A purple plaque in a patient with systemic sclerosis

Abstract

We present the case of a 43-year old woman with anti-U3 ribonucleoprotein antibody-positive systemic sclerosis presenting with an enlarging purple plaque on the left upper arm. The skin was not sclerotic; however, there had been a cluster of long-standing telangiectases preceding the plaque. Histology and immunohistochemistry confirmed an angiosarcoma. There are five reported cases in the literature about angiosarcoma arising in the skin of patients with systemic sclerosis; however, to our knowledge, this is the first to have arisen from non-sclerotic skin. We would urge clinicians to adopt a high index of suspicion for atypical vascular tumours presenting in patients with systemic sclerosis.

Introduction

Angiosarcoma is a highly aggressive, rare malignant tumour of endothelial origin comprising 1% of all soft tissue sarcomas. They most commonly occur in the skin; however, they can also present in the visceral organs, soft tissue, bones and retroperitoneum. There is a high rate of local recurrence and metastasis, and due to the clinical heterogeneity, diagnosis can prove challenging. To achieve the best possible outcomes, early diagnosis is of paramount importance.

Angiosarcoma arising in the setting of systemic sclerosis (SSc) is rare, with just five case reports to date. Here we describe a sixth case, but the first occurring on non-sclerotic skin.

Case description

A 43-year-old woman with anti-U3 ribonucleoprotein antibody-positive (anti-fibrillarin (AFA)) limited cutaneous SSc presented to our Dermatology Department with a 5-cm purple plaque on her left upper arm that arose from a pre-existing cluster of telangiectases; however, the skin at that site was not sclerotic (Figure 1).

Figure 1.

(a) A large purple plaque on the left upper arm with surrounding telangiectasia. (b) A closer view of the plaque with a central nodule.

Her clinical manifestations of disease included Raynaud’s, sclerodactyly, digital calcinosis and striking extensive telangiectases over her limbs, face and torso. She had never been on immunosuppressive therapy.

An urgent incisional biopsy was performed. Histological examination revealed an endothelial tumour that stained positive with CD31, CD34 and ERG in keeping with an angiosarcoma (Figure 2). A magnetic resonance imaging (MRI) showed no evidence of muscle invasion, and this patient underwent a wide local excision with a flap reconstruction. Although adjuvant radiotherapy would usually be offered following surgery for local disease, it was thought that radiotherapy might complicate this patient’s SSc, and so she underwent surgery only but remains under close follow-up.

Figure 2.

(a) The tumour consists of vascular channels lined by atypical endothelial cells, with nuclear pleomorphism and increased mitotic activity. (b) The atypical endothelial cells show strong diffuse expression with CD31 (immunoperoxidase).

Conclusion

Angiosarcoma is a rare malignant tumour of endothelial origin, most frequently occurring on the skin. It most commonly develops on the head and neck and affects older people. Other risk factors are chronic lymphoedema and radiotherapy. They are associated with a high rate of local recurrence, and metastasis at presentation is estimated to be between 16% and 40%. ¹

SSc is characterised by vascular damage and widespread fibrosis of the skin and internal organs. About 7% of patients develop a malignancy, the higher incidences being in autoantibody subgroups RNA polymerase III (11%) and PM/Scl (20%). ² Angiosarcoma arising from a benign vascular malformation/haemangioma is extremely rare, and to our knowledge, telangiectases undergoing malignant transformation has not been described in the literature. Furthermore, angiosarcoma occurring in the setting of SSc is rare with only five previous case reports.^3,4 Of those five, all occurred on sclerotic skin and four on the head and neck. Our case differed, occurring on non-sclerotic skin and on a limb.

The pathways involved in the pathogenesis of angiosarcoma are complex. However, two key components are transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF). Vasculopathy is a hallmark of SSc pathogenesis and accounts for early manifestations of her disease such as Raynaud’s phenomenon but also severe complications such as pulmonary hypertension (PAH) and cardiopulmonary involvement. ⁵ It involves endothelial cell dysfunction and overexpression of proangiogenic factors – two of the most important being VEGF and TGF-β, highlighting overlapping mechanisms between angiosarcoma and SSc. These microvascular changes happen in the context of intricate inflammation involving both innate and adaptative immunity, with specific autoantibody production. Later on, it leads to endothelial to mesenchymal transition and fibrosis.

The anti-U3RNP antibody is a highly specific antibody for SSc. It is associated with significant vascular dysfunction. A study looking at over 1300 patients with SSc and aiming to classify their disease outcomes according to their antibody profile showed that although AFA is associated with a low incidence of pulmonary fibrosis, it related to the highest incidence of vascular complications, namely, PAH and cardiovascular disease. ⁶ It would not be unusual for these patients to have extensive telangiectases, very abnormal nail fold capillaries and PAH.

This case was memorable as the angiosarcoma arose from telangiectases on non-sclerotic skin of a patient with a U3RNP + SSc presenting with a striking vasculopathic phenotype. We would urge clinicians to adopt a high index of suspicion when patients with SSc present with atypical vascular tumours.