Approach to cardiac masses: Thinking inside and outside the box

Abstract

In this editorial we comment on the article by Huffaker et al, published in the current issue of the World Journal of Clinical Cases. Cardiac masses encompass a broad range of lesions, potentially involving any cardiac structure, and they can be either neoplastic or non-neoplastic. Primitive cardiac tumors are rare, while metastases and pseudotumors are relatively common. Cardiac masses frequently pose significant diagnostic and therapeutic challenges. Multimodality imaging is fundamental for differential diagnosis, treatment, and surgical planning. In particular cardiac magnetic resonance (CMR) is currently the gold standard for noninvasive tissue characterization. CMR allows evaluation of the relationship between the tumor and adjacent structures, detection of the degree of infiltration or expansion of the mass, and prediction of the possible malignancy of a mass with a high accuracy. Different flow charts of diagnostic work-up have been proposed, based on clinical, laboratory and imaging findings, with the aim of helping physicians approach the problem in a pragmatic way (“thinking inside the box”). However, the clinical complexity of cancer patients, in particular those with rare syndromes, requires a multidisciplinary approach and an open mind to go beyond flow charts and diagnostic algorithms, in other words the ability to “think outside the box”.

Key Words: Cardiac masses; Cardiac tumors; Cardio-oncology; Cardiac magnetic resonance; Primitive cardiac tumors

Core Tip: Cardiac masses pose significant diagnostic and therapeutic challenges. Multimodality imaging is fundamental for diagnosis, treatment, and surgical planning. Different flow charts of diagnostic work-up have been proposed to help physicians approach the problem in a pragmatic way (“thinking inside the box”). However, the clinical complexity of cancer patients, in particular those with rare syndromes, requires an open mind to go beyond diagnostic algorithms, and the ability to “think outside the box.”

INTRODUCTION

Cardiac masses pose significant diagnostic and therapeutic challenges. Multimodality imaging is fundamental for diagnosis, treatment and surgical planning. Different flow charts of diagnostic work-up have been proposed to help physicians approach the problem in a pragmatic way (“thinking inside the box”). However, the clinical complexity of cancer patients, in particular those with rare syndromes, requires an open mind to go beyond diagnostic algorithms, and the ability to “think outside the box”.

HOW TO APPROACH CARDIAC MASSES

Cardiac masses encompass a broad range of lesions, potentially involving any cardiac structure, and they can be either neoplastic (benign or malignant primary cardiac tumors and secondary cardiac tumors/metastases) or non-neoplastic (thrombi, vegetations, and normal variant structures) (Table 1 and Figure 1). Primitive cardiac tumors are rare, while metastases and pseudotumors are relatively common[1,2]. The updated classification of cardiac masses, published by World Health Organization in 2015[3] includes benign tumors, non-neoplastic masses, malignant lesions, and pericardial masses (Table 2). The prevalence of primary cardiac tumors is 1:2000 autopsies and that of secondary tumors (metastases) it is 1:100 autopsies. Secondary tumors are more common than primary lesions (secondary/primary ratio 20:1). Approximately 10% of primary cardiac tumors are malignant and 90% benign (especially myxomas and fibroelastomas). Myxomas and fibroelastomas represent > 80% of benign cardiac neoplasms in adults and are uncommon in infancy. Some studies suggest that papillary fibroelastomas may have an even higher prevalence than myxomas[1,2]. The most common benign tumor in pediatric patients is rhabdomyoma, representing about 50% of the cases. Other benign lesions include fibromas, lipomas, hemangiomas, cystic tumors, and paragangliomas. Malignant tumors account for the remaining 10%-20% of primary lesions. Cardiac sarcomas are the most common of these, and account for 1% of all soft tissue sarcomas. Among cardiac sarcomas, 76% are angiosarcomas/unclassified sarcomas. Rhabdomyosarcoma is the most represented type of cardiac sarcoma in infancy. Secondary tumors are more frequent than primary forms, but because metastatic lesions of any malignant tumor can involve the heart, the incidence of cardiac metastasis is not exactly known.

Figure 1 Localization, pathophysiology, and histopathological aspects of cardiac masses. Citation: Castrichini M, Albani S, Pinamonti B, Sinagra G. Atrial thrombi or cardiac tumours? The image-challenge of intracardiac masses: a case report. Eur Heart J Case Rep 2020; 4: 1-6. Copyright© The Authors 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. The authors have obtained the permission for figure using from the European Heart Journal - Case Reports (Supplementary material).

Table 1 Classification of cardiac masses.

Site of mass	Normal variant structures	Abnormal masses
Left ventricle	False tendon, trabeculations, papillary muscle	Thrombus, tumor
Left atrium	Coumadin ridge, fibromuscular membrane	Thrombus, tumor
Right ventricle	Moderator band, trabeculations, pacemaker leads	Thrombus, tumor
Right atrium	Crista terminalis, eustachian valve, Chiari network, lipomatous hypertrophy of atrial septum, pacemaker leads	Thrombus, tumor
Valves	Lambl’s excrescence (aortic valve), annular calcification	Thrombus, infective vegetations (native valve and prosthesis), tumor (native valve)
Pericardium	Pericardial fat	Pericardial malignant mesothelioma
Paracardiac	Hiatal hernia	Mediastinal/thoracic tumor compression

Table 2 Simplified World Health Organization classification of heart and pericardial tumors[3].

Group	Histologic type
Benign congenital/childhood	Rhabdomyoma, histiocytoid cardiomyopathy, congenital or childhood fibroma, cystic tumor of the atrioventricular node, hamartomas, germ cell tumors, schwannoma, granular cell tumor
Non-neoplastic tumors of adults	Papillary fibroelastoma, lipomatous hypertrophy of atrial septum
Neoplastic benign tumors	Myxoma, lipoma, hemangioma
Malignant tumors	Angiosarcoma, rhabdomyosarcoma, leiomyosarcoma, osteosarcoma, synovial sarcoma, pericardial malignant mesothelioma, lymphoma
Intermediate behavior	Inflammatory myofibroblastic tumor, low-grade angiosarcoma, infiltrating hemangiomas, cardiac paraganglioma, solitary fibrous tumor of the pericardium, adult cellular rhabdomyoma

Cardiac masses frequently pose significant diagnostic and therapeutic challenges, moreover they may be asymptomatic or found incidentally during evaluation for an apparently unrelated problem[4,5]. The first-level noninvasive examination is echocardiography, which has excellent diagnostic accuracy for thrombi, valvular vegetations, and primary benign tumors (like myxomas and fibroelastomas). On the other hand, echocardiography provides little information of other types of masses, especially in cases of suspected malignancy, because of poor tissue characterization. An in-depth diagnostic approach with second-line and third-line examinations (computed tomography, magnetic resonance, positron emission tomography) may allow the diagnosis of malignant cardiac masses without the need of biopsy and histology, and expedite the subsequent therapeutic process[6,7]. Different flow charts of diagnostic work-up have been proposed, based on clinical, laboratory and imaging findings, with the aim of helping physicians approach the problem in a pragmatic way (“thinking inside the box”) (Figure 2).

Figure 2 Flow chart of the diagnostic workup in patients with cardiac masses. CT: Computed tomography; MRI: Magnetic resonance imaging; PET: Positron emission tomography; TEE: Trans esophageal echocardiography; TTE: Trans thoracic echocardiography.

In the article by Huffaker et al[8], published in the current issue of the World Journal of Clinical Cases, the authors describe a case of a 30-year-old woman with Li-Fraumeni syndrome (LFS) with a tricuspid valve mass, that was detected during a routine echocardiography in the cardio-oncology clinic, in absence of symptoms or clinical signs. The finding was not evident in previous echocardiographic examinations. The patient had a remarkable cancer history (breast and ovarian cancer, soft tissue, and bone sarcoma), so this new cardiac mass raised a reasonable suspicion for a primary cardiac tumor or metastasis. After a multi-disciplinary approach (cardio-oncology specialist, multimodality cardiac imaging, cardiothoracic surgeons, and interventional cardiologists) a decision was made to surgically remove the mass. Quite surprisingly, the mass was histologically identified as a thrombus with no evidence of malignancy.

LFS, firstly described in 1969, is an inherited autosomal dominant disorder, associated with abnormalities in the tumor suppressor protein P53 gene (TP53) located on chromosome 17p13. LFS predisposes to different types of malignant tumors in several organs and at a relatively young age; it is also known as the sarcoma, breast, leukemia, and adrenal gland cancer syndrome[8].

Tricuspid valve masses are usually related to cardiac thrombi or infective vegetations in endocarditis, especially in patients with central venous lines, vascular catheters, or pacemaker/defibrillator leads. Primary tumors are less frequently encountered, and papillary fibroelastoma is the most frequent (and benign) tricuspid tumor. The mean age of occurrence is 70-80 years with no sex difference.

The patient described by Huffaker et al[8] had a high pretest probability of primary cardiac malignancy or metastasis but the final diagnosis was valve thrombus, in line with the well-known association between cancers and thrombosis. It is important to note that the mass showed enhancement on cardiac magnetic resonance (CMR), suggesting the presence of vascularization, which is common in tumors but is an exceedingly rare finding on CMR in cases of thrombus.

CONCLUSION

Multimodality imaging in patients with cardiac masses is fundamental for differential diagnosis, treatment, and surgical planning. The characteristics of the mass defined by echocardiography, CMR, cardiac computed tomography, and positron emission tomography-computed tomography surely serve to guide clinicians. In particular, CMR is currently the gold standard for noninvasive tissue characterization. CMR evaluates the relationship between the tumor and adjacent structures, detects expansion and infiltration of the lesion, and predicts the malignant nature of a mass with a high precision. However, as demonstrated in this case report, the clinical complexity of cancer patients, in particular those with rare syndromes, requires a multidisciplinary approach and an open mind to go beyond flow charts and diagnostic algorithms. In other words it requires the ability to “think outside the box”.