A 49-Year-Old Man with Subacute Respiratory Failure and Interstitial Lung Opacities

Abstract

Patient: Male, 49Final Diagnosis: Pulmonary tumor thrombotic microangiopathySymptoms: Cough • dyspnea • fatigue • lightheadednessMedication: —Clinical Procedure: Trans-bronchial biopsy • right heart catheterizationSpecialty: PulmonologyObjective:Rare diseaseBackground:Pulmonary arterial hypertension (PAH) results from proliferative vasculopathy involving all layers of the blood vessel. Similar findings may be present in pulmonary hypertension (PH) associated with microscopic tumor embolism, which are thought to be related to the phenomenon of pulmonary tumor thrombotic microangiopathy (PTTM). PTTM is associated with the activation of the coagulation system at the surface of the tumor emboli, resulting in stenosis or occlusion of the vessel.Case Report:A 49-year-old man with stage IV gastro-esophageal junction adenocarcinoma presented with complaints of cough and shortness of breath. These symptoms coincided with the initiation of trastuzumab with a new experimental medication with receptor tyrosine kinase blocking activity. A trans-thoracic echocardiogram demonstrated severely increased right ventricle (RV) cavity size with severely decreased RV systolic function. A computed tomography angiography was negative for pulmonary embolism but demonstrated new bilateral pulmonary infiltrates. Bronchoalveolar lavage ruled out an infectious etiology. Trans-bronchial biopsies (TBBx) showed arteriole obliteration by smooth muscle proliferation suggestive of pulmonary vasculopathy. The right heart catheterization (RHC) confirmed severe pulmonary hypertension. Unfortunately, shortly after the RHC, the patient developed pulseless electrical activity cardiac arrest and died. Autopsy results were similar to those of the TBBx, except for diffuse dissemination of tumor cells in the lymphatic channels and small pulmonary vessels, confirming a diagnosis of PTTM.Conclusions:We highlight the limitations of trans-bronchial biopsies in evaluating PTTM. The final diagnosis of PTTM was not made until the autopsy was done.

Pulmonary tumor thrombotic microangiopathy: a systematic review

“…The pathophysiology of PTTM involves a complex interplay between tumor cells, endothelial cells, smooth muscle cells, inflammatory cells, mediators of inflammation (PDGF and VEGF released by tumor cells) and tissue repair (OPN released by tumor cells, macrophages, and fibrointimal cells), and activators of the coagulation system (TF released by tumor cells and endothelial cells). 20,35,36 Upon the embolization of tumor cells into pulmonary vasculature, endothelial injury releases TF which initiates the coagulation cascade and formation of fibrin clots. Platelet aggregation occurs and platelets release cytokines and chemokines, including PDGF, which attract macrophages to the area of inflammation.…”

“…35 VEGF promotes the cleavage of OPN, creating fragments that act as a chemoattractant for smooth muscle cells, suggesting a role in smooth muscle cell proliferation and angiogenesis. 35,37,38…”

“…Finally, RHC may allow for sampling of blood from the pulmonary artery, which in some cases reveals the presence of tumor cells, allowing for a diagnosis of the primary malignancy and/or tumor emboli. 35 RHC need not always be pursued, especially if there is sufficient evidence, based on the overall clinical picture, to suspect a diagnosis of PTTM.…”

“…20 PDGF upregulates the production of OPN, a glycoprotein, that is released at sites of endothelial damage and inflammation, and may be involved in vascular remodeling. 35 VEGF promotes the cleavage of OPN, creating fragments that act as a chemoattractant for smooth muscle cells, suggesting a role in smooth muscle cell proliferation and angiogenesis. 35,37,38 PDGF and VEGF levels have been measured in the serum.…”

Pulmonary tumor thrombotic microangiopathy of patient with both hepatocellular carcinoma and gastric signet-ring cell carcinoma: a case report and review of literature

“…The condition of our patient with both hepatocellular carcinoma (HCC) and gastric signet-ring cell carcinoma who developed PTTM deteriorated faster than that of patients with gastric carcinoma only. Furthermore, we have reviewed 19 reported cases (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). We present the following article in accordance with the CARE reporting checklist (available at http://dx.doi.org/10.21037/tcr-20-3107).…”