Benign Metastasizing Leiomyoma Causing Severe Tricuspid Regurgitation and Heart Failure

Introduction

Benign metastasizing leiomyoma (BML) is a rare condition in which benign smooth muscle tumors, known as leiomyomas, grow and spread to distant sites in the body. Although the tumors are benign, they can behave like malignant tumors by invading and growing in other organs. Benign metastasizing leiomyoma is more commonly diagnosed in women who have had a history of uterine leiomyomas (fibroids). The exact cause of BML is unknown.

Of all the cardiac smooth muscle tumors, BML is the least common and least reported in the literature. Although leiomyomas are considered benign, BML has been documented to metastasize to the lungs, axial skeleton, and rarely to heart or lymphatic system. These metastases are often found after hysterectomy has been completed, and may cause mild symptoms, but are commonly asymptomatic. ¹ We present a case of BML to the tricuspid valve causing severe regurgitation and heart failure.

Case Presentation

A 51-year-old woman with a history of hypertension, type 2 diabetes, and dysfunctional uterine bleeding presented with progressive lower extremity swelling of 3 weeks duration. The swelling was associated with pain and tenderness when palpated, without warmth or erythema. She reported having regular heavy menses for 5 years, that stopped after menopause 2 years prior. She denied exertional chest pain, shortness of breath, paroxysmal nocturnal dyspnea, cough, fever, weight loss, or dysuria. The patient denied any history of intravenous drug use. On physical examination, she was afebrile, with jugular vein distention and +3 bilateral lower limb edema. Lungs were clear and cardiac sounds had regular rate and rhythm. A grade III/VI holosystolic murmur was heard on the left lower sternal border. The abdomen was distended, but soft, with mild tenderness on suprapubic area with active bowel sounds. No skin rash, Janeway lesions, Osler nodes, or splinter hemorrhages were noticed on examination. No stigmata of chronic liver disease were seen. Initial labs revealed mild thrombocytopenia with normal erythrocyte sedimentation rate and C-reactive protein. Electrocardiogram showed sinus rhythm and incomplete right bundle branch block. Transthoracic echocardiogram showed severe tricuspid regurgitation and tricuspid valve vegetation with normal ejection fraction (Figure 1 and Supplemental Video 1). Computed tomography (CT) pulmonary angiogram showed a filling defect in the left lower pulmonary artery suspicious for calcified embolus and multiple bilateral sub-centimeter pulmonary nodules in the lower lungs that appeared to be contiguous with the vasculature. A transesophageal echocardiogram showed a large vegetation oscillating between the right ventricle and right atrium on the posterior and septal leaflets of the tricuspid valve, and small vegetations on the anterior leaflet.

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Figure 1.

This is a 2-dimensional transthoracic echocardiogram apical 4-chamber view that visually demonstrates vegetation attached to the tricuspid valve (red arrow). The vegetation is protruding through the valve to the right atrium during systole (white arrow).

Infectious workup, including multiple blood cultures, Chlamydophila pneumoniae, Chlamydophila psittaci, Brucella, Bartonella, Coxiella burnetii antibodies, and Legionella antigen were all negative. All autoimmune workup was negative.

Potential causes for tricuspid valve vegetation include infectious, aseptic from autoimmune disease, or, rarely, malignancy. Computed tomography pulmonary angiogram appeared to be consistent with septic emboli; however, given the lack of infectious and autoimmune source, metastasis was suspected.

Abdominal imaging including CT and magnetic resonance imaging showed a large fundal fibroid with cystic degeneration and an exophytic fibroid extending toward the left adnexa. Endometrial biopsy showed endometrial and endocervical tissue with tubal metaplasia without atypia or malignancy.

Due to severe symptomatic primary tricuspid regurgitation due to aseptic vegetation, the patient underwent cardiothoracic surgery. Intraoperatively, a discrete mass attached to the tricuspid valve tissue was found, measuring 2.37 cm × 1.15 cm. Severe degeneration and destruction of all valve leaflets was noticed, sub-valvular abscess was debrided, and the valve was replaced with #31 Epic St Jude tissue valve. The patient tolerated the surgery well without any complications. During her follow-up in the cardiology clinic, her symptoms of shortness of breath and lower limb swelling showed a significant improvement.

Microscopically (Figure 2), it was smooth muscle neoplasm without significant nuclear atypia and no identifiable mitosis or necrosis. Diffuse and strong positivity for desmin and smooth muscle antibodies were positive. In addition, there was diffuse positivity for estrogen, progesterone, and Wilms tumor gene 1, suggesting likely uterine origin, and represented BML. Post-operatively, total hysterectomy is planned, with risk/benefits discussion of hormonal blocking agents to follow.

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Figure 2.

Tricuspid valve tissue pathology, significant for smooth muscle neoplasm consistent with benign metastasizing leiomyoma.

Discussion

To our knowledge, there have been 9 prior reported cases of BML with metastasis to the heart, 4 of them involving the tricuspid valve.^2-5 One case affected the anterior leaflet papillary muscle of the tricuspid valve. ⁶ Others appear to primarily affect the right atrium or ventricle, while no cases document BML in the left side of the heart. The clinical presentations of these patients appear to be a new murmur, shortness of breath, and lower extremity edema. Eight of the 9 cases, including the present case, presented with other likely sites of metastasis, particularly pulmonary nodules.

Most cases have a prior history of myomectomy/hysterectomy, so the mechanism of post-operative seeding has been suggested. ² One review found the mean time difference between gynecologic procedure and BML diagnosis to be 8.8 years. ⁷ Delayed diagnosis may be due to the asymptomatic nature of pulmonary BML. Our patient was first diagnosed with the tricuspid valve mass, prior to the official leiomyoma diagnosis (although she had a history suspicious of fibroids), prior to gynecologic surgery. There is only one other case that reported discovering cardiac BML in the preoperative workup for a hysterectomy. ⁸ This is the second case without any prior history of surgical intervention to the primary site of leiomyoma before the cardiac diagnosis. Thus, in this case, there is no known precipitating event leading to hematogenous or lymphatic spread questioning the exact mechanism of spread.

There is no established treatment for BML, but options include observation, primary leiomyoma resection, metastatic mass resection, and systemic hormonal blocking agents, depending on presence of symptoms and shared decision-making. ¹ Few reports with BML to the heart comment on treatment beyond surgery. One case reported treating with aromatase inhibitor, followed by a gonadotropin releasing hormone (GnRH) agonist. ⁸ Other reports show a singular therapy of either an aromatase inhibitor ⁶ or a GnRH agonist.^4,9

Due to the rarity of this condition and lack of established guidelines, it is not clear what therapeutic options to pursue. In cardiac BML with significant involvement requiring surgical resection, hormonal blocking agents in addition to hysterectomy may be considered, to prevent recurrence of cardiac metastasis. As prior hysterectomy has been found to be associated with possible post-operative seeding and subsequent distant metastasis, in cases like these, where the metastasis occurred even prior to the surgical resection of primary leiomyomas, they may be at a higher risk of recurrence especially after hysterectomy. Hence, in these forms of aggressive cases, additional systemic antihormonal therapy may have a potential benefit in preventing the new valve from being involved. Pathology in this case was positive for estrogen and progesterone, and despite the fact that the patient is postmenopausal, considering the extent of valvular involvement and upcoming hysterectomy, hormonal blockade may be beneficial. In the future, next-generation sequencing may help determine any genetic abnormalities associated with aggressive BML cases and guide the management.

Conclusion

Benign metastasizing leiomyoma is a metastatic, though not malignant, mass that typically manifests as pulmonary nodules, but rarely may also affect the right side of the heart. To our knowledge, we report the 10th case of BML of the heart, and only the second case in which it metastasized to the heart prior to hysterectomy. In our patient, all 3 leaflets of the tricuspid valve were affected, causing regurgitation and right heart failure, and requiring tricuspid valve replacement. With concerns for recurrence of metastasis with surgical resection of the primary tumor and possibility of seeding of the replaced valve, we propose aggressive approach in terms of concurrent hormonal therapy to reduce any chances of metastasizes post hysterectomy.