Pulmonary Tumor Thrombotic Microangiopathy

Abstract

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinical entity where tumor cell embolisms in pulmonary circulation induce thrombotic microangiopathy (TMA), respiratory failure, and subacute cor pulmonale.We describe 3 cases of PTTM that presented as the initial manifestation of metastatic gastric adenocarcinoma with TMA and pulmonary infiltrates.All 3 cases had similar clinical and laboratory features, which included moderate thrombocytopenia without renal failure, hemolysis with extremely high serum lactate dehydrogenase levels, leukoerythroblastosis in peripheral blood smear, altered coagulation tests, lymphadenopathies, and interstitial pulmonary infiltrates. All patients died within 2 weeks of diagnosis. Two cases were initially misdiagnosed as idiopathic thrombotic thrombocytopenic purpura and treated with plasma exchange with no response. One patient had bone marrow infiltration by malignant cells. Autopsies revealed PTTM associated with gastric disseminated adenocarcinoma (signet-ring cell type in 2 patients and poorly differentiated type in 1).PTTM should be considered in the differential diagnosis of patients with fulminant microangiopathic hemolytic anemia, such as atypical thrombotic thrombocytopenic purpura, mainly those with pulmonary infiltrates, disseminated intravascular coagulation, or Trousseau syndrome.

Fallo agudo de ventrículo derecho debido a microangiopatía

“…Es una causa poco común de hipertensión pulmonar secundaria, de rápida evolución, mediada por la migración de embolismos neoplásicos altamente trombogénicos hacia la circulación vascular pulmonar. El tumor primario más frecuente con el que se relaciona es el adenocarcinoma gástrico 4 . Se trata de un cuadro de elevada mortalidad, con sintomatología inicial insidiosa y una evolución rápidamente progresiva 5 .…”

Improvement of Breast Cancer-Associated Pulmonary Tumor Thrombotic Microangiopathy With Carboplatin and Gemcitabine

“…The most commonly reported symptom of PTTM is rapidly progressive dyspnea on exertion, which often initially presents with exertion. In addition, many patients present with some degree of hypoxia, which can also rapidly progress to respiratory failure [ 2 - 4 , 6 - 9 ]. These symptoms are thought to be due in part to metastatic disease of the lung parenchyma, resulting in abnormalities in gas exchange and shunting.…”

“…The pathophysiology of PTTM is thought to be due to tumor emboli in the pulmonary vasculature. The cancer cells in the vasculature result in intimal damage, activation of coagulation, and recruitment of inflammatory markers [ 2 , 5 - 6 , 9 ]. In addition, trapped microtumors secrete local growth factors such as vascular endothelial growth factor (VEGF), tissue factor (TF), platelet-derived growth factor (PDGF), and osteopontin (OPN), which cause vascular remodeling [ 10 - 11 ].…”

“…Radiographic findings can be non-specific and cannot be used alone to reliably diagnose PTTM. Chest radiography can show Kerley B lines, reticular or nodular opacities, or be normal [ 2 , 4 , 9 ]. However, chest CT has been reported to show GGOs due to tumor infiltration of the alveolar septa, interlobular septal thickening due to engorgement of lymphatics, and tree-in-bud opacities [ 2 , 5 , 7 - 8 ].…”

Pulmonary Tumor Thrombotic Microangiopathy: A New Paraneoplastic Syndrome

“…Due to this paraneoplastic-like secretion of vascular and vascular smooth muscle mitogens, we suggest that PTTM meets the definition of a PNS. In the absence of a biopsy, echocardiographic and coagulation studies [ 8 ] are the diagnostic tests of choice.…”