Pulmonary Tumor Thrombotic Microangiopathy R3 김형오

Introduction Lungs can be embolized with any material in venous circulation, larger than 10um Tumor cells access to the vessels –Invasion of small veins –Releasings of tumor fragments with neovasculature Most circulating tumor cells are destroyed –Mechanical forces –Host’s immune system –However, some tumor cells reach the lungs and become trapped within pulmonary capillaries

Pathophysiology

PTTM(Pulmonary Tumor Thrombotic Microangiopathy) –Activation of the coagulation system at the surface of the tumor embolism –Intimal proliferation in small pulmonary arteries

Pathophysiology Tumor cells metastasize to the pulmonary vascular system at a microscopic level –Adhere to the vascular endothelium –Activate the coagulation cascade Release inflammatory mediators –Platelets and fibrin depositions –Fibrocellular subintimal proliferation Smooth muscle colonization →Pulmonary arteriolar system narrowing Vascular resistance increased →Pulmonary hypertension (PH)

Pathophysiology VEGF(Vascular endothelial growth factor) –Endothelial cell-specific angiogenetic mitogen –Involved in Proliferation of endothelial cells 2ndary pulmonary hypertension –Congenital heart disease –Collagen vascular disease –Upregulated by TF(tissue factor) Initiation of hemostasis Intracellular signalling Cellular proliferation Development of blood vesssels

Pathophysiology Recently, VEGF and TF by tumor cells has been confirmed in many PTTM cases TF-VEGF system has been reported to be involved in the pathogenesis of PTTM →TF-VEGF may be the most promising candidate factor involved in the pathogenesis of PTTM

Pathophysiology Others related –Type 2A serotonin receptors (5-HT 2A ) Intimal myofibroblast surface, inducing intimal proliferation –Osteopontin Fibrocellular intimal proliferation Thrombus formation Neointima formation –PDGF –Vasoactive molecules may be involved in the pathogenesis of PH Thromboxane A 2, endothellin-1, nitric oxide

Histology

Clinical presentation Symptoms –Dyspnea –Pleuritic chest pain –Less frequent presentations Fatigue Weight loss Cough Hemoptysis Physical examination –Tachypnea –Tachycardia –Jugular venous distention –Clear lung sound

Diagnostic test Ventilation-perfusion lung scans –Multiple small, peripheral defects Pulmonary angiography –Insensitive for pulmonary tumor emboli –Delayed filling of segmental arteries Right heart catheterizations –Pulmonary artery pressures > 50mmHg –Subacute pulmonary hypertension –Typically in tumor emboli

Hypoxemia Respiratory alkalosis Increased alveolar-arterial gradient Right ventricular hypertrophy Chest radiographs / CT unremarkable Diagnostic test

Confirmation requires that tumor cells in the pulmonary vasculature –Lung biopsy Thoracoscopy is the gold standard test –Cytologic examination of pulmonary arterial blood Wedged pulmonary artery catheter aspiration

Pathology

Treatment Complete resection of the primary tumor Chemotherapy does not generally affect prognosis of patients except –Wilm’s tumor, trophoblastic malignancy has a very responsive course