From Uterus to Pulmonary Embolus
An Uncommon Association
A 36-year-old Afro-Caribbean woman presented with recurrent syncope and shortness of breath after a long-haul flight. On admission, ECG revealed sinus tachycardia at 130 bpm and mildly flattened T waves in V2 through V5 (Figure 1a). D-Dimers were elevated (663 ng/mL), and blood gases showed hypoxia. Chest x-ray was unremarkable (Figure 1b). Family history revealed that the patient’s mother had suffered a previous deep venous thrombosis.
The initial clinical presentation was consistent with pulmonary embolism, confirmed by computed tomographic scan that showed a large saddle-shaped embolus in the pulmonary trunk extending into the right main pulmonary artery (Figure 2a), the right ventricle, the right atrium, and the inferior vena cava (IVC). There was also a smaller extension into the left main pulmonary artery as well as smaller, segmental, and subsegmental thrombi.
Given the extensive radiological findings along with clinical deterioration, the patient received a thrombolytic regimen with streptokinase. A repeat scan 12 hours after initiation of thrombolytic therapy showed that the saddle-shaped embolus in the pulmonary trunk had resolved (Figure 2b), but thrombotic elements in the right heart cavities and the IVC remained. An echocardiogram confirmed the presence of a large mobile mass in the right atrium, prolapsing through the tricuspid valve into the right ventricle, which was believed to be at high risk of embolization. The patient subsequently received a second thrombolysis regimen with alteplase, 110 hours after the first one, without complications.
Despite the 2 thrombolytic therapies, there was no resolution of the intracardiac elements. Cardiac magnetic resonance imaging (MRI) was then requested, which revealed a large lobulated soft tissue mass extending from the inferior cava to the right atrium and into the right ventricle (Figure 3a and 3b; Movies I, II, and III in the online-only Data Supplement). The structure was vascular in nature, without invasion of the right atrial wall or of the tricuspid valve, and with a thrombus at the tip of the mass (Figure 3c). Gadolinium-enhanced magnetic resonance angiography confirmed the partial obstruction of the suprarenal IVC. The infrarenal IVC and the iliac veins were unobstructed, without evidence of tumor extension into these vessels. The hepatic veins were not involved (Figure 4a). There was, however, a filling defect in the left renal vein (Figure 4b) and distention of the left ovarian vein, raising suspicion of an extension of the mass into this vessel, via the left ovarian vein. Abdominal MRI images revealed several large heterogeneous uterine masses (Figure 4c). Overall, the MRI findings strongly suggested leiomyomatosis with intravenous and intracardiac extension via an unusual route, as described earlier.
Surgical removal of the intravascular and intracardiac portion of the tumor was performed under routine cardiopulmonary bypass. A large mobile rubbery tumor was removed from the right ventricle and out of the right atrium (Figure 5a). The tumor extended into the left renal vein as well as into the left ovarian vein, confirming the MRI findings, all of which was removed. Histological examination showed that the tumor consisted of smooth muscle cells (Figure 5b) as confirmed with immunostaining for smooth muscle actin (Figure 5c). Mitosis or nuclear polymorphism was absent, confirming the clinical impression of leiomyomatosis.
The patient remains well and asymptomatic. Follow-up MRI 1 year after the cardiac surgery revealed no recurrences (Figure 3d and 3e). The patient will continue to be screened regularly because recurrences have been described up to 15 years after the initial presentation.1 Contrast-enhanced MRI offers the ideal, comprehensive screening tool for this young woman, allowing for repeated examinations free of radiation and iodine-containing contrast agents.
Intracardiac extension of leiomyomatosis has been described previously.2 Intravenous leiomyoma is a rare histologically benign smooth muscle cell tumor occurring in women, which arises either from the wall of a vein (usually pelvic, but it can also originate from other veins) or from a uterine leiomyoma. It is a very slow and insidiously growing tumor that extends into vessel lumens without invading them. In the vast majority of cases, intravenous leiomyomatosis remains localized within the pelvic vessels. In rare cases, however, the tumor extends into the central veins and the IVC, with easy access from there into the right cardiac chambers, leading to intracardiac leiomyomatosis. Fewer than 100 cases of intracardiac leiomyomatosis have been described thus far in the literature. Routes of extension are usually unilateral, via the uterine veins. Interestingly, these intracardiac tumors have also been reported in patients who had undergone previous hysterectomy. In these cases, it is thought that part of the tumor had been left in the pelvic veins at the time of surgery, presumably because of undiagnosed intravenous leiomyomatosis at its early stage. The tumor then slowly extended up the central veins toward the cardiac chambers over the years.
Because of the very slow-growing characteristics of this nonfriable tumor, patients may remain asymptomatic for a many years. Symptoms may appear only when significant venous obstruction, valvular impairment, or cavity compromise has occurred, leading in most cases to decompensated cardiac failure. Other presenting symptoms include dyspnea, leg edema, or abdominal distention from IVC syndrome, deep venous thrombosis, syncope from obstruction of the tricuspid or right ventricular outflow tract, and, rarely, pulmonary embolism or even sudden death due to extension of the tumor into the pulmonary vessels. Interestingly, ventricular ejection fraction itself may remain unaffected.
Preoperative imaging by venography, ultrasound, computed tomographic scan, or MRI invariably helps to identify the site of origin of the tumor and allows delineation of its route and venous extent, which is required for surgical planning. However, no imaging technique is adequate to make the differentiation between a benign and a malignant neoplasm preoperatively because often these tumors imitate growth patterns that are similar to more aggressive cancers. A histological diagnosis is therefore mandatory.
The unusual feature of this case report is that the tumor followed a less common route of extension, with intravenous spread progressing via the ovarian vein into the left renal vein and through the suprarenal IVC as opposed to the more commonly described pathway from the uterine vein into the internal iliac vein, common iliac vein, and IVC.3
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/120/3/e16/DC1.