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Cardiac metastasis from yolk sac tumor: case report and review

Cardiac metastasis of germ cell tumors is extremely rare, particularly in females. We report a case of a 26-year-old previously healthy woman who presented with a 5-month history of abdominal pain, weight loss, fever, generalized lymphadenopathy, and acanthosis nigricans. Biopsy of cervical lymph nodes revealed a poorly differentiated neoplasm. Immunohistochemical staining was positive for alpha-fetoprotein suggesting the diagnosis of a germ cell tumor. During the investigation, the patient developed heart failure and a mass attached to the right ventricle was detected by the echocardiogram. In a few days, she developed multiple organ failure and died. Post-mortem examination revealed a malignant mixed germ cell tumor of the right ovary with extensive hematogenic and lymphatic dissemination, a polypoid mass attached to the right ventricle, emboli in the endocardial and epicardial vessels, and infiltration surrounding the coronary arteries. To the best of our knowledge this is the third report of grossly visible heart metastases from a yolk sac tumor in a female patient. A summary of all published cases of germ cell tumors with cardiac metastasis over the last 20 years is also presented.


Background
Ovarian germ cell neoplasm includes tumors with multiple histological patterns, and variable biologic behaviors [1]. These tumors grow rapidly, are usually unilateral and confined to one ovary in two thirds of the cases, and predominate in girls and young women. Mixed germ cell tumors consist of two or more admixed types of ovarian germ cell neoplasms and account for 5.3% of all malignant ovarian germ cell tumors [2]. Components of dysgerminoma mixed with endodermal sinus tumor (also called yolk sac tumors) are found most commonly. As a highly malignant neoplasm, yolk sac tumors metastasize at an early stage as well invade the surrounding structures and organs [1,[3][4][5][6].
Although cardiac metastases can arise from different cancers, they are more frequently associated with carcinoma of the lung, breast and esophagus (due to the higher prevalence of these tumors), hematological malignancies including lymphoma and leukemia, and malignant melanoma, which shows the highest affinity to metastasize to the heart [4]. Cardiac metastasis of germ cell tumors is extremely rare, particularly in the female gender. We hereby report a case of a 26-year-old woman with mixed germ cell tumor of the right ovary who presented with widespread metastases including to the right ventricle. Post-mortem examination also showed neoplastic emboli in the endocardial and epicardial vessels and infiltration surrounding the coronary arteries.

Case presentation
A 26-year-old previously health woman presented with a 5-month history of abdominal pain, weight loss, fever, generalized lymphadenopathy, and acanthosis nigricans. Except for anemia (hemoglobin 11.1 g/dl), blood counts were within the normal ranges. Serological tests for human immunodeficiency virus (HIV), hepatitis viruses, syphilis, toxoplasmosis and cytomegalovirus were negative. Blood chemistry was unremarkable, and blood and urine cultures were negative. Thoracic, abdominal and pelvic computed tomography (CT) showed extensive lymphadenopathy and a solid mass with ill-defined borders near the uterus. The ovaries were not seen. Biopsy of cervical lymph nodes revealed a poorly differentiated neoplasm. Immunohistochemical staining was positive for alpha-fetoprotein suggesting the diagnosis of a germ cell tumor. During the investigation, the patient developed heart failure. A transthoracic echocardiography showed right ventricular (RV) dilatation, pericardial effusion, and a mobile mass attached to the endocardial surface of the apex of the RV (Figure 1, panel A). In the following days, she developed multiple organ failure and died before she could be subjected to any type of anticancer treatment. Post-mortem examination revealed a malignant mixed germ cell tumor of the right ovary with predominance of endodermal sinus (yolk sac) tumor elements, and extensive hematogenic and lymphatic dissemination to the lungs, kidneys, liver, intestines, uterine tube, mediastinum, and thyroid gland. A polypoid mass was found attached to the apex of the RV (Figure 1, panels B and C). Neoplastic emboli in the endocardial and epicardial vessels, and infiltration surrounding the coronary arteries were also detected ( Figure 1, panel D).
The guardian of the patient provided written informed consent in accordance with the Declaration of Helsinki.

Conclusions
Intracardiac metastasis is an extremely rare manifestation of germ cell tumors. It occurs by hematogenous spread, direct invasion from neighboring chest tumors or through the pericardial space, usually to the right side of the heart [3][4][5][6]. In our case, the neoplastic cells probably reached the heart hematogenously, through the inferior vena cava. Although there were mediastinal metastases, they did not present any continuity with the cardiac lesions.
In a review of the cases of germ cell tumors with cardiac metastasis published over the last 20 years (Table 1) [7-24] we found 17 cases: 16 of them were male with testicular seminoma or nonseminomatous germ cell tumor, and only one case of a yolk sac tumor was reported in a female child of 18 months old. In 11 of these reported cases, the metastasis was located in the right-side of the heart; in four, in a left-side chamber; and in two, in the pericardium. Five of the 17 patients  died early in the chemotherapy treatment, and in eight, the disease was in remission at the time of the publication. Surgical resection of the metastasis followed by chemotherapy was the therapeutic approach performed in most cases. A more extensive review, without limiting period of time, revealed just another case of germ cell tumor with cardiac metastasis in female. It was a primary chorion carcinoma of the right ovary with metastases to the left atrium in a 35-year-old woman, who presented with multiple metastases and died of respiratory failure, three months after the diagnosis [25].
A high level of suspicion is needed to establish the diagnosis of cardiac tumors. Frequently, the tumor is found incidentally during evaluation for a seemingly unrelated problem. Cardiac metastases often occur late in the course of a malignant disease and produce clinical symptoms in only about 10% of the affected patients [4][5][6]. Site, size, and tendency to cause embolism determine the clinical findings. In symptomatic patients, a mass is commonly detected by imaging methods, especially echocardiography. As the symptoms may mimic other cardiac conditions, the clinical challenge is to consider the possibility of a cardiac tumor; so that the appropriate diagnostic test can be conducted. Specific signs and symptoms are generally determined by the location of the tumor in the heart and not by the histological type [4][5][6]. Cardiac tamponade is one of the earliest and most frequent symptoms. Cardiac malignant disease may also cause arrhythmias and heart failure. The classic triad includes: symptoms resulting from intracardiac obstruction, signs of systemic embolization, and systemic symptoms [5,6].
Recommended treatment for patients with advanced malignant ovarian germ cell tumors and non-dysgerminoma histology is maximal cytoreduction followed by platinumbased combination chemotherapy [26,27]. Emergency surgical resection of intra-cardiac metastases has been recommended in the compromised patient and can be lifesaving [21]. New technical modalities (e.g., modern echocardiography, computed tomography, magnetic resonance imaging) provide noninvasive visualization of the intracardiac mass, which assists in designing the surgical approach not only to eliminate tumor tissue, but also to restore or maintain the hemodynamic status [14,24]. Most patients treated aggressively will be long-term survivors even if they have advanced disease. However, despite the sensitivity of ovarian germ cell tumors to platinum-based chemotherapy, tumor volume still remains one of the most important prognostic factors for outcome, as evident in the case presented, where outcome was poor due to highly disseminated metastatic disease.
To the best of our knowledge this is the third report of grossly visible heart metastases from a yolk sac tumor in a female patient.

Consent
Written informed consent was obtained from the mother of the patient for publication of this case report and any accompanying images.