Pulmonary Artery Sarcoma

Pulmonary artery sarcoma is a rare malignant mesenchymal tumour arising from the intima or wall of the main pulmonary artery or its branches. It is usually an intimal sarcoma (undifferentiated, or with leiomyosarcoma, angiosarcoma or fibrosarcoma features), and accounts for fewer than 300 reported cases.

It occurs between 40 and 70 years (mean about 50 years), with a slight female predominance. It is nearly always misdiagnosed as chronic or recurrent pulmonary embolism for months, and diagnosis is often made at pulmonary endarterectomy or autopsy. Amplification of MDM2 is found in most intimal sarcomas.

Pathophysiology. The tumour grows along the vessel lumen as a lobulated, polypoid mass that fills the artery and obstructs flow, and may extend through the wall into the mediastinum and lung, or distally. Distant spread to the lung, lymph nodes, brain and bone happens late. Tumour thrombus may embolise.

Progressive dyspnoea (the commonest), cough, chest pain, haemoptysis, fever, weight loss, fatigue, anaemia and raised inflammatory markers, which would not be expected in chronic thromboembolic disease. Signs of right heart failure and pulmonary hypertension develop, with syncope.

New unexplained weight loss, systemic features or failure of anticoagulation to improve the picture should raise the question of sarcoma.

• CT pulmonary angiography: a large heterogeneous filling defect that expands the vessel (diameter greater than the normal artery), with convex margins, extension beyond the vessel wall, and enhancement after contrast (unlike bland thrombus). It is often unilateral and involves the proximal arteries and pulmonary valve.
• MRI: heterogeneous enhancement, high T2 signal, and a lobulated tumour that enhances with gadolinium, in contrast to thrombus.
• Positron emission tomography (FDG-PET): increased uptake (maximum uptake value over 3.5) in the mass, distinguishing it from thrombus in most.
• Echocardiography: right ventricular strain, pulmonary pressure, and tumour extension to the right ventricular outflow tract.
• Tissue diagnosis: endovascular catheter biopsy, transthoracic or endobronchial ultrasound directed biopsy, thoracoscopic biopsy or surgical specimen. Histology and immunostaining (MDM2, CDK4, vimentin, smooth muscle markers).
• Staging CT of the chest, abdomen and brain.
• Failure of the lesion to resolve after 3 months of anticoagulation is a clue.

Differential diagnosis.

• Chronic thromboembolic pulmonary disease
• Acute pulmonary embolism
• Pulmonary artery thrombosis in situ
• Takayasu arteritis
• Lung cancer with vascular invasion
• Mediastinal tumour invading the vessel

• Complete surgical resection is the only potentially curative treatment: pulmonary endarterectomy or pulmonary trunk resection with reconstruction (graft or patch), pneumonectomy for unilateral disease, or resection with valve replacement and cardiopulmonary bypass. Heart lung or lung transplantation has been used rarely.
• Adjuvant therapy after resection: chemotherapy with doxorubicin 75 mg/m2 on day 1 with ifosfamide 3 g/m2 on days 1 to 3 every 21 days for up to 6 cycles, or gemcitabine 900 mg/m2 on days 1 and 8 with docetaxel 75 mg/m2 on day 8 every 21 days, and radiotherapy (50 to 60 Gy) to the tumour bed, which may reduce local recurrence.
• Palliative treatment for unresectable or metastatic disease: doxorubicin based or gemcitabine based chemotherapy, trabectedin 1.5 mg/m2 as a 24-hour infusion every 3 weeks, or pazopanib 800 mg daily, and radiotherapy for local control. Palliative stenting or debulking to relieve obstruction.
• Anticoagulation is not effective and is used only for confirmed thrombus, with caution for bleeding.
• Supportive care: oxygen, diuretics for right heart failure, pulmonary hypertension therapy only as the specialist directs, and early palliative care.
• Treat anaemia and nutrition.

Complications and prognosis. Right heart failure, tumour embolisation, local recurrence in most, and distant metastases. Median survival is 1.5 months without treatment, about 18 months with surgery plus adjuvant therapy, and 3-year survival is 25 to 35% after complete resection.

Monitoring. CT chest every 3 months for 2 years and then every 6 months, echocardiography and symptom review, and tolerance of chemotherapy (blood counts, cardiac function).

Referral and escalation. Refer to a sarcoma multidisciplinary team and a cardiothoracic surgical centre with pulmonary endarterectomy experience, with oncology and palliative care.