Cardiac fibroma in adults

Cardiovascular Pathology 20 (2011) e146 – e152

Review Article

Cardiac fibroma in adults Harriet Nwachukwu a , Alice Li a , Vidhya Nair a,e , Elsie Nguyen d , Tirone E. David b , Jagdish Butany a,c,⁎ a

Department of Pathology, Toronto General Hospital/University Health Network, Toronto, Canada Division of Cardiac Surgery, Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Canada c Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada d Cardiothoracic Division, Department of Medical Imaging, University Health Network, Toronto General Hospital, Toronto, Canada e Department of Pathology, McMaster University, Hamilton, Ontario, Canada b

Received 21 August 2009; received in revised form 15 July 2010; accepted 15 August 2010

Abstract We present the case of a 61-year-old woman with nonspecific symptoms who on investigation and treatment had a fibroma of the right ventricular free wall. She underwent surgical resection of the mass and is doing well. The literature pertaining to cardiac fibromas in adults is reviewed and discussed. Crown Copyright © 2011 Published by Elsevier Inc. All rights reserved. Keywords: Cardiac fibroma; Cardiac tumors; Soft tissue tumors; Mesenchymal tumors

1. Introduction

2. Case presentation

Cardiac fibromas are benign neoplasms of fibroblasts in the myocardium. Most commonly originating from the left ventricle, these lesions are rarely observed in adults and are the second most common tumor in the pediatric population following rhabdomyomas [1–4]. The clinical manifestations vary according to the size and location of the tumor. Less frequently, cardiac fibromas may be asymptomatic, appearing as incidental findings during diagnostic imaging procedures for other indications. Cardiac fibromas can be treated by complete surgical excision, incomplete resection, or orthotopic heart transplantation depending on site, size, and resectability. In this report, we present a 61-year-old woman with a cardiac fibroma as well as a detailed review of the English-language medical literature, pertaining to fibromas in adults.

A 61-year-old woman presented with a history of shortness of breath (SOB) and a past history of a right renal angiomyolipoma and an occult micropapillary thyroid carcinoma. Six years prior to the present admission, the patient had an episode of SOB, and upon investigation, her baseline cardiogram was found to be abnormal. Five years later, a right ventricular (RV) mass (unknown etiology) was noted, incidental to a breast MRI, and later confirmed by transesophageal echocardiogram (TEE). Cardiac MRI showed a solid mass confined to the anterior right ventricular free wall near the right ventricular apex (Fig. 1). There was no significant pericardial effusion or nodularity. Selective coronary angiography, left heart catheterization, and fluoroscopy showed no significant abnormality. The RV lesion had a broad-based attachment to the distal right ventricular free wall and apex. The superior aspect extended into the right ventricular outflow tract, but no obstruction was observed. The patient was clinically well, denied palpitations, syncope, chest pain, and dyspnea. Seven months later, a repeat TEE apparently showed a significant increase in size, leading to surgical excision of the mass.

The guest editor for this paper is Dr John Veinot. The authors declare no external sources of funding that might pose or imply a conflict of interest with the submitted manuscript. ⁎ Corresponding author. Department of Pathology, Toronto General Hospital, 11th floor, 200 Elizabeth St., Toronto, ON, Canada M5G 2C4. Tel.: +1 416 340 3008; fax: +1 416 340 4213.

1054-8807/10/$ – see front matter. Crown Copyright © 2011 Published by Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2010.08.006

H. Nwachukwu et al. / Cardiovascular Pathology 20 (2011) e146–e152

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Fig. 1. (A) Axial proton density double inversion recovery spin-echo images demonstrate an approximately 3×4-cm mass at the right ventricular apex attached to the anterior wall of the right ventricle. (B) Sagittal oblique steady-state free precession image demonstrating that the mass extends to the right ventricular outflow tract but does not obstruct the pulmonary valve. The right ventricular mass is slightly hyperintense to the myocardium.

At surgery, the RV mass appeared to originate in the distal RV free wall of the interventricular septum (IVS). It was resected en bloc, including the base of the anterior papillary muscle (APM). The RV was reconstructed with bovine pericardium and the APM was reimplanted into the anterior wall of the right ventricle. The APM was reconstructed. A tricuspid valve annuloplasty was performed using a Dacron band along the base of the anterior and posterior leaflet. Postoperative echocardiography showed trace residual tricuspid regurgitation. Repeat echocardiography 1 year postoperatively showed a normal-size right ventricular cavity with mild reduction in contractility. 2.1. Pathology The surgically excised tissue was tan colored, had one smooth epicardial surface, weighed 38.5 g, and measured 5.5×3.5×3.4 cm. All the surgical margins showed normallooking myocardium of a darker tan color. The cut surface

of the mass showed bulging, gray-white tissue with a somewhat whorled appearance. The endocardial surface of the mass showed a layer of myocardium, trabeculae carneae, and endocardium. Tiny microfoci of calcification were noted. Microscopic examination showed a rim of cardiac muscle enclosing a benign neoplasm composed of hyalinized collagen and elastic tissue (Fig. 2). Cellularity was sparse, with spindle cells scattered through the hyalinized collagen. No mitoses were evident in any part of the lesion, nor was necrosis or hemorrhage seen. No capsule was seen and the cell nuclei were striking in their monomorphic appearance. Trapped bundles of myocytes were seen at the margins. Elastic trichrome stains showed elastic tissue scattered in and among the collagen bundles. The neoplastic cells were positive on immunohistochemical stains for vimentin, while stains for vascular endothelial cells (CD31) were very sparsely positive in small vessels in the tumor. The morphology is that of a cardiac fibroma (Fig. 3).

Fig. 2. (A) Gross photograph showing the large RV mass with smooth and shiny tan-colored epicardial surface (asterisk) and tan-colored myocardium at the cut margin (asterisk). (B) The entire cut surface showing a covering of myocardium. The ventricular (endocardial surface) shows myocardium with trabeculae carneae (arrows). The cut surface shows the bulging gray-white tumor. (C) Serial sections of the entire mass show a well-encapsulated gray-white tumor with a bulging whorled appearance. The tumor is homogenous with no evidence of hemorrhage or necrosis. The rim of myocardium (arrows) and epicardium (arrowheads) is seen. Upon sectioning the mass, it was found that the overlying myocardium has contracted and retracted.

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Fig. 3. (A) Cardiac muscle tumor cells. This section shows the tumor (pale pink) with scattered small spindly, monomorphic nuclei, and areas of cardiac muscle (asterisk). The tumor has a blunt edge, which in focal areas appears to mix in with the cardiac muscle. Cardiac muscle fibers are for a very short distance surrounded by tumor cells. There is abundant collagen with very few fibroblasts (arrows). (Hematoxylin and eosin stain, original magnification ×100.) (B) Elastic tissue admixed with collagen. This section shows the abundance of elastic tissue mixed with the collagen. (Elastic trichrome stain, original magnification ×100.) (C) Microfoci of calcification. This microphotograph of the fibroma shows a cellular area (arrowhead) and foci of calcification (arrow). (Hematoxylin and eosin stain, original magnification ×20.) (D) Unencapsulated mass admixed with myocytes. This section shows a well-circumscribed, unencapsulated fibroma (asterisks) admixed with myocytes at the periphery (arrows). (Hematoxylin and eosin stain, original magnification ×40.)

3. Discussion Primary cardiac neoplasms are extremely rare, to the extent that metastatic cardiac neoplasms are at least 100 times more common. A cardiac fibroma is a rare, benign neoplasm of the myocardium [1–4]. It is, however, the most commonly resected tumor in the pediatric population, with the mean age at the time of diagnosis being 13 years. Only 15% of all cardiac fibromas are diagnosed in adolescents and adults [3,5]. Most originate from the left ventricular free wall and rarely involve the atria [1,2,4,6–8]. A review of the English-language medical literature was performed, concentrating on cardiac fibroma cases focusing specifically on patients aged 16 and over. The review included articles published in the past 14 years (January

1995 to May 2010), accessible through our institution. Our findings are listed in Table 1. We have presented the case of a 61-year-old woman who presented at our institution with a cardiac fibroma involving the right ventricular free wall. The patient underwent successful, surgical resection of the bulk of the tumor. Of the cases reported in the literature, 41 of 51 patients for whom treatment was recorded underwent a similar treatment modality. With the exception of five cases, these patients remained stable at follow-up, suggesting that complete surgical resection is an effective treatment approach. In particular, it may decrease the risk of conduction disturbances and cardiac failure. Complete surgical excision is performed less frequently in the neonatal and pediatric populations, both of which have higher fatality rates compared to the adult population [5,7].

Table 1 Literature review of patients over the age of 16 with cardiac fibroma Year

Age

Sex

Symptoms

Comorbidities

Primary Site

Treatment

Prognosis

Agrawal et al. [9]

2009

34

F

N/A

LV

Surgical excision

Stable at 15 months

Ackerman et al. [10]

1995

20

F

SOB, palpitations, T-wave inversion Asymptomatic

N/A

LV

Surgical excision

Agrawala et al. [11] Alotti et al. [12] Araji et al. [13] Attali et al. [14]

2004 2008 2009 2000

30 60 36 48

M F N/A M

Murmur Asymptomatic Chest pain MI

None Aphasia N/A N/A

RV LV LV AV

Surgical Surgical Surgical Surgical

Basso et al. [15] Caralps et al. [16] Centofanti et al. [17] Centofanti et al. [17]

1997 2005 1999 1999

40 25 59 60

F F F M

Septal hypertrophy Chest pain N/A N/A

RV LV IVS RV

OHT Surgical excision Partial resection Surgical excision

Chachques et al. [18] Chachques et al. [18] Darwazah et al. [19]

2002 2002 2010

38 22 24

F F M

Cardiac failure Ventricular arrhythmia Syncope

LV, RV RV LV

Surgical excision Surgical excision Surgical resection

N/A N/A Uncomplicated postoperative course

Efthymiou et al. [20]

2007

52

F

Palpitations, JVP+

N/A N/A N/A Coronary artery disease, poor LV function N/A N/A Fever, hemiplegia, bilateral limb ischemia, impaired speech N/A

Uncomplicated postoperative course Stable at 18 months N/A Stable at 6 months Postoperative course complicated by stenosis of the RCA and inferior akinesia of the LV Stable at 7 years Stable at 3 years Stable at 11 years Stable at 4 years

Surgical excision

ElBardissi a et al. [21]

2008

22.5±24.3

F (10), M (8)

N/A

Surgical excision

Uncomplicated postoperative course Mean survival of 26.87 years

Gasparovic et al. [22]

2006

21

F

Hypertension, dyspnea, chest pain, palpitations, syncope, constitutional symptoms, thromboembolism, VT Chest pain, VT

RA, intrapericardium LV (15), RV (3)

N/A

LV

Surgical excision

Goel et al. [23]

2003

29

M

Chest pain, dyspnea

N/A

LV

Surgical excision

Goldstein et al. [24]

1995

17

F

N/A

N/A

LV

Grinda et al. [25] Henaine et al. [26] Hoey et al. [27] Hull et al. [28]

1998 2008 2009 2007

31 40 32 56

F F F F

Syncope, cardiomegaly Syncope Syncope, VT Palpitations, SOB,

N/A Narcolepsy disturbance Pericardial effusion Type 2 diabetes mellitus,

RV RV LV RA

Tumor unresectable, OHT Surgical excision Partial resection N/A Surgical excision

excision excision excision excision

Postoperative streptococcal line infection Stable at 3 months, mild redundancy of the anterior mitral leaflet Died after acute OHT rejection

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Author

Stable at 3 years Stable at 2 months N/A N/A e149

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Table 1 (continued) Author

Year

Age

Sex

Comorbidities

Primary Site

Treatment

Prognosis

murmur Chest pain, SOB, cardiac ischemia Palpitations, dizziness, VT Syncope VT Asymptomatic

hypertension N/A

LV, IVS

Surgical excision

IVS

N/A

Uncomplicated postoperative course Stable at 3 years

RV RV, LV, IVS LV

None None Revascularization

Stable at 6 months N/A Stable at 14 months

LV LV LV RV LV RV LV

Surgical excision Partial resection Surgical excision N/A Surgical excision Surgical excision Surgical excision

Stable at 22 months Stable at 6 years N/A N/A Stable at 2 years Stable at 3 years N/A

N/A Subvalvular aortic stenosis, impaired diastolic relaxation Gorlin syndrome

LV IAS

None Surgical excision

LV

Surgical excision

Hypertension, hyperlipidemia, bradycardia, ectopic atrial rhythm, multiple colonic polyps, multiple subcutaneous lipomas, seborrheic keratoses, Gardner syndrome

Pulmonary veins, LA, RA, IAS

None

Autopsy finding Uncomplicated postoperative course Developed postoperative mitral regurgitation requiring valve replacement Stable at 6 months

Iqbal et al. [29]

2006

45

F

Khan and Dewhurst [30]

1997

48

M

Kluger et al. [31] Kusano and Ohe [2] Lee et al. [32]

2007 2002 1999

59 78 44

F F M

Nease et al. [33] Ohashi et al. [34] Pauliks et al. [35] Reddy et al. [36] Sakata b et al. [37] Stiller et al. [5] Veinot b et al. [38]

1997 2006 2006 2009 1997 2001 1996

19 29 40 24 77 17 55

F F F F M M M

Vougiouklakis et al. [39] Walpot et al. [40]

2001 2007

83 56

M F

Yan et al. [41]

2006

33

F

Dyspnea, palpitations, syncope, mitral regurgitation

Yang et al. [42]

2008

72

M

Bradycardia, ectopic atrial rhythm

VT Ventricular arrhythmia Murmur, VT Fatigue N/A RVOT obstruction Palpitations, dyspnea, syncope Asymptomatic Asymptomatic

Erythematous skin and eyelid lesions Gorlin syndrome N/A MI, pericardial effusion, anterolateral ventricular akineses, apical dyskinesis N/A N/A Gorlin syndrome RV lipoma N/A N/A Hypertrophic cardiomyopathy

F: female; N/A: information not available; LV: left ventricle; M: male; RV: right ventricle; MI: myocardial infarct; AV: aortic valve; RCA: right coronary artery; OHT: orthotopic heart transplantation; IVS: interventricular septum; JVP+: elevated jugular venous pressure; RVH: right ventricular hypertrophy: VT: ventricular tachycardia; RVOT: right ventricular outflow tract; LA: left atrium; IAS: interatrial septum; RA: right atrium. a b

Series study (18 cases examined). Information from abstract.

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Symptoms

H. Nwachukwu et al. / Cardiovascular Pathology 20 (2011) e146–e152

The clinical manifestations of cardiac fibromas depend on the location and extent of the tumor [7]. Patients often present with symptoms relating to conduction defects, such as arrhythmia, ventricular fibrillation, or intractable congestive heart failure [4,7,8] due to compression or invasion of the cardiac conduction system [3,4,8]. Cardiac fibromas arising in the ventricular wall may result in symptoms secondary to inflow or outflow tract obstruction [1,4]. Approximately one third of patients diagnosed with cardiac fibroma are asymptomatic, with the lesion being discovered incidental to physical examination or chest radiography [3]. A variety of diagnostic techniques have been used including chest X-rays [4], MRI scans [3], echocardiography, and computed tomography scans [3,43]. Less frequently, cardiac fibromas can be detected prenatally through the use of prenatal sonography or echocardiography [7,43]. Pathologically, cardiac fibromas are well circumscribed, unencapsulated solitary lesions ranging in size from approximately 1 to 10 cm [3]. They appear sharply demarcated, but close histological examination shows the tumor mixed in with the normal myocardium [1,4,7,43] and often extending into or obliterating the ventricular lumen [3]. Cut sections of these masses demonstrate a whorled pattern [4,43]. Occasionally, necrosis and cystic degeneration may be observed [4,8]. Microscopic examination of cardiac fibromas in children demonstrates fibroblast-rich tumors, with little collagen [3] and a fibromyxoid stroma [4,7,43] with possible occurrence of mitotic activity [4,7,43]. In the adult population, cardiac fibromas are acellular masses composed primarily of collagen [1,4,7]. The cells of cardiac fibromas appear spindled, monomorphic, and cytologically unremarkable [3]. Calcification is demonstrated in approximately one quarter to one half of these lesions and may be multifocal [3]. Less common is ossification. Lymphocytes and mononuclear inflammatory cells may be present, particularly in the regions surrounding the vessels and at the junction between the lesion and myocardium [3,43]. Left untreated, cardiac fibromas increase the risk of fatality, particularly due to lethal ventricular arrhythmia [6]. Surgical excision typically yields satisfactory results in the palliation of cardiac fibroma [2,3], but due to their infiltrative nature, surgical excision is not always an option [6,7]. In these cases, the implantation of a cardioverter defibrillator should be considered [2]. For patients in whom complete excision is not possible, partial tumor excision can also be beneficial [2,3] by providing adequate relief from obstruction or compression while promoting long-term survival [7]. Cardiac transplantation should be considered in patients whose tumors are very large and unresectable [4,6,7], since patients with large masses and recurrent arrhythmias often have less favorable surgical outcomes [3]. These lesions may remain stable in size over an extended period of time [3], but there is conflicting evidence as to whether tumor regression is in fact possible. Patients for

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