Pulmonary tumor thrombotic microangiopathy associated with right ventricular rupture and hemopericardium: A case report

Introduction

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare form of pulmonary tumor embolism. It is typically associated with an underlying malignancy and is rarely diagnosed antemortem. We report an exceedingly rare case of PTTM causing right ventricular (RV) infarction, RV free wall rupture, and ensuing fatal hemopericardium.

Case report

A 67-year-old Caucasian woman presented with the acute onset of shortness of breath, chest pain, and three witnessed syncopal events the day prior to admission. Her past medical history was significant for breast cancer treated with resection and chemotherapy. She had been free of tumor recurrence at 5-year follow-up. Information regarding receptor status, type of chemotherapy, and adjuvant radiotherapy was not available at the time of admission. On presentation, she was tachypneic, hypotensive, and hypoxemic. The electrocardiogram showed sinus tachycardia, right axis deviation, and negative T-waves in the inferior and lateral leads. The electrocardiographic S₁Q₃ pattern classically described in acute pulmonary embolism was not present. Cardiac troponin I was marginally elevated at 0.11 ng/mL (reference range, <0.04 ng/mL). The chest radiograph showed no clear pathology. Transthoracic echocardiography demonstrated RV dilatation and severely decreased RV function. Empiric treatment with intravenous heparin was initiated given the high clinical suspicion for acute pulmonary thromboembolism. A contrasted computerized tomography study of the chest and a ventilation–perfusion scan were obtained after initial hemodynamic stabilization. Both studies were unremarkable. A few hours later, the patient became acutely unresponsive and expired despite aggressive resuscitation measures, including mechanical ventilation, pharmacological and electrical cardioversion of atrial fibrillation with rapid ventricular response, vasopressor support, and large volume fluid resuscitation. Echocardiographic imaging was not available during cardiopulmonary resuscitation.

Autopsy identified a rupture of the anterior RV wall causing a large hemopericardium as the proximate cause of death (Fig. 1A). The coronary arteries showed no occlusive or thrombotic lesions. Microscopic sections near the site of rupture demonstrated hypereosinophilic shrunken cardiomyocytes with a mild inflammatory infiltrate and intracellular edema, indicative of an acute myocardial infarction (Fig. 1B). No large pulmonary emboli were identified on gross examination of the lungs. However, the pulmonary vasculature demonstrated extensive microscopic occlusion of small arteries and arterioles by metastatic breast carcinoma (confirmed by immunostaining) in association with acute fibrin thrombi. There were widespread chronic vascular changes including intimal and medial proliferation, fibrosis, and recanalization in association with carcinoma cells, suggesting a subacute accumulation of tumor emboli prior to the current presentation (Fig. 1C and D). A reservoir of carcinoma was identified in the bone marrow and in several peri-aortic lymph nodes completely effaced by tumor cells.

Fig. 1

Gross pathology and histopathology. (A) Dilated right ventricle with rupture of the anterior right ventricular wall. (B) Myocardial infarct with hypereosinophilic myofibers, edema, and mild interstitial inflammation (original magnification 200×). (C) Pulmonary arterial recanalization in response to chronic occlusion by tumor emboli with superimposed acute fibrin thrombi (original magnification 100×). (D) Myxoid fibrosis and intimal–medial proliferative response to adherent tumor cells in a pulmonary arteriole (original magnification 200×). All stains are hematoxylin–eosin.

Discussion

PTTM is a rare clinicopathological form of pulmonary tumor embolism with fulminant clinical course, no effective treatment, and poor prognosis 1, 2, 3. It is clinically indistinguishable from pulmonary thromboembolism and is usually diagnosed postmortem. It is found in 0.9–3.3% of autopsies of patients with adenocarcinomas of the breast, stomach, liver, colon, and lung. Histologically, it is characterized by concentric fibrocellular intimal and medial proliferation of small pulmonary arteries and arterioles with associated thrombus formation. The proliferative process of smooth muscle cells and fibroblasts is triggered by the activation of the coagulation cascade in the pulmonary vasculature and the release of inflammatory mediators and growth factors, including endothelial growth factor, platelet-derived growth factor, and pleiotropic cytokines [4]. Clinically, acute or sub-acute cor pulmonale, sudden cardiovascular collapse, pulmonary hypertension, and increased pulmonary vascular resistance are manifestations of the disease.

RV infarction is known to occur in the acute phase of large pulmonary thromboembolism in the absence of obstructive coronary lesion or thrombosis [5]. Pathophysiologically, low cardiac output, hypoxemia, systemic hypotension, and increased RV afterload result in decreased coronary perfusion pressure and increased myocardial oxygen consumption. These factors likely led to RV subendocardial ischemia and infarction with subsequent rupture of the RV free wall despite the lack of significant obstructive coronary lesions in the presented case. We also carefully considered whether cardiopulmonary resuscitation might have contributed to RV rupture and hemopericardium. The sternal plate was carefully examined at autopsy. Particular attention was focused on the integrity of the sternum and articulating ribs for signs of fracture and internal organ damage. The sternal plate was found to be intact and free of fractures. Furthermore, there was no laceration of the pericardium or contusion of any other cardiac structure or of the left lung parenchyma; there was no hemothorax, leading us to believe that the extensive burden of PTTM resulted in RV infarction and rupture of the RV free wall with ensuing hemopericardium.

Conclusions

PTTM is an under-recognized clinical entity that should be considered in patients with a history of malignancy and symptoms suggestive of pulmonary embolism, provided that pulmonary thromboembolic disease has been excluded. The diagnosis of PTTM has implications for treatment options, prognosis, and outcome.

Conflict of interest

The authors declare no conflict of interest.