| Abstract|| |
Primary cardiac sarcomas are extremely rare with only a few large case series and isolated case reports in the literature. In spite of their aggressive nature with high chances of local recurrence and distant metastases, these tumors and their treatment strategies remain incompletely defined. We report an unsuspected case of primary cardiac pleomorphic undifferentiated sarcoma in a 52-year-old female who presented with progressive dyspnea and palpitation. In the postoperative period, she was detected to have secondaries in brain and thyroid, confirmed thereafter, by fine-needle aspiration cytology.
Keywords: Cardiac sarcoma, primary, thyroid metastasis
|How to cite this article:|
Yesodharan J, Kandamuthan S, Poothiode U. Primary cardiac sarcoma with metastases to thyroid and brain. Indian J Pathol Microbiol 2015;58:345-7
| Introduction|| |
Primary neoplasms of the heart are rare with an incidence of only 0.0017-0.03% in autopsy series.  Of these, less than 25% are malignant, and most of them are sarcomas. Secondary cardiac involvement by direct invasion or metastases from tumors elsewhere is commoner than primary tumors.  However, both primary and secondary neoplasms present with highly variable, often overlapping symptoms and their distinction is clinically and radiologically difficult. Only a meticulous histopathological examination together with ancillary tests can provide the diagnosis. Furthermore, the intra and extra-cardiac extent of tumor must be carefully ascertained to guide treatment. Still, the overall survival is dismal.
| Case Report|| |
A 52-year-old female presented with progressive breathlessness and palpitation of 2 months duration, which worsened 3 days prior to her admission. There was no history of any significant past illness. On examination, her vitals were stable, and she had a firm to hard thyroid swelling of approximate size 3 cm × 2 cm. A pansystolic murmur was detected along the left lower sternal border. Echocardiography revealed a 4 cm × 2 cm mobile mass attached to anterior mitral leaflet causing severe mitral obstruction, which was suspected to be a myxoma or large healed vegetation. The patient was posted for excision of the same. Intra-operatively, the surgeon noted two pedunculated masses - one measuring 2 cm × 1.5 cm arising from anterior mitral leaflet extending to left atrium and the other, 3 cm × 7 cm arising from medial papillary muscle extending to posterior mitral leaflet. The tumor could not be separated completely from the atrial myocardium and was removed piecemeal, followed by a mitral valve replacement.
The specimen received for histopathology examination consisted of multiple whitish and glistening soft tissue bits with part of a valve together measuring about 6 cm × 6 cm × 3 cm. Microscopy showed a neoplasm composed of moderately pleomorphic cells scattered diffusely in a loose myxoid stroma with 3-4 mitoses/high power field including atypical forms [Figure 1]a. Focal inflammation, necrosis, hemorrhage and cartilage like areas were noted. The cells were diffusely positive for vimentin [Figure 1]b and negative for CD34, desmin and S100 on immunohistochemistry. Thus, a diagnosis of pleomorphic undifferentiated sarcoma was made.
|Figure 1: (a) Pleomorphic cells in a loose myxoid stroma in the cardiac tumor, H and E, ´200. (b) Cardiac tumor cells are showing diffuse positivity for vimentin, ´400. (c) Computed tomography brain showing lesion in left frontoparietal cortex. (d) Giemsa stained fine needle aspiration smear of thyroid nodule showing pleomorphic cells and follicular cells, ´400|
Click here to view
Postoperatively, the patient had clouding of consciousness. On computed tomography (CT) scan, a nonhomogenously enhancing 3 cm × 3 cm lesion, suspected to be metastatic, was identified in the left frontoparietal cortex [Figure 1]c. A 4 cm × 4 cm nodule in the left lobe of thyroid was also noted, with no suprarenal or lung masses. Fine-needle aspiration (FNA) from the thyroid nodule yielded dyscohesive clusters of large ovoid to spindly pleomorphic cells in a background of thyroid follicular epithelial cells, colloid and macrophages, suggestive of metastasis from a sarcoma [Figure 1]d. Immunohistochemistry for thyroid transcription factor 1 (TTF-1) done subsequently on the cardiac tumor, to exclude the remote possibility of metastases from a thyroid primary, was negative.
The patient underwent five cycles of whole brain irradiation for metastasis. Unfortunately, she succumbed to her illness 2 weeks later.
| Discussion|| |
Primary cardiac sarcomas are malignant neoplasms derived from the mesenchymal cells of the heart. Among these, the more frequent are angiosarcoma, followed by pleomorphic undifferentiated sarcoma, together accounting for up to 66% of sarcomas in two large case series published in 1996 and 2004. , About 50% of all cardiac sarcomas and 81% of undifferentiated pleomorphic sarcomas are located in the left atrium.  These tumors may arise at any age without gender predilection; however, the mean age is 40 years. Symptoms are often nonspecific and of varying duration depending on the location and extent of tumor. These include dyspnea, orthopnea, arrhythmias, cardiac failure and chest pain. The main diagnostic modalities are transthoracic and transesophageal echocardiogram, three-dimensional echocardiogram, CT scan and cardiac magnetic resonance imaging. However, very often, these tumors are mistaken for myxomas and the true diagnosis comes as a surprise on the operating table, as in our case. Transvenous endomyocardial biopsy may enable a preoperative histological diagnosis and guide further management, but is less frequently resorted to.
Exhaustive sampling is absolutely necessary for surgical specimens of suspected cardiac sarcoma in order to arrive at the correct diagnosis and for grading as they can have heterogeneous areas of differentiation. Ancillary studies like immunohistochemistry and electron microscopy aid in the histopathologic typing of these tumors. They are classified based on the WHO system (2004), which includes only the more frequent malignant lesions. The FNCLCC (French Fédération Nationale des Centres de Lutte Contre le Cancer) grading system used to assess the prognosis of soft tissue sarcomas is applicable to cardiac sarcomas too. 
Since 80% cases of cardiac sarcomas may have systemic metastases at the time of diagnosis, a thorough search for the same by whole body imaging, is mandatory. Metastases have been reported in a variety of sites including liver, lung, brain, lymph node, kidney, adrenals, bone, spleen and chest wall.  Our patient was radiologically detected to have brain and thyroid secondaries in the immediate postoperative period, of which, the thyroid metastasis could be established through FNA cytology. In spite of extensive literature search, we could not find a cytologically or histologically proven case of metastasis to the thyroid from a primary cardiac sarcoma.
As a whole, the incidence of thyroid metastases from primaries elsewhere, varies from 1.25% to 24% in autopsy series.  TTF-1, though a useful immunohistochemical marker in primary thyroid tumors, many undifferentiated carcinomas and sarcomas may be negative. Hence negative TTF-1 alone does not exclude a thyroid primary, and clinical correlation holds the key in difficult cases. FNA may help confirm suspected thyroid secondaries, thereby avoiding unwanted surgery in cases with a bad prognosis.
Due to the paucity of large studies on cardiac sarcomas, there is no consensus on the therapeutic approach. Though complete removal is often difficult, wide local excision remains the mainstay, and it offers effective palliation. The benefit of adjuvant chemotherapy and radiotherapy is uncertain, and the overall prognosis is poor. 
Since primary cardiac sarcomas are extremely rare, reporting of additional cases will enable further characterization of these tumors and their therapeutic strategies. We have presented a rare case with rarer sites of metastases, and this highlights the importance of a thorough metastatic work-up in patients with primary cardiac sarcomas.
| References|| |
Silverman NA. Primary cardiac tumors. Ann Surg 1980;191:127-38.
Burke AP, Virmani R. Tumors of the Heart and Great Vessels. Atlas of Tumor Pathology. Vol. 16. Washington, DC: Armed Forces Institute of Pathology; 1996. p. 127-69.
Burke A, Veinot J, Loire R, Virmani R, Tazelaar H, Kamiya H, et al
. Tumours of the heart. In: Travis W, Brambilla E, Muller-Hermelink HK, Harris CC, editors. Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC Press; 2004. p. 251-88.
Okamoto K, Kato S, Katsuki S, Wada Y, Toyozumi Y, Morimatsu M, et al.
Malignant fibrous histiocytoma of the heart: Case report and review of 46 cases in the literature. Intern Med 2001;40:1222-6.
Orlandi A, Ferlosio A, Roselli M, Chiariello L, Spagnoli LG. Cardiac sarcomas: An update. J Thorac Oncol 2010;5:1483-9.
Burke AP, Cowan D, Virmani R. Primary sarcomas of the heart. Cancer 1992;69:387-95.
Gerges AS, Shehata SR, Gouda IA. Metastasis to the thyroid gland; unusual site of metastasis. J Egypt Natl Canc Inst 2006;18:67-72.
Shanmugam G. Primary cardiac sarcoma. Eur J Cardiothorac Surg 2006;29:925-32.
Dr. Jyotsna Yesodharan
113, Sivaranjani, GCDA Colony, Thottakkattukara, Aluva - 683 108, Kerala
Source of Support: None, Conflict of Interest: None