Cardiac intimal sarcomas are very rare. In contrast to vascular intimal sarcoma, cardiac involvement is an infrequent finding especially in children. A retrospective study of 100 cardiac sarcomas however, describes intimal sarcoma as the predominant primary sarcoma of the heart (1). These tumors are known to be very aggressive with high metastatic potential and often (micro-)metastatic disease at the time of diagnosis. Prognosis is therefore reserved with full surgical resection as the major outcome parameter for prolonged survival (2–4).

We present a case of a 4-year old child presenting with an intimal sarcoma located in the right ventricle with need for urgent surgical resection. This is a one of the few reports of cardiac intimal sarcoma and the first report of a ventricular localization in a young child.

A 4-year old child was admitted to the pediatric cardiology department with suspicion of right heart failure: ascites, edema and poor circulation. There was a history of progressive fatigue and exertional dyspnea for some days. Medical history was negative apart from food allergy.

The patient presented with edema of the lower limbs with poor circulation, abdominal distention with hepatomegaly. There was no cardiac murmur, heart rate was 53 BPM, blood pressure of 101/73 mmHg and oxygen saturation of 100%.

Abdominal ultrasound confirmed ascites and hepatomegaly. Chest x-ray showed cardiomegaly with presence of bilateral pleural effusion. The cardiac ultrasound revealed a large mass in the right ventricle bulging through tricuspid valve into the right atrium; delineation of the leaflets of the tricuspid valve was impossible due to the mass. (Figure 1) The right atrium was importantly dilated. No regurgitation of the tricuspid or pulmonary valve could be observed. Pericardial and pleural effusion were confirmed.

Urgent surgical resection was needed within 24 h after admission. The tumor was steeled on the anterior papillary muscle of the tricuspid valve (Figure 2A,B). A complete resection could be performed and subsequent a De Vega plasty of the tricuspid valve was established. The post-operative course was uneventful and the patient could be discharged from hospital 4 days after surgery.

Macroscopically the lesion was nodular and white with a diameter of 3.7〉× 3.5 × 3.5 cm (Figure 3A). After fixation with 4% buffered formalin, samples were paraffin-embedded and 5-µm-thick sections were stained with haematoxylin and eosin (H&E). Light microscopy revealed a sharply demarcated lesion, not invading the residual myocardial tissue. The lesion consisted of spindle cells arranged in a storiform and herringbone pattern (Figure 3B). Less cellular, more fibrous and sometimes myxoid areas were admixed with cellular and atypical looking zones. Focally there was marked nuclear atypia with bizarre, giant nuclei (Figure 3C). The mitotic count ranged up to 5mitoses/10HPF. This not-specific morphology allows a very broad differential diagnosis. To narrow it down immunohistochemical stains were performed (Table 1). Strong expression of MDM2 and EGFR was seen (Figure 3D). In addition, there was some expression of alfa-SMA neurofilament and EMA. The remaining stains were all negative.

FISH analysis was performed, and showed a gross amplification of MDM2 gene in >50% of tumor cells. There was no amplification of KIT, PDGFRA or EGFR genes. A homozygous loss of CDKN2A on 9p21 was also present. As an intimal sarcoma is malignant, further tumor staging was performed. Blood work-up was unremarkable. Whole-body PET-CT-scan showed multiple hypermetabolic lymph nodes bilaterally in the retromandibular region, in the right supraclavicular and in the anterior part of the mediastinum. Bone scan using 99mTc-MDP as a tracer was unable to show skeletal metastases.

Adjuvant chemotherapy with doxorubicin (60 mg/m² day1) and ifosfamide (3 g/m² day1, 2 and 3) was proposed, but parents refused postoperative chemotherapy. Cardiac magnetic resonance imaging did not show any macroscopic neoplasm 6 months after surgical resection.

Follow-up was performed initially every 3 months the first year and yearly afterwards. To date 8 years after surgical resection echocardiography does show an unchanged small fibrotic zone at the base of the papillary muscle of the tricuspid valve, without tumor recurrence. There is a residual low grade of tricuspid valve regurgitation (1–2/4) and no stenosis.

Primary cardiac sarcomas are rare but represent the majority of primary malignant cardiac tumors. There are few series describing sarcomas of the heart, and the majority of publications are case reports (2, 5–10). Ramlawi et al. reports a single-institution experience on 95 cases over 25-year period and Isambert et al. on 124 cases in 33-year period of the French Sarcoma Group with a mean age of 43 and 47.1 years respectively (11, 12). Recently a large multi-institutional cohort of 747 patients with primary cardiac malignancies is reported from the US National Cancer Database (13). Among the reported sarcomas, angiosarcomas appear to be the most prominent type (32.3–40.4%) (5, 11–14). The most common sites for the sarcomas are the right (38.8–39%) and left atrium (33–37.2%), and far less frequent the right ventricle (5%–5.8%) (11, 12). Neuville et al. reports in a retrospective clinicopathologic and molecular analysis of one hundred primary sarcomas, intimal sarcoma as the predominant tumor type with occurrence rate of 42%, followed by angiosarcoma in only 26 of 100 cases (1). All but one angiosarcoma originated from the right heart, whereas 83% of intimal sarcomas were from the left heart. Most mentioned case series and case reports are findings in adult population, occurring mostly in fourth and fifth decade of life (7, 8, 15, 16). In children, the estimated incidence of all cardiac tumors, benign or malignant, is 0.0017%–0.027%, and primary malignancy is approximately 10% (13, 17). Primary cardiac malignancies have been studied in the SEER experience (4). A total of 25 pediatric patients (<20 years of age) were identified with primary cardiac tumor in a period between 1973 and 2008. Age-adjusted incidence is 0.00686 per 100,000 US population. Most common histology type was soft tissue sarcoma (40%), which was not further specified, followed by non-Hodgkin lymphoma and teratoma with the incidence of each of them being 12%.

Intimal sarcoma is a malignant mesenchymal tumor which is usually a poorly differentiated sarcoma composed of atypical spindle cells and/or pleomorphic cells with the possibility of myxoid areas or epithelioid morphology. Tumor cells generally exhibit immunoreactivity for vimentin and variable expression for smooth muscle actin but are usually negative for desmin and endothelial markers (18). In the study by Neuville et al. all cases showed overexpression and amplification of MDM2. More than two thirds were also positive for CDK4 and HMGA2, which has been confirmed in earlier reports (1, 18).

Primary cardiac sarcomas are highly aggressive tumors which rapidly infiltrate all the layers of the heart and metastasize rapidly, especially when right-sided (11). At the time of diagnosis up to 80% of patients have metastatic disease (19). Mean survival rates are poor and range from 3 months to 20 months (11, 12, 15, 20). The overall 5-year survival in the US National Cancer Database was 11.5% (13). Therapy is primarily surgical, with achievement of negative resection margins significantly prolonging patient survival (5, 11, 12, 15). Unfortunately complete tumor resection is only possible in less than 50% of patients. Adjuvant chemo- and/or radiation therapy remains controversial (13). Some groups suggest that these adjuvant therapies have no added value, while others suggest better survival rates in patients who had received chemotherapy and radiation therapy (5, 11, 12, 20).

The presented case is exceptionally rare for age of presentation as well as for tumor location for this type of tumor. According to the literature this is the first report of an intimal sarcoma within the ventricle in a young child. Previously a case of pulmonary artery intimal sarcoma has been reported in an infant and in the left atrium in another child (21, 22). Soft tissue sarcoma has been reported as the predominant tumor type in primary malignant pediatric cardiac tumors, though no further tumor type specification was mentioned. The location of the tumor in the presented case is rare as 83% of intimal sarcomas arise from the left heart (1, 4). On the other hand, intimal sarcoma is more often reported as a tumor of the large vessels, especially pulmonary artery and thus in some way arising from the right heart. Given the disproportion between reported cases of cardiac intimal sarcoma and the retrospective finding of intimal sarcoma as the predominant primary cardiac sarcoma in adults, it might be that intimal sarcoma of the heart in children is more prevalent than is assumed, however still extremely rare (1, 23). In cases of (pediatric) sarcoma of the heart it is important to search for amplification by FISH at least for MDM2 (22, 24). In our case morphology and immune histochemistry results suggested the presence of intimal sarcoma. FISH analysis with amplification of MDM2, as well as loss of CDKN2A, supported the diagnosis.

In the case reported here complete resection of tumor could be obtained. Further tumor staging was negative apart from presence of multiple hypermetabolic lymph nodes on PET-CT scan. The lymphadenopathy could happen due to multiple reasons, as inflammation, a recent infection or more likely due to congestion caused by the sarcoma blocking the flow in the right ventricle and causing the effusions in the pericardium and the pleura, as well as causing the ascites. In the diagnostic work-up of intimal sarcomas CT and MRI are optimal for assessing tissue characteristics, infiltration and metastases (25). Given the high probability of occult dissemination at the time of diagnosis in this type of malignancy adjuvant chemotherapy was proposed, which was refused by the parents. Close follow-up is performed and with disease-free survival up to currently 8 years after surgical resection.

Intimal sarcomas, undifferentiated mesenchymal tumors arising from the intimal layer of the ventricle are an extremely rare entity in children. The molecular diagnosis is confirmed by a MDM2 amplification. Although the prognosis of primary cardiac sarcomas is overall poor, the presented case did show a good survival up to 8 years after surgical resection of the tumor.