Introduction

Cardiac metastasis (CM) of mucosal head and neck squamous cell carcinoma is an incredibly rare but universally fatal phenomenon. The incidence of cardiac metastasis of all squamous cell carcinoma has been found to be between 5 and 10 percent when examining autopsies. The incidence of cardiac metastases is substantially higher in malignancies from other sites such as melanoma, lung, breast, esophagus, and lymphoma. There are 12 reported cases of cardiac metastasis from squamous cell carcinoma of the tongue in the English-language medical literature [1-6]. There are 34 cases of cardiac metastasis (CM) from multiple locations of mucosal head and neck squamous cell carcinoma (HNMSCC) [2-18]. When distant metastases of HNMSCC occur, they most often involve the lung, skin, liver or bone. The mechanism of metastasis from the head and neck to the myocardium is poorly understood. Pathways that have been proposed are hematogenous spread through the coronary arteries, direct extension, and retrograde dissemination through lymphatic channels [5, 12, 13]. Involvement of the cardiac conduction system is much less common. In decreasing order of frequency, tumors usually metastasize to the pericardium, myocardium, epicardium, endocardium, and intracavitary regions [14]. Clinical manifestations of CM are rare and nonspecific therefore they are often not detected until an advanced stage or at autopsy [5]. Symptoms can include sudden onset heart failure and new arrhythmia. In those patients with advanced HNMSCC and new onset cardiac symptoms, metastatic cardiac lesion should be suspected. Helpful diagnostic testing includes electrocardiogram, echocardiography, computed tomography, and magnetic resonance imaging [19]. Cardiac biopsy providing histologic diagnosis is the gold standard; however myocardial biopsy is often a perilous undertaking. Despite advances in cancer treatment, management of metastatic cardiac lesions remains challenging. Currently, there is no standardized therapeutic approach. Options include palliative chemotherapy and radiation, and for specific cases surgical resection.

Case Presentation

A 55-year-old female presented in October 2012 with a tender right floor of mouth/ventral tongue lesion that was present for one month. She had difficulty tolerating oral feeds secondary to the tenderness. Over the previous month she had lost 10 pounds. The patient reported persistent right otalgia, treated regularly with hydrocodone. Her speech changed slightly. The patient denied any shortness of breath, hemoptysis, or aural fullness. She smoked 10 cigarettes daily and drank 4 beers daily for many years. Biopsy and imaging revealed squamous cell carcinoma. On November 16, 2012 she underwent composite resection of right floor of mouth/ ventral tongue cancer and right hemiglossectomy, right selective neck dissection, tracheotomy, and reconstruction with anterior lateral thigh flap. Pathology results described a T2N1N0 squamous cell carcinoma of the right floor of mouth and tongue. Margins were negative, but lymphovascular and perineural invasion were identified. After multidisciplinary tumor board discussion, it was recommended that she receive adjuvant radiation therapy (RT). She was not compliant with this recommendation.

Eight months after surgery, on June 27, 2013, the patient underwent a combined positron emission tomography (PET)/computed tomography (CT) scan (Figure 1a, 1b, 1c) for follow up of disease which noted a 2.7-cm mass in the right floor of mouth as well as several enlarged lymph nodes with hypermetabolic activity in the right level 2B region, the largest of which was 3 cm. The patient was subsequently taken to the operating room for radical right neck dissection. Significant disease was noted in right neck areas level 2B, as well as a soft tissue mass that extended through the mylohyoid and into the base of the tongue musculature. Multiple areas were biopsied and surgical pathology showed moderate to poorly differentiated squamous cell carcinoma diffusely invading soft tissue with tumor present at cauterized excision margins. Postoperatively the Medical Oncology Service was consulted, and plans were made for the patient to follow up for chemotherapy and radiation in light of positive surgical margins. On the third postoperative day, a CT scan of the abdomen and thorax was obtained which showed no evidence of metastatic disease involving the abdomen or pelvis. The patient’s postoperative course continued uneventfully. The patient was discharged home. The patient failed to present for multiple Medical Oncology and Radiation Oncology appointments. Several months later, she presented in October 2013 and underwent a PET scan. Unfortunately, this showed interventricular septum metastasis of the heart. No biopsy was attempted. She was placed on hospice and passed away in her sleep 11 months later. She never experienced any cardiac symptoms. She denied chest pain, dyspnea, and palpitations.

Figure 1a: Axial view of interventricular septum mass filling most of right ventricle

Figure 1b: Coronal View

Figure 1c: Sagittal View

Discussion

In the last 35 years (1985 - 2020) this is the 34th reported case of CM from HNMSCC (Table 1) and only the 25th diagnosed in a living patient. Ages ranged widely from 32 to 73 years old (mean 60.0±13.5 years), with a slight male predominance (57%). These tumors represent uncommon and late stage sequelae of HNMSCC. CM from HNMSCC does not seem to have geographic distribution, as they have been reported across the world in our series. Previously published reports were from the United States, Asia, and Europe. In the reviewed literature sites of initial head and neck malignancies included: tongue (12), larynx (6), oral cavity (9), oropharynx (4), hypopharynx (2), and unknown primary (1). Interestingly, none of the patients in this series had a nasopharynx primary, even though nasopharynx malignancy is reported to metastasize more often than other head and neck mucosal malignancies. Hypopharynx cancer tends to have a worse prognosis that other HNMSCC but has not been found to have more cardiac metastasis. Oral tongue cancer is reported to have skip metastasis in the neck. It is also found to have a higher incidence of CM as well. Fittingly this was the most common primary tumor site in this review. Cardiac metastasis of tumors arising from head and neck and particularly of the larynx are reported to be extremely rare [14]. In this cohort of patients TNM stage at initial presentation was mostly advanced: stage I (1), stage II (4), stage III (5), stage IV (7). The staging was unknown for 19 of the patients. Initial treatment for the primary lesions included: surgery (3), surgery then postoperative radiation or chemoradiation (3), concurrent chemoradiation (2), concurrent chemoradiation then surgery then chemotherapy (2), concurrent chemoradiation then surgery (1), induction chemotherapy then surgery then radiation (1), and radiation then surgery (1).

Patients with CM are most often asymptomatic. The most common presenting symptoms were chest pain (16.7%), dyspnea (16.7%), EKG changes (13.9%), and edema (13.9%). Other reported symptoms included syncope and fatigue. Initial, nonspecific symptoms include syncope, dizziness, and dyspnea. Three of the CM was noted as incidental findings on routine surveillance imaging. The CM ranged from being asymptomatic to causing heart failure to causing sudden death. Symptoms varied widely, including dyspnea, lower extremity edema, substernal pressure, arrhythmia, and sudden death. Twenty-two of the 34 patients in this series were symptomatic. Two of the previous reports of tongue cancer involved patients who presented with arrhythmias due to conduction disturbances from tumor invasion of the septum [6, 9]. In a 3rd case, a patient presented with angina decubitus due to the presence and location of her cardiac tumors [10]. Another presented with a large pericardial effusion [2]. One patient’s syncopal episodes could be attributed to an uncontrolled seizure disorder that resulted from extensive brain metastases [5]. Another patient's palpitations were due to atrial fibrillation that was most likely caused by widespread pulmonary disease [5]. Symptomatic cardiac metastases from squamous cell carcinoma are an uncommon situation [5]. Cardiac metastasis should be suspected when new cardiovascular symptoms are observed in patients with a history of head and neck malignancy [13]. Length of time from initial cancer diagnosis to discovery of CM averaged 24.5 months (10 patients), and the time from initial cancer treatment to CM averaged 15.6 months (14 patients).

The development of symptoms depends on the size and location of the tumor. As the mass grows patients can develop chest pain, valvular abnormalities, heart failure, pericardial effusion, cardiogenic shock, or tamponade. Symptoms, when present, depend upon the location and size of the mass. Location of CM was: ventricle (10), pericardium (7), interventricular septum (6), atrium (3), septum (3), atrium and ventricle (2), ventricle and intraventricular and epicardium (2), all 4 chambers (1), intra- and extracardiac (1). This is in contrast to prior studies to reported the most common sites in descending order as the pericardium, myocardium, epicardium, endocardium, and intracavitary regions [14]. Initial diagnostic modality in all cases was an electrocardiogram (EKG) [13]. In several cases, the EKG demonstrated non-specific changes including ST- elevation in the absence of troponin elevation, development of atrial fibrillation [17], or complete AV block [20]. In one particular case the patient demonstrated right bundle branch block seven months before diagnosis of the cardiac metastasis [21]. Imaging that was pertinent in diagnosing CM in our series was: echocardiogram (38.9%), CT (19.4%), PET (11%), and cardiac MRI (5.6%). Previously, cardiac imaging to detect malignancy included CT, magnetic resonance imaging, 3-dimensional transthoracic echocardiography, and PET [2-5, 16]. The use of PET/CT yields functional and morphologic information with excellent resolution, and valuable follow- up information in difficult cases [22]. To date, no study has shown the superiority of a single imaging technique in this patient group. Echocardiography is relatively inexpensive, readily available, repeatable, and portable. Onwuchekwa recommended that patients with head and neck malignancies undergo early echocardiographic evaluation when cardiac symptoms arise [5]. The patient presented in this case report underwent a PET scan at the time of CM diagnosis. Within the literature 7 cases (19.4%) of CM diagnoses were made at the time of autopsy.

CM diagnosis is confirmed by at least one of the following methods: myocardial biopsy (1), pericardial fluid drainage (2), CT guided pericardial biopsy (2), and surgical excision of CM (2). Seven underwent biopsy postmortem. Only 3 of these patients had other known sites of metastasis prior to discovery of their CM. With imaging, 15 patients (41.7%) were found to have other sites of metastases in addition to CM. Diagnosis relies primarily on clinical suspicion and imaging. Most physicians do not biopsy these. While histologic examination is the gold standard for diagnosis, cardiac biopsy is fraught with risk [23]. It offers no benefit in patients with cardiac metastasis. Nagata (2012), Suda (2007), and Werbel (1985) did obtain a biopsy [4, 6, 12]. Tsai (2010) performed pericardial drainage, and Ito (2008) performed autopsy [2, 9]. Treatment options for patients with cardiac metastases are limited. Due to the extent and location of the intracardiac lesions, most patients are not candidates for surgical resection [5]. In this series, 6 patients were placed on hospice, 4 were administered palliative chemotherapy, 2 were medically managed for heart failure, 2 underwent immunotherapy, 2 underwent surgical resection, 1 had a pacemaker placed, and 1 was administered radiation. There is no support to placing these patients on cardiac medications, as only two patients in this series were placed on cardiac medication. Treatment is usually palliative and the prognosis is poor [3]. The prognosis of HNMSCC typically is fatal [10]. The 34 patients uniformly died of this disease, with the longest survival after diagnosis of CM of 26 months. The patient presented here passed away 11 months after diagnosis.

Table 1: Cases of cardiac metastasis of mucosal head and neck squamous cell carcinoma between 1985 and 2020.

Conclusion

CM from the head and neck most often originates from primary tongue and larynx malignancies. Most patients initially have stage IV HNMSCC. Initial treatment in 79% of patients included surgery, and 67% of patients underwent combined surgery with nonsurgical therapy. CM does not necessarily present in patients with other known local, regional, or distant disease. CM usually occurs in the ventricle or interventricular septum. Echocardiogram and CT have most commonly been used for diagnosis. CM usually presents around 1 year after diagnosis/treatment of HNMSCC. Cardiac metastasis should be suspected in any patient with HNMSCC in whom new cardiac symptoms develop. Most physicians do not obtain premortem tissue diagnosis of CM. Presentation of CM varies widely, from an asymptomatic incidental finding to sudden death. Death occurs within months of diagnosis of CM. This entity is distributed evenly across the world. It is advisable to consider cardiac metastasis in the differential diagnosis when a patient with a history of HNMSCC presents with new onset cardiac symptoms including EKG changes or syncope. It may be worth considering adding routine EKG to the annual surveillance regimen for patients who have been treated for HNMSCC.

Abbreviations

squamous cell carcinoma (SCCa); Head and Neck Mucosal Squamous Cell Carcinoma (HNMSCC); cardiac metastasis (CM); radiation therapy (RT); positron emission tomography (PET); computed tomography (CT); electrocardiogram (EKG)

References

1. Shafiq A, Samad F, Roberts E, et al. Squamous Cell Carcinoma of the Tongue with Metastasis to Myocardium: Report of a Case and Literature Case Rep Cardiol (2019): 1649580.
2. Ito T, Ishikawa N, Negishi T, et al. Cardiac metastasis of tongue cancer may cause sudden death. Auris Nasus Larynx 35 (2008): 423-425.
3. Rivkin A, Meara JG, Li KK, et al. Squamous cell metastasis from the tongue to the myocardium presenting as pericardial Otolaryngol Head Neck Surg 120 (1999): 593-595.
4. Werbel GB, Skom JH, Mehlman D, et al. Metastatic squamous cell carcinoma to the heart. Unusual cause of angina decubitus and cardiac murmur. Chest 88 (1985): 468-469.
5. Onwuchekwa J, Banchs J. Early cardiac metastasis from squamous cell carcinoma of the tongue in 2 Tex Heart Inst J 39 (2012): 565-567.
6. Nagata S, Ota K, Nagata M, et Cardiac metastasis of head and neck squamous cell carcinoma. Int J Oral Maxillofac Surg 41 (2012): 1458-1462.
7. Fouladi R, Pirgousis P, Fernandes RP. Metastatic squamous cell carcinoma of an unknown primary site with cardiac involvement: case report. J Oral Maxillofac Surg 71 (2013): 1998-2003.
8. Kavanagh MM, Janjanin S, Prgomet Cardiac metastases and a sudden death as a complication of advanced stage of head and neck squamous cell carcinoma. Coll Antropol 2 (2012): 19-21.
9. Tsai YT, Kuo SW, Hao SP. Cardiac tamponade: a rare presentation from a rare metastatic site in oral squamous cell carcinoma. Eur Arch Otorhinolaryngol 267 (2010): 1483-1485.
10. Hans S, Chauvet D, Sadoughi B, et Cardiac metastasis after squamous cell carcinoma of the base of tongue. Am J Otolaryngol 30 (2009): 206-208.
11. Alhakeem M, Arabi A, Arab L, et al. Unusual sites of metastatic involvement: intracardiac metastasis from laryngeal carcinoma. Eur J Echocardiogr 9 (2008): 323-325.
12. Suda T, Ishii A, Hukuda K, et [Cardiac metastasis by hypopharyngeal carcinoma. Case report]. Nihon Jibiinkoka Gakkai Kaiho 110 (2007): 466-469.
13. Gullulu S, Ozdemir B, Senturk T, et al. Cardiac metastasis in a laryngeal carcinoma and associated electrocardiographic changes. Otolaryngol Head Neck Surg 135 (2006): 645-647.
14. Renders F, Vanderheyden M, Andries E. Secondary cardiac tumour originating from laryngeal carcinoma: case report and review of the literature. Acta Cardiol 60 (2005): 57-60.
15. Schwender FT, Wollner I, Kunju LP, et al. Squamous cell carcinoma of the buccal mucosa with metastases to the pericardial cavity, lung and thyroid. Oral Oncol 38 (2002): 114-116.
16. Iyer S, Sanghvi V, Lala M. Atypical distant metastases from hypopharyngeal cancer. Indian J Cancer 39 (2002): 66-68.
17. Larkin M, Maycon RZ, Schreiner Cardiac metastasis from laryngeal carcinoma presenting as syncope. Chest 105 (1994): 1304.
18. Harrer WV, Lewis PL. Carcinoma of the larynx with cardiac Arch Otolaryngol 91 (1970): 382-384.
19. Mark-Adjeli P, Cirrone J, Gupta R, et al. Tonsillar carcinoma as a rare cause of cardiac metastases. J Community Hosp Intern Med Perspect 9 (2019): 524-528.
20. Cho JY, Kim KH, Park H, et Complete atrioventricular block as an initial manifestation of recurred oral cavity cancer: a case report. BMC Cardiovasc Disord 18 (2018): 142.
21. Fujio H, Otsuki N, Horichi Y, et Cardiac metastasis in a living patient with oral cancer. Auris Nasus Larynx 46 (2019): 902-906.
22. Sulkes A, Weshler Z, Dolberg L, et Isolated pericardial metastasis of parotid tumor origin. Head Neck Surg 4 (1982): 344-348.
23. Pattni N, Rennie A, Hall T, et al. Cardiac metastasis of oral squamous cell carcinoma. BMJ Case Rep (2015).