Authors: Edoardo Romano, Jonathan Schütze, Florian Schönhoff, Franziska Siegenthaler, Yara Banz, Christoph Gräni
Categories: Cardio-Oncology, atrial flutter, beta-blockers, cancer, echocardiography, hemodynamics, imaging, pitting edema, systolic heart failure, tricuspid valve, valve replacement
Source: JACC Case Reports
Authors: Edoardo Romano, Jonathan Schütze, Florian Schönhoff, Franziska Siegenthaler, Yara Banz, Christoph Gräni
Masses in the right ventricle are uncommon, but if present, they are most often attributed to either primary cardiac tumors or metastatic disease.
A 50-year-old woman presented with progressive lower extremity edema and was diagnosed with a right ventricular mass causing severe tricuspid insufficiency and near-total obstruction of the pulmonary artery. She had a history of hysterectomy for uterine leiomyomatosis. Based on imaging and histological findings, a diagnosis of benign metastasizing leiomyoma (BML) was made. The patient underwent successful resection of the mass, tricuspid valve replacement, and implantation of a right ventricle–pulmonary artery conduit.
Cardiac metastasis from BML is extremely rare, particularly in the right heart. Although histologically benign, BML can lead to life-threatening cardiac complications. This case emphasizes the importance of thorough cardiac assessment in patients with a history of leiomyoma and unexplained symptoms. Early diagnosis and surgical management are essential to prevent serious outcomes.
BML, though rare, can cause life-threatening cardiac involvement. Clinicians should consider a comprehensive cardiac evaluation for patients with unexplained cardiac symptoms and a history of leiomyoma.
Right ventricular masses are uncommon and can originate from primary cardiac neoplasms, metastatic lesions, or thrombotic sources. One exceptionally rare cause is metastatic cardiac involvement from benign metastasizing leiomyoma (BML). Although rare, this condition is clinically significant and is more frequently observed after surgical interventions such as hysterectomy. BML is characterized by the spread of benign uterine leiomyomas to distant organs, most frequently the lungs.^1^ Cardiac metastases occur in <1% of BML cases, with right heart involvement being more prevalent owing to its direct connection to the venous system and its proximity to systemic circulation.^2^ Imaging plays a key role not only in diagnosing cardiac masses by evaluating size, location, and functional impact but also in guiding biopsy and surgical planning.^3^^,^^4^ This involves multimodality imaging, including echocardiography, cardiac magnetic resonance imaging (MRI), and cardiac computed tomography (CT).^5^Take-Home Messages•Benign metastasizing leiomyoma, although rare, can cause life-threatening cardiac involvement.•Clinicians should consider a comprehensive cardiac evaluation for patients with unexplained cardiac symptoms and a history of leiomyoma.
A 50-year-old woman presented with progressive symptoms, including weight loss, night sweats, and worsening leg edema. She had a history of total hysterectomy performed 12 years earlier for multiple intramural and submucosal uterine leiomyomas. In January 2024, she was diagnosed with atrial flutter (Figure 1) and was initiated on beta-blocker therapy to manage her heart rate. Despite treatment, she experienced ongoing fatigue and continued lower extremity edema. As her symptoms worsened, she was referred to a cardiologist for further evaluation. A transthoracic echocardiography (TTE) performed at a local regional hospital in February 2024 revealed a hypertrophic left ventricle with moderately reduced systolic function (ejection 40%-45%) and systolic-diastolic D-shaping of the interventricular septum. The right ventricle was severely dilated, with impaired systolic function. An inhomogeneous echodensity with a maximum diameter of 8 cm was observed attached to the tricuspid valve leaflet, causing severe regurgitation with a flail leaflet and a coaptation gap of 1.2 cm (Videos 1 and 2). Additionally, the inferior vena cava was dilated, with diminished respiratory variability.Figure 1Electrocardiogram of the Patient at Initial Presentation
Because of the patient's elevated heart rate with atrial flutter, which could cause electrocardiogram-gated artifacts on cardiac MRI, a cardiac CT scan was chosen for downstream imaging. The cardiac CT confirmed a mass within the right ventricle that measured 3 × 4 × 8 cm and extended toward the tricuspid valve and into the pulmonary artery, with near-complete obstruction of the pulmonary trunk, significantly compromising hemodynamics (Figure 2). The tumor's extension into the tricuspid valve caused severe tricuspid regurgitation, which further worsened the patient's clinical condition. Given the imaging findings and the patient's history, the differential diagnosis suggested a malignant process—such as metastasis or leiomyosarcoma—over a benign etiology. The case was therefore presented to the interdisciplinary sarcoma board, where various treatment strategies were considered, including whether surgery would be appropriate or if neoadjuvant radiotherapy should be performed first. A positron emission tomography–CT scan was considered during the meeting but was ultimately deferred in favor of immediate surgical management owing to the patient's hemodynamic instability and the risk of rapid deterioration. A biopsy of the intracardiac mass was not attempted because of the high risk of procedural complications, including embolization and hemodynamic compromise, given the tumor's critical location. Faced with these concerns, surgical resection was selected as the initial approach. Intraoperative planning aimed to remove as much affected tissue as possible, based on preoperative imaging suggesting potential infiltration of surrounding cardiac structures.Figure 2Transesophageal Echocardiography and Cardiac Computed Tomography Images(A) Initial echocardiography showing tumor mass in the right ventricle (RV) and D-Shaping of the left ventricle (LV). (B to D) Cardiac computed tomography showing a tumor mass in the right ventricular outflow tract (RVOT) and a total obstruction of the pulmonary artery (PA). RA = right atrium.
The patient underwent tumor resection from the pulmonary artery and right ventricle, along with tricuspid valve replacement using a 33-mm St Jude Medical Epic prosthesis and implantation of a right ventricle–pulmonary artery conduit with a 28-mm Vascutek prosthesis and a 25-mm Perimount Magna Ease prosthesis (Edwards Lifesciences). Intraoperatively, transesophageal echocardiography (TEE) was used to assess the cardiac structures and the extent of valvular involvement. The preresection TEE demonstrated an echogenic mass prolapsing through the tricuspid valve into the right atrium and ventricle (Video 3), clearly adherent to the tricuspid valve leaflets. Additionally, there was a markedly dilated tricuspid annulus with a large coaptation gap between the leaflets, associated with severe eccentric tricuspid regurgitation (Video 4, Video 5, Video 6).
After surgical resection and valve replacement, intraoperative TEE confirmed normal function of the bioprosthetic tricuspid valve, with no evidence of paravalvular leak (Video 7), as well as normal function of the bioprosthetic pulmonary valve, without signs of paravalvular leak (Video 8). Postoperatively, the patient continued beta-blocker therapy, with telemetry confirming stable sinus rhythm and no recurrence of atrial flutter throughout recovery.
On postoperative day 6, a TTE was performed to evaluate prosthetic valve function. The TTE demonstrated that both the surgical biological pulmonary and tricuspid valve prostheses were functioning normally, without evidence of regurgitation or prosthetic obstruction (Videos 9 and 10).
Histopathological and immunohistochemical evaluation of the resected mass revealed the classic presentation of a leiomyoma, consisting of a proliferation of bland, mitotically minimally active smooth muscle cells without atypia or other features suggestive of malignancy, almost identical to the initial samples from the hysterectomy specimen, which was reviewed for comparison (Figures 3 and 4). The final histopathological diagnosis of a BLM was therefore unexpected and retrospectively redefined the understanding of the disease and therapeutic course. The patient completed outpatient cardiac rehabilitation and remained asymptomatic 6 months after diagnosis and successful surgery. A subsequent CT scan incidentally revealed a large 18-cm pelvic mass, which was successfully removed via laparotomy and confirmed histopathologically as a benign leiomyoma, consistent with the previously excised cardiac tumor.Figure 3Overview of Microscopic PathologyRepresentative images of one of the many leiomyomas detected in the original hysterectomy specimen. (A) The hematoxylin and eosin (H&E) stain reveals in this overview a proliferation of spindle-shaped cells with relatively abundant pink cytoplasm and ill-defined cell margins. (B) Higher magnification H&E staining shows hyalinized stroma interspersed between the neoplastic smooth muscle cell proliferation. There is no nuclear atypia, no mitotic activity or necrosis. (C) The neoplastic cells typically show immunohistochemical expression of smooth muscle markers (brown color) such as smooth muscle actin. (D) In accordance with the lack of histologically detectable mitotic figures, immunohistochemical staining for phosphohistone H3, a marker of cells in the late G2 and M phases of the cell cycle—used to identify mitotic activity—is essentially negative in the neoplastic population.Figure 4Overview of Macroscopic Pathology(A and B) Gross presentation as well as histopathological presentation of the tumorous mass removed from the right heart. The lesion corresponds to a firm white to tan-colored, well-demarcated, slightly bosselated solid mass. Cross-sectional analysis reveals a typical gross presentation commonly observed in well-differentiated benign leiomyomatous lesions, with a whorled appearance, revealing no necrosis or relevant hemorrhage. (C) Hematoxylin and eosin staining reveals the smooth muscle proliferation with relatively abundant hyalinized stroma interspersed, morphologically almost identical with the presentation in the hysterectomy specimen years prior. Again, no nuclear atypia and no mitotic activity or necrosis is observed. (D) The neoplastic cells typically show immunohistochemical expression of smooth muscle markers (brown color) such as smooth muscle actin.
This case involves a middle-aged woman presenting with cardiac symptoms and a right cardiac mass from underlying BML, affecting both the tricuspid and pulmonary valves. While BML is a rare cause of cardiac tumors, it should be considered in the differential diagnosis for female patients with cardiac masses and a history of uterine leiomyomas. Despite its histologically benign nature, BML exhibits metastatic behavior and can cause life-threatening cardiac obstructions. This case highlights the importance of early diagnosis and collaborative management to prevent severe complications related to BML with cardiac involvement. BML is a rare condition that primarily affects premenopausal or perimenopausal women, with a mean age at diagnosis of approximately 47 years. The disease often manifests years after initial surgical treatment for uterine leiomyomas, with a latency period ranging between 8 and 15 years. This latent course, as seen in our patient, highlights the indolent progression of BML, in contrast to the aggressive nature of leiomyosarcomas, which exhibit rapid metastasis and more severe clinical manifestations.^6^
Cardiac involvement in BML is extremely rare, occurring in <1% of reported cases, with right ventricular involvement being one of the rarest manifestations. Right heart masses can cause significant hemodynamic compromise, such as tricuspid valve insufficiency and pulmonary artery obstruction, as observed in our patient. Additionally, mechanical compression of cardiac structures may lead to electrical disturbances, contributing to arrhythmias such as atrial flutter. In BML cases, intracardiac masses can irritate the right atrium, disrupting normal electrical activity.^7^ The right atrium is particularly susceptible to arrhythmias when mechanically compressed or irritated by masses or structural abnormalities, which can alter conduction pathways and trigger re-entrant circuits. This disruption, especially near the sinoatrial node or conduction pathways, can promote ectopic firing and sustain atrial flutter, a common arrhythmia in patients with cardiac masses.^8^
BML lesions typically appear as well-defined, homogeneous masses lacking necrosis, consistent with their benign nature. Conversely, leiomyosarcomas frequently present with irregular borders and areas of necrosis, reflecting their malignant behavior. Considering both the timeline and imaging findings is crucial when evaluating patients with a history of leiomyoma presenting with new symptoms, as prompt recognition of cardiac involvement in BML is essential for timely intervention. Echocardiography is typically the first-line diagnostic tool, enabling initial assessment of mass location and functional impact. However, when more detailed imaging is required, particularly before surgery, advanced modalities such as cardiac MRI or cardiac CT should be performed. Surgical resection remains the most effective treatment, particularly when mechanical obstruction or valvular dysfunction is present.^9^
This case is particularly notable as the first reported instance to our knowledge of BML involving both the tricuspid and pulmonary valves. The near-total obstruction of the pulmonary outflow tract and the severe tricuspid insufficiency underscore the need for long-term clinical and imaging surveillance to monitor for recurrence in cardiac BML. Unlike leiomyosarcomas, which metastasize rapidly and present with aggressive symptoms, BML typically follows a more indolent course.^10^
Although BML is an uncommon cause of cardiac tumors, it should be considered in the differential diagnosis in symptomatic female patients with cardiac masses and a history of uterine leiomyomas. Despite its histologically benign nature, BML demonstrates metastatic behavior and can result in life-threatening cardiac obstructions. This case highlights the critical need for early recognition and interdisciplinary management to mitigate the severe complications associated with cardiac metastases of BML.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.