Pulmonary tumour thrombotic microangiopathy.

Abstract

Pulmonary tumour thrombotic microangiopathy (PTTM) describes tumour cell microemboli with occlusive fibrointimal remodelling in small pulmonary arteries, veins and lymphatics. Progressive vessel occlusion ultimately results in pulmonary hypertension, which is often severe and rapid in onset. PTTM is associated with carcinomas, notably gastric carcinoma, with vascular endothelial growth factor and platelet-derived growth factor (PDGF) signalling implicated in driving the intimal remodelling. PTTM is a rare cause of pulmonary hypertension, but given that up to a quarter of autopsy specimens from patients dying of carcinoma show evidence for PTTM, it is probably underdiagnosed. Until recently, prognosis in PTTM was universally abysmal from weeks to a few months. Diagnostic utilities include aspiration of tumour cells at wedged right heart catheterization, high-resolution computed tomography (HRCT) findings and computed tomography-positron emission tomography (CT-PET), although definitive diagnosis requires histological analysis. Reports of PTTM treated with a combination of targeted pulmonary vasodilator therapies, anticoagulation, specific chemotherapy and PDGF inhibition, for example using imatinib, suggest that these approaches can prolong survival. PTTM is increasingly recognized as an important cause of pulmonary hypertension, often in patients presenting with new-onset pulmonary hypertension and as yet undiagnosed malignancy. Prospects of survival are improving with targeted combination therapy, and early recognition and diagnosis are likely to be the key factors to improve outcome.