Cardiac metastasis of uterine cervical squamous cell carcinoma: A case report and review of the literature

Cardiac metastasis of uterine cervical squamous cell carcinoma: A case report and review of the literature

Journal of Cardiology Cases 10 (2014) 221–225 Contents lists available at ScienceDirect Journal of Cardiology Cases journal homepage: www.elsevier.c...

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Journal of Cardiology Cases 10 (2014) 221–225

Contents lists available at ScienceDirect

Journal of Cardiology Cases journal homepage:

Case Report

Cardiac metastasis of uterine cervical squamous cell carcinoma: A case report and review of the literature Yoshihiro Takeda (MD)a, Ryu-ichiro Fujimoto (MD)a, Hideaki Morita (MD)a, Kazushi Sakane (MD)a, Satoshi Tsunetoh (MD)b, Yoshito Terai (MD)b, Masahide Ohmichi (MD)b, Hideki Ozawa (MD)c, Takahiro Katsumata (MD)c, Motomu Tsuji (MD)d, Jun Tanigawa (MD)a, Koichi Sohmiya (MD)a, Masaaki Hoshiga (MD, FJCC)a, Nobukazu Ishizaka (MD, FJCC)a,* a

Department of Cardiology, Osaka Medical College, Osaka, Japan Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan c Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Osaka, Japan d Division of Pathology, Osaka Medical College, Osaka, Japan b



Article history: Received 24 April 2014 Received in revised form 16 July 2014 Accepted 3 August 2014

A 48-year-old woman was referred to the cardiology department due to a large mobile mass in the right ventricle. The patient had undergone radical hysterectomy and bilateral salpingo-oophorectomy for a uterine squamous cell carcinoma approximately 3.5 years before. In order to protect the patient from circulatory collapse, the intracardiac mass was resected surgically. A diagnosis of cardiac metastasis of the uterine cervical squamous cell carcinoma was confirmed histologically. Herein we discuss the possible therapeutic approach to and prognosis of this rare condition by reviewing 24 papers on intracardiac uterine cancer metastasis published in the past 10 years. ß 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Keywords: Uterine cancer Cardiac metastasis Squamous cell carcinoma

Introduction Metastasis of malignancies into the heart may also develop, albeit at a low reported frequency of 1.6–8% [1]. This frequency might be underestimated, however, because cardiac metastasis often remains clinically silent, leading to a difficulty of diagnosis during life. In fact, cardiac metastasis has been reported to increase to a frequency of 10–20% among cases with known malignancies during autopsy [2]. Metastasis of cervical cancer occurs usually to the liver, bone, brain, lung, and supraclavicular lymph nodes [3]. It

* Corresponding author at: Department of Cardiology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan. Tel.: +81 72 683 1221; fax: +81 72 684 6598. E-mail addresses: [email protected], [email protected] (N. Ishizaka).

may occur to the heart, although far less frequently. Herein, we present the case of a 48-year-old woman who was diagnosed to have metastasis of the cervical cancer into the right ventricle 3.5 years after the resection of the primary lesion. Case report A 48-year-old woman was referred to our cardiology department for the diagnosis and treatment of a cardiac mass in the right ventricle. The patient had been diagnosed with cervical cancer four years before. After chemotherapy by the BOAI (balloon-occluded arterial infusion) method with cisplatin and CPT-11, the patient underwent radical hysterectomy and bilateral salpingo-oophorectomy (Table 1) under the diagnosis of cervical cancer (FIGO IIA2). A post-operation diagnosis of pT2aN1M0 squamous cell carcinoma was made, and chemoradiation therapy was performed. 1878-5409/ß 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Y. Takeda et al. / Journal of Cardiology Cases 10 (2014) 221–225

222 Table 1

Summary of treatments for uterine carcinoma.



Treatment for the uterine carcinoma



Diagnosis of uterine cervical squamous cell carcinoma (stage IIA2) Preoperative chemotherapy (2 courses: BOAI of CDDP and CPT-11) Radical hysterectomy and bilateral salpingooophorectomy Postoperative chemotherapy (5 courses: CDDP), Pelvic radiation therapy Radiation for paraaortic lymph node metastasis Left supraclavicular lymph node metastasis by FDG-PET/CT Chemotherapy (6 courses: CDDP and CPT-11) Chemotherapy (9 courses: CBDCA and PTX) Radiation to the left supraclavicular lymph nodes Tumor marker elevation (SCC 6.2 ng/mL) 18 F-FDG uptake in the right ventriculum and diagnosis of the intracardiac mass Surgical resection of the intracardiac mass Radiation for heart and mediastinal lymph nodes Chemotherapy (CBDCA and PTX)



January June

2012 2013

March January December


February March

BOAI: balloon-occluded arterial infusion chemotherapy; FDG-PET: fluorodeoxyglucose-positron emission tomography; CDDP: cisplatin; CPT-11: irinotecan; CBDCA: carboplatin; PTX: paclitaxel.

Metastasis to the paraaortic lymph nodes (11 months later) and to the left subclavian lymph nodes (1.5 years later) was subsequently diagnosed after the initial diagnosis, and thus, chemo- and/or radiation therapy was performed. It was found that serum levels of a tumor marker, squamous cell carcinoma (SCC) antigen, were gradually increasing after the initial diagnosis (SCC 6.2 ng/mL 44-months post-operation). Despite searching for possible tumor recurrence, no obvious local recurrence of metastasis was evident; therefore 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) was performed that illustrated enhanced 18F-FDG uptake within the right ventricle (RV) (Fig. 1A and B, arrows). Echocardiography demonstrated a tumorous lesion of 3.7 cm  1.9 cm in the RV, which seemed to be attached to the free wall of the RV (Fig. 1C, arrow). On admission, the patient exhibited normal sinus rhythm (75 beats per minute) and systolic blood pressure (122/75 mmHg). The patient did not have exertional dyspnea and the blood oxygen saturation (SpO2) was 98% on room air. On echocardiography, left ventricular diastolic and systolic dimensions, and left ventricular

Fig. 1.

ejection fraction were 41 mm, 25 mm, and 71%, respectively. Right ventricular was not enlarged, with the dimension of 28 mm  31 mm. Tricuspid regurgitation was only trivial and the echocardiographic estimate of right ventricular systolic pressure was 36.1 mmHg. A chest roentgenogram showed normal cardiac size and electrocardiography showed normal sinus rhythm with mild ST-T abnormalities in leads II, III, and aVF (Fig. 1D). No abnormal cardiac sounds or murmurs could be auscultated. Contrast enhanced CT showed that peripheral pulmonary artery embolization (Fig. 1E, arrows), in addition to the intraventricular mass, and cardiac magnetic resonance (MR) demonstrated a tumor in the RV that was attached to the free wall and/or apex. On MR imaging, contrast enhancement of the tumor was weaker than that of the myocardium. Laboratory studies showed a white blood cell count of 5660 cells/mL, a hemoglobin level of 12.1 g/dL, a platelet count of 74  104 cells/mL, and a C-reactive protein concentration of 0.12 mg/dL; and the D-dimer level was elevated to 2.8 mg/mL. Coronary angiograms showed no apparent coronary artery stenosis, but small-diameter arteries that might be feeding the intraventricular tumor were observed (data not shown). Under the tentative diagnosis of metastatic cardiac malignancy, a surgical approach was selected for the purpose of prevention of a further embolic episode, right ventricular collapse, or sudden death due to the large mass dislodging. The operation was carried out on cardiopulmonary bypass through a median sternotomy. The tumor was observed to be located in the RV, attached to the base of the anterior papillary muscle of the tricuspid valve (Fig. 2A). The tumor was considered to have widely invaded the neighboring myocardium; therefore, it could not be completely resected from the heart. The resected mass was histologically confirmed as a metastatic squamous cell carcinoma surrounded by eosinophilic amorphous necrotic tissue (Fig. 2B and C). The cardio-pulmonary bypass time was 7.3 h and bleeding 40 mL. The length-of-stay in the intensive care unit was 2 days, and the patient was discharged uneventfully 25 days after the surgery. The patient received radiation therapy (total dose of 450 Gy) that started 5 weeks after the surgery. In addition, the patient is receiving chemotherapy (combined therapy with paclitaxel and carboplatin). At the moment, 5.5 months has passed, without any significant events, since the patient was discharged from our hospital. The patient has been continuing chemotherapy and is still under careful observation, because her prognosis with metastatic intracardiac lesions is considered to be poor.

Clinical images and electrocardiogram. (A) Whole body 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). Increased uptake in the heart was observed (arrow). (B) Transverse section of the PET-computed tomographic (CT) merged image. Increased FDG uptake is observed in the heart (arrow). (C) Echocardiography. A tumorous lesion is observed in the right ventricle (arrow). (D) Electrocardiogram obtained on admission. Slight abnormalities in ST-T segments were observed. (E) The CT image showed pulmonary artery embolization (arrows) and mass lesion in the right ventricle.

Y. Takeda et al. / Journal of Cardiology Cases 10 (2014) 221–225

Fig. 2.


Intraoperative photograph in surgeon’s view and histology the resected tumor. (A and B) Intraoperative photograph. The tumor occupied the right ventricular cavity (A, arrowheads). The surface of the tumor was very fragile and easily broken by forceps (B). (C and D) Histological analysis. Histology of the tumor tissue sampled from the right ventricle (C). Histology of the cervical cancer resected four years ago (D) showed irregularly shaped nests of non-keratinized squamous epithelium. The intracardiac tumor was diagnosed to be a metastasis of the uterine squamous cell carcinoma.

Discussion We herein reported a patient who was referred to the cardiology department due to an intracardiac mass coupled with elevated levels of tumor marker approximately 3.5 years after resection of a uterine cervical cell carcinoma. Although the patient was free from cardiac symptoms, surgical resection of the intracardiac tumor was performed to avoid sudden death due to tumor dislocation and subsequent cardiogenic shock. We performed a PubMed literature search of recent studies between 2004 January and 2014 January, by entering the search terms ‘‘uterus’’, ‘‘cancer (or carcinoma)’’, ‘‘heart’’, and ‘‘metastasis’’. These terms returned 40 articles with possibilities, among which 24 reported a diagnosed case of cardiac metastasis of uterine cancer [1,4–26] (Table 2). Among these metastasized cancers, squamous cell carcinoma was the most prevalent (11 cases, 50%); the other types were leiomyosarcoma 5 (21%), adenocarcinoma 4 (17%), stromal sarcoma 2 (8%), and neuroendocrine carcinoma 1 (4%). The right side of the heart (right atrium, right ventricle, and tricuspid valve, inferior vena cava, coronary sinus) was the dominant cardiac region (21 cases [88%]) involved in the uterine cancer metastasis as compared with the left side of the heart (2 cases [8%]); in addition, two cases showed metastasis to the pericardium [12,15]. Among 11 cases of metastasized squamous cell carcinoma, 10 (91%) showed metastasis to the right side of the

heart, and the remaining one showed that to the pericardium. The fact that the right cardiac chamber was far more susceptible to metastasis of the carcinomas regardless of the cell type may be attributed to the filtering role of the pulmonary circulation and the slower flow in the right chambers [27]. The interval between the therapy for the primary lesion and the cardiac metastasis varied, and some patients experienced an interval of 10 years or longer before cardiac metastasis. Surgical resection, which was not curative in most of instances, was performed in about two thirds of the cases, and chemotherapy and/or radiation was performed either with surgery or by itself. The period between diagnosis of the cardiac metastasis and death varied between 7 months and more than two years. One patient with cardiac metastasis of the endometroid adenocarcinoma was reported to have remained disease-free for 6.5 years after cardiac radiation with concurrent chemotherapy [23]. In particular, regarding metastasis of squamous cell carcinoma, the interval ranged between a few days and 13 months; thus, the prognosis after diagnosis of cardiac metastasis seems to be poor. In general, cardiac metastasis from cervical cancer, albeit very rare, is difficult to diagnose, and no standard treatment regimen for chemotherapy currently exists [4]. In our case, pulmonary artery embolization, presumably with tumor cells, was demonstrated by CT imaging. We selected surgical resection of the intracardiac mass to avoid acute cardiogenic


Table 2

Cases of intracardiac uterine cervical carcinoma reported in the past 10 years. Published year



Surgical excision


Interval to cardiac metastasis

Histologic type

Cardiac metastasis

Death from cardiac metastasis




Exertional dyspnea


15 M

Squamous cell carcinoma

RA and RV

13 M




Arrhythmia nausea, vomiting

1.9 Y

Squamous cell carcinoma






Dyspnea palpitation

No (biopsy), autopsy Yes

Chemotherapy (carboplatin with paclitaxel) Radiotherapy 60 Gy Chemotherapy, radiotherapy


Squamous cell carcinoma

Coronary sinus to RA

[6] [7]

2013 2012

49 56

Yes Yes

No Chemotherapy

N/A 2M

Leiomyosarcoma Leiomyosarcoma

Tricuspid valve RA






14 Y

Neuroendocrine carcinoma

Pulmonary vein to LA




No (biopsy)

Chemotherapy, radiotherapy


Squamous cell carcinoma

Tricuspid valve

No recurrence at 2 Y 8M

[10] [11] [12]

2010 2009 2008

64 43 38

No (biopsy) No No

N/A Chemotherapy warfarin Chemotherapy (paclitaxel)

6M 4Y 14 M

Adenocarcinoma Leiomyosarcoma Adenocarcinoma

RA LA, RV, LV Pericardium

N/A 1Y 6M





2009 2008 2007 2006

62 64 42 63

No (biopsy) No Yes Yes

Chemotherapy (ifosfamide, adriamycin), radiotherapy Palliative care Chemotherapy, radiotherapy N/A N/A


[14] [15] [16] [17]

Lower extremity swelling Right central chest discomfort, tachycardia, right heart failure and shock Cerebral infarction without any sequelae No symptom at the time of diagnosis, heart failure within several months of diagnosis Lightheadedness Dyspnea Leg swelling, chest pain, shortness of breath Leg swelling, acute respiratory distress Shortness of breath Dry cough, dyspnea Respiratory distress, chest pain Fatigue, dyspnea on exertion

No recurrence at 6 M N/A N/A

14 M 6M 6M 33 Y

Low-grade endometrial stromal sarcoma Endometrial adenocarcinoma Squamous cell carcinoma Squamous cell carcinoma Squamous cell carcinoma

RA, RV (intravenous extension via IVC) RV Pericardium RA, RV PA, RV, tricuspid valve







No, autopsy



Squamous cell carcinoma



Dyspnea on effort, right heart failure symptom Asymptomatic

No recurrence at 1 Y 17 days 10 M N/A Terminal stage at 5 M 3 days





13 M



Chest pain, shortness of breath


Chemotherapy for pulmonary nodule Palliative care

10 M

Squamous cell carcinoma








Squamous cell carcinoma








[23] [24]

2005 2005

61 37

Yes No

Chemotherapy, radiotherapy Chemotherapy, radiotherapy


Endometrial adenocarcinoma Squamous cell carcinoma

[25] [26]

2004 2004

58 48

Shortness of breath, palpitation, malaise Lower abdominal pain and distension Pedal edema No symptom at the time of diagnosis Dyspnea, cough, right chest pain Lower abdominal discomfort

RA (intravenous extension via IVC) RV

Yes Yes

No Chemotherapy

3Y 4Y

Squamous cell carcinoma Low-grade endometrial stromal sarcoma

RA, RV, LA, LV, PA, IVC indicate right atrium, right ventricle, left atrium, left ventricle, pulmonary artery, and inferior vena cava, respectively. N/A: not assessed.

RA (intravenous extension via IVC) RV RV RV, and PA IVC and RV

5M N/A 6.8 Y No recurrence at 8 M 4M N/A

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Y. Takeda et al. / Journal of Cardiology Cases 10 (2014) 221–225

collapse due to a shut-down of the pulmonary circulation. It is thought that reducing the obstruction to the blood flow caused by the tumor may provide symptomatic relief leading to an improvement in quality of life, although resection of the metastasized cardiac tumor is, in general, palliative [16]. Nevertheless, considering the very poor prognosis after cardiac metastasis [28], the indication of such palliative tumor resection may not depend solely on the symptoms of the condition. In summary, here we have reported a patient who had a uterine squamous cell cancer metastasis to the RV of the heart approximately 3.5 years after resection of the primary lesion. Such an intracardiac metastasis seems to occur rarely – only 24 cases of cardiac metastasis of a uterine cancer, including 12 cases of squamous cell carcinoma, have been reported in the past 10 years. Intracardiac metastasis may remain clinically silent; therefore, we should be aware of this condition, especially among patients with elevated tumor markers, as in the present case. Surgical resection of the intracardiac mass may be selected to avoid acute cardiogenic collapse; however, considering the poor prognosis after intracardiac metastasis, the indication of palliative tumor resection and chemotherapy needs to be carefully assessed for individual cases. Conflict of interest The authors declare no conflict of interest. References [1] Al-Ebrahim KE. Coronary sinus metastasis from cervical carcinoma. J Card Surg 2013;28:22–4. [2] Chiles C, Woodard PK, Gutierrez FR, Link KM. Metastatic involvement of the heart and pericardium: CT and MR imaging. Radiographics 2001;21:439–49. [3] Brenner DE. Carcinoma of the cervix—a review. Am J Med Sci 1982;284: 31–48. [4] Byun SW, Park ST, Ki EY, Song H, Hong SH, Park JS. Intracardiac metastasis from known cervical cancer: a case report and literature review. World J Surg Oncol 2013;11:107. [5] Togo A, Muramatsu T, Tsukada H, Ikeda M, Shida M, Hirasawa T, Maeda H, Mikami M. Case of metastatic uterine cervical squamous cell carcinoma in the right atrium. Tokai J Exp Clin Med 2013;38:42–5. [6] Marak CP, Ponea AM, Alappan N, Shaheen S, Guddati AK. Uterine leiomyosarcoma manifesting as a tricuspid valve mass. Case Rep Oncol 2013;6: 119–26. [7] Nguyen SK, Wong F. Right atrial metastasis of uterine leiomyosarcoma causing obstructive shock. Curr Oncol 2012;19:e292–4. [8] Lee S, Park IK, Cho SH. Extension of metastatic lung cancer from cervix cancer through pulmonary vein into the left atrium. Ann Thorac Surg 2011;92:1131.


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