Correspondence

Cardiac Myxomas

N Engl J Med 1996; 334:1407-1409May 23, 1996

Article

To the Editor:

Reynen (Dec. 14 issue)1 provides an extensive and informative review of cardiac myxomas. He points out that myxomas are histologically benign but may be lethal because of their strategic position. He further states that the malignant potential of cardiac myxomas remains doubtful. A few malignant atrial myxomas have been reported, however.2,3 We describe a cardiac left atrial tumor that resembled malignant myxoma clinically and grossly.

An 18-year-old woman presented with fever, joint pain, and a diastolic murmur. She was treated for rheumatoid arthritis, but signs of increased intracranial pressure developed 16 months later. Radiologic studies revealed tumors in the mitral valve and the left temporal lobe. The brain tumor was removed, and the atrial tumor was resected. The brain lesion and the primary heart tumor were histologically similar, representing high-grade sarcoma with spindle-cell and pleomorphic features. Immunohistochemically, the tumor cells showed focal reactivity of muscle actin but were negative for desmin, as is compatible with a diagnosis of pleomorphic sarcoma (malignant fibrous histiocytoma).

Despite brain and cardiac irradiation and cytotoxic treatment (with ifosfamide, epirubicin, dacarbazine, and etoposide), another lesion developed in the brain, first visualized by antibody scanning and then verified by computed tomography. An indium-111–labeled monoclonal antimyosin antibody (R11D10) specific for cardiac myosin, with some cross-reactivity with skeletal myosin, was used to detect distant metastases.4 Figure 1AFigure 1Brain Metastasis of a Cardiac Tumor. shows a single-photon-emission computed tomographic (SPECT) study of the brain recorded 72 hours after injection, demonstrating pronounced intracranial uptake of antibody.

The patient died two years after the first symptoms. The autopsy showed extensive tumor growth in both the left atrium and the left ventricle, as well as regrowth of the metastasis in the left temporal lobe (Figure 1B).

Two patients with malignant atrial myxoma have been described in the literature,2,3 both presenting with an intracranial mass like that in our patient. Although the histologic features in our patient were different, her clinical course was similar to that in these two described cases of malignant atrial myxoma.

Kalevi J.A. Kairemo, M.D., Ph.D.
Carl P. Blomqvist, M.D., Ph.D.
Helsinki University Central Hospital, FIN-00290 Helsinki, Finland

Markku Miettinen, M.D., Ph.D.
Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107

4 References

1. 1

   Reynen K. Cardiac myxomas. N Engl J Med 1995;333:1610-1617
   Full Text | Web of Science | Medline

2. 2

   Rankin LI, DeSousa AL. Metastatic atrial myxoma presenting as intracranial mass. Chest 1978;74:451-452
   CrossRef | Web of Science | Medline

3. 3

   Pastakia B. Malignant atrial myxoma presenting as intracranial mass. Chest 1979;75:531-532
   CrossRef | Web of Science | Medline

4. 4

   Kairemo KJ, Wiklund TA, Liewendahl K, et al. Imaging of soft-tissue sarcomas with indium-111-labeled monoclonal antimyosin Fab fragments. J Nucl Med 1990;31:23-31
   Web of Science | Medline

To the Editor:

Dr. Reynen reports that “myxomas consist of a myxoid matrix composed of an acid-mucopolysaccharide–rich stroma.” The term “acid mucopolysaccharide” reflects the histologic appearance when conventional staining procedures are used. However, the term should be replaced, now that the biochemical bases of the staining reactions have been elucidated. The proteoglycans, consisting of straight-chain sugars or glycosaminoglycans covalently attached to a protein core, are the chief component of acid mucopolysaccharides. The only glycosaminoglycan not attached to a protein core, hyaluronan (also known as hyaluronic acid), present in tissue undergoing rapid turnover and in association with cancers is found in particularly rich concentration in embryonic tissues. My colleagues and I have established that the stroma of myxomas contains predominantly hyaluronan.1,2 This finding supports the suggestion that such tumors arise from embryonic rests remaining from the period when septation of the heart was occurring, which also explains the prevalence of myxomas in the atrial septum.

Robert Stern, M.D.
University of California, San Francisco, School of Medicine, San Francisco, CA 94143-0506

2 References

1. 1

   Hendin BN, Longaker MT, Finkbeiner WE, Roberts LJ, Stern R. Hyaluronic acid deposition in cardiac myxomas: localization using a hyaluronate-specific binding protein. Am J Cardiovasc Pathol 1991;3:209-215
   

2. 2

   Longaker MT, Chiu ES, Hendin B, Finkbeiner WE, Stern R. Hyaluronic acid in a cardiac myxoma: a biochemical and histological analysis. Virchows Arch A Pathol Anat Histopathol 1991;418:435-437
   CrossRef | Medline

Author/Editor Response

The author and a colleague reply:

To the Editor: Kairemo et al. report the very rare case of a malignant fibrous histiocytoma in the left atrium. Histologically, such histiocytomas represent pleomorphic sarcomas with partial fibroblastic and histiocytic differentiation. Because of preferential left atrial growth, malignant fibrous histiocytoma may clinically mimic left atrial myxoma. Furthermore, in patients with myxoid variants of this tumor, thorough microscopical examination of multiple sections may be needed to achieve reliable histologic differentiation from myxoma.1 In this case, as well as in the case described by Pastakia,2 a malignant tumor of the heart, not a myxoma, metastasized to the brain. In contrast, cardiac myxomas are histologically benign, without nuclear atypia or mitoses. Nevertheless, such myxomas are considered sometimes to possess malignant potential: In histologically benign myxomas, extensive local invasion of cardiac tissue3 and remote growth of embolized tumor material have been observed, with and without malignant transformation.4,5

Histologically, the bulk of myxomas consists of a myxoid matrix in which acid mucopolysaccharides are the predominant substances. Polygonal cells with scant eosinophilic cytoplasm are embedded in the matrix. In addition, reticular, collagen, and elastic fibers, as well as smooth-muscle cells, are found in differing amounts. The systematic name of mucopolysaccharides is glycosaminoglycans. With the exception of hyaluronic acid, acid glycosaminoglycans such as chondroitin sulfate A and C, dermatan sulfate, heparin, heparan sulfate, and keratan sulfate are covalently bound to specific proteins and are accordingly called proteoglycans. Keratan sulfate, hyaluronic acid, and chondroitin sulfate A and C have been identified in myxomas6; in the myxoid matrix of an excised myxoma, hyaluronic acid was found at a level 30 times higher than that in normal atrial septum.7 We agree with Dr. Stern that since the glycosaminoglycan pattern is characteristic of embryonic tissue, it is reasonable to assume that myxomas arise from embryonic rests remaining from the period of septation of the heart.

Klaus Reynen, M.D.
Werner G. Daniel, M.D.
University Clinic Dresden, D-01307 Dresden, Germany

7 References

1. 1

   Laya MB, Mailliard JA, Bewtra C, Levin HS. Malignant fibrous histiocytoma of the heart: a case report and review of the literature. Cancer 1987;59:1026-1031
   CrossRef | Web of Science | Medline

2. 2

   Pastakia B. Malignant atrial myxoma presenting as intracranial mass. Chest 1979;75:531-532
   CrossRef | Web of Science | Medline

3. 3

   Hannah H III, Eisemann G, Hiszcznskyj R, Winsky M, Cohen L. Invasive atrial myxoma: documentation of malignant potential of cardiac myxomas. Am Heart J 1982;104:881-883
   CrossRef | Web of Science | Medline

4. 4

   Kotani K, Matsuzawa Y, Funahashi T, et al. Left atrial myxoma metastasizing to the aorta, with intraluminal growth causing renovascular hypertension. Cardiology 1991;78:72-77
   CrossRef | Web of Science | Medline

5. 5

   Wada A, Kanda T, Hayashi R, Imai S, Suzuki T, Murata K. Cardiac myxoma metastasized to the brain: potential role of endogenous interleukin-6. Cardiology 1993;83:208-211
   CrossRef | Web of Science | Medline

6. 6

   Mikuz G, Hofstadter F, Hausen A, Hager J. Das sog: Endokardmyxom: histologische, elektronenmikroskopische, immunfluoreszenz- und biochemische Untersuchungen an drei Fällen. Virchows Arch A Pathol Anat Histopathol 1978;380:221-236
   CrossRef

7. 7

   Longaker MT, Chiu ES, Hendin B, Finkbeiner WE, Stern R. Hyaluronic acid in a cardiac myxoma: a biochemical and histological analysis. Virchows Arch A Pathol Anat Histopathol 1991;418:435-437
   CrossRef | Medline

Citing Articles (3)

Citing Articles

1. 1

   Augusto Orlandi, Alessandro Ciucci, Amedeo Ferlosio, Antonio Pellegrino, Luigi Chiariello, Luigi Giusto Spagnoli. (2005) Increased Expression and Activity of Matrix Metalloproteinases Characterize Embolic Cardiac Myxomas. The American Journal of Pathology 166:6, 1619-1628
   CrossRef

2. 2

   Amihay Shinfeld, Takahiro Katsumata, Stephen Westaby. (1998) Recurrent cardiac myxoma: seeding or multifocal disease?. The Annals of Thoracic Surgery 66:1, 285-288
   CrossRef

3. 3

   (1996) More on Cardiac Myxomas. New England Journal of Medicine 335:19, 1462-1464
   Full Text