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Primary cardiac neoplasms: Coexistence of papillary fibroelastomas of the tricuspid valve and myxoma of the mitral valve
Journal Pre-proof Primary cardiac neoplasms: Coexistence of papillary fibroelastomas of the tricuspid valve and myxoma of the mitral valve Zhipan Wei, Bangtian Peng, Yulin Bai, Zaiqiang Wu, Yanwei Zhang, Feng Ai, Wanli Gao PII:
S2213-5766(19)30340-9
DOI:
https://doi.org/10.1016/j.epsc.2019.101353
Reference:
EPSC 101353
To appear in:
Journal of Pediatric Surgery Case Reports
Received Date: 6 November 2019 Revised Date:
12 November 2019
Accepted Date: 13 November 2019
Please cite this article as: Wei Z, Peng B, Bai Y, Wu Z, Zhang Y, Ai F, Gao W, Primary cardiac neoplasms: Coexistence of papillary fibroelastomas of the tricuspid valve and myxoma of the mitral valve, Journal of Pediatric Surgery Case Reports (2019), doi: https://doi.org/10.1016/ j.epsc.2019.101353. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.
Primary cardiac neoplasms: Coexistence of papillary fibroelastomas of the tricuspid valve and myxoma of the mitral valve Zhipan Wei1, Bangtian Peng2, Yulin Bai1, Zaiqiang Wu1,Yanwei Zhang2, Feng Ai2, Wanli Gao1
Highlights • • •
This is the first case report of a heterogeneous pediatric cardiac tumor involving the coexistence of myxoma of the mitral valve and papillary fibroelastomas of the tricuspid valve. Heterogeneous cardiac tumors reported in the literature are limited to adults, with only sporadic reported cases. The prognosis after tumorectomy of a heterogeneous tumor of the mitral valve accompanied by a tricuspid valve tumor is still unclear.
1. Abstract: Both cardiac myxomas and papillary fibroelastomas are primary benign cardiac tumors, but it is very rare for tumors with different histologies to occur in different valves of the same heart. A 5-month-old infant underwent resection of a mitral valve mass + mitral valvuloplasty at our hospital. The tricuspid valve mass was still small, and no tricuspid regurgitation was observed; therefore, the tricuspid valve mass was not treated. The postoperative pathology showed that the mitral valve mass was a myxoma. The patient presented to our hospital for a follow-up examination two years later, and color Doppler ultrasound showed enlargement of the mitral valve and tricuspid valve mass as well as aggravation of regurgitation of the two valves. We performed resection of the mitral valve mass with mechanical valve replacement + resection of the tricuspid valve mass together with tricuspid valvuloplasty for this child. Postoperative pathology showed myxoid degeneration of the mitral valve and papillary fibroelastoma/tumor-like hyperplasia of the tricuspid valve. One month after the patient underwent surgery, the follow-up examination was satisfactory. Keywords: cardiac myxoma, cardiac papillary fibroelastoma, myxomatous degeneration, heterogeneous tumor
2. Case report: 1
Henan Provincial People’s Hospital, School of Medicine Henan University, Zheng Zhou, P.R. China. Corresponding author: Zhipan Wei, School of Medicine Henan University, Henan Province No. 7 Wei wu, Zheng Zhou, 450018, P.R. China, Tel: +8618538707215; E-mail: [email protected]. 2
Fu Wai Central China Cardiovascular Hospital, Zheng Zhou, P.R. China
A 5-month-old infant presented at a local hospital due to diarrhea but was asymptomatic and was found to have a heart murmur. The patient underwent a transthoracic color Doppler ultrasound examination at our hospital. The ultrasound revealed an echogenic mass at the anterior mitral leaflet, with a moderate size of approximately 1.36*1.81 cm, that was shuttling between the left ventricle and the left atrium. The left ventricular inflow tract was obstructed, the left heart was enlarged, mild mitral regurgitation was observed, and the ejection fraction was normal. The patient’s mother was gravida 2, para 2 (G2P2); the patient had a birth weight of 3.7 kg and did not have a family history of cardiac tumors. Physical examination showed that the patient’s body temperature was 36.7°C, the respiratory rate was 25 breaths/min, and the heart rate was 136 beats/min. The patient was conscious but was in poor spirits, and the conjunctiva and lips were pale. Chest auscultation revealed clear breath sounds in both lobes. Palpation showed precordial tremor, apparent apical pulsation, systolic to diastolic murmur in the precordium, and sinus arrhythmia revealed by electrocardiogram. Chest radiograph showed an enlarged cardiac shadow. These findings led us to suspect that the lesion was a myxoma, but of course, thrombus or excrescence was not excluded. After general anesthesia was administered, median sternotomy and cardiopulmonary bypass were performed. After the heart stopped beating, the right atrium was opened. Through the interatrial septal incision, it was observed that the chordae tendineae of the anterior leaflet of the mitral valve was connected to a white lumpy mass, which was approximately 2.5*2.0 cm in size. A hiatus with a diameter of 0.5 cm was visible in the center of the mass, but no obvious structure of the anterior mitral leaflet was observed, which resulted in limited opening of the mitral orifice. Partial prolapse of the left atrium occurred during closure, and the valve orifice was misaligned. No stenosis of the right ventricular outflow tract was observed, and no prolapse of the aortic valve was seen. A lumpy mass approximately 0.8 cm in size was observed near the junction of the septal leaflet and the anterior leaflet of the tricuspid valve. No significant tricuspid regurgitation was observed. Limited by the child’s age, the mitral valve mass was only partially removed during surgery to preserve as much of the mitral valve and its accessory tissues as possible. Then, 6/0 prolene sutures and a double-tipped needle and gasket were used to close the central hiatus of the mass. The mitral regurgitation was relieved during a water injection test. The cardiopulmonary bypass time was 52 min, and the aortic occlusion time was 30 min. Postoperative pathology showed that the size of the myxoma of the anterior leaflet of the mitral valve (Fig. 1A) was 0.3*0.3*0.2 cm. Since this operation did not completely remove the tumor tissue, we considered the possibility of tumor regrowth and recurrence; we informed the child’s guardian, who signed and agreed to our surgical procedure. The patient underwent a follow-up examination at our hospital. Transthoracic echocardiography showed that the left heart was enlarged (the anteroposterior diameter of the left atrium was 44 mm), and an echogenic mass with a size of approximately 2.16*1.76 cm was observed at the anterior leaflet of the mitral valve and was closely associated with the anterior leaflet (Fig. 2A). An echogenic mass with an approximate size of 1.27*1.25 cm was observed at the septal leaflet of the tricuspid valve and was closely associated with the septal leaflet (Fig. 2B). The regurgitation of the two valves was aggravated. The child's guardian complained of decreased physical activity. Therefore, surgical treatment was performed again. Intraoperative findings revealed severe pericardial and mediastinal adhesions and severe cardiac enlargement, which was primarily enlargement of the left atrium and left ventricle. Mitral annulus enlargement was also found as was thickening of the mitral valve leaflets; a white mass with a size of 3.0*4.0 cm was visible at the anterior leaflet (Fig. 3A and B) and was completely fused with the anterior leaflet, which resulted in severe mitral valve insufficiency (Fig. 4A). An impingement spot was visible in the left atrium, and a 1.0*1.5 cm white mass was observed in the body of the septal leaflet of
the tricuspid valve (Fig. 4A). No stenosis of the outflow tract of the right ventricle was observed. An in situ median sternotomy was then performed. Cardiopulmonary bypass was routinely established, the ascending aorta was occluded, and HTK cardioplegia solution was perfused through the aortic root, which caused cessation of the heartbeat. The right atrium and interatrial septum were incised. Due to the severe loss of the anterior leaflet of the mitral valve and the chordae tendineae, the mitral valve could not be repaired after tumor removal. After communicating this situation to the patient’s family members, it was decided to perform a mitral valve replacement. The mitral valve tissue was resected, and a size 25 St. Jude mechanical valve was placed in the mitral valve position. The mechanical valve of the mitral valve was tested and demonstrated to close well. The septal tumor of the tricuspid valve was removed, and the septal leaflet of the tricuspid valve was formed and closed. The interatrial septal incision was sutured. After de-airing, the circulation was open, the heartbeat automatically recovered with a sinus rhythm, and no regurgitation was observed at the tricuspid valve. The right atrial incision was closed with suture, and the patient was successfully weaned from the extracorporeal circulation machine. The extracorporeal circulation time was 130 min, and the aortic occlusion time was 73 min. The postoperative pathological diagnosis showed that the fibrous valvular tissue of the mitral valve was accompanied by hyaline degeneration and myxoid degeneration (Fig. 5). Moreover, a small amount of fibrous valvular tissue of the tricuspid accompanied the hyaline degeneration and myxoid degeneration, and multinodular tissue was attached to the valve. Using a combination of immunohistochemistry and special stains, the lesion was found to be consistent with papillary fibroelastoma/tumor-like hyperplasia. Follow-up was recommended. Immunohistochemical results showed the following: cluster of differentiation 31 (CD31) (epithelium +), cytokeratins 5/6 (CK5/6) (-), CR (-), Hector Battifora mesothelial-1 (HBME-1) (mesenchyme +), Ki67 (approximately 2% +), S-100 (+), Vimentin (+), Mucin 4 (MUC-4) (-), MUC-6 (-), B-cell lymphoma 2 (Bcl-2) (-), CD99 (-), β-catenin (epithelium +). Special stains showed elastic fibers (small amount of blue-green color) (Fig. 6). Transthoracic color Doppler ultrasound follow-up examination was performed one month after surgery and showed that the artificial mechanical valve was at the position of the mitral valve; the position was fixed, the shape was good, and the opening and closing functions were normal and without perivalvular leakage (Fig. 7). The tricuspid root and annulus showed strong echoes, and the opening and closure of the leaflets of the valve were good.
3. Discussion: Many reports of single or multiple homogeneous cardiac tumors have been published. However, this paper reports a very rare case of a heterogeneous tumor involving two valves. To date, only sporadic similar cases have been reported, and the reported heterogeneous tumors are myxomas and papillary fibroelastomas1-10. Agaimy A et al. reported a case of heterogeneous tumors during biopsy, which consisted of a papillary fibroelastoma of the aortic valve and a cystic tumor11. This rare case of heterogeneous cardiac double-valve tumors reported here has the following special features: 1) this is the youngest reported patient at only 5 months of age; 2) the valves involved were the mitral and tricuspid valves; 3) the mitral valve tumor and the tricuspid valve tumor were heterogeneous (the pathological examination of the mitral valve tumor resected during the first operation showed myxoma, while that of the tricuspid valve tumor resected during the second operation showed papillary fibroelastoma); 4) the location of the myxoma growth, which was the anterior leaflet of the mitral valve,
is uncommon; and 5) the mitral valve was replaced by a mechanical valve. These unique features have either not been seen or are rarely seen in the previous literature. The tricuspid tumor was not found when the child underwent color Doppler ultrasound examination at the first hospital admission, which indicates a certain probability of a missed diagnosis of a smaller papillary fibroelastoma when evaluated by transthoracic color Doppler ultrasound. Of course, the diagnosis would also be limited by the experience of the sonographers. When reporting a case of heterogeneous cardiac tumors, a left atrial myxoma coexistent with a papillary fibroelastoma of the aortic valve, N Jallad et al. also indicated the importance of performing a thorough preoperative or intraoperative examination of cardiac tumors4. The left atrial myxoma they reported was discovered by transthoracic echocardiography, while the papillary fibroelastoma of the aortic valve was discovered by transesophageal echocardiography. For the patient with heterogeneous cardiac tumors reported by J. Roque9, the aortic tumor was also initially missed and was eventually identified intraoperatively as a papillary fibroelastoma. The experience of these prior cases has provided us with a warning. At present, all patients with congenital heart disease who are admitted to our hospital undergo a routine intraoperative transesophageal color Doppler ultrasound examination to evaluate the heart again before the operation but after anesthesia is administered. As for why the pathological findings of the mitral valve were inconsistent after the two surgeries, after a detailed consultation with a pathologist, the speculations were as follows: during the first operation, the mature tumor tissue had been removed, and the myxoma required time to mature. The interval between the two operations was only 2 years, which caused the mitral valve tumor tissue removed during the second operation to appear as immature myxoid degenerative tissue, and therefore, the pathological findings were fibrous valvular tissue of the mitral valve accompanied by myxoid degeneration and hyalinization. In terms of the cause of the myxomatous degeneration of the mitral valve, no specific conclusion is evident in the existing literature. Loardi C et al. suggested that the cause is extracellular matrix synthesis and metabolic disorders caused by the overexpression of metalloproteases as well as excessive cell proliferation12. Freed LA et al. suggested that a mitral valve with myxomatous degeneration often causes mitral valve prolapse13. Based on the literature on mitral valve prolapse and sudden cardiac death reported by Nalliah CJ14, young patients with myxomatous degeneration of the mitral valve will experience complications such as infective endocarditis, sudden death, and stroke. Mitral valve prolapse is closely associated with sudden cardiac death. A patient with myxomatous degeneration of the mitral valve reported by Lazar Neto F underwent mitral valve replacement15. In our pediatric patient, the mitral valve already exhibited myxomatous degeneration and was in a state of loss of function, and thus, we weighed the advantages and disadvantages of a mechanical valve versus a biological valve. S. Chauvaud performed mitral valve replacement with biological valves in 13 patients aged 3 – 25 years who were followed up for 0.6 – 6.6 years and found that all of the biological valves were associated with issues such as contractures, thickening, and calcification16. Therefore, the author did not recommend mitral valve replacement with biological valves in young patients. Eventually, we chose to perform mitral valve replacement with a mechanical valve. Currently, the patient's mechanical mitral valve function is good. Regarding the clinical manifestation and complications of these heterogeneous cardiac tumors, the current literature reports the symptoms that often occur in patients with cardiac myxoma and cardiac papillary fibroelastoma; these include embolism, valvular stenosis, and insufficiency. Takano et al. reviewed previous studies that reported similar diseases and found that among the eight patients, five
showed symptoms, the most common of which was dyspnea, followed by palpitations and stroke. Our patient was still young, the disease was detected early, and the patient only had decreased activity endurance upon second admission. Furthermore, no perioperative complications were found. In addition, these heterogeneous cardiac tumors are very rare, and due to our lack of experience, we did not perform a blood draw from the patient to test for tumor markers, and we also did not perform a brain computed tomography (CT) examination to assess the risk of cerebrovascular obstruction. However, this pediatric patient did not experience cerebrovascular complications such as mental abnormalities or limb motor dysfunction during the perioperative period. 4. Conclusion: We report a case of a 5-month-old infant with a rare myxoma of the mitral valve coincident with a papillary fibroelastoma of the tricuspid valve. Once the tumor was diagnosed, it was immediately surgically resected. Thus far, the prognosis is good. Many mysteries in the etiology and prognosis of this heterogeneous tumor remain unsolved and require further exploration.
References 1. Akiyama, K.; Hirota, J.; Tsuda, Y.; Ebishima, H.; Li, C., Double primary cardiac tumors: possible association with a variety of cardiac diseases. J Cardiovasc Surg (Torino) 2006, 47 (1), 81-2. 2. Buttan, A. K.; Panagiotides, G.; Barnes, M. J.; Vorobiof, G., Multimodality imaging in the diagnosis of coexisting left atrial myxoma and aortic valve papillary fibroelastoma. Circulation 2012, 125 (23), e1003-5. 3. Challa, S.; Chaliki, H. P.; Najib, M. Q.; Ganji, J. L.; Click, R. L., An unusual case of left atrial myxoma and papillary fibroelastoma. Echocardiography 2013, 30 (1), E25. 4. Jallad, N.; Parikh, R.; Daoko, J.; Albareqdar, E.; Al-Dehneh, A.; Goldstein, J.; Shamoon, F.; Connolly, M. W., Concurrent primary cardiac tumors of differing histology and origin: case report with literature review. Tex Heart Inst J 2009, 36 (6), 591-3. 5. Jutley, R. S.; Melham, N.; Skinner, H.; Richens, D., Unusual case of two synchronous intracavitary primary cardiac tumors. Ann Thorac Surg 2008, 85 (3), 1086-7. 6. Matsushita, A.; Manabe, S.; Tabata, M.; Fukui, T.; Shimokawa, T.; Amano, J.; Takanashi, S., Heterogeneous double cardiac tumor: myxoma concomitant with papillary fibroelastoma. J Card Surg 2010, 25 (1), 35-7. 7. Menon, T.; Watanabe, Y.; Andrews, D., Concurrent primary cardiac tumors. J Thorac Cardiovasc Surg 2007, 134 (1), 263-4. 8. Prifti, E.; Bonacchi, M.; Salica, A., Mitral valve myxoma concomitant with papillary fibroelastoma. Ann Thorac Surg 2000, 70 (1), 335-6. 9. Roque, J.; Silva, F.; Arruda Pereira, R.; Cravino, J., Multiple causes for an ischemic stroke: myxoma, papillary fibroelastomas and patent foramen ovale. HSR Proc Intensive Care Cardiovasc Anesth 2012, 4 (3), 187-91. 10. Takano, T.; Kakuta, T.; Takahashi, S., A potential concomitance of papillary fibroelastoma in the case with cardiac myxoma. Gen Thorac Cardiovasc Surg 2017, 65 (8), 474-477. 11. Agaimy, A.; Strecker, T., Left atrial myxoma with papillary fibroelastoma-like features. Int J Clin Exp Pathol 2011, 4 (3), 307-11.
12. Loardi, C.; Alamanni, F.; Trezzi, M.; Kassem, S.; Cavallotti, L.; Tremoli, E.; Pacini, D.; Parolari, A., Biology of mitral valve prolapse: the harvest is big, but the workers are few. Int J Cardiol 2011, 151 (2), 129-35. 13. Freed, L. A.; Levy, D.; Levine, R. A.; Larson, M. G.; Evans, J. C.; Fuller, D. L.; Lehman, B.; Benjamin, E. J., Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999, 341 (1), 1-7. 14. Nalliah, C. J.; Mahajan, R.; Elliott, A. D.; Haqqani, H.; Lau, D. H.; Vohra, J. K.; Morton, J. B.; Semsarian, C.; Marwick, T.; Kalman, J. M.; Sanders, P., Mitral valve prolapse and sudden cardiac death: a systematic review and meta-analysis. Heart 2019, 105 (2), 144-151. 15. Neto, F. L.; Marques, L. C.; Aiello, V. D., Myxomatous degeneration of the mitral valve. Autops Case Rep 2018, 8 (4), e2018058. 16. Chauvaud, S.; Waldmann, T.; d'Attellis, N.; Bruneval, P.; Acar, C.; Gerota, J.; Jarraya, M.; Carpentier, A., Homograft replacement of the mitral valve in young recipients: mid-term results. Eur J Cardiothorac Surg 2003, 23 (4), 560-6.
Fig.1A: the myxoma of the anterior leaflet of the mitral valve, myxoid cells were stained with Haematoxylin and Eosin. (H+E)x100.
Fig.2A:
an echogenic mass with a size of approximately 2.16*1.76 cm was observed at the anterior leaflet of the mitral valve and was closely associated with the anterior leaflet
Fig.2B:
An echogenic mass with an approximate size of 1.27*1.25 cm was observed at the septal leaflet of the tricuspid valve and was closely associated with the septal leaflet
Fig.3A: a white mass with a size of 3.0*4.0 cm was visible at the anterior leaflet and was completely fused with the anterior leaflet.
Fig.3B: myxoma of the mitral valve.
Fig.4A: papillary fibroelastomas of the tricuspid valve.
Fig.5: the fibrous valvular tissue of the mitral valve was accompanied by hyaline degeneration and myxoid degeneration.
Fig.6: a small amount of fibrous valvular tissue of the tricuspid accompanied the hyaline degeneration and myxoid degeneration, and multinodular tissue was attached to the valve. Using a combination of immunohistochemistry and special stains, the lesion was found to be consistent with papillary fibroelastoma/tumor-like hyperplasia. Special stains showed elastic fibers (small amount of blue-green color).
Fig.7: the position was fixed, the shape was good, and the opening and closing functions were normal and without perivalvular leakage.
Patient consent Consent to publish the case report was obtained. This report does not contain any personal information that could lead to the identification of the patient.
Funding No funding or grant support.
Authorship All authors attest that they meet the current ICMJE criteria for Authorship.
Declaration of competing interest The authors declare that there are no conflicts of interest in this manuscript.
Acknowledgements
Wei is the postgraduate student in School of Medicine Henan University. Peng is my postgraduate tutor in Henan Provincial People’s Hospital, meanwhile, he is also the chief physician of children heart center ward 2. Ai and Zhang are the surgeons of children heart center ward 2 in Fu Wai Central China Cardiovascular Hospital.Fu Wai Central China Cardiovascular Hospital is the heart center of Henan Provincial People’s Hospital.
S2213-5766(19)30340-9
DOI:
https://doi.org/10.1016/j.epsc.2019.101353
Reference:
EPSC 101353
To appear in:
Journal of Pediatric Surgery Case Reports
Received Date: 6 November 2019 Revised Date:
12 November 2019
Accepted Date: 13 November 2019
Please cite this article as: Wei Z, Peng B, Bai Y, Wu Z, Zhang Y, Ai F, Gao W, Primary cardiac neoplasms: Coexistence of papillary fibroelastomas of the tricuspid valve and myxoma of the mitral valve, Journal of Pediatric Surgery Case Reports (2019), doi: https://doi.org/10.1016/ j.epsc.2019.101353. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.
Primary cardiac neoplasms: Coexistence of papillary fibroelastomas of the tricuspid valve and myxoma of the mitral valve Zhipan Wei1, Bangtian Peng2, Yulin Bai1, Zaiqiang Wu1,Yanwei Zhang2, Feng Ai2, Wanli Gao1
Highlights • • •
This is the first case report of a heterogeneous pediatric cardiac tumor involving the coexistence of myxoma of the mitral valve and papillary fibroelastomas of the tricuspid valve. Heterogeneous cardiac tumors reported in the literature are limited to adults, with only sporadic reported cases. The prognosis after tumorectomy of a heterogeneous tumor of the mitral valve accompanied by a tricuspid valve tumor is still unclear.
1. Abstract: Both cardiac myxomas and papillary fibroelastomas are primary benign cardiac tumors, but it is very rare for tumors with different histologies to occur in different valves of the same heart. A 5-month-old infant underwent resection of a mitral valve mass + mitral valvuloplasty at our hospital. The tricuspid valve mass was still small, and no tricuspid regurgitation was observed; therefore, the tricuspid valve mass was not treated. The postoperative pathology showed that the mitral valve mass was a myxoma. The patient presented to our hospital for a follow-up examination two years later, and color Doppler ultrasound showed enlargement of the mitral valve and tricuspid valve mass as well as aggravation of regurgitation of the two valves. We performed resection of the mitral valve mass with mechanical valve replacement + resection of the tricuspid valve mass together with tricuspid valvuloplasty for this child. Postoperative pathology showed myxoid degeneration of the mitral valve and papillary fibroelastoma/tumor-like hyperplasia of the tricuspid valve. One month after the patient underwent surgery, the follow-up examination was satisfactory. Keywords: cardiac myxoma, cardiac papillary fibroelastoma, myxomatous degeneration, heterogeneous tumor
2. Case report: 1
Henan Provincial People’s Hospital, School of Medicine Henan University, Zheng Zhou, P.R. China. Corresponding author: Zhipan Wei, School of Medicine Henan University, Henan Province No. 7 Wei wu, Zheng Zhou, 450018, P.R. China, Tel: +8618538707215; E-mail: [email protected]. 2
Fu Wai Central China Cardiovascular Hospital, Zheng Zhou, P.R. China
A 5-month-old infant presented at a local hospital due to diarrhea but was asymptomatic and was found to have a heart murmur. The patient underwent a transthoracic color Doppler ultrasound examination at our hospital. The ultrasound revealed an echogenic mass at the anterior mitral leaflet, with a moderate size of approximately 1.36*1.81 cm, that was shuttling between the left ventricle and the left atrium. The left ventricular inflow tract was obstructed, the left heart was enlarged, mild mitral regurgitation was observed, and the ejection fraction was normal. The patient’s mother was gravida 2, para 2 (G2P2); the patient had a birth weight of 3.7 kg and did not have a family history of cardiac tumors. Physical examination showed that the patient’s body temperature was 36.7°C, the respiratory rate was 25 breaths/min, and the heart rate was 136 beats/min. The patient was conscious but was in poor spirits, and the conjunctiva and lips were pale. Chest auscultation revealed clear breath sounds in both lobes. Palpation showed precordial tremor, apparent apical pulsation, systolic to diastolic murmur in the precordium, and sinus arrhythmia revealed by electrocardiogram. Chest radiograph showed an enlarged cardiac shadow. These findings led us to suspect that the lesion was a myxoma, but of course, thrombus or excrescence was not excluded. After general anesthesia was administered, median sternotomy and cardiopulmonary bypass were performed. After the heart stopped beating, the right atrium was opened. Through the interatrial septal incision, it was observed that the chordae tendineae of the anterior leaflet of the mitral valve was connected to a white lumpy mass, which was approximately 2.5*2.0 cm in size. A hiatus with a diameter of 0.5 cm was visible in the center of the mass, but no obvious structure of the anterior mitral leaflet was observed, which resulted in limited opening of the mitral orifice. Partial prolapse of the left atrium occurred during closure, and the valve orifice was misaligned. No stenosis of the right ventricular outflow tract was observed, and no prolapse of the aortic valve was seen. A lumpy mass approximately 0.8 cm in size was observed near the junction of the septal leaflet and the anterior leaflet of the tricuspid valve. No significant tricuspid regurgitation was observed. Limited by the child’s age, the mitral valve mass was only partially removed during surgery to preserve as much of the mitral valve and its accessory tissues as possible. Then, 6/0 prolene sutures and a double-tipped needle and gasket were used to close the central hiatus of the mass. The mitral regurgitation was relieved during a water injection test. The cardiopulmonary bypass time was 52 min, and the aortic occlusion time was 30 min. Postoperative pathology showed that the size of the myxoma of the anterior leaflet of the mitral valve (Fig. 1A) was 0.3*0.3*0.2 cm. Since this operation did not completely remove the tumor tissue, we considered the possibility of tumor regrowth and recurrence; we informed the child’s guardian, who signed and agreed to our surgical procedure. The patient underwent a follow-up examination at our hospital. Transthoracic echocardiography showed that the left heart was enlarged (the anteroposterior diameter of the left atrium was 44 mm), and an echogenic mass with a size of approximately 2.16*1.76 cm was observed at the anterior leaflet of the mitral valve and was closely associated with the anterior leaflet (Fig. 2A). An echogenic mass with an approximate size of 1.27*1.25 cm was observed at the septal leaflet of the tricuspid valve and was closely associated with the septal leaflet (Fig. 2B). The regurgitation of the two valves was aggravated. The child's guardian complained of decreased physical activity. Therefore, surgical treatment was performed again. Intraoperative findings revealed severe pericardial and mediastinal adhesions and severe cardiac enlargement, which was primarily enlargement of the left atrium and left ventricle. Mitral annulus enlargement was also found as was thickening of the mitral valve leaflets; a white mass with a size of 3.0*4.0 cm was visible at the anterior leaflet (Fig. 3A and B) and was completely fused with the anterior leaflet, which resulted in severe mitral valve insufficiency (Fig. 4A). An impingement spot was visible in the left atrium, and a 1.0*1.5 cm white mass was observed in the body of the septal leaflet of
the tricuspid valve (Fig. 4A). No stenosis of the outflow tract of the right ventricle was observed. An in situ median sternotomy was then performed. Cardiopulmonary bypass was routinely established, the ascending aorta was occluded, and HTK cardioplegia solution was perfused through the aortic root, which caused cessation of the heartbeat. The right atrium and interatrial septum were incised. Due to the severe loss of the anterior leaflet of the mitral valve and the chordae tendineae, the mitral valve could not be repaired after tumor removal. After communicating this situation to the patient’s family members, it was decided to perform a mitral valve replacement. The mitral valve tissue was resected, and a size 25 St. Jude mechanical valve was placed in the mitral valve position. The mechanical valve of the mitral valve was tested and demonstrated to close well. The septal tumor of the tricuspid valve was removed, and the septal leaflet of the tricuspid valve was formed and closed. The interatrial septal incision was sutured. After de-airing, the circulation was open, the heartbeat automatically recovered with a sinus rhythm, and no regurgitation was observed at the tricuspid valve. The right atrial incision was closed with suture, and the patient was successfully weaned from the extracorporeal circulation machine. The extracorporeal circulation time was 130 min, and the aortic occlusion time was 73 min. The postoperative pathological diagnosis showed that the fibrous valvular tissue of the mitral valve was accompanied by hyaline degeneration and myxoid degeneration (Fig. 5). Moreover, a small amount of fibrous valvular tissue of the tricuspid accompanied the hyaline degeneration and myxoid degeneration, and multinodular tissue was attached to the valve. Using a combination of immunohistochemistry and special stains, the lesion was found to be consistent with papillary fibroelastoma/tumor-like hyperplasia. Follow-up was recommended. Immunohistochemical results showed the following: cluster of differentiation 31 (CD31) (epithelium +), cytokeratins 5/6 (CK5/6) (-), CR (-), Hector Battifora mesothelial-1 (HBME-1) (mesenchyme +), Ki67 (approximately 2% +), S-100 (+), Vimentin (+), Mucin 4 (MUC-4) (-), MUC-6 (-), B-cell lymphoma 2 (Bcl-2) (-), CD99 (-), β-catenin (epithelium +). Special stains showed elastic fibers (small amount of blue-green color) (Fig. 6). Transthoracic color Doppler ultrasound follow-up examination was performed one month after surgery and showed that the artificial mechanical valve was at the position of the mitral valve; the position was fixed, the shape was good, and the opening and closing functions were normal and without perivalvular leakage (Fig. 7). The tricuspid root and annulus showed strong echoes, and the opening and closure of the leaflets of the valve were good.
3. Discussion: Many reports of single or multiple homogeneous cardiac tumors have been published. However, this paper reports a very rare case of a heterogeneous tumor involving two valves. To date, only sporadic similar cases have been reported, and the reported heterogeneous tumors are myxomas and papillary fibroelastomas1-10. Agaimy A et al. reported a case of heterogeneous tumors during biopsy, which consisted of a papillary fibroelastoma of the aortic valve and a cystic tumor11. This rare case of heterogeneous cardiac double-valve tumors reported here has the following special features: 1) this is the youngest reported patient at only 5 months of age; 2) the valves involved were the mitral and tricuspid valves; 3) the mitral valve tumor and the tricuspid valve tumor were heterogeneous (the pathological examination of the mitral valve tumor resected during the first operation showed myxoma, while that of the tricuspid valve tumor resected during the second operation showed papillary fibroelastoma); 4) the location of the myxoma growth, which was the anterior leaflet of the mitral valve,
is uncommon; and 5) the mitral valve was replaced by a mechanical valve. These unique features have either not been seen or are rarely seen in the previous literature. The tricuspid tumor was not found when the child underwent color Doppler ultrasound examination at the first hospital admission, which indicates a certain probability of a missed diagnosis of a smaller papillary fibroelastoma when evaluated by transthoracic color Doppler ultrasound. Of course, the diagnosis would also be limited by the experience of the sonographers. When reporting a case of heterogeneous cardiac tumors, a left atrial myxoma coexistent with a papillary fibroelastoma of the aortic valve, N Jallad et al. also indicated the importance of performing a thorough preoperative or intraoperative examination of cardiac tumors4. The left atrial myxoma they reported was discovered by transthoracic echocardiography, while the papillary fibroelastoma of the aortic valve was discovered by transesophageal echocardiography. For the patient with heterogeneous cardiac tumors reported by J. Roque9, the aortic tumor was also initially missed and was eventually identified intraoperatively as a papillary fibroelastoma. The experience of these prior cases has provided us with a warning. At present, all patients with congenital heart disease who are admitted to our hospital undergo a routine intraoperative transesophageal color Doppler ultrasound examination to evaluate the heart again before the operation but after anesthesia is administered. As for why the pathological findings of the mitral valve were inconsistent after the two surgeries, after a detailed consultation with a pathologist, the speculations were as follows: during the first operation, the mature tumor tissue had been removed, and the myxoma required time to mature. The interval between the two operations was only 2 years, which caused the mitral valve tumor tissue removed during the second operation to appear as immature myxoid degenerative tissue, and therefore, the pathological findings were fibrous valvular tissue of the mitral valve accompanied by myxoid degeneration and hyalinization. In terms of the cause of the myxomatous degeneration of the mitral valve, no specific conclusion is evident in the existing literature. Loardi C et al. suggested that the cause is extracellular matrix synthesis and metabolic disorders caused by the overexpression of metalloproteases as well as excessive cell proliferation12. Freed LA et al. suggested that a mitral valve with myxomatous degeneration often causes mitral valve prolapse13. Based on the literature on mitral valve prolapse and sudden cardiac death reported by Nalliah CJ14, young patients with myxomatous degeneration of the mitral valve will experience complications such as infective endocarditis, sudden death, and stroke. Mitral valve prolapse is closely associated with sudden cardiac death. A patient with myxomatous degeneration of the mitral valve reported by Lazar Neto F underwent mitral valve replacement15. In our pediatric patient, the mitral valve already exhibited myxomatous degeneration and was in a state of loss of function, and thus, we weighed the advantages and disadvantages of a mechanical valve versus a biological valve. S. Chauvaud performed mitral valve replacement with biological valves in 13 patients aged 3 – 25 years who were followed up for 0.6 – 6.6 years and found that all of the biological valves were associated with issues such as contractures, thickening, and calcification16. Therefore, the author did not recommend mitral valve replacement with biological valves in young patients. Eventually, we chose to perform mitral valve replacement with a mechanical valve. Currently, the patient's mechanical mitral valve function is good. Regarding the clinical manifestation and complications of these heterogeneous cardiac tumors, the current literature reports the symptoms that often occur in patients with cardiac myxoma and cardiac papillary fibroelastoma; these include embolism, valvular stenosis, and insufficiency. Takano et al. reviewed previous studies that reported similar diseases and found that among the eight patients, five
showed symptoms, the most common of which was dyspnea, followed by palpitations and stroke. Our patient was still young, the disease was detected early, and the patient only had decreased activity endurance upon second admission. Furthermore, no perioperative complications were found. In addition, these heterogeneous cardiac tumors are very rare, and due to our lack of experience, we did not perform a blood draw from the patient to test for tumor markers, and we also did not perform a brain computed tomography (CT) examination to assess the risk of cerebrovascular obstruction. However, this pediatric patient did not experience cerebrovascular complications such as mental abnormalities or limb motor dysfunction during the perioperative period. 4. Conclusion: We report a case of a 5-month-old infant with a rare myxoma of the mitral valve coincident with a papillary fibroelastoma of the tricuspid valve. Once the tumor was diagnosed, it was immediately surgically resected. Thus far, the prognosis is good. Many mysteries in the etiology and prognosis of this heterogeneous tumor remain unsolved and require further exploration.
References 1. Akiyama, K.; Hirota, J.; Tsuda, Y.; Ebishima, H.; Li, C., Double primary cardiac tumors: possible association with a variety of cardiac diseases. J Cardiovasc Surg (Torino) 2006, 47 (1), 81-2. 2. Buttan, A. K.; Panagiotides, G.; Barnes, M. J.; Vorobiof, G., Multimodality imaging in the diagnosis of coexisting left atrial myxoma and aortic valve papillary fibroelastoma. Circulation 2012, 125 (23), e1003-5. 3. Challa, S.; Chaliki, H. P.; Najib, M. Q.; Ganji, J. L.; Click, R. L., An unusual case of left atrial myxoma and papillary fibroelastoma. Echocardiography 2013, 30 (1), E25. 4. Jallad, N.; Parikh, R.; Daoko, J.; Albareqdar, E.; Al-Dehneh, A.; Goldstein, J.; Shamoon, F.; Connolly, M. W., Concurrent primary cardiac tumors of differing histology and origin: case report with literature review. Tex Heart Inst J 2009, 36 (6), 591-3. 5. Jutley, R. S.; Melham, N.; Skinner, H.; Richens, D., Unusual case of two synchronous intracavitary primary cardiac tumors. Ann Thorac Surg 2008, 85 (3), 1086-7. 6. Matsushita, A.; Manabe, S.; Tabata, M.; Fukui, T.; Shimokawa, T.; Amano, J.; Takanashi, S., Heterogeneous double cardiac tumor: myxoma concomitant with papillary fibroelastoma. J Card Surg 2010, 25 (1), 35-7. 7. Menon, T.; Watanabe, Y.; Andrews, D., Concurrent primary cardiac tumors. J Thorac Cardiovasc Surg 2007, 134 (1), 263-4. 8. Prifti, E.; Bonacchi, M.; Salica, A., Mitral valve myxoma concomitant with papillary fibroelastoma. Ann Thorac Surg 2000, 70 (1), 335-6. 9. Roque, J.; Silva, F.; Arruda Pereira, R.; Cravino, J., Multiple causes for an ischemic stroke: myxoma, papillary fibroelastomas and patent foramen ovale. HSR Proc Intensive Care Cardiovasc Anesth 2012, 4 (3), 187-91. 10. Takano, T.; Kakuta, T.; Takahashi, S., A potential concomitance of papillary fibroelastoma in the case with cardiac myxoma. Gen Thorac Cardiovasc Surg 2017, 65 (8), 474-477. 11. Agaimy, A.; Strecker, T., Left atrial myxoma with papillary fibroelastoma-like features. Int J Clin Exp Pathol 2011, 4 (3), 307-11.
12. Loardi, C.; Alamanni, F.; Trezzi, M.; Kassem, S.; Cavallotti, L.; Tremoli, E.; Pacini, D.; Parolari, A., Biology of mitral valve prolapse: the harvest is big, but the workers are few. Int J Cardiol 2011, 151 (2), 129-35. 13. Freed, L. A.; Levy, D.; Levine, R. A.; Larson, M. G.; Evans, J. C.; Fuller, D. L.; Lehman, B.; Benjamin, E. J., Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999, 341 (1), 1-7. 14. Nalliah, C. J.; Mahajan, R.; Elliott, A. D.; Haqqani, H.; Lau, D. H.; Vohra, J. K.; Morton, J. B.; Semsarian, C.; Marwick, T.; Kalman, J. M.; Sanders, P., Mitral valve prolapse and sudden cardiac death: a systematic review and meta-analysis. Heart 2019, 105 (2), 144-151. 15. Neto, F. L.; Marques, L. C.; Aiello, V. D., Myxomatous degeneration of the mitral valve. Autops Case Rep 2018, 8 (4), e2018058. 16. Chauvaud, S.; Waldmann, T.; d'Attellis, N.; Bruneval, P.; Acar, C.; Gerota, J.; Jarraya, M.; Carpentier, A., Homograft replacement of the mitral valve in young recipients: mid-term results. Eur J Cardiothorac Surg 2003, 23 (4), 560-6.
Fig.1A: the myxoma of the anterior leaflet of the mitral valve, myxoid cells were stained with Haematoxylin and Eosin. (H+E)x100.
Fig.2A:
an echogenic mass with a size of approximately 2.16*1.76 cm was observed at the anterior leaflet of the mitral valve and was closely associated with the anterior leaflet
Fig.2B:
An echogenic mass with an approximate size of 1.27*1.25 cm was observed at the septal leaflet of the tricuspid valve and was closely associated with the septal leaflet
Fig.3A: a white mass with a size of 3.0*4.0 cm was visible at the anterior leaflet and was completely fused with the anterior leaflet.
Fig.3B: myxoma of the mitral valve.
Fig.4A: papillary fibroelastomas of the tricuspid valve.
Fig.5: the fibrous valvular tissue of the mitral valve was accompanied by hyaline degeneration and myxoid degeneration.
Fig.6: a small amount of fibrous valvular tissue of the tricuspid accompanied the hyaline degeneration and myxoid degeneration, and multinodular tissue was attached to the valve. Using a combination of immunohistochemistry and special stains, the lesion was found to be consistent with papillary fibroelastoma/tumor-like hyperplasia. Special stains showed elastic fibers (small amount of blue-green color).
Fig.7: the position was fixed, the shape was good, and the opening and closing functions were normal and without perivalvular leakage.
Patient consent Consent to publish the case report was obtained. This report does not contain any personal information that could lead to the identification of the patient.
Funding No funding or grant support.
Authorship All authors attest that they meet the current ICMJE criteria for Authorship.
Declaration of competing interest The authors declare that there are no conflicts of interest in this manuscript.
Acknowledgements
Wei is the postgraduate student in School of Medicine Henan University. Peng is my postgraduate tutor in Henan Provincial People’s Hospital, meanwhile, he is also the chief physician of children heart center ward 2. Ai and Zhang are the surgeons of children heart center ward 2 in Fu Wai Central China Cardiovascular Hospital.Fu Wai Central China Cardiovascular Hospital is the heart center of Henan Provincial People’s Hospital.