among the many causes of dyspnea associated with ph in a patient with history of cancer , paraneoplastic thrombotic pe is the most common aetiology and must be considered in priority .
but tumour cells can metastasize in the pulmonary vasculature in three mechanisms : occlusion of the small pulmonary arteries , pulmonary tumour thrombotic microangiopathy , or reach the lymphatic system .
a 72yearold woman was admitted to a hospital 2  months ago for exerciseinduced dyspnea .
she had history of left breast cancer pt2pn1m0 treated 2  years before with mastectomy , chemotherapy , and chest radiation .
ddimer serum level was elevated , so a ct angiogram was performed and showed no evidence of pulmonary embolus , whereas ventilation perfusion lung scan revealed two perfusion defects throughout superiors lobes with normal ventilation .
distal pe was suspected , and oral anticoagulation therapy was initiated and the patient discharged .
two months later , an echocardiogram revealed elevated right ventricular systolic pressure at 78  mmhg .
the right ventricle was moderately dilated ( 30  mm ) , nonhypertrophic , with good systolic function .
she had severe hypoxemia of 52  mmhg , a ph of 7.46 , a pc02 of 34 , and hco3 
  of 24  mmol / l with 10  l / min of oxygen .
the pulmonary function tests , the viral serologies , and the immune checkup were normal .
a second chest ct showed nonspecific groundglass opacities and lung fibrosis consistent with previous radiation therapy but no sign of pe , nor interlobular septal thickening , adenopathy , or mass .
right cardiac catheterization established precapillary ph with mean pa pressure of 48  mmhg and not elevated pulmonary wedge pressure ( 4  mmhg ) .
atrial pressure was low ( 5  mmhg ) , cardiac output was normal ( 2.66  l / min / m ) , and pulmonary vascular resistance were increased at 8.6 wood units .
a specific ph tritherapy was administrated ( sildenafil , ambrisartan , and epoprostenol ) , but her condition worsened rapidly with acute rhf , respiratory distress , acute renal failure , and microangiopathic hemolytic anaemia . in this context , in absence of diagnostic , we decided to withhold invasive ventilator support .
the autopsy showed three etiologies of ph consistent with hematogenous metastasis of breast cancer in pulmonary vasculature : carcinomatous cell inside lymph vessels ( lymphangitis carcinomatosis ) ( figure 
 1 ) , tumour cell embolization inside small arteries ( tumoural cells emboli ) ( figure 
 2 ) and pulmonary tumour thrombotic microangiopathy ( pttm ) ( figures 
 3 and 4).this latter is histologically characterized by intimal and medial fibromuscular thickening with accumulation of carcinomatous cells in the residual lumen of the small arteries and arterioles .
( haematoxylin and eosin ) : tumoural cells inside lymph vessels ( black arrow ) ; pleura ( dotted arrow ) .
( haematoxylin and eosin ) : tumoural cells inside arteriole lumen ( black arrow ) ; intimal fibroblastic proliferation ( black star ) ; fibrinrich thrombus ( * ) ; internal elastic lamina destruction .
( haematoxylin and eosin ) : tumoural cells inside arteriole lumen ( black arrow ) ; intimal fibroblastic proliferation ( black star ) ; internal elastic lamina destruction ( dotted black arrow ) ; hypertrophic arteriole wall ( double black arrow ) .
it was first described in 1990 in 3.3% of an autopsic series of patients , who had died of metastatic adenocarcinoma , mostly of gastric origin.1 recently , a large case series estimated the incidence of 1.4% among 2215 autopsy patients with carcinoma and confirmed the stomach as the primary site of cancer associated with pttm .
most of the time , there is evidence of metastatic disease , but many occult cancers have been reported as in our description .
previous studies have shown that tumour cells have the abilities to activate coagulation pathway and local thrombus formation and trigger fibroblastic intimal proliferation via production of cytokines such as tissue factor,2 vascular growth factor , or plateletderived growth factor.3 high vegf expression associated with gastric cancer could explain the high incidence of pttm .
in addition to mechanical occlusion , these phenomena rapidly lead to arterioles remodelling and stenosis , increased pulmonary vascular resistance , and ph .
the tumoural cells are beyond the resolution of the ct angiogram , but their presence explains the perfusion defect on lung scan . recently , a treeinbud pattern , usually seen in bronchiolitis and characterized by small centrilobular nodules and branching linear opacities , was reported on thinsection ct of pttm patients.4 
  disseminated intravascular coagulation5 or cancer associated hemolytic anaemia has often been described consistent with elevated ddimer .
a study has estimated the median survival as 5  days from admission to hospital.6 pttm may be identified using videoassisted thoracoscopic surgery , transbronchial biopsy , right heart catheterization , and ctguided biopsy.7 
  in the rare antemortem diagnosis case , specific chemotherapy was administrated often associated with empiric treatment such as corticosteroids or anticoagulation .
the best survival reported was 15  months probably because diagnosis was made prior to the development of ph.8 
  chronic pe is the main cause of unexplained progressive dyspnea with precapillary ph in the context of cancer .
but when large proximal pe is absent in ct angiogram whereas lung scan show multiple perfusion defects , clinicians must consider other tumoural embolic causes in the differential , especially pttm .
thereby , they will be able to perform pulmonary cytology or biopsy before the patient 's condition deterioration .
a rapid specific chemotherapy administration is the only way to improve the survival of patients .
 abstracta 72yearold woman with history of breast cancer only treated surgically was referred to our department for pulmonary hypertension ( ph ) suspicion . 
 echocardiogram revealed elevated right ventricular systolic pressure . 
 computed tomography ( ct ) angiogram showed no pulmonary embolism ( pe ) , but lung scan revealed two ventilationperfusion mismatch areas . 
 right cardiac catheterization established precapillary ph . despite treatment with ph specific therapy ( sildenafil , ambrisentan , and epoprostenol ) , her condition worsened rapidly with acute right heart failure ( rhf ) . 
 she died 22  days after admission . 
 postmortem microscopic examination showed a rare combination of ph etiologies consistent with metastasis of breast cancer in pulmonary vasculature including the rare pulmonary tumour thrombotic microangiopathy ( pttm ) . 
Introduction
Case report
Discussion