrombosis associated with venous devices (pacemaker; central venous catheter).⁴

In addition to AS, other subtypes of sarcomas can affect large arteries and veins of the systemic and pulmonary circulation, having already been described in the literature, such as undifferentiated intimal sarcoma, osteosarcoma, synovial sarcoma and rhabdomyosarcoma, can rarely cause SVC syndrome.⁹

Outcome and follow-up

The patient remained hospitalised for 3 months after surgery, with multiple postoperative complications recorded, notably the development of a sacral pressure ulcer (grade III) and various urinary tract infections that required intravenous antibiotic therapy. A global respiratory failure followed, CT angiography excludes defects suggestive of pulmonary embolism but demonstrated bilateral pleural effusion. The biochemical analysis of the pleural fluid resulting from ultrasound- guided thoracentesis was compatible with a transudate, and the cultural analysis was negative. Another PET scan demonstrated, compared with the previous study, a hypermetabolic thickening adjacent to the proximal portion of the vascular prosthesis which, although it may correspond, in part, to an inflammatory compromise secondary to recent surgery, raises the suspicion of disease persistence; persistence of more extensive, lower right parasternal hypermetabolic adenopathy with a higher degree of metabolic activity, suggestive of ganglionar metastasis, in progression compared with the previous study. The appearance of multiple hypermetabolic right pleural thickening associated with homolateral pleural effusion that raises the suspicion of pleural metastasis (figure 5).

Figure 5.

Postsurgical PET with evidence of multiple hypermetabolic right pleural thickening associated with homolateral pleural effusion, in likely relationship with pleural metastasis. PET, positron emission tomography.

The patient never presented a performance status capable of benefiting from any adjuvant cancer therapy (G8 <14, irreversible fragility), in a multidisciplinary meeting, referral to palliative care was chosen. However, she died shortly after clinical decision making, 5 months after diagnosis.

Discussion

AS is a rare and aggressive tumour of endothelial origin (lymphatic or vascular endothelial cell) counting for less than 2% of all human tissue sarcomas. AS of SVC has only two cases reported in the medical literature. One of them presented with an SVC syndrome⁵ and the other one with only chest pain.⁶ In this last one, multiple diagnostic tests were performed, including cardiac MRI that showed the lesion that was surgically excised with the histological diagnosis of SVC AS. There are several reports of cardiac AS extended to adjacent vascular structures.^{10 11} In these cases, the diagnosis is usually delayed, related to the rarity of the condition and non-specificity of the symptoms, such as symptoms related to the obstruction of intracardiac blood flow, cardiac valve malfunctioning, tumour embolism and systemic symptoms. In our patient, in particular, she presented with neck discomfort, head fullness and dyspnoea lasting 3 months. The need for intervention and the timing to do so in SVC syndrome is highly dependent on the clinical presentation,¹² which may be evaluated using some severity scores.¹³ Kishi et al¹⁴ proposed a scoring system to assist the decision to initiate stent therapy, recommended in patients with a score above 4.^{12 14 15} Yu et al also proposed a grading system from 0 to 5, assuming grade 4 and some grade 3 patients need urgent intervention, which might include stenting.^{3 14} According to this, we would classify our patient with a Kishi score of 8 and in the system proposed by Yu et al, as a grade 3, having, according to the scoring system indication for revascularisation procedure that was performed (balloon angioplasty). The diagnostic path after an SVC syndrome is established must include chest imaging, essential to find the abnormality underlying. Contrast-enhanced CT imaging can elucidate the physical characteristics of the obstruction.¹³

The importance of a histological study cannot be put aside. We can distinguish through imaging if we have a mass or thrombi or both, but if we have a mass and the suspicion of a malignant tumour is high, making a biopsy and a histological study is mandatory. The appearance of AS histologically varies from well to poorly differentiated variants. The mediastinal mass excised from our patient appeared as a solid mass, with a storiform pattern composed of spindle cells with eosinophilic cytoplasm and oval nuclei. These characteristics can be found in poorly differentiated AS. These various cytoarchitectural features can make the histological identification of AS a challenge.¹⁶ The immunohistochemical examination may be helpful. AS typically express Factor-VIII-related antigen (Factor-VIIIRA), CD31 (most commonly), CD34 and vascular growth factor, as markers of endothelial origin.¹⁷

There are not enough reports that could help predict the overall outcome of SVC AS in specific, because of such a low number of reported cases. It seems to behave similarly as cardiac AS, which as an inferior outcome, with a mean time survival ranging from 3 to 9 months.¹⁸ In the most recent case report of SVC AS, the patient died 4 months after curative surgery of progressive disease (brain metastasis).⁵ Our patient, despite medical complications during her hospital stay (spinal compression syndrome, with after-surgery low potential recovery) had a postoperative of the mediastinal mass excision with no complications. Later she performed a second PET that showed metastatic disease.

The optimal approach to this complex disease is unknown, mostly because of its rarity and consequent lack of evidence. Current treatment might include surgery, radiotherapy or/and chemotherapy. The choice of treatment should be made by an interdisciplinary team, also considering the patient’s preferences.¹⁹ The radical surgical treatment is still the cornerstone treating AS that may optimal when negative surgical margins are achieved. However, due to the aggressiveness of the primary disease and its ability to metastasise, even when we have negative margins, the patient can benefit from doing adjuvant radiotherapy. The chemotherapy is usually the first treatment option for metastatic disease or irresectable disease, mainly taxanes, doxorubicin, doxorubicin liposome and ifosfamide.¹⁶ Besides, the postoperative survival does not seem to differ in patients treated with or without surgery, independent of the extension of the surgical resection.

AS is an aggressive disease that remains a challenge both in the diagnosis and treatment approach, despite daily advances in new therapies.

Learning points.

• Superior vena cava (SVC) is an infrequent primary location of angiosarcoma (AS).

• Diagnosis can be challenging: unspecific clinical presentation (SVC syndrome can be the initial presentation of a vast number of pathologies); can course with totally normal blood work in less specific imaging workout; histological findings can be nonspecific and hinder the diagnosis.

• Surgical resection, even when optimal does not mean cure or better long survival.

• AS has a poor prognosis and optimal treatment is yet to be found.