Cardiovascular Pathology

Cardiac Sarcoma, Pleomorphic Undifferentiated Type, Arising on Mitral Valve

Allen P. Burke
University of Maryland Medical System
Baltimore, MD


Clinical History
A 24-year old man presented with shortness of breath. Imaging demonstrated multiple masses in the lungs, which were believed to represent septic emboli. Echocardiography demonstrated a vegetation of the anterior mitral valve leaflet, which was excised, and measured 2.5 x 1.2 x 1.1 cm. Further evaluation demonstrated multiple masses the liver, which demonstrated high-grade sarcoma on biopsy.


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Figure 1
Polypoid growth pattern
Figure 2
Surface fibrin
Figure 3
Bland spindle-cell growth, deep

Figure 4
Marked cellular atypia, predominantly on surface
Figure 5
Surface mitotic activity


Gross Findings
The lesion was fragmented, bulbous to bosselated tissue, the largest 2.5 cm in diameter, as well as portions of mitral valve leaflet.

Diagnosis
Cardiac sarcoma, pleomorphic undifferentiated type, arising on mitral valve

Discussion
Tumors of heart valves are rare. The most common is papillary fibroelastoma, which is not a neoplasm, but probably a reactive proliferation. Histologically, papillary fibroelastoma has no features in common with sarcomas, as an avascular, paucicellular papillary structure lined by a single lining of endothelial cells. Papillary fibroelastomas occasionally occur in areas of previous endocardial damage or in patients with preexisting heart disease [1]. Most symptoms arise from left-sided lesions that shower fibrin clots into the cerebral circulation or prolapse into the coronary orifice. The most common symptoms are transient neurological defects and myocardial ischemia, and rarely sudden death. These lesions are considered a form of Lambl's excrescence, but unlike Lambl's excrescences, papillary fibroelastomas can become quite large, and occur on any valve surface or area of the endocardium [2]. Thrombi may occur on the surface of the proliferation, and dislodged clots are responsible for embolic symptoms. Histologically, they are avascular papillary structures lined by endothelial cells. They are often mistaken for cardiac myxoma, which are vascular and of heterogeneous cell types. Papillary fibroelastoma is cured by surgery, whether there are pre-existing embolic symptoms, or if a lesion is incidentally discovered. Asymptomatic patients could be treated surgically if the tumor is mobile, as the tumor mobility is the independent predictor of death or nonfatal embolization. Asymptomatic patients with nonmobile lesions can be followed-up closely with periodic clinical evaluation and echocardiography, and receive surgical intervention when symptoms develop or the tumor becomes mobile. Recurrences are rare, and valve-sparing surgery should be considered whenever possible, as regrowth of partially resection lesions does not always occur.

Cardiac inflammatory myofibroblastic tumors are probably the second most common heart valve tumor, although distinctly uncommon. Inflammatory myofibroblastic tumors (IMFTs) are proliferations of uncertain histogenesis, which vary in appearance from inflammatory, reactive-appearing proliferations to low-grade sarcomas. These lesions occur in children and young adults, with a mean age at presentation younger than cardiac sarcoma (10 years, as compared to 40-50 years for sarcomas). [3] There is probably organ-specific variation in the histologic characteristics of IMFT. In the heart, they invariably arise from the endocardium, including valve leaflets, may have areas that are cellular, and usually have abundant myxoid matrix and surface fibrin. There is generally a background lymphocytic infiltrate. However, embolic symptoms and sudden death from coronary occlusion may occur. Several pediatric heart tumors, reported in the medical literature as sarcomas, are likely IMFT, given good prognosis, location on valves, and available histologic descriptions. The current designation for these lesions is still debated, the term low-grade myofibroblastic sarcoma sometimes favored. [4]

Cardiac sarcomas fall into two general groups: angiosarcomas, and a more heterogeneous group of sarcomas that appear to derive from the intimal and form luminal masses. Angiosarcomas are typically right-sided, and are infiltrative lesions that may involve the tricuspid valve, but do not arise from the endocardial surface [5]. In contrast, so-called "intimal" sarcomas arise from and spread long the left atrial endocardium, and often have a large intraluminal growth mass before significantly infiltrating the atrial wall. [6] Histologically, these lesions are pleomorphic, and typically show undifferentiated areas similar to MFH, as well as blander areas with fibroblastic spindle cell growth. Spread along the intimal surface with "in situ" growth is occasionally identified. Other forms of differentiation may occur, including osteo- chondro- and synovial sarcoma; the latter are usually monophasic and possess typical translocation.

When primary intimal sarcomas of the heart involve the valves, it is typically the mitral valve, as the left atrium is the most common site. Although the valve may be secondarily involved by an enlargement mass arising on the atrial endocardium, origin on the valve surface is distinctly rare [7, 8, 9, 10, 11]. The second most common valve involved by sarcoma is the pulmonary valve, and these lesions overlap with primary sarcomas of the pulmonary intima. [12, 13] Intimal sarcomas in the pulmonary artery are more likely to demonstrating heterologous elements and matrix formation than their left atrial counterparts.

The current case shows difficulty in separating cardiac sarcomas from IMFTs, as they both arise from intima; the distinction is especially difficult when the valve is the site of origin. Tin contrast to intimal sarcoma, hose cardiac sarcomas reported on heart valves in children are likely either benign IMFT or low-grade lesions, in contrast to intimal sarcomas, as this case, which have a dismal prognosis [14, 15]. Histologic features that distinguish the two lesions are several: those that are characteristic of sarcomas include mitotic activity, severe atypia especially on the surface, and (somewhat counter intuitively) areas of bland monomorphous growth with dense collagen. Features of IMFT are the presence of larger myofibroblastic cells with open nuclei ("tissue culture" appearance), inflammation, and lack of monomorphous spindle cell areas. Features common to both include surface fibrin, areas of dense collagen, and a polypoid growth pattern.

References
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  2. Gowda RM, Khan IA, Nair CK, Mehta NJ, Vasavada BC, Sacchi TJ. Cardiac papillary fibroelastoma: a comprehensive analysis of 725 cases. Am Heart J 2003;146:404-10.

  3. Burke A, Li L, Kling E, Kutys R, Virmani R, Miettinen M. Cardiac inflammatory myofibroblastic tumor: a "benign" neoplasm that may result in syncope, myocardial infarction, and sudden death. Am J Surg Pathol 2007;31:1115-22.

  4. Eisenstat J, Gilson T, Reimann J, Sampson B. Low-grade myofibroblastic sarcoma of the heart causing sudden death. Cardiovasc Pathol 2008;17:55-9.

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  6. Burke AP, Tazelaar H, Butany JW, et al. Cardiac sarcomas. In: Travis W, Brambilla E, Muller-Hermelink HK, Harris CC, eds. Pathology and Genetics of Tumours of the Lung, Thymus, Pleura and Heart. Lyon: ARC Press, 2004:273-281.

  7. Hajar R, Roberts WC, Folger GM, Jr. Embryonal botryoid rhabdomyosarcoma of the mitral valve. Am J Cardiol 1986;57:376.

  8. Kolli S, Ziaee A, Lee R, Lim MJ, Levy B, Labovitz AJ. Myofibroblastic sarcoma of mitral valve: a case report. J Am Soc Echocardiogr 2005;18:285-6.

  9. Lee JR, Chang JM, Lee C, Kim CJ. Undifferentiated sarcoma of the mitral valve with unique clinicopathologic presentation. J Cardiovasc Surg (Torino) 2003;44:621-3.

  10. Miller DV, Deb A, Edwards WD, Zehr KJ, Oliveira AM. Primary synovial sarcoma of the mitral valve. Cardiovasc Pathol 2005;14:331-3.

  11. Sudarshan G, Vamsy M, Murthy SS, Kumar VS. Undifferentiated sarcoma of the mitral valve with secondaries in brain in a girl of 22 years. J Cancer Res Ther 2007;3:47-9.

  12. Bloomberg RD, Butany JW, Cusimano RJ, Leask RL. Primary cardiac sarcoma involving the pulmonary artery and valve. Can J Cardiol 2003;19:843-7.

  13. Ozbek C, Emrecan B, Calli AO, Gurbuz A. Intimal sarcoma of the pulmonary artery with retrograde extension into the pulmonic valve and right ventricle. Tex Heart Inst J 2007;34:119-21.

  14. Itoh K, Matsumura T, Egawa Y, et al. Primary mitral valve sarcoma in infancy. Pediatr Cardiol 1998;19:174-7.

  15. McElhinney DB, Carpentieri DF, Bridges ND, Clark BJ, Gaynor JW, Spray TL. Sarcoma of the mitral valve causing coronary arterial occlusion in children. Cardiol Young 2001;11:539-42.