Cardiac Metastasis in a Patient with Head and Neck Cancer: A Case Report and Review of the Literature

Cardiac metastasis from a primary head and neck cancer is a rare finding. Most patients with cardiac metastases have nonspecific symptoms that may vary depending on the severity and location of the lesion. Due to the infrequency of reported cases, there are no clear guidelines for the diagnosis or management of cardiac metastasis in head and neck cancer patients. In this report, we discuss the case of a patient with a primary diagnosis of oral tongue cancer who developed a cardiac metastasis that was detected antemortem.


Introduction
Cardiac metastases in patients with head and neck squamous cell carcinoma (HNSCC) are a very rare finding [1]. Most cases of cardiac metastasis are clinically silent with a majority of cases detected in the postmortem setting. If cardiac metastasis is diagnosed in a living patient, the clinical presentation is often variable with nonspecific symptoms. Here, we discuss the clinical presentation, diagnosis, and management of a patient with oral cavity cancer who developed a metastasis to the heart.

Case Presentation
A 46-year-old white female with a 15 pack-year smoking history initially presented 3 years ago with intense pain in the left side of the mouth that radiated to her left ear for 2 months. She was found to have a 2 cm exophytic lesion on the left lateral border of her tongue that was diffusely keratotic and extremely tender on examination. Fiberoptic laryngoscopy revealed normal findings in the nasopharynx, oropharynx, and hypopharynx. Histological biopsy of the tongue lesion confirmed well-differentiated squamous cell carcinoma of the left lateral border of the tongue. Radiographical findings on positron emission tomography (PET) scan showed hyperactivity along the left lateral aspect of the tongue and a mildly hypermetabolic left level IIa cervical lymph node with no evidence of distant metastases ( Figure 1). e patient was treated with a left hemiglossectomy and bilateral neck dissection. Pathologic evaluation revealed a 2.4 cm moderately differentiated, infiltrating squamous cell carcinoma of the left lateral tongue lesion invading into the skeletal muscle with a 0.5 cm maximal thickness. ere was perineural invasion, but no lymphovascular invasion, and all margins were free of cancer. A total of 3 out of 22 lymph nodes were positive for carcinoma: 0 out of 10 in right neck level II-III, 2 out of 5 left level I with no extracapsular extension (ECE), 0 out of 1 left level II, and 1 out of 6 left level III with no ECE.
She was staged as pT2 pN2b M0 (stage IVA, AJCC 7th edition 2010) squamous cell carcinoma of the left lateral tongue. She received adjuvant treatment with concurrent afatinib and radiotherapy to a total dose of 6000 cGy in 30 fractions over 6 weeks to the oral cavity and bilateral necks, which was completed in 3 months after diagnosis.
Interval radiographical imaging did not show any evidence of disease recurrence or distant metastases until 2018. At that time, the patient had developed increasing left arm pain, left ear pain, and left throat pain. She also reported intermittent chest pressure, exertional dyspnea, and intermittent dizziness with positional changes.
In early 2018, a PET scan ( Figure 2) and magnetic resonance imaging (MRI) of the chest ( Figure 3) showed a new 3.4 cm left apical pleural mass encasing the left subclavian artery and abutting the left subclavian vein, both of which were patent. A computed tomography-guided fineneedle aspiration (CT-FNA) of the apical lung mass revealed squamous cell carcinoma.
Shortly after, the patient began systemic therapy with cisplatin and etoposide and radiation therapy to the left apical lung lesion. Following the 20th fraction of radiation therapy, a repeat computed tomography (CT) scan of the chest revealed a new 1.2 cm lesion in the inferior interventricular septum of the heart. A cardiac ultrasound was performed and demonstrated a mass in the left ventricle. e patient went on to complete radiation therapy to a total of 6000 cGy in 30 fractions. Further diagnostic imaging with a cardiac MRI was performed, which revealed a mass infiltrating the left ventricle, inferior myocardium, epicardial fat, and pericardium with associated mobile thrombus formation ( Figure 4). A PET/CT scan demonstrated hypermetabolic lesions in the left neck, right thigh muscles, lung parenchyma, heart, anterior mediastinum, left scapula, and posterior right rib ( Figure 2). Transthoracic echocardiogram (TTE) showed a 1.6 × 1.4 cm mobile mass in the left ventricle cavity that appeared to be attached to the base of the papillary muscle and a normal left ventricular ejection fraction of 60%. An electrocardiogram (ECG) revealed normal sinus rhythm with T-wave inversion in the inferior leads and V 3 -V 6 . e patient initiated anticoagulation and systemic therapy with nivolumab.

Discussion
Cardiac metastases are a rare finding. Since patients are often clinically silent or have nonspecific symptoms, metastases to the heart are difficult to diagnose and usually detected in the postmortem setting during an autopsy. When patients present with symptoms, they can have highly variable    [2]. Four different mechanisms have been postulated by which cancer spreads to the heart, including direct extension, hematologic spread, lymphatic spread, and intracavitary diffusion via the inferior vena cava or pulmonary veins [2][3][4].
In patients with oral cavity cancer, distant metastases are seen in 4.2-23.8% of patients, with the lung, bone, and liver as the most commonly involved sites [5]. However, metastatic disease to the heart is highly unusual in patients with oral cavity cancer. e patient in this case report had an especially long duration between primary diagnosis and cardiac metastasis at almost 3 years. In a review of the literature, we found 24 cases of patients with head and neck cancer with cardiac metastases that were detected in the antemortem setting.
Due to the wide range of clinical presentations in patients with cardiac metastases, detection is often incidental. e routine use of imaging is not generally recommended in patients with head and neck cancer to detect metastatic disease unless prompted by clinical signs and symptoms or if the patient is not amenable to clinical examination. Echocardiography is the most frequent noninvasive imaging modality used to evaluate the heart. In our present literature review, echocardiography was the initial imaging modality in more than 50% of the cases of cardiac metastasis from a primary head and neck cancer (Table 1). Echocardiography allows for assessment of cardiac function, including valvular and ventricular competency, as well as identification of any intraventricular masses or structural wall abnormalities [6]. e diagnostic accuracy of echocardiography has been reported to be as high as 80%, which makes it a good initial method to evaluate suspected cardiac tumors [7]. Other imaging modalities such as CT and MRI may provide a more comprehensive assessment with additional detail, including evaluation of the pericardium and extracardiac disease [8]. Cardiac MRI offers the advantages of excellent contrast resolution and distinction of tumor from the myocardium or thrombus in comparison with CT or ultrasound [9]. MRI also allows for simultaneous assessment of the surrounding structures, including the mediastinum, lungs, and pleura [6]. Particularly in patients with primary tumor of the head and neck, PET/CT may provide additional utility in detecting metastatic disease involving the heart. In a long-term outcome study of PET/CT imaging in head and neck cancer patients treated with definitive or adjuvant radiation therapy, PET/CT had a 99% negative predictive value in the assessment of the primary site and neck, and negative findings were associated with significantly improved diseasefree survival and overall survival. However, there was a high rate of false-positive results at the primary site, with a positive predictive value of 32.1% [10]. erefore, the use of PET/CT at 3 months post-RT is generally practiced. Current National Comprehensive Cancer Network (NCCN) guidelines do not recommend the use of routine follow-up imaging unless clinically indicated and no evidence to demonstrate a benefit of surveillance imaging after 6 months [11]. However, multiple case reports have reported that the use of PET/CT may lead to improved accuracy and earlier detection of cardiac metastases in patients with head and neck cancer [4,[12][13][14][15]. Some studies have suggested that routine ECG may have a diagnostic value, but findings are often nonspecific, and further confirmation with imaging would be required [15][16][17]. Table 1 provides a literature review of patients with an antemortem diagnosis of cardiac metastasis from a primary head and neck cancer. In our present study, the patient had already developed metastatic disease in the lung prior to detection of the cardiac metastasis, which was incidentally detected on a review staging CT scan.
ere is no standard of care in the treatment of cardiac metastases. Many patients are not surgical candidates due to the location of disease and are treated with palliative chemotherapy and supportive care, but prognosis is often poor. In our present study, the patient initially had presented with metastatic disease to the lung and began treatment with    Case Reports in Otolaryngology cisplatin-based chemotherapy and radiotherapy, but developed progression of disease and a new cardiac metastasis.
In the current era, novel immunotherapeutic drugs, such as pembrolizumab or nivolumab (anti-PDL-1 antibodies), may have a significant impact on the survival outcomes of these patients [27][28][29]. Upon detection of the cardiac metastasis, the patient began treatment with nivolumab, which is approved for patients with recurrent and metastatic head and neck cancer that is refractory to cisplatin chemotherapy.
In conclusion, metastatic disease to the heart in oral cavity cancer is an uncommon finding, lacking optimal guidelines in terms of diagnosis and management. Diagnosis is quite challenging since cardiac metastases are often clinically silent, and there is no clear beneficial role of routine surveillance imaging. In symptomatic patients, a multimodality approach using imaging such as PET/CT, cardiac MRI, echocardiogram, and ECG findings should be used to confirm the location and extent of disease, which may help to guide treatment options.