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Vasc Specialist Int
Vasc Specialist Int
Vascular Specialist International
2288-7970
2288-7989
The Korean Society for Vascular Surgery

10.5758/vsi.240048
vsi-40-28
Case Report
Three Cases of Intracardiac Leiomyomatosis with Very Long-term Follow-up
https://orcid.org/0000-0001-5101-1541
Gonzalez-Urquijo Mauricio
https://orcid.org/0000-0003-3406-4769
Valdes Francisco
https://orcid.org/0000-0001-6929-4850
Mertens Renato
https://orcid.org/0000-0002-2135-4559
Mariné Leopoldo
https://orcid.org/0000-0003-3158-5411
Vargas Jose Francisco
https://orcid.org/0000-0002-8900-1645
Bergoeing Michel
Department of Vascular and Endovascular Surgery, School of Medicine, Pontifical Catholic University of Chile, Santiago, Chile
Corresponding author: Francisco Valdes, Department of Vascular and Endovascular Surgery, School of Medicine, Pontifical Catholic University of Chile, Av. Apoquindo 3990 Of. 601, Santiago 7550112, Chile, Tel: 56-2-22070721, E-mail: pancho.valdes.e@gmail.com, https://orcid.org/0000-0003-3406-4769
2024
12 9 2024
12 9 2024
40 288 5 2024
27 7 2024
5 8 2024
Copyright © 2024 The Korean Society for Vascular Surgery
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Uterine intravascular leiomyomatosis (IVL) with extension into the right heart is uncommon, with no more than 400 cases reported in the literature since 1907. The present study aims to report three patients with intracardiac IVL surgically treated in our institution, with long-term follow-up. Three female patients in their third to fifth decades of life, with a history of difficult hysterectomy due to extensive myomatosis, presented with symptoms of right-sided heart failure. Echocardiography and computed tomography were performed, where IVL extending from the pelvis into the right heart was observed. All three patients underwent a one-stage operation under extracorporeal circulation through a right auriculotomy and inferior vena cavotomy, accessed via a sterno-laparotomy. The tumors were extirpated without complications, with ligation of the vena cava or iliac vein. The patients at 10-, 13-, and 37-year follow-up were well and alive with mild lower extremities symptoms.

Intravascular leiomyomatosis
Intracardiac leiomyomatosis
Uterine leiomyomatosis
Vena cava tumor
Right heart tumor
FUNDING None.
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pmcINTRODUCTION

Intravascular leiomyomatosis (IVL) is an uncommon benign tumor originating from smooth muscle cells within the uterine veins. IVL can extend beyond the uterine wall into the iliac veins, inferior vena cava (IVC), and, less commonly, the right atrial and ventricular cavities, as well as the pulmonary artery [1]. Due to the rarity of this disease, the exact incidence is unknown; however, no more than 400 cases of IVL have been reported in the literature since 1907 [2]. The disease is known to be benign; nevertheless, when the tumor reaches the right atrium, lethal complications, such as sudden death caused by total outflow obstruction, may arise [3]. In a review of 323 patients with IVL, 212 patients had intracardiac IVL, of which 11 (3.4%) died [2]. Most patients are middle-aged females in their fourth or fifth decade of life [3]. In the early stages, patients may be asymptomatic or present with symptoms such as pelvic congestion or lower limb edema. In advanced stages, when the tumor reaches the right heart cavity, symptoms may be similar to those of right-sided heart failure, including dyspnea, orthopnea, chest pain, massive bilateral lower limb edema, and syncope [2].

The present study aims to report three patients with intracardiac IVL surgically treated in a single academic institution, with extended long-term follow-up.

This study was performed with prior consideration from the Institutional Review Board of the Pontifical Catholic University of Chile under number 231003003 and abides by the norms established in the Helsinki Conference of 1964 as well as its revision in 2012.

Informed consent has been obtained from the patients for publication of the case reports and accompanying images.

CASE

1) Case 1

A 35-year-old female with a history of a complex hysterectomy at her local hospital in January 1986 due to extensive uterine myomatosis, which resulted in a large vesico-vaginal fistula, was referred to our hospital 6 months later. She presented with incapacitating dyspnea, orthopnea, ascites, and lower extremities edema. Right-sided heart failure was suspected by her local cardiologist after an echocardiogram. Despite treatment with warfarin, her symptoms did not improve.

On physical examination, she was cyanotic and cachectic, weighing 36.5 kg, with prominent jugular veins, hepatomegaly, jaundice, ascites, and lower extremities edema. A chest radiograph revealed cardiomegaly and bilateral pleural effusion. An ascending phlebography via the right femoral vein revealed complete ilio-caval occlusion with an enlarged azygos and hemiazygos network draining into the heart. Echocardiography revealed a large mass inside the right heart chambers. Computed tomography (CT) angiography confirmed that the supra- and infrarenal IVC was fully occupied by a mass originating in the pelvic veins, extending through the retrohepatic vena cava into the right atrium, right ventricle, and main pulmonary artery (Fig. 1A). An enlarged liver showed a spider vascular pattern confirming severe venous congestion (Fig. 1B).

The patient underwent one-stage surgery through a median sternotomy and laparotomy. Under cardiopulmonary bypass, a right auriculotomy and inferior vena cavotomy below the renal vein confluence were performed, exposing a large, whitish, firm tumor that was not adherent to the caval endothelium. Complete intracardiac and IVC tumor removal was achieved by dividing the tumor and extracting the lower part through the vena cava and the upper part through the right atrium. Finally, ligation of the infrarenal IVC was performed (Fig. 1C, D).

The patient stayed in the intensive care unit for 20 days requiring inotropic and respiratory support, and enteral nutrition. One week after surgery, reinforcement of the laparotomy was required due to an ascitic fistula. She was discharged home on 33rd postoperative day on aspirin 100 mg per day. Biopsy confirmed an angioleiomyoma of intrauterine origin (Fig. 1E). A discharge CT confirmed that the heart and IVC were free from residual disease. At 21 months of follow-up, she had gained 28 kg, was fully active, with lower extremities elastic support. Twenty-five years after surgery, CT angiography showed an absence of intracavitary tumor and patent IVC from the level of the renal veins (Fig. 1F). However, a large heterogeneous pelvic mass, similar to those seen in previous scans, was observed, associated with chronic occlusion of the pelvic veins and significant development of ascending subcutaneous veins of the abdominal wall, which has been managed conservatively. At the 37-year follow-up, the patient was fully active, free of dyspnea and edema, with no significant clinical incapacitation. The patient declined further gynecologic surgery, so no further attempts have been made to operate on the remaining pelvic mass.

2) Case 2

A 51-year-old female with a medical history of dyslipidemia, systemic arterial hypertension, and a hysterectomy due to large uterine myomatosis 10 years prior, was referred to our institution. She presented with a lower abdominal mass and worsening dyspnea over the past year. A CT scan showed a large pelvic mass associated with IVC and left iliac vein thrombosis, and initiation of anticoagulation therapy was advised. Thoracoabdominal CT revealed a non-occlusive intravascular mass inside the IVC, extending to the right heart chambers and the tricuspid valve (Fig. 2A, B).

The patient underwent one-stage surgery under extracorporeal circulation through a sternotomy and midline laparotomy. The tumor was removed through a right auriculotomy and an infrarenal cavotomy. The left iliac vein, to which the tumor was firmly adherent, was ligated together with pelvic tumor removal. The right iliac vein was preserved.

The postoperative course was uneventful, and the patient was discharged on the 7th postoperative day on aspirin 100 mg daily and rivaroxaban 10 mg daily for 20 days. Biopsy revealed a leiomyoma with hyaline degeneration. At 13-year follow-up, the patient had mild left lower extremity edema, which improved with compression stockings. Her lastest CT scan showed the previously ligated left iliac vein with multiple collaterals and no tumor recurrence (Fig. 2C).

3) Case 3

A 55-year-old female with a medical history of systemic arterial hypertension, dyslipidemia, diabetes mellitus, and a hysterectomy for uterine myomatosis (1.8 kg) five years prior, complained of abdominal pain, dyspnea, orthopnea, and palpebral edema for seven days. An initial ultrasound revealed thrombosis of the IVC, thus prompting referral to our outpatient clinic for further work-up. A CT scan was obtained, in which a uterine tumor was observed extending through the IVC into the right atrium and ventricle beyond the tricuspid valve (Fig. 3A) along with a small pedicled mass (1.9 cm) in the pelvic cavity.

She was scheduled for one-stage surgery, through a median sternotomy and laparotomy under extracorporeal circulation. During auriculotomy, the tumor was observed to be free-floating in the right atrium and ventricle and easily removed. The rest of the tumor, which was not adherent to the IVC but occupied nearly 80% of the lumen, was removed via infrarenal cavotomy. The IVC was ligated distally, preserving the lumbar and ovarian veins, just above the confluence of the iliac veins.

She was discharged on the 7th postoperative day on aspirin 100 mg daily after four days in the ICU. At a 10-year follow-up, she remained fully active. Repeat thoracoabdominal CT scan was performed, which revealed a patent suprarenal IVC and right heart, with occlusion of the infrarenal IVC (Fig. 3B-D). Additionally, a well-defined 72 mm rounded mass was located on the uterine bed with no lymph nodes detected, which has been managed without further treatment to date. Table 1 summarized the three cases.

DISCUSSION

Uterine leiomyoma is a common condition among females of reproductive age, being the most common tumor in the female genital tract. However, the occurrence of leiomyoma with intravenous extension reaching the heart is rare [4]. We present three cases treated in our institution and operated on by the same team in a period of four decades, all of them with acceptable results and long-term follow-up.

This condition was first described in 1897 by Birch-Hirshfield from an autopsy, and the first case with intracardiac extension was published 10 years later by Dürck [5]. Since then, no more than 300 cases with intracardiac extension have been reported in the literature [2]. The three cases in the present series represent the longest follow-up reported among patients with IVL and intracardiac extension. These tumors are benign, and prolonged survival can be achieved with timely treatment before the tumor completely obstructs the cardiac chambers.

Intravascular leiomyomatosis has no confirmed pathogenesis, but three primary hypotheses have been proposed. The first is that the tumor arises from the wall of the vein. The second suggests that the tumor grows through a vascular invasion of the myometrium from a primary uterine leiomyoma. Finally, the third hypothesis proposes that the IVL originates from the myometrium rather than from the tumor itself [6]. Kir et al. [7] reported the immunohistochemical analysis of seven cases with IVL. They discovered low levels of estrogen and progesterone receptor expression in endothelial cells compared to high levels of expression in intravenous tumor cells, discarding the theory of the tumor arising from the vessel wall and supporting the idea of the tumor arising from a pre-existing leiomyoma. If the origin was in the smooth muscle cells of the veins, it would likely be a more common tumor originating from vessels in other body areas. Our three patients had a history of difficult hysterectomies due to extensive myomatosis and all of them had proliferation of smooth muscle cells within the extracted tumor. Thus, we suspect that the tumor arose from a uterine leiomyoma rather than from the vessel itself. This theory is also supported by Chen et al. [2]. In their systematic review, 97.4% and 91.7% of the patients with IVL tested positive for PR and ER expression, respectively.

Imaging studies include CT angiography, magnetic resonance angiography, and echocardiography [8]. The first two are used to evaluate the tumor's size and extension, whereas the last one can provide real-time information on the cardiac tumor and overall cardiac function [3]. Differential diagnoses for IVL include right atrial myxoma, renal cell carcinoma extending to the IVC, vena cava thrombosis, and leiomyosarcoma arising from the IVC wall [3,8].

The only proposed treatment for IVL with cardiac extension is surgical resection of the tumor. Depending on the extent, the approach may differ. If the tumor extends into the heart, combined exploration of the chest, abdomen, and pelvis is recommended [3]. Most of these operations are performed with cardiopulmonary bypass and total circulatory arrest, although the on-pump beating heart technique has been used in some cases [9]. If the tumor only extends into the IVC without extension to the superior vena cava or right heart, chest exploration may be avoided, and a laparotomy alone may suffice [8]. Furthermore, hysterectomy with bilateral salpingo-oophorectomy is recommended to avoid the risk of recurrence due to the estrogen-dependent characteristic of the tumor. Ligation of the involved vein may also be sufficient to prevent recurrent tumor invasion into the proximal veins [3].

In our three cases, we employed extracorporeal circulation to assist in tumor removal, particularly due to the possibility of adherence to the endocardium. However, the tumors, which had firm, rubbery consistencies, were freely movable in all three cases, and complete removal from major vessels was achieved swiftly. We opted for a combined sternotomy and laparotomy approach to directly visualize the heart chambers and protect the tricuspid valve during tumor extraction. Additionally, we chose to ligate the vena cava in two cases, and the left iliac vein in one case to prevent future recurrences through endovenous propagation, considering that residual pelvic tumor remained in all three patients. The long absence of tumor recurrence in major veins suggests that simple mechanical ligation, following complete removal of all accessible intravascular tumor, may be sufficient treatment, and complete radical removal of the pelvic tumor may not be mandatory. Notably, the patients’ quality of life has not been adversely affected in the long-term follow-up, except for occasional mild lower extremity edema, which improves with use of compression stockings.

Some authors have reported recurrence rates of up to 30% in patients with intracardiac leiomyomatosis. Li et al. [3], in their systematic review of 194 patients, found a 0% recurrence rate among those who underwent complete tumor removal, compared to a 33.3% recurrence rate among those with incomplete removal, with the longest follow-up period extending up to 12 years. Notably, the performance of vena cava ligation was not specified in this review. Similarly, Chen et al. [2] reported an 18% recurrence rate, with a median follow-up of 9 months. Timmis et al. [10] reported a case of intracardiac IVL with recurrence into the atrium following complete tumor removal, indicating that inadvertent residual tumor tissue may have been left behind, leading to subsequent slow re-extension into the heart. Furthermore, in 1966, Edwards and Peacock [11] also suggested that intravenous extension of the tumor is unlikely if it disconnected from the primary source (uterus). In our current series, all three patients experienced local recurrence after hysterectomy; however, none exhibited recurrence in the vena cava or heart after IVL tumor removal, possibly due to the vena cava ligation.

In conclusion, we present three cases of patients with intracardiac leiomyomatosis who were successfully treated with tumor extirpation via sternotomy, extracorporeal circulation, and laparotomy. This series presents the longest follow-up of patients with intracardiac leiomyomatosis, supporting the idea that the disease is benign.

ACKNOWLEDGEMENTS

We would like to express our gratitude to Dr. Manuel J. Irarrazaval and Dr. Cecilia Muñoz, cardiac surgeons at the Pontificia Universidad Católica de Chile, Santiago, Chile, for their invaluable surgical assistance in these cases. We also thank Dr. Alexis Lama, cardiologist at the Hospital Regional de Concepción, Concepción, Chile, for his crucial role in diagnosing the first case.

Fig. 1 (A) Preoperative CT scan showed leiomyomatosis inside the right ventricle (white arrow). (B) Preoperative CT scan showed leiomyomatosis inside the retrohepatic vena cava causing significant hepatic congestion (white arrow). (C) Intraoperative auriculotomy showed a large tumor inside the right heart chambers. (D) Macroscopic appearance of leiomyomatosis after complete extirpation. (E) Microscopic haematoxyilin and eosin stain showed proliferation of smooth muscles cells. (F) Postoperative CT scan after 25 years showed a normal vena cava without any intravascular tumor (white arrow). CT, computed tomography.

Fig. 2 (A) Preoperative CT scan showed leiomyomatosis inside the vena cava and right heart (white arrow). (B) Preoperative CT scan showed the tumor inside the vena cava (white arrow). (C) Postoperative CT scan after 13 years showed a vena cava free of tumor (white arrow). CT, computed tomography.

Fig. 3 (A) Preoperative CT scan showed leiomyomatosis inside the vena cava and right heart (white arrow). (B) Postoperative CT scan after 10 years showed a tumor-free heart (white arrow). (C) Postoperative CT scan after 10 years showed the tumor-free inferior vena cava (white arrow). (D) The infrarenal inferior vena cava was ligated (white arrow). CT, computed tomography.

Table 1 Summary of the three report cases with intracardiac leiomyomatosis

Year of surgery	Sex/Age (y)	Prior hysterectomy	Symptom	Tumor location	Treatment	Follow-up	
1986	F/35	Yes
6 mo	Dyspnea, orthopnea, ascites, lower extremities edema	IVC, right heart, pulmonary artery	Sternotomy and laparotomy, tumor removal, IVC ligation	37 y	
2011	F/51	Yes
10 y	Dyspnea	IVC, right heart	Sternotomy and laparotomy, tumor removal, left iliac vein ligation	13 y	
2013	F/55	Yes
5 y	Dyspnea, orthopnea, palpebral edema, abdominal pain	IVC, right heart	Sternotomy and laparotomy, tumor removal, IVC ligation	10 y	
F, female; IVC, inferior vena cava.

CONFLICTS OF INTEREST

The author has nothing to disclose.
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