Primary angiosarcomas of the chest wall and pleura

Abstract

Primary angiosarcomas of the chest wall and pleura are extremely rare and carry a dismal prognosis. Two cases are reported. One patient (case 1), presented with massive recurrent haemothorax, was found to have multifocal angiosarcoma of the pleura, treated with surgical de-bulking, chemical pleurodesis and chemotherapy, achieving control of the bleeding. She died 10 months later from complications related to chemotherapy. A full post-mortem examination confirmed this was a primary pleural angiosarcoma with no evidence of disease elsewhere. Another patient (case 2) with a large solitary angiosarcoma of the chest wall, discovered incidentally on a routine physical examination, was successfully treated with surgical excision and subsequent radical radiotherapy, remaining well 15 years post-operatively.

Primary angiosarcoma, Chest wall, Pleura

Introduction

Angiosarcoma is a rare tumour of the endothelial cells usually originating in small blood vessels. It may affect every organ but most commonly occurs in the skin and soft tissues, liver, spleen, heart and breast [1]. Primary angiosarcomas of the chest wall and pleura are extremely rare [2],[3],[4],[5],[6],[7]. Two cases of angiosarcomas different in presentation, topography, behaviour and malignancy are reported. In the first patient a picture of diffuse pleural angiosarcoma is described, shown at post-mortem to be the only site of the disease process. The second patient had a localized angiosarcoma which was quite clearly a primary tumour of the chest wall.

Case 1

A 57-year-old lady presented with a 6-week history of shortness of breath and fever. A chest X-ray showed opacification of the right hemithorax due to haemothorax. This was drained several times necessitating transfusion of 52 units of blood. A CT demonstrated a massive haemothorax and pleural soft tissue masses in both hemithoraces invading the mediastinum (Fig. 1 a). Fine needle aspiration biopsies and cytological examination were unhelpful. At thoracotomy multiple blood filled cysts were found over the parietal and visceral pleurae. These were de-bulked and all bleeding points diathermized. Talc was insuflated into the pleural cavity. She did not require further blood transfusions. Histopathological examination showed areas of spindle cells and epithelioid foci both containing very pleomorphic nuclei (Fig. 1b). A vascular marker (CD 31) and vimentin were strongly positive. The appearances were those of angiosarcoma. Post-operatively she was treated with chemotherapy (ifosfamide) with good symptomatic relief. Ten months later though, she developed diabetes insipidus and septicaemia and died in the intensive care unit. A full post-mortem examination revealed residual tumour on the visceral pleural surface of the left lung and no evidence of disease process elsewhere. There were also brain changes present consistent with ifosfamide induced ischaemic encephalopathy.

Fig. 1

(a) Case 1, CT scan shows large right haemothorax and a pleural mass in the left hemithorax. (b) Case 1, Pleomorphic spindle cells lining spaces together with atypical epithelioid cells associated with abundant haemorrhage (H&E magnification ×125)

Case 2

A 24-year-old female was, during a routine examination following a cold, found to have a continuous murmur over the left side of her chest, posteriorly. A chest X-ray showed a large mass in the left posterior hemithorax confirmed by a CT scan (Fig. 2 a). An aortogram demonstrated the mass was communicating with left lower intercostal arteries. At thoracotomy an ovoid mass 10×9×6 cm, sitting in front of the vertebral bodies and the ribs with numerous connections to the intercostal vessels was excised and the major vessels ligated. On section, the tumour had a soft haemorrhagic appearance and was largely encapsulated although tongues of tumour appeared to extend through the capsule to the margin of excision. Microscopical examination revealed angiosarcoma comprised of multiple anastomosing blood vessels lined by endothelial cells showing malignant features but with little nuclear pleomorphism (Fig. 2b). Mitotic figures were scanty. Epithelial immunostains were negative but factor VIII antibody stained the tumour cells. The malignant cells were extending up to the margin of the excision. Post-operatively she received a radical course of radiotherapy to the area of the tumour. She made an excellent recovery and on follow-up 15 years later she remains well without clinical or radiological evidence of tumour recurrence.

Fig. 2

(a) Case 2, CT scan shows large mass in the left hemithorax abating the left paravertebral gutter and posterior chest wall with adjacent contrast following aortography. (b) Case 2, Uniform spindle cells arranged in perivascular arrays but with little nuclear pleomorphism consistent with low grade angiosarcoma (H&E magnification ×125).

Discussion

There is some confusion regarding the terminology of the borderline and malignant vascular tumours. In early reports malignant vascular tumours were termed haemangioendothelioma [3] or haemangiosarcoma [7]. More recently the term haemangioendothelioma has been applied to borderline tumours; malignant tumours now being termed angiosarcomas. Both haemangioendotheliomas and angiosarcomas may have a predominant epithelioid appearance resembling carcinoma, hence the entities of epithelioid haemangioendothelioma and epithelioid angiosarcoma [8].

Pleural and chest wall angiosarcomas have been described in patients with a history of irradiation [9],[10],[11] and chronic tuberculous pyothorax [12]. None of these factors were present in our two patients which could therefore be regarded as de novo primary angiosarcomas.

Primary chest wall or pleural angiosarcomas present mainly with chest wall pain, dyspnoea, tender swelling and/or haemothorax (Table 1 ) or they may be asymptomatic (Our case 2).

Table 1

Previous reports of de novo (unrelated to irradiation or chronic pyothorax) primary angiosarcomas of the pleura and chest wall

Although the histopathological features of angiosarcoma have been described by Stout in the 1940s [3], the definitive diagnosis and definition of its primary or secondary origin may be difficult [1]. Confirmation of their endothelial origin is facilitated by immunohistochemical staining with Factor VIII-related antigen, Ulex Europaeus, CD31, CD34 and von Villebrand factor. Epithelial markers (cytokeratins Cam 5.2, MNF 116 (pan-cytokeratin), and epithelial membrane antigen) are used to exclude an epithelial origin. Case 1 was morphologically overtly malignant and microscopically easily classifiable as angiosarcoma. It was positive for CD 31 (factor VIII and Ulex Europeus were not done). Case 2 had a spindle cell appearance with minimal mitotic activity and could be classified as low grade angiosarcoma/haemangioendothelioma. This tumour was excised in 1988 before the advent of CD31 and CD34 hence only factor VIII positivity is documented; CD31 and CD34 have subsequently been applied but were negative. This could be due to deterioration of antigen over time [13]. Cytokeratins Cam 2.5 and MNF 116, were negative in both cases (a significant number of epithelioid vascular tumours will stain with cytokeratins). Neither of our cases had a significant number of epithelioid tumour cells.

Primary pleural and chest wall angiosarcomas can be highly malignant most of the patients dying within a few months despite the variety of therapeutic modalities (radiation therapy, chemotherapy and surgical intervention) employed (Table 1).

Our first patient exhibited diffuse angiosarcoma of the pleural cavities. Pleural involvement by angiosarcoma has been well reported in cases of primary and secondary lung angiosarcoma [1] but primary disease of the pleural cavity is extremely rare. Aozasa et al. [12] described in an all-Japan review study, nine cases of pleural angiosarcomas all developing in patients with chronic tuberculous pyothorax all dying within 6 months following the diagnosis, regardless of the type of treatment they received. In another report [9] a 38-year-old woman presented with diffuse angiosarcoma of the mediastinum and pleura 17 years after radiotherapy for malignant tumour of the right hemithorax and eventually she succumbed to her disease. Epithelioid haemangioendothelioma has, however, recently been reported as arising in the pleura and mimicking mesothelioma.

Two cases of de-novo (unrelated to irradiation or pyothorax) primary pleural angiosarcoma (Table 1, Nos. 1 and 2) similar to our case 1 were previously reported. Both patients received no active treatment and had a rapid fatal outcome. Our patient was treated with high dose ifosfamide and had good symptomatic relief but died in 10 months. At post-mortem there was evidence of good response to chemotherapy but there were brain parenchymal changes of ischaemic encephalopathy, a recognized side effect of ifosfamide.

Our second patient presented with a much more localized form of chest wall angiosarcoma supplied directly by the intercostal arteries. The gross and microscopic appearance suggested a low grade tumour but the behaviour of soft tissue tumours is not always reflected by their morphology. Excision appeared incomplete, therefore post-operative radiotherapy was performed. Through a Medline literature search (1965–1998), six cases of de-novo primary angiosarcomas of the chest wall (Table 1, Nos. 3–8) were identified. They all had chest wall pain as the main presenting feature. Cases No. 3, 4 and 5 had aggressive tumours and an unfavourable outcome. The patient No. 6 was lost to follow up. In contrast, cases No. 7 and 8 seem to closely resemble our second patient. They describe two young males with well circumscribed, localized right chest wall tumour treated by surgical excision alone with at least 3 and 2 years of disease-free survival, respectively.

Our patient being well and asymptomatic after 15 years follow-up represents a rare case although histologically there were favourable prognostic features.