- Email: [email protected]
A vascular malformation: an unusual primary cardiac tumor in children
Accepted Manuscript A vascular malformation: an unusual primary cardiac tumor in children Jose Manuel Siurana, MD, Joaquin Fernández, MD, Alexandra Navarro, MD, Georges Akel, MD, Raul Felipe Abella, MD, Dimpna Calila Albert, MD, PhD PII:
S0003-4975(19)30402-3
DOI:
https://doi.org/10.1016/j.athoracsur.2019.02.047
Reference:
ATS 32460
To appear in:
The Annals of Thoracic Surgery
Received Date: 11 November 2018 Revised Date:
13 February 2019
Accepted Date: 17 February 2019
Please cite this article as: Siurana JM, Fernández J, Navarro A, Akel G, Abella RF, Albert DC, A vascular malformation: an unusual primary cardiac tumor in children, The Annals of Thoracic Surgery (2019), doi: https://doi.org/10.1016/j.athoracsur.2019.02.047. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.
ACCEPTED MANUSCRIPT A vascular malformation: an unusual primary cardiac tumor in children Running Head: Venous malformation as a cardiac tumor
RI PT
Jose Manuel Siurana (MD)1, Joaquin Fernández (MD)2, Alexandra Navarro (MD)3, Georges Akel (MD)4, Raul Felipe Abella (MD)2, Dimpna Calila Albert (MD, PhD)5
Institutions and affiliations
M AN U
SC
1. Autonomous University of Barcelona. Nens Hospital Foundation. Calle Consell de Cent, 437, 08009 Barcelona (Spain). Cardiology Department 2. Vall d'Hebron University Hospital. Paseo de la Vall d'Hebron, 119-129, 08035 Barcelona (Spain). Pediatric Cardiac Surgery Department 3. Vall d'Hebron University Hospital. Anatomy Department 4. Nens Hospital Foundation. Cardiology Department 5. Vall d'Hebron University Hospital. Pediatric Cardiology Department
Classifications: Cardiac tumors; Pediatric; Venous disease
Corresponding Author
TE D
Word Count: 1.480
José Manuel Siurana
EP
Nens Hospital Foundation. Consell de Cent, 437, 08009 Barcelona (Spain)
AC C
email: [email protected]
ACCEPTED MANUSCRIPT Abstract This article presents a primary cardiac tumor, classified as venous malformation, diagnosed in asymptomatic child. The tumor was located in the left atrium near the mitral valve without affecting its functioning. A complete resection of the lesion was performed due
RI PT
to the risk of systemic embolism. The lesion was constituted of fibrous tissue with multiple venous vascular channels. The patient did not present similar lesions in other locations. Vascular primary cardiac tumors are extremely rare. Hemangiomas and lymphangiomas have been described previously, but, to our knowledge, this is the first primary cardiac tumor
AC C
EP
TE D
M AN U
SC
identified as venous malformation.
ACCEPTED MANUSCRIPT Primary cardiac tumors are rare conditions, with a very low incidence among children (0.1-0.2%). Rhabdomyomas are the most frequent, while vascular primary tumors, such as hemangioma or lymphangioma, are extremely rare. In this article, we present an infrequent
RI PT
case of primary cardiac tumor with multiple venous channels.
A 14-year-old girl was referred to the pediatric cardiology department due to joint hypermobility. She had an history of prematurity of 30 weeks of gestation and neonatal sepsis. She reported several bronchitis episodes during childhood, treated with fluticasone,
SC
vilanterol inhalations and immunotherapy with omalizumab for severe allergic asthma. In 2018, she was operated on for right femoropatellar ligament reconstruction by recurrent
M AN U
luxation.
At diagnosis, the patient was asymptomatic, in New York Heart Association class I, and she practiced competitive sport. Cardiovascular examination showed a left parasternal I/VI murmur without irradiation. The electrocardiogram tracing was normal without signs of
TE D
ischemia. In the echocardiography study, a mass in the left atrium was found. It measured 18x16 mm and was located attached to the septum primum close to the mitral valve, but without compromising correct functioning (Figure 1). The tumor was slightly mobile without
EP
protruding through the valve. The left ventricular ejection fraction was conserved. The color Doppler showed few echoes inside. A cardiac MRI to define tumor contours was performed.
AC C
The mass presented regular edges, not pedunculated or mobile, located at the base of the anterior mitral leaflet (Figure 2). In T1 it displayed isointense signal to the myocardium, while in T2 it was hyperintense. After contrast with gadolinium, the tumor presented a late and heterogeneous diffuse uptake. An atrial myxoma was the first diagnosis, owing to location and image characteristics. The election treatment was a complete resection of the lesion because the risk of systemic embolism. The surgery was performed under extracorporeal circulation and cardiac arrest. The left atrium was small and a transseptal approach was decided. The tumor was inserted in the mitral annulus, at A2 mitral leaflet level. The tumor was nacreous, sessile and measured
ACCEPTED MANUSCRIPT 20x30 mm. The lesion was completely resected, and the anterior mitral leaflet was repaired. The postoperative course was uneventful and the echocardiography before discharge showed mild residual mitral insufficiency without residual lesions. The pathological anatomy showed a whitish-nacreous tumor of soft consistency, by
a
sclerosis
fibrous
tissue
with
multiple
vascular
channels.
RI PT
constituted
Immunohistochemical stains demonstrated endothelium cells positive to CD31 and CD34 and negative to C2-40 (Figure 3). The vessels were identified as venous type. The primary cardiac tumor with multiple venous channels was diagnosed as a venous malformation
SC
without malignant cells.
Cutaneous vascular malformations were not present. Brain MRI and abdominal
M AN U
ultrasound were performed to locate other lesions, but these were not found.
Comment
Primary cardiac tumors in childhood have a very low incidence (0.1-0.2%), although
TE D
in recent years, this is increasing due to improvements in heart imaging techniques. Around 90% are benign and the location is variable. The symptomatology is nonspecific and variable, and the first clinical manifestation varies from nonspecific signs to a heart failure. In
EP
most cases it depends on the tumor location and size (1-3). In this case, the patient was asymptomatic, although, over time, she could present mitral regurgitation. In the published
AC C
series, the percentage of asymptomatic cases is low (± 30%). The types of benign tumor vary according to the presentation age. Thus, in adults the
most frequent benign tumors are myxomas, whereas in neonates they are extremely rare. In childhood the most frequent are rhabdomyomas, fibromas and teratomas (1). The patient presented a tumor with a solid and whitish appearance with a fibrous sclerosing component, but with a large number of channels. The positive stains for CD31 and CD34 demonstrate that they were vascular endothelium and the elastic fibers stain showed them as venous vessels. Vascular tumors are extremely rare. Haemangiomas and lymphangiomas have been described but no venous malformations as cardiac tumor have been found in the
ACCEPTED MANUSCRIPT literature. Venous malformations are a type of vascular anomaly, usually found in the skin, although they can affect any tissue. It is typical to find organized and calcified thrombi inside (4). Surgical treatment of cardiac tumors is indicated in symptomatic patients or to prevent
RI PT
complications derived from the lesion: valvular affectation, embolisms or arrhythmias. The surgical results are satisfactory with a very low mortality rate (<3% in benign tumors) (5). Total or partial tumor resection will be performed depending on the involvement of other heart structures, but the risk of recurrence of benign tumors is very low (the greatest risk is
SC
<5% in myxomas and teratomas). On the other hand, small rhabdomyomas diagnosed prenatally or during childhood have a possibility of spontaneous regression, so a
M AN U
conservative medical management is indicated (6). In this case, the consensual treatment was the complete resection because of the risk of systemic embolism that is very characteristic of myxomas, the first suspected diagnosis. Similarly, in vascular tumors there is also a risk of generating thrombi, so a surgical resection is indicated.
TE D
Five months prior to the tumor diagnosis, the patient had initiated an immunomodulatory treatment with omalizumab. It is a humanized recombinant monoclonal anti-IgE antibody developed for the treatment of severe allergic asthma. A higher risk of
EP
cardiovascular events, especially thromboembolic effects, has been reported in patients with omalizumab (7-8). In this case a causal relationship is improbable between omalizumab and
AC C
the vascular cardiac tumor because vascular malformations usually develop during the process of fetal vasculogenesis and there was no tumor progression during the preoperative follow-up.
In summary, this article describes an uneventful complete surgical resection of an unusual type of primary cardiac tumor with multiple vessel channels diagnosed as a venous malformation.
ACCEPTED MANUSCRIPT References 1. Uzun O, Wilson DG, Vujanic GM, Parsons JM, De Giovanni JV. Cardiac tumors in children. Orphanet J Rare Dis. 2007;2:11. 2. Delmo Walter EM, Javier MF, Sander F, Hartmann B, Ekkernkamp A, Hetzer R.
outcome. Ann Thorac Surg. 2016;102(6):2062-2069.
RI PT
Primary cardiac tumors in infants and children: surgical strategy and long-term
3. Tzani A, Doulamis IP, Mylonas KS, Avgerinos DV, Nasioudis D. Cardiac tumors in
2017;8(5):624-632. 4. Wassef
M,
Blei
F,
Adams
D
et
al.
SC
pediatric patients: A systematic review. World J Pediatr Congenit Heart Surg.
Vascular
Anomalies
Classification:
M AN U
Recommendations From the International Society for the Study of Vascular Anomalies. Pediatrics. 2015;136(1):e203-14.
5. Padalino MA, Vida VL, Boccuzzo G et al. Surgery for primary cardiac tumors in children: early and late results in a multicenter European Congenital Heart Surgeons
TE D
Association study. Circulation. 2012;126(1):22-30.
6. Padalino MA, Reffo E, Cerutti A et al. Medical and surgical management of primary cardiac tumors in infants and children. Cardiol Young. 2014;24(2):268-74.
EP
7. Iribarren C, Rahmaoui A, Long AA et al. Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort
AC C
study in moderate to severe asthma. J Allergy Clin Immunol. 2017;139(5):1489-1495. 8. Dompmartin A, Acher A, Thibon P et al. Association of localized intravascular coagulopathy with venous malformations. Arch Dermatol. 2008;144(7):873-7.
ACCEPTED MANUSCRIPT Figure Legends Figure 1: Echocardiographic images show the venous malformation (yellow arrows) as an echogenic not pedunculated mass in the left atria in a short-axis plane (A), an apical four-
RI PT
chamber plane (B) and a long-axis plane (C).
Figure 2: Cardiac MRI in oblique view shows the venous malformation (yellow arrows) with myocardium isointensity
SC
Figure 3: (A) 2,50x H&E, (B) 10x H&E, (C) positive for CD34 that stains vascular endotheliums, and (D) staining of elastic fibers, where only one layer is observed, so they are
AC C
EP
TE D
M AN U
venous structures.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S0003-4975(19)30402-3
DOI:
https://doi.org/10.1016/j.athoracsur.2019.02.047
Reference:
ATS 32460
To appear in:
The Annals of Thoracic Surgery
Received Date: 11 November 2018 Revised Date:
13 February 2019
Accepted Date: 17 February 2019
Please cite this article as: Siurana JM, Fernández J, Navarro A, Akel G, Abella RF, Albert DC, A vascular malformation: an unusual primary cardiac tumor in children, The Annals of Thoracic Surgery (2019), doi: https://doi.org/10.1016/j.athoracsur.2019.02.047. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.
ACCEPTED MANUSCRIPT A vascular malformation: an unusual primary cardiac tumor in children Running Head: Venous malformation as a cardiac tumor
RI PT
Jose Manuel Siurana (MD)1, Joaquin Fernández (MD)2, Alexandra Navarro (MD)3, Georges Akel (MD)4, Raul Felipe Abella (MD)2, Dimpna Calila Albert (MD, PhD)5
Institutions and affiliations
M AN U
SC
1. Autonomous University of Barcelona. Nens Hospital Foundation. Calle Consell de Cent, 437, 08009 Barcelona (Spain). Cardiology Department 2. Vall d'Hebron University Hospital. Paseo de la Vall d'Hebron, 119-129, 08035 Barcelona (Spain). Pediatric Cardiac Surgery Department 3. Vall d'Hebron University Hospital. Anatomy Department 4. Nens Hospital Foundation. Cardiology Department 5. Vall d'Hebron University Hospital. Pediatric Cardiology Department
Classifications: Cardiac tumors; Pediatric; Venous disease
Corresponding Author
TE D
Word Count: 1.480
José Manuel Siurana
EP
Nens Hospital Foundation. Consell de Cent, 437, 08009 Barcelona (Spain)
AC C
email: [email protected]
ACCEPTED MANUSCRIPT Abstract This article presents a primary cardiac tumor, classified as venous malformation, diagnosed in asymptomatic child. The tumor was located in the left atrium near the mitral valve without affecting its functioning. A complete resection of the lesion was performed due
RI PT
to the risk of systemic embolism. The lesion was constituted of fibrous tissue with multiple venous vascular channels. The patient did not present similar lesions in other locations. Vascular primary cardiac tumors are extremely rare. Hemangiomas and lymphangiomas have been described previously, but, to our knowledge, this is the first primary cardiac tumor
AC C
EP
TE D
M AN U
SC
identified as venous malformation.
ACCEPTED MANUSCRIPT Primary cardiac tumors are rare conditions, with a very low incidence among children (0.1-0.2%). Rhabdomyomas are the most frequent, while vascular primary tumors, such as hemangioma or lymphangioma, are extremely rare. In this article, we present an infrequent
RI PT
case of primary cardiac tumor with multiple venous channels.
A 14-year-old girl was referred to the pediatric cardiology department due to joint hypermobility. She had an history of prematurity of 30 weeks of gestation and neonatal sepsis. She reported several bronchitis episodes during childhood, treated with fluticasone,
SC
vilanterol inhalations and immunotherapy with omalizumab for severe allergic asthma. In 2018, she was operated on for right femoropatellar ligament reconstruction by recurrent
M AN U
luxation.
At diagnosis, the patient was asymptomatic, in New York Heart Association class I, and she practiced competitive sport. Cardiovascular examination showed a left parasternal I/VI murmur without irradiation. The electrocardiogram tracing was normal without signs of
TE D
ischemia. In the echocardiography study, a mass in the left atrium was found. It measured 18x16 mm and was located attached to the septum primum close to the mitral valve, but without compromising correct functioning (Figure 1). The tumor was slightly mobile without
EP
protruding through the valve. The left ventricular ejection fraction was conserved. The color Doppler showed few echoes inside. A cardiac MRI to define tumor contours was performed.
AC C
The mass presented regular edges, not pedunculated or mobile, located at the base of the anterior mitral leaflet (Figure 2). In T1 it displayed isointense signal to the myocardium, while in T2 it was hyperintense. After contrast with gadolinium, the tumor presented a late and heterogeneous diffuse uptake. An atrial myxoma was the first diagnosis, owing to location and image characteristics. The election treatment was a complete resection of the lesion because the risk of systemic embolism. The surgery was performed under extracorporeal circulation and cardiac arrest. The left atrium was small and a transseptal approach was decided. The tumor was inserted in the mitral annulus, at A2 mitral leaflet level. The tumor was nacreous, sessile and measured
ACCEPTED MANUSCRIPT 20x30 mm. The lesion was completely resected, and the anterior mitral leaflet was repaired. The postoperative course was uneventful and the echocardiography before discharge showed mild residual mitral insufficiency without residual lesions. The pathological anatomy showed a whitish-nacreous tumor of soft consistency, by
a
sclerosis
fibrous
tissue
with
multiple
vascular
channels.
RI PT
constituted
Immunohistochemical stains demonstrated endothelium cells positive to CD31 and CD34 and negative to C2-40 (Figure 3). The vessels were identified as venous type. The primary cardiac tumor with multiple venous channels was diagnosed as a venous malformation
SC
without malignant cells.
Cutaneous vascular malformations were not present. Brain MRI and abdominal
M AN U
ultrasound were performed to locate other lesions, but these were not found.
Comment
Primary cardiac tumors in childhood have a very low incidence (0.1-0.2%), although
TE D
in recent years, this is increasing due to improvements in heart imaging techniques. Around 90% are benign and the location is variable. The symptomatology is nonspecific and variable, and the first clinical manifestation varies from nonspecific signs to a heart failure. In
EP
most cases it depends on the tumor location and size (1-3). In this case, the patient was asymptomatic, although, over time, she could present mitral regurgitation. In the published
AC C
series, the percentage of asymptomatic cases is low (± 30%). The types of benign tumor vary according to the presentation age. Thus, in adults the
most frequent benign tumors are myxomas, whereas in neonates they are extremely rare. In childhood the most frequent are rhabdomyomas, fibromas and teratomas (1). The patient presented a tumor with a solid and whitish appearance with a fibrous sclerosing component, but with a large number of channels. The positive stains for CD31 and CD34 demonstrate that they were vascular endothelium and the elastic fibers stain showed them as venous vessels. Vascular tumors are extremely rare. Haemangiomas and lymphangiomas have been described but no venous malformations as cardiac tumor have been found in the
ACCEPTED MANUSCRIPT literature. Venous malformations are a type of vascular anomaly, usually found in the skin, although they can affect any tissue. It is typical to find organized and calcified thrombi inside (4). Surgical treatment of cardiac tumors is indicated in symptomatic patients or to prevent
RI PT
complications derived from the lesion: valvular affectation, embolisms or arrhythmias. The surgical results are satisfactory with a very low mortality rate (<3% in benign tumors) (5). Total or partial tumor resection will be performed depending on the involvement of other heart structures, but the risk of recurrence of benign tumors is very low (the greatest risk is
SC
<5% in myxomas and teratomas). On the other hand, small rhabdomyomas diagnosed prenatally or during childhood have a possibility of spontaneous regression, so a
M AN U
conservative medical management is indicated (6). In this case, the consensual treatment was the complete resection because of the risk of systemic embolism that is very characteristic of myxomas, the first suspected diagnosis. Similarly, in vascular tumors there is also a risk of generating thrombi, so a surgical resection is indicated.
TE D
Five months prior to the tumor diagnosis, the patient had initiated an immunomodulatory treatment with omalizumab. It is a humanized recombinant monoclonal anti-IgE antibody developed for the treatment of severe allergic asthma. A higher risk of
EP
cardiovascular events, especially thromboembolic effects, has been reported in patients with omalizumab (7-8). In this case a causal relationship is improbable between omalizumab and
AC C
the vascular cardiac tumor because vascular malformations usually develop during the process of fetal vasculogenesis and there was no tumor progression during the preoperative follow-up.
In summary, this article describes an uneventful complete surgical resection of an unusual type of primary cardiac tumor with multiple vessel channels diagnosed as a venous malformation.
ACCEPTED MANUSCRIPT References 1. Uzun O, Wilson DG, Vujanic GM, Parsons JM, De Giovanni JV. Cardiac tumors in children. Orphanet J Rare Dis. 2007;2:11. 2. Delmo Walter EM, Javier MF, Sander F, Hartmann B, Ekkernkamp A, Hetzer R.
outcome. Ann Thorac Surg. 2016;102(6):2062-2069.
RI PT
Primary cardiac tumors in infants and children: surgical strategy and long-term
3. Tzani A, Doulamis IP, Mylonas KS, Avgerinos DV, Nasioudis D. Cardiac tumors in
2017;8(5):624-632. 4. Wassef
M,
Blei
F,
Adams
D
et
al.
SC
pediatric patients: A systematic review. World J Pediatr Congenit Heart Surg.
Vascular
Anomalies
Classification:
M AN U
Recommendations From the International Society for the Study of Vascular Anomalies. Pediatrics. 2015;136(1):e203-14.
5. Padalino MA, Vida VL, Boccuzzo G et al. Surgery for primary cardiac tumors in children: early and late results in a multicenter European Congenital Heart Surgeons
TE D
Association study. Circulation. 2012;126(1):22-30.
6. Padalino MA, Reffo E, Cerutti A et al. Medical and surgical management of primary cardiac tumors in infants and children. Cardiol Young. 2014;24(2):268-74.
EP
7. Iribarren C, Rahmaoui A, Long AA et al. Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort
AC C
study in moderate to severe asthma. J Allergy Clin Immunol. 2017;139(5):1489-1495. 8. Dompmartin A, Acher A, Thibon P et al. Association of localized intravascular coagulopathy with venous malformations. Arch Dermatol. 2008;144(7):873-7.
ACCEPTED MANUSCRIPT Figure Legends Figure 1: Echocardiographic images show the venous malformation (yellow arrows) as an echogenic not pedunculated mass in the left atria in a short-axis plane (A), an apical four-
RI PT
chamber plane (B) and a long-axis plane (C).
Figure 2: Cardiac MRI in oblique view shows the venous malformation (yellow arrows) with myocardium isointensity
SC
Figure 3: (A) 2,50x H&E, (B) 10x H&E, (C) positive for CD34 that stains vascular endotheliums, and (D) staining of elastic fibers, where only one layer is observed, so they are
AC C
EP
TE D
M AN U
venous structures.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT