Cervical cancer with patent foramen ovale metastasis to the left ventricle: a case report

Abstract

Background

Metastasis of malignant tumors to the cardiac endocardium is rare and mainly involves the right side of the heart. It is extremely rare to involve the left cardiac endocardium, especially when there is neither pulmonary metastasis nor primary lung cancer, which we call “isolated” left cardiac endocardium metastasis in this paper. Few such cases previously reported in the literature were not screened for patent foramen ovale (PFO).

Case presentation

This article reports a case of a young woman with a history of surgery for cervical cancer, who was transferred to our hospital with a suspected diagnosis of PFO after recent recurrent multiple cerebral infarctions. On admission, transthoracic echocardiography revealed multiple stringy vegetations in the left ventricle, which were subsequently removed surgically, with intraoperative confirmation of a patent foramen ovale and closure of it simultaneously. According to her medical history and pathological results, she was diagnosed with left ventricular metastasis of cervical cancer, a rare case of isolated left heart endocardium metastasis without previous pulmonary metastasis, presumably through the patent foramen ovale.

Conclusion

PFO may play an important role in the process of isolated left heart endocardium metastasis in patients with distant malignancies and paradoxical embolism. Screening for PFO in high-risk patients may have significant clinical significance.

Background

The heart may be involved by malignant tumors through four pathways: retrograde lymphatic spread (a phenomenon in which cancer cells spread in the opposite direction of normal lymphatic flow), direct invasion of adjacent organs, hematogenous metastasis (from the coronary arteries to the myocardium, a part of the distant organ metastasis through the aorta), and metastasis from vena cava reflux to the right cardiac chambers (right heart endocardium metastasis) and further into the pulmonary circulation [1]. The pericardium is the most commonly affected site, followed by the epicardium and myocardium. Given these pathways, the heart’s ceaseless rhythmic contraction-relaxtion, the rapid blood flow, together with the filtering effect of the pulmonary circulation, endocardial metastases, particularly in the left heart, are exceptionally rare. Left heart endocardium metastases were basically observed in cases of primary or metastatic lung cancer [2, 3]. Only a few sporadic reports of extrapulmonary tumors metastasizing to the left heart endocardium alone in the absence of obvious lung metastases exist in the literature. Those cases involve various types of primary tumors, and their potential metastatic pathways were not clarified.

In this report, we present a rare case of isolated left ventricular endocardial metastases from cervical cancer with patent foramen ovale (PFO) and suggest a new idea on the route of metastasis of malignant tumors. A patent foramen ovale (PFO) is a flap like opening between the rigt and the left atrium at the level of the fossa ovalis, that didn’t close the way it should after birth. It usually causes no symptoms and requires no treatment. Rarely, a patent foramen ovale can cause hypoxemia by a significant right-to-left shunt and unexplained strokes by paradoxical embolism [4].(Fig. 1).

Fig. 1

Illustrations of Patent Foramen Ovale (PFO) and the proposed mechanism of paradoxical embolism

Case presentation

Patient Information: On November 6th, 2023, a 47-year-old female with a proposed PFO after recent recurrent multiple cerebral infarctions was referred to the cardiology department of our hospital for the interventional closure of the PFO. The patient was diagnosed with FIGO stage IIA2 cervical cancer (squamous cell carcinoma) in January 2021 and underwent multimodal therapies including radical hysterectomy, bilateral salpingo-oophorectomy and pelvic and periaortic lymphadenectomy, followed by six cycles of chemotherapy and pelvic external beam radiotherapy.

Clinical Findings: On admission, the patient had stable vital signs with a normal sinus rhythm on electrocardiogram. Systolic murmurs were audible in the 3rd − 4th intercostal spaces at the left sternal border, and most likely originated from the left ventricular outflow tract. Her muscle strength was Grade II in the right lower limb and Grade III in the left lower limb, with a positive Babinski sign on the right side (the Babinski sign is a neurological reflex indicating potential central nervous system damage or disease).

Diagnostic Tests: Transthoracic echocardiogram on admission revealed multiple stringy vegetations attached to the basal segment of the interventricular septum and anterolateral wall near the cardiac apex in the left ventricle, one of which extended to the left ventricle outflow tract, and was approximately 3.1x1.4 cm in size, with high mobility (Fig. 2A). Otherwise the structure and function of the heart were normal. Cerebral MRI revealed multiple patchy abnormal signals. CT scans of the chest and abdomen did not show obvious signs of malignancy. Additionally, multiple brain infarctions were seen on 18-FDG PET-CT at the external hospital on October 19th, 2023, but no signs of malignant neoplastic lesions were detected at that time.

Fig. 2

Echocardiogram of the patient. (2A) The echocardiogram at admission. Stringy vegetation, approximately 3.1*1.4 cm in size, was observed in the left ventricle outflow tract, with high mobility, and can be thrown into the left ventricular outflow tract. (2B) The echocardiogram 4 days later showed that the previous vegetation in the left ventricle outflow tract had increased in size

Treatment: Infective endocarditis was excluded by bacterial and fungal cultures of three sets of blood samples one hour apart before empirical antibiotic administration. Given that the D-dimer level, which was 6.43 µg/mL, was significantly elevated, intracardiac thrombus could not be excluded. Enoxaparin, a low-molecular-weight heparin was injected subcutaneously twice a day. Some of the vegetations were enlarged on the echocardiogram 4 days later (Fig. 2B). On November 17th, 2023, the patient underwent cardiac surgery to reduce the risk of embolism from vegetation debris and left ventricular outflow tract obstruction caused by growing vegetation. The presence of a patent foramen ovale was confirmed during the operation and closed. Multiple friable pink stringy and flocculent vegetation was found in the left ventricle, rooted among the left ventricular pectinate muscles and extending into the left ventricular outflow tract. Some were attached to the interventricular septum opposite to the anterior bicuspid valve, and some were entangled with the chordae tendineae. One of the vegetations pulled out from the left ventricle into the left atrium through the bicuspid valve is shown in Fig. 3.

Fig. 3

Gross appearance of vegetation. The illustration shows the appearance of stringy vegetation dragging from the left ventricle into the left atrium through the bicuspid valve

Diagnostic Results: Pathological examination revealed that the lesion was metastatic squamous cell carcinoma, which was histologically similar to her previous cervical cancer. Finally, she was diagnosed with left ventricular metastasis of cervical cancer, a rare case of isolated left heart endocardium metastasis without previous pulmonary metastasis.

Follow-up: The heart size and left ventricular function of the patient were normal, and a little pericardial effusion and no vegetation were observed on the echocardiogram eight days after the surgery. She recovered well from the operation and was discharged from the hospital on December 4th, 2023. Thus far, the neurologic dysfunction rehabilitation is very slow. The prognosis of patient with this malignancy is poor. However, she was temporarily in good condition until the last telephone follow-up on March 23rd, 2024.

Discussion

Intracardiac masses are classified into nonneoplastic and neoplastic lesions. Nonneoplastic lesions include mural thrombi and infective endocarditis vegetations. Neoplastic lesions can be benign, such as atrial myxoma, or malignant. Secondary malignant cardiac tumors are approximately 20 times more common than primary tumors, though the overall incidence remains relatively low. This low incidence may be due to the heart’s continuous rhythmic contraction and rapid blood flow [1, 5, 6]. Based on the 2023 Duke-ISCVID IE criteria, infective endocarditis was ruled out. The elevated D-dimer level suggested the possibility of a mural thrombus in the left ventricle. However, the patient did not have conditions like ventricular aneurysm, dilated cardiomyopathy or very low LVEF that typically cause thrombus formation. Furthermore, ineffective anticoagulant therapy with LMWH pointed to an alternative diagnosis.

As she had a previous history of cervical cancer, cancer metastasis into the heart was highly suspected. Although the prognosis of cardiac metastasis of malignant tumors is poor, to prevent recurrent cerebral embolism and the risk of sudden death caused by left ventricular outflow tract obstruction or aortic valve blockage by the growing vegetation, with the informed consent of the family, surgery was performed to remove the vegetation in the LV and close the PFO simultaneously. Metastatic squamous cell carcinoma was confirmed by pathological examination, with histological features similar to those of previous cervical cancer. Therefore, left ventricular metastases from cervical squamous cell carcinoma were the final diagnosis.

Typically, extrapulmonary tumors metastasize to the left heart endocardium only after pulmonary metastasis. In cases where there is no pulmonary metastasis or metastasis to the pericardium, myocardium, or right heart, it is termed “isolated left heart endocardium metastasis” in this paper. From 1975 to 2023, only sporadic reports of extrapulmonary tumors metastasizing to the left heart alone in the absence of obvious lung metastases were reported in the literature. We obtained 9 case reports from PUBMED and Chinese literature, which include cervical cancer, renal cell carcinoma, gallbladder carcinoma, uterine leiomyosarcoma, breast cancer, thyroid follicular carcinoma, bladder cancer, and choriocarcinoma. Those cases are summarized in Table 1 [2, 7,8,9,10,11,12,13,14]. In those cases, cardiac metastases were detected simultaneously with the primary tumor or years later. Two cases were diagnosed postmortem, while six patients underwent immediate surgery upon discovery. Four patients presented with neurological symptoms such as dizziness and headache, but none investigated the underlying mechanism.

Table 1 Information on 9 cases of left cardiac endocardium metastasis from an extrapulmonary malignancy

How did the tumor cells or emboli enter the left heart chamber without pulmonary circulation involvement? In this case, the patient presented with dizziness and numbness, leading to the diagnosis of acute cerebral infarction and subsequent discovery of PFO, the most common cause of paradoxical embolism in clinical practice. The prevalence of PFO can reach approximately 25-30%, but only a small proportion of cases result in paradoxical embolism, which means that various types of emboli originating from the systemic veins pass through the PFO and enter the left heart and then the systemic circulation, causing embolism of the intracranial or peripheral arteries [4]. Some anatomical and functional features of PFO are prone to cause paradoxical embolism. For example, PFOs with a residual elongated eustachian valve (protruding into the right atrium) or Chiari network, and a small angle to the inferior vena cava (≤ 10°), anatomically lead to inferior vena cava reflux toward the foramen ovale [8].

In this case, we speculated that the malignant embolus from the inferior vena cava flowed directly toward the PFO and then entered the left atrium and ventricle in sequence. Some of them may directly enter the intracranial artery with the ejection of the left ventricle to lead to cerebral infarction, because no intracardiac vegetation was found when the first acute cerebral infarction occurred. Others dwelled in the endocardium in the pectinate muscle interspace and grew increasingly larger, and the free part of the vegetation extended to the left ventricular outflow tract and oscillated within the blood flow, as seen on the echocardiogram as well as during the operation. Recent recurrent cerebral infarction may be caused by brittle vegetation debris from the left ventricle.

Conclusion

This case report presents a unique instance of isolated left ventricular endocardium metastasis from an extrapulmonary malignancy, with the added complication of a patent foramen ovale (PFO). Previous cases of isolated left heart metastasis have not typically included screening for PFO. This report highlights the potential role of PFO, as a shortcut, in facilitating such metastases, adding a new dimension to our understanding of cardiac metastasis. This has important implications for diagnostic and therapeutic strategies, as screening for PFO, especially one with high-risk characterizations, in patients with distant malignancies, and to perform a percutaneous interventional occlusion, could potentially prevent serious complications such as left heart endocardium metastasis as well as paradoxical embolism.

Given the potential implications of PFO in isolated left heart endocardium metastasis, further research is needed to explore the prevalence of PFO in similar cases and assess the impact of routine PFO screening on patient outcomes. This could lead to more informed management strategies for patients with distant malignancies.