Intravascular Lipoleiomyoma With Expansion Into the Right Atrium and Subsequent Debulking Surgery

Abstract

Backround

Lipoleiomyomas are rare, benign tumors combining smooth muscle and adipose tissue, most commonly found in the uterus.

Case Summary

A 61-year-old woman with a history of surgical treatment of uterine leiomyoma presented with syncopal episodes. Echocardiography revealed masses in the right atrium that led to urgent partial resection of a 10-cm tumor originating from the iliac veins. Three years later, recurrence was detected, extending from the iliac vessels to the atrium. This required complex thoracoabdominal surgery with an R1/2 resection, indicating a high likelihood of tumor recurrence. Pathologic examination confirmed an angioleiomyomatous tumor. Given its hormone receptor positivity, adjunctive letrozole therapy was initiated. Follow-up scans showed tumor regression, and the patient remains asymptomatic.

Discussion

For hormone receptor–positive cases, aromatase inhibitors may offer a viable option for managing recurrent tumors when complete resection is unachievable.

Take-Home Message

This case underscores the importance of a multidisciplinary approach for intravenous leiomyomas with cardiac involvement.

Graphical Abstract

History of Presentation

The initial presentation of the 61-year-old patient occurred in an outpatient setting following a syncopal episode with preceding symptoms. Preceding symptoms included a general feeling of discomfort, a rising sensation of warmth, and transient vision blackouts. Additionally, the patient had reported a mild limitation in physical endurance for several weeks before the syncopal episode.

Take-Home Messages

• •The successful management of complex intravenous leiomyomas with cardiac involvement relies heavily on a collaborative, multidisciplinary team approach to optimize both surgical and therapeutic strategies.
• •HR positivity in lipoleiomyomas provides a unique opportunity for adjunctive treatment with aromatase inhibitors, which can be particularly valuable in cases of incomplete resection.

Past Medical History

The patient’s medical history included 4 previous surgical procedures for leiomyomatous tumors, starting with an initial myoma resection, followed by a hysterectomy, a rectal resection, and a subsequent rectal extirpation. Additionally, the patient had a family history of lipomatosis. At this point, no cardiac preexisting conditions were known.

Differential Diagnosis and Investigations

Cardiac diagnostics included both a 12-lead electrocardiogram (ECG) and 24-hour Holter monitoring, neither of which revealed any relevant arrhythmias such as ventricular tachycardia or atrioventricular blocks. At the time of clinical evaluation, the patient’s vital signs were unremarkable and within normal ranges, with no indications of hemodynamic instability. Urgent echocardiography raised suspicion of a right atrial mass, prompting hospitalization and indicating surgical removal. In-hospital echocardiography supported the preliminary diagnosis, revealing a mass in the right atrium, which partially prolapsed into the right ventricle (Figures 1A and 1B). As part of the preoperative diagnostic work-up, coronary angiography was performed, which showed no evidence of significant coronary artery stenosis or underlying ischemic heart disease.

Figure 1.

Intracardiac Tumor Imaging With Echocardiography, Computed Tomography, and Magnetic Resonance Imaging

(A) Echocardiographic 4-chamber view with a round mass in the area of the right atrium that measured 28 mm × 27 mm. (B) Echocardiographic subxiphoid view with a pronounced mass extending from the inferior vena cava into the right atrium. (C) Axial T1-weighted gradient echo sequence with fat suppression, 7 minutes post contrast medium administration, shows the tumor in the right iliac vein. (D) Electrocardiogram-triggered heart computed tomography, axial imaging, slice thickness 1 mm, shows a smoothly marginated, approximately 30 mm × 27 mm mass located centrally in the right atrium, without contact with the intra-atrial septum. (E) Venous computed tomography, coronal reformation from 1-mm slices, shows the long course of the tumor extending from the right common iliac vein through the inferior vena cava into the right side of the heart.

Management

Urgent surgical removal of the tumor was indicated and performed through a right anterior minithoracotomy and cardiopulmonary bypass through the right femoral vessel under mild hypothermia. A 10-cm soft tissue tumor in the right atrium was resected in segments, with the origin identified in the inferior vena cava. All visible tumor tissue was successfully excised, and the patient had an uneventful recovery and was discharged home.

Three years later, an outpatient cardiology follow-up identified a recurrence of the tumor in the right atrium, prompting readmission, although the patient was asymptomatic at that time. Magnetic resonance angiography and ECG-triggered heart computed tomography (CT) revealed a tumor extending from the right iliac vessels into the right atrium, partially obstructing the vessel (Figures 1C to 1E). Following a tumor board review, multidisciplinary, 2-cavity surgery was planned, involving resection of the tumor from the common iliac vein and inferior vena cava through the right atrium (Figures 2A and 2B). The cardiac tumor was removed using general hypothermia (28 °C) without complications. Significant adhesions were noted in the internal iliac vein region, suspected as the tumor’s origin. Given the severe adhesions, further dissection was not possible, and partial resection of the common, internal, and external iliac veins was performed. The internal iliac vein was partially resected, and reinsertion was not performed, to avoid recurrent growth from this area. The common iliac vein was reconnected to the external iliac vein with a Dacron (polyethylene terephthalate, Invista) graft (Figure 2C). The histopathologic examination identified a histologically benign angioleiomyoma (Figures 2D and 2E).

Figure 2.

Macroscopic and Microscopic Views

(A) The right iliac vein. (B) The vein lumen is completely filled by the tumor. (C) A vascular prosthesis was sutured after resection (absorbable hemostasis around the graft). (D) Low-power view of intravascular lipoleiomyomatosis showing an admixture of fat vacuoles and eosinophilic smooth muscle cells; note the muscular venous wall on the left. (E) Higher magnification of the tumor showing biphasic differentiation of the tumor cells (fat and smooth muscle cells). (F) Diffuse and strong cytoplasmic expression of h-caldesmon in the smooth muscle tumor cells. (G) Strong nuclear expression of progesterone receptor in the tumor cells.

Complete resection (R0) was unachievable because of anatomical constraints, resulting in an R1 resection and a subsequent palliative prognosis. Postoperative CT imaging revealed residual soft tissue proliferation at the right iliac bifurcation and right-sided pelvic vein thrombosis extending from the femoral vein to the inferior vena cava junction. Further immunohistochemical staining for h-caldesmon, estrogen receptor (ER), and progesterone receptor (PR) confirmed the smooth muscle phenotype (h-caldesmon positive) and the genital origin (positive for ER [∼80%] and PR [∼40%]) (Figures 2F and 2G). The fumarase was retained in the tumor cells. Consequently, additive therapy with the aromatase inhibitor letrozole was initiated.

According to institutional protocol for sarcomas and sarcoma-like tumors, the case was reviewed in context of the Molecular Tumor Board (MTB) at the University Cancer Center Schleswig-Holstein (Lübeck, Germany). Whole-exome sequencing and immunohistochemistry were performed, and classical compound markers were analyzed. No mutations in tumor suppressor genes or oncogenes were identified, and none of the compound markers revealed actionable findings. Although these results support the benign nature of the disease, no additional treatment options were uncovered.

Outcome and Follow-Up

Follow-up CT scans 6- and 12-months post-treatment could not identify soft tissue proliferation along the psoas muscle, with no evidence of further tumor recurrence. The patient remains symptom free and maintains full weightbearing capacity.

Discussion

Lipoleiomyomatous tumors are rare, benign neoplasms composed of a unique mix of smooth muscle and adipose tissue. Primarily located in the uterus, they can also develop in other genital structures such as the ovaries and broad ligaments. Although benign, these tumors are diagnostically challenging because of their complex composition and rarity, requiring an in-depth understanding of their histogenesis, clinical presentation, and optimal management strategies. The exact histogenesis of lipoleiomyomas remains unclear, but they are thought to arise from multipotent mesenchymal stem cells capable of differentiating into multiple tissue types.¹ Hormonal influences, particularly from estrogen and progesterone, likely contribute to the development and growth of these tumors, similar to other uterine leiomyomas.²

Clinically, lipoleiomyomas often manifest with symptoms akin to uterine fibroids, including abnormal uterine bleeding, pelvic pain, and the presence of a palpable mass. The adipose component may make these tumors softer and more compressible than typical leiomyomas.³ The diagnosis relies on a combination of imaging and histopathologic examination, including immunohistochemical analysis to prove their smooth muscle composition. Imaging modalities such as ultrasound and magnetic resonance imaging (MRI) can reveal a well-circumscribed mass with mixed tissue characteristics, including fat-containing areas.¹ However, definitive diagnosis requires histologic analysis following biopsy or surgical excision.

Treatment generally involves surgical excision, which is typically curative. Given the benign nature of these tumors, complete resection usually prevents recurrence, and the prognosis is excellent. In asymptomatic cases where the tumor is incidentally discovered, a conservative approach with regular monitoring may be appropriate. Although hormonal therapy is not routinely indicated, it may be considered in cases where local therapies are not feasible and hormonal influence is suspected to contribute to tumor growth.

In this case, given the patient’s previous hysterectomy, the tumor may have originated from her previous uterine leiomyomas or from the pelvic and retroperitoneal veins. Cardiac involvement occurs in approximately 10% of cases. These tumors are generally highly mobile, do not attach to the walls of the cardiac chambers, and can easily be misdiagnosed as a primary cardiac tumor or thrombus in transit.⁴

Optimal treatment for intravenous leiomyoma involves complete tumor resection, often accompanied by hysterectomy and bilateral salpingo-oophorectomy. The primary factor in preventing recurrence is achieving full resection of the lesion. In our patient, hysterectomy and bilateral salpingo-oophorectomy had already been completed before the tumor extended to the cardiac cavity. With cardiac involvement, the surgical approach is determined by comparing the tumor’s diameter with the diameter of the inferior vena cava. In cases such as ours, where the tumor’s diameter exceeds the vena cava entry, a combined thoracoabdominal procedure under cardiopulmonary bypass is recommended. This approach allows direct access to the heart for tumor removal, thereby enabling both chest and vascular operations in a single session.

In view of the ER and PR positivity in our patient, targeted therapy with aromatase inhibitors appears promising for treating hormone receptor (HR)–positive lipoleiomyomas. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, are typically used for treatment of ER-positive breast cancer by inhibiting the aromatase enzyme (cytochrome P450 19A1), which converts androgens into estrogens in peripheral tissues. By suppressing estrogen synthesis, aromatase inhibitors significantly reduce circulating estrogen levels, thus limiting the growth stimulus for estrogen-dependent tumor cells.⁵ Unlike selective ER modulators such as tamoxifen, which only block ERs, aromatase inhibitors reduce estrogen synthesis by up to 95% in postmenopausal women, making them the standard adjuvant therapy for ER-positive breast cancer.⁶ In premenopausal women, however, aromatase inhibitors are typically combined with ovarian suppression therapy to prevent compensatory estrogen production.⁷

The discussion of difficult-to-treat cancers—whether the result of rarity or unique biological behavior—in the MTB is a cornerstone of interdisciplinary treatment at our institution. In this case, general histopathologic examination indicated a benign tumor, and mutations in classical oncogenes or tumor suppressors were not anticipated. However, the analysis of compound markers often offers promising avenues for additional treatment options. Recent preliminary data from malignant sarcoma cases presented to the board revealed that in 90% of cases, new treatment options were identified, with approximately 75% of these based on compound markers.⁸ In this specific case, only an amino acid substitution in the UBE2A gene and numerous copy number variations with partial deletions were found. Unfortunately, neither finding currently provides an alternative treatment option.

Because of the extensive recurrence and the sometimes rapid progression of leiomyomas, it becomes obvious that there is a high need for a well-structured surveillance protocol, particularly in cases with incomplete resection. For patients with incomplete resection, surveillance intervals should be tailored on the basis of clinical factors such as the extent of residual disease, HR status (because growth is dependent on progesterone and estrogen), and previous growth patterns. In this case, recurrence was observed within 3 years, thus underscoring the need for more frequent imaging, such as every 6 months, in the initial years following surgery, with adjustments based on stability or progression. Contrast-enhanced MRI and CT are considered the gold standards for evaluating intravenous leiomyomas. Echocardiography may remain an important complementary tool for cardiac involvement surveillance, even if its importance lies in the field of primary diagnostics. Combining these modalities may provide comprehensive monitoring in cases with extensive vascular and cardiac involvement.

Additionally, leiomyoma proliferation rates can vary, influenced by hormonal activity and other biological factors. Studies have shown that higher proliferation indices, such as antigen Kiel 67 (Ki-67), correlate with more aggressive growth. Leiomyomas generally have a low proliferation rate, whereas atypical leiomyomas or leiomyomas with increased cellular activity show increased Ki-67 values. This is particularly important because leiomyomas are fundamentally benign tumors; however, given their rapid growth, they can exert pressure on surrounding tissues and cause bleeding. In clinical practice, leiomyomas with a high proliferation rate but without signs of malignancy are often treated more aggressively (eg, early myomectomy or hysterectomy). Additionally, in some cases, high proliferation may indicate an insufficient response to hormone therapy.⁹ In this case, Ki-67 staining was not available but may have provided valuable insight into the tumor’s biological behavior and informed follow-up strategies. Incorporating such biomarkers into routine histopathologic evaluation could help stratify patients by recurrence risk and guide the intensity of follow-up. However, because of the rarity of the disease, there are no clear evidence-based guidelines for action.

Given the patient’s age and the incomplete R1/R2 resection, we opted for an additive therapy with the reversible aromatase inhibitor letrozole. Although data on aromatase inhibitor use for lipoleiomyomas are limited by the rarity of intravascular forms, a 2008 study showed that 5 mg of letrozole daily for 3 months significantly reduced leiomyoma diameter and menstrual bleeding.¹⁰ This finding suggests that aromatase inhibitors may offer a viable treatment option for hormone-responsive lipoleiomyomas. Therefore, we hereby assume that aromatase inhibitors, such as letrozole, may offer a promising treatment option for hormone-responsive intravenous leiomyomas, especially in cases where complete surgical resection is challenging.

Conclusions

Surgical resection remains the first-line therapy for HR-positive lipoleiomyomas. In cases of likely incomplete resection, adjunctive aromatase inhibitor therapy should be reconsidered as a potential strategy to achieve remission.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.