Clinical History
This 56-year-old previously healthy caucasian male presented with severe congestive heart failure. He
had a two-month history of increasing shortness of breath on exertion. He was in florid pulmonary edema
and had to be intubated on admission. He needed large does of inotropes, and was ventilated on 100%
oxygen. A transesophageal echo (TEE) revealed a large tumor mass in the left atrium. A CT scan showed
no lesions in the lungs.
Clinical Diagnosis: Benign myxoma
The patient was taken for emergent surgery. At surgery a 7.0 cm diameter, firm to hard atrial mass
was seen, attached to the left atrium, posterior wall, and to the posterior leaflet of the mitral valve.
A quick section was reported as a "myxoma".The surgeon "carefully shelled out", "debulked" the tumor,
with plans to do a "second stage" mitral valve replacement, if feasible. Patient was transferred to
CV-ICU on a) lower does of inotropes and b) with pulmonary artery pressures which had fallen from
supra-systemic to approximately two-thirds systemic.
A section of the neoplasm is available for review.
Gross Pathological Findings
The 7.0 cm mass, which was excised, was firm to hard in consistency and weighed 92.2 grams. The
entire tissue mass was grey-white in color and roughly oval in shape. It measured 6.0 x 4.5 x 3.0 cm and
had attached to it a portion of the atrial wall measuring 3.7 x 2.1 x 0.15 cm. On cross section, the cut
surface had a lobulated, fleshy, solid appearance, a grey-white color. A few small brown (hemorrhagic
foci) and glistening areas were seen. Minute foci of calcification were noted on sectioning.
Histologic, immunohistochemical findings:
Histologic examination showed a variably cellular neoplasm comprising virtually the entire mass. The
surface and the immediately subjacent portions were somewhat less cellular, while the core of the mass
was significantly more cellular. The neoplastic cells showed a variegated appearance. Parts of the mass
had a storiform pattern and other parts showed a somewhat clear cell appearance. Yet other areas showed
focal neoplastic cartilaginous tissue. Multifocal areas of tumor necrosis were evident. Nuclear
pleomorphism was prominent and scattered but relatively few multinuclear giant cells were seen. Mitoses
were few.
In addition to the small foci of neoplastic cartilage, much larger areas of osteoid were seen and
small focal areas of calcification of this osteoid were also evident. The deep margin was not clear, in
fact the tumor was, at least in some areas, shaved off the atrial wall. Invasion of the myocardium was
seen in the deeper parts of the lesion.
Immunohistochemical staining showed no immediate reactivity in the tumor cells, except with vimentin.
Actin and myoglobin were positive in the residual cardiac muscle fibers. S100 was negative in tumor
cells.
Based on the finding of spindle cells with large pleomorphic nuclei, occasional giant cells, areas of
tumor necrosis, this lesion was diagnosed as an Atrial sarcoma. Based on the finding of malignant
cartilage and of malignant osteoid, this tumor is a non-osseous or extra-osseus osteogenic sarcoma.
Reviews with experts in soft tissue tumors, and based on the morphological findings, the tumor was rated
as a grade 3 sarcoma.
Clinical Course
The patient did well and left the hospital as scheduled. At thirteen months postoperative, the
patient is alive and well. A repeat echocardiogram showed a 2.5 inch, 2.0 cm area of thickening along
the posterior left atrial wall. This likely represents tumor (recurrence or growth). No radiation or
chemotherapy has been given thus far.
Final Diagnosis: Left atrial sarcoma (extra-osseus osteogenic sarcoma)
Comment
Primary cardiac neoplasms are rare with an incidence of less than 10% at autopsy. Seventy-five
percent of these neoplasms are benign with close to 50% of the benign cardiac neoplasms being myxomas.
Most of the rest are lipomas, papillary fibroelastoma and rhabdomyomas. About 25% of all cardiac
neoplasms are malignant and of these 95% are sarcomas, while the remaining 5% are primary
lymphomas
[2,
3]
. Amongst the malignant primary cardiac neoplasms, the commonest, are the
undifferentiated sarcomas followed by angiosarcoma, leiomyosarcoma and rhabdomyosarcomas [4].
Most cardiac neoplasms are picked up at investigation for otherwise non-specific symptoms(Table 1).
Symptoms relatable to the heart and great vessels occur late. Until recently, most cardiac neoplasms
were seen at autopsy and diagnosed at this time. Increasingly though, especially in the last 20 or so
years, cardiac neoplasms are diagnosed clinically and often examined at surgical pathology. The mean
age at which primary and secondary sarcomas involve the heart is 55.0 and 35.0 years,
respectively
[5,
6]
. Cardiac sarcomas are extremely rare in the pediatric age groups. In some
studies, sarcomas are reportedly more common in males than in females with a ratio of 2:1.
Presenting symptoms
These are usually dependent on the location of the neoplasm and its size, rather than the histologic
type of the lesion. Dyspnea is reportedly the most common presentation [5] and in left atrial
lesions is attributed to venous obstruction, with the symptoms being similar to those of significant
mitral stenosis. About 300 cases of primary cardiac sarcomas have been reported in the
literature [7]. The confirmation and further identification of differentiation or cardiac
sarcomas follows the same histological and immunohistochemical path, as other soft tissue sarcomas. It
is done objectively through the use of appropriate immunohistochemical stains, to detect or exclude
neural, endothelial, skeletal muscle, histiocytic, cartilaginous and adipocyte differentiation. The more
common sarcomas are: angiosarcomas (37%), undifferentiated (24%), malignant fibrous histiocytoma (MFH)
(11 - 24%), leiomyosarcoma (8 - 9%) and osteosarcoma (3 - 9%) [8].
Angiosarcoma
These occur primarily in the right atrium, usually between the third and fifth decades of life with a
male to female ratio of 2:1 (Reference 9). Metastases can develop in 45 to 90% of patients, generally to
the lungs, though the brain, bones and colon have been reported. The signs and symptoms are non-specific
and may include chest pain, shortness of breath, malaise, and fever. ECG findings may include
arrhythmias, heart block, and non-specific ST and T-wave changes. Morphologically, the lesions are
usually hemorrhagic, with ill-defined margins. Involvement of the pericardium is common and aggressive
lesions show invasion of contiguous structures such as the vena cavae and the atrioventricular valve.
The histologic appearance is that of irregular, anastomosing, sinusoidal microstructures with
intraluminal papillary tufting. Atypical and pleomorphic cells line the vascular spaces and mitotic
rates, as well as necrosis, correlate with outcome. Helpful immunohistochemical stains are those for
factor VIII, Von Willebrand Factor and CD31.
Undifferentiated sarcoma
These lesions have no specific histologic patterns. The histologic features are those of a malignant
spindle cell sarcoma (usually) with varying degrees of nuclear pleomorphism and atypia. Ultrastructural
features, immunohistochemical staining are both unrewarding, that is, the features do not help decide the
specific nature of the sarcoma. Their incidence ranges from 0 - 24% [8]. Detailed histologic
examination often shows the presence of pleomorphic, epithelioid as well as small cell types of
unclassifiable sarcoma.
Pleomorphic Malignant Fibrous Histiocytomas / Undifferentiated High Grade Pleomorphic Sarcoma
Undifferentiated high-grade pleomorphic
sarcomas have a mean age at presentation of 44 years, with no gender predisposition. Grossly the lesions
are lobulated, sessile or pedunculated and often reach a diameter of up to 10.0 cm. Histologically, they
show proliferating spindle cells, as well as pleomorphic cells with a storiform pattern. Histocytes or
foamy cells with a pleomorphic infiltrate of inflammatory cells, including mononuclear cells, may be
present. In some areas, this stoma may be myxoid and on occasion, these lesions may be misdiagnosed as a
myxoma, if only a small part of the lesion is examined. This diagnosis is usually one of exclusion,
following adequate sampling use of ancillary diagnostic techniques. Molecular studies may show changes
in chromosomes 11, 13, and 16, as well as 15-pter, 7-32 and 1p31 (WHO classification of Soft Tumors,
2002) [9].
Leiomyosarcoma
Primary leiomyosarcomas are rare and highly aggressive, as well as being locally invasive, with an
incidence of 0.25% [10]. Presenting symptoms usually include dyspnea, chest pain and a
non-productive cough. Many of these lesions develop in the pulmonary artery and right heart failure,
valvular stenosis, as well as changes in rhythm and conduction abnormalities may develop [11].
Usually seen in the posterior left atrium, they present as sessile masses, which may have a mucoid
appearance. Histologically, the neoplasm is composed of bundles of spindle cells [8].
Osteosarcoma - Extra-osseus
Extra-osseus osteosarcomas are rare neoplasms, account for about 3 - 9% of primary cardiac sarcomas
and are usually seen in the left atrium. The common clinical presentation is that of shortness of
breath, or other respiratory symptoms. Osteosarcomas may arise in the left ventricle and then usually
present with recurrent ventricular tachyarrhythmias.
Grossly, the lesion is comprised of bulky, sessile masses with diameters ranging from 4.0 to 10.0 cm.
Usually attached to the left atrial wall, these masses may have small foci of thrombus on the surface.
The lining endocardium often appears intact, however, ulceration may occur. Histologically,
osteosarcomas are a fairly heterogenous group and may show a spindle cell pattern suggestive of a
fibrosarcoma or a pattern suggestive of MSH. It is essential to look at a sufficient sampling of the
tissue to find foci of osteosarcoma and perhaps foci of chondrosarcoma, amongst the spindle cell areas.
Areas of tumor necrosis are frequently seen, and occasionally, especially in the marginal areas, small
islands of cardiac muscle fibers may still be seen. Amplifications at 1q21-23 and 17p are frequent
findings in conventional osteosarcomas. They have not been reported in these cardiac lesions.
Rhabdomyosarcoma
Rhabdomyosarcomas are exquisitely rare. When seen, they are more likely to occur in males and may
involve many of the cardiac chambers. The presentation is usually non-specific. The neoplastic masses
are often bulky and invasive, reaching a diameter of up to 10.0 cm [12].
Liposarcomas
These are very rare and often not represented in most surgical series of neoplasms. The gross
appearance is that of a soft, bulky neoplasm with a diameter of 10.0 cm or more and having an
embossulated surface. Histologically, they are similar in appearance to the extra cardiac liposarcomas.
Pleomorphic and cellular areas resembling MFH or fibrosarcoma may be seen. Lipoblasts with multiple
vacuoles may help to make the diagnosis [13].
Hemological neoplasms
Primary cardiac lymphomas are rare, and a few documented cases have been reported. The incidence is
believed to be somewhat more common in association with the acquired immune deficiency syndrome and
approximately 50 cases have been reported to date. Complete radiological as well as clinical examination
is essential to exclude generalized involvement by lymphoma.
Table 1 - Clinical manifestations of malignant tumors
| Angiosarcoma | Nonspecific and may include chest pain, shortness of breath, malaise and fever. |
| Osteosarcoma | Atrial: presents with respiratory symptoms.
Ventricular: presents with recurrent ventricular tachyarrhythmia. |
| Leiomyosarcoma | Pulmonary: Dyspnea, chest pain, and non-productive cough.
Cardiac: Right heart failure, valve stenosis, rhythm alterations, conduction abnormalities, hemopericardium and sudden death have been reported. |
| Rhabdomyosarcoma | Nonspecific symptoms, though pleuro-pericardial symptoms and distal embolization may occur. Arrhythmias and obstructive symptoms may develop. |
| Cardiac Lymphoma | Cardiac tamponade, heart failure, exertional dyspnea, and atrial fibrillation and features of right-sided heart obstruction. |
| Pericardial Mesothelioma | Chest pain, cough, dyspnea and palpitations. |
| Metastatic Cardiac Tumor | The development of tachycardia, arrhythmias, cardiomegaly or heart failure in a patient with carcinoma should raise the suspicion of cardiac metastasis. Rarely, cardiac involvement such as a pericardial effusion or incipient cardiac tamponade may be the first clinical feature of malignancy, though 90% are clinically silent. |
References
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- Shapiro LM: Cardiac tumors: diagnosis and management. Heart 2001, 85: 218-222
- Sarjeant JM, Butany J, Cusimano RJ: Cancer of the heart: epidemiology and management of primary neoplasms and metastases. Am J Cardiovasc Drugs 2003, 3: 407-421
- Grandmougin D, Fayad G, Decoene C, Pol A, Warembourg H: Total orthotopic heart transplantation for primary cardiac rhabdomyosarcoma: factors influencing long-term survival. Ann Thorac Surg 2001, 71: 1438-1441
- Burke AP, Cown D, Virmani R: Primary sarcomas of the heart. Cancer 1992, 69: 387-395
- Becker AE: Primary heart tumors in the pediatric age group: a review of salient pathologic features relevant for clinicians. Pediatr Cardiol 2000, 21: 317-323
- Donsbeck AV, Ranchere D, Coindre JM, Le Gall F, Cordier JF, Loire R: Primary cardiac sarcomas: an immunohistochemical and grading study with long-term follow-up of 24 cases. Histopathology 1999, 34: 295-304
- Burke A, Virmani R, Armed Forces Institute of Pathology (U.S), Universities Associated for Research and Education in Pathology: neoplasms of the heart and great vessels. Washington, D.C., Published by the Armed Forces Institute of Pathology: Available from the American Registry of Pathology, 1996, pp 231
- Corso RB, Kraychete N, Nardeli S, Moitinho R, Ourives C, Silva RM, Pereira RE: Spontaneous rupture of a right atrial angiosarcoma and cardiac tamponade. Arq Bras Cardiol 2003, 81: 611-613, 608-610
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