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In vivo diagnosis of cardiac angiosarcoma by endomyocardial biopsy
89
Cardiovasc Pathol Vol. 2, No. I January-March 1993:89-91
In Vivo Diagnosis of Cardiac Angiosarcoma by Endomyocardial Biopsy Alessandro Poletti, M D , Patrizia Cocco, M D , Marialuisa Valente, M D , G i u s e p p e Fasoli, MD,* Raffaello Chioin, MD,* and G a e t a n o Thiene, M D From the Institutes of Pathological Anatomy and *Cardiology, University of Padua Medical School, Padua, Italy
++ The present-day diagnosis of primary heart tumors is achieved by cardiac imaging and confirmed by morphological examination after surgical resection. We describe the case of a 36-year-old man with a right atrioventricular mass in whom angiosarcoma was diagnosed by transvenous endomyocardial biopsy. Surgery was not attempted because of pulmonary metastases, and the patient died 12 months later. This experience indicates that precise in vivo histological diagnosis of malignant primary cardiac tumor is possible without thoracotomy.
Angiosarcoma is the most frequent form of malignant primary cardiac tumor. This very aggressive neoplasia occurs most commonly in the right atrium of male adults (1). The very poor prognosis is related to its usual recognition in clinically advanced stages when veins, atrioventricular valves, and pericardium are involved and metastases are present. Thus early diagnosis offers the only possibility for successful therapy, and in this setting endomyocardial biopsy may constitute a valid diagnostic tool. We report a case of right atrial angiosarcoma in which diagnosis was made in vivo by transvenous endomyocardial biopsy.
Case Report A 36-year-old male physician was in excellent health until December 1989, when he started coughing, with episodes of dyspnea and fever. A chest X-ray disclosed a normal cardiac silhouette and a right pleural effusion. In January 1990, palpitations and chest pain on effort appeared. Two-dimensional echocardiography demonstrated an intramural and endocavitary right atrioventricular mass 8 × 6 cm in size; the tumor had an irregular surface and obstructed the tricuspid orifice Manuscript received May 13, 1992; accepted November 20, 1992. Address for reprints: Alessandro Poletti, MD, Istituto di Anatomia Patologica, Via A. Gabelli, 61, 1-35121 Padova, Italy. Supported by the National Council for Research, Target Project "BT.BS.," Milan, Italy ©1993 by ElsevierScience PublishingCo., Inc.
and right ventricular inflow (Fig. 1A). Magnetic resonance imaging confirmed the echo pictures and suggested that the tumor origin was the anterolateral free wall of the right ventricle. Using the right internal jugular vein approach, a transcutaneous endomyocardial biopsy was performed; 3 samples of 2 × 3 mm each were obtained and were processed for histologic and immunohistochemical study. Histologic sections were stained according to the hematoxylin-eosin, periodic acid schiff (PAS), Gomorisilver impregnation, and Weigert-van Gieson procedures. At the light microscope, the myocardium appeared to be infiltrated by a solid neoplastic infiltration consisting of spindle cells with hyperchromatic nuclei, frequent mitotic figures, and rare giant cells. The spindle cells tended to create vascular channels (Fig. 1B). Extensive areas of necrosis were also observed. Sections were stained for immunohistochemistry with an appropriate panel of antibodies using the avidin-biotin peroxidase method. A negative and positive control was performed for each antibody. A strong positivity for vimentin and Factor VIII-related antigen was observed in both vascular and solid areas (Fig. 1C); Ulex europaeus lectin reacted only with the vascular component of the tumor. The tumor tissue did not express cytokeratins, neurofilaments, desmin, neuron specific emolase (NSE), epithelial membrane antigen (EMA) or myoglobin (Fig. 1D). 1054-8807/93/$6.00
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Figure 1. A. Two-dimensional four-chamber echocardiogram; the arrows indicate the right endocavitary mass. B. The myocardium lppears infiltrated by a neoplastic proliferation of spindle cells with hyperchromatic and irregularly shaped nuclei, tending to form tascular channels. (Hematoxylin-eosin stain x40.) C. Immunohistochemistry with antibody against Factor VIII-related antigen: clear 9ositivity is observed throughout the neoplastic tissue and only within the vascular component of the normal myocardium (x40). D. [mmunohistochemistry with antibody against myoglobin shows negativity of the tumor and strong positivity of the normal myocardium
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Cardiovasc Pathol Vol. 2, No. 1
January-March 1993:89-91
Discussion As reported in the literature, cardiac angiosarcoma has usually been diagnosed at postmortem examination (2-5). In a few cases, this diagnosis was suspected in vivo on the basis of invasive or noninvasive clinical investigations and was then confirmed by histological examination of the surgical specimen neoplasm following thoracotomy (6-15). Recently, metastatic cardiac involvement was also diagnosed on an endomyocardial biopsy specimen (16). To the best of our knowledge, right atrial angiosarcoma was diagnosed on endomyocardial biopsy in only one case (17), in which immunohistochemical tumor phenotype characterization was not performed. In our case it was possible to employ a large panel of antibodies and thus obtain a clear-cut demonstration of the tumor's vascular origin, with strong positivity for Factor VIII-related antigen, ulex europaeus lectin, and vimentin, which are good and sensitive markers of endothelial cells. We suggest that endomyocardial biopsy with immunohistochemical phenotype characterization might constitute a fundamental procedure for early diagnosis, precise tumor identification, and prompt decision making as to surgical therapy and even cardiac transplantation. References 1. McAllister HA, Fenoglio JJ. Tumors of the cardiovascular system. In: Atlas of Tumor Pathology, fascicle 15, series 2. Washington DC: Armed Forces Institute of Pathology, 1978:81-88. 2. Bjerregaard P, Baandrup U. Haemangioendotheliosarcoma of the heart: diagnosis and treatment. Br Heart J 1979;42:734-737.
POLETTI ET AL. ENDOMYOCARDIALBIOPSY OF CARDIACANGIOSARCOMA
91
3. Shackell M, Mitko A, Williams PL, Sutton GC. Angiosarcoma of the heart. Br Heart J 1979;41:498-503. 4. Moore L, Bignold LP, Generalised angiosarcoma of the heart. Virchows Arch [Pathol Anat] 1988;413:87-90. 5. Lantz DA, Dougherty TH, Lucca MJ. Primary angiosarcoma of the heart causing cardiac rupture. Am Heart J 1989;118:186188. 6. Thompson DS, Westaby S, Lincoln JCR. Ventricular haemangioendothelioma diagnosed in life. Br Heart J 1977;39:462-465. 7. Yang HT, Wasielewski JF, Lee W, Lee E, Paik YK. Angiosarcoma of the heart: ultrastructural study. Cancer 1981;47:7280. 8. Bennett MT, Weber PM, Killebrew ET. Primary angiosarcoma of the heart detected by technetium-labeled erythrocyte cardiac imaging. Cancer 1982;49:2587-2590. 9. Sorlie D, Myhre ESP, Stalsberg H. Angiosarcoma of the heart: unusual presentation and survival after treatment. Br Heart J 1984;51:94-97~ 10. Janigan DT, Husain A, Robinson NA. Cardiac angiosarcomas: a review and a case report. Cancer 1986;57:852-859. 11. Wakely PE. Angiosarcoma of the heart in an adolescent. Arch Pathol Lab Med 1987;111:472-475. 12. Dichek DA, Holmvang G, Fallon JT, et al. Angiosarcoma of the heart: three-year survival and follow-up by nuclear magnetic resonance imaging. Am Heart J 1986;115:1323-1324. 13. Keohane ME, Lazzam C, Halperin JL, Strauchen JA, Ergin MA. Angiosarcoma of the left atrium mimicking myxoma: case report. Hum Pathol 1989;20:599-601. 14. Putnam JB, Sweeney MS, Colon R, Lanza LA, Frazier OH, Cooley DA. Primary cardiac sarcomas. Ann Thorac Surg 1991;51: 906-910. 15. Herrmann MA, Shankerman RA, Edwards WD, Shub C, Schaff HV. Primary cardiac angiosarcoma: a clinicopathologic study of six cases. J Thorac Cardiovasc Surg 1992;103:655-664. 16. Flipse TR, Tazelaar HD, Holmes DR. Diagnosis of malignant cardiac disease by endomyocardial biopsy, Mayo Clin Proc 1990; 65:1415-1422. 17. Adachi K, Tanaka H, Toshima H, Morimatsu M. Right atrial angiosarcoma diagnosed by cardiac biopsy. Am Heart J 1988;115: 482-485.
Cardiovasc Pathol Vol. 2, No. I January-March 1993:89-91
In Vivo Diagnosis of Cardiac Angiosarcoma by Endomyocardial Biopsy Alessandro Poletti, M D , Patrizia Cocco, M D , Marialuisa Valente, M D , G i u s e p p e Fasoli, MD,* Raffaello Chioin, MD,* and G a e t a n o Thiene, M D From the Institutes of Pathological Anatomy and *Cardiology, University of Padua Medical School, Padua, Italy
++ The present-day diagnosis of primary heart tumors is achieved by cardiac imaging and confirmed by morphological examination after surgical resection. We describe the case of a 36-year-old man with a right atrioventricular mass in whom angiosarcoma was diagnosed by transvenous endomyocardial biopsy. Surgery was not attempted because of pulmonary metastases, and the patient died 12 months later. This experience indicates that precise in vivo histological diagnosis of malignant primary cardiac tumor is possible without thoracotomy.
Angiosarcoma is the most frequent form of malignant primary cardiac tumor. This very aggressive neoplasia occurs most commonly in the right atrium of male adults (1). The very poor prognosis is related to its usual recognition in clinically advanced stages when veins, atrioventricular valves, and pericardium are involved and metastases are present. Thus early diagnosis offers the only possibility for successful therapy, and in this setting endomyocardial biopsy may constitute a valid diagnostic tool. We report a case of right atrial angiosarcoma in which diagnosis was made in vivo by transvenous endomyocardial biopsy.
Case Report A 36-year-old male physician was in excellent health until December 1989, when he started coughing, with episodes of dyspnea and fever. A chest X-ray disclosed a normal cardiac silhouette and a right pleural effusion. In January 1990, palpitations and chest pain on effort appeared. Two-dimensional echocardiography demonstrated an intramural and endocavitary right atrioventricular mass 8 × 6 cm in size; the tumor had an irregular surface and obstructed the tricuspid orifice Manuscript received May 13, 1992; accepted November 20, 1992. Address for reprints: Alessandro Poletti, MD, Istituto di Anatomia Patologica, Via A. Gabelli, 61, 1-35121 Padova, Italy. Supported by the National Council for Research, Target Project "BT.BS.," Milan, Italy ©1993 by ElsevierScience PublishingCo., Inc.
and right ventricular inflow (Fig. 1A). Magnetic resonance imaging confirmed the echo pictures and suggested that the tumor origin was the anterolateral free wall of the right ventricle. Using the right internal jugular vein approach, a transcutaneous endomyocardial biopsy was performed; 3 samples of 2 × 3 mm each were obtained and were processed for histologic and immunohistochemical study. Histologic sections were stained according to the hematoxylin-eosin, periodic acid schiff (PAS), Gomorisilver impregnation, and Weigert-van Gieson procedures. At the light microscope, the myocardium appeared to be infiltrated by a solid neoplastic infiltration consisting of spindle cells with hyperchromatic nuclei, frequent mitotic figures, and rare giant cells. The spindle cells tended to create vascular channels (Fig. 1B). Extensive areas of necrosis were also observed. Sections were stained for immunohistochemistry with an appropriate panel of antibodies using the avidin-biotin peroxidase method. A negative and positive control was performed for each antibody. A strong positivity for vimentin and Factor VIII-related antigen was observed in both vascular and solid areas (Fig. 1C); Ulex europaeus lectin reacted only with the vascular component of the tumor. The tumor tissue did not express cytokeratins, neurofilaments, desmin, neuron specific emolase (NSE), epithelial membrane antigen (EMA) or myoglobin (Fig. 1D). 1054-8807/93/$6.00
=r.<
"o
ix40).
I
¢3
d ~-:,
0
~0
Figure 1. A. Two-dimensional four-chamber echocardiogram; the arrows indicate the right endocavitary mass. B. The myocardium lppears infiltrated by a neoplastic proliferation of spindle cells with hyperchromatic and irregularly shaped nuclei, tending to form tascular channels. (Hematoxylin-eosin stain x40.) C. Immunohistochemistry with antibody against Factor VIII-related antigen: clear 9ositivity is observed throughout the neoplastic tissue and only within the vascular component of the normal myocardium (x40). D. [mmunohistochemistry with antibody against myoglobin shows negativity of the tumor and strong positivity of the normal myocardium
%
!
Cardiovasc Pathol Vol. 2, No. 1
January-March 1993:89-91
Discussion As reported in the literature, cardiac angiosarcoma has usually been diagnosed at postmortem examination (2-5). In a few cases, this diagnosis was suspected in vivo on the basis of invasive or noninvasive clinical investigations and was then confirmed by histological examination of the surgical specimen neoplasm following thoracotomy (6-15). Recently, metastatic cardiac involvement was also diagnosed on an endomyocardial biopsy specimen (16). To the best of our knowledge, right atrial angiosarcoma was diagnosed on endomyocardial biopsy in only one case (17), in which immunohistochemical tumor phenotype characterization was not performed. In our case it was possible to employ a large panel of antibodies and thus obtain a clear-cut demonstration of the tumor's vascular origin, with strong positivity for Factor VIII-related antigen, ulex europaeus lectin, and vimentin, which are good and sensitive markers of endothelial cells. We suggest that endomyocardial biopsy with immunohistochemical phenotype characterization might constitute a fundamental procedure for early diagnosis, precise tumor identification, and prompt decision making as to surgical therapy and even cardiac transplantation. References 1. McAllister HA, Fenoglio JJ. Tumors of the cardiovascular system. In: Atlas of Tumor Pathology, fascicle 15, series 2. Washington DC: Armed Forces Institute of Pathology, 1978:81-88. 2. Bjerregaard P, Baandrup U. Haemangioendotheliosarcoma of the heart: diagnosis and treatment. Br Heart J 1979;42:734-737.
POLETTI ET AL. ENDOMYOCARDIALBIOPSY OF CARDIACANGIOSARCOMA
91
3. Shackell M, Mitko A, Williams PL, Sutton GC. Angiosarcoma of the heart. Br Heart J 1979;41:498-503. 4. Moore L, Bignold LP, Generalised angiosarcoma of the heart. Virchows Arch [Pathol Anat] 1988;413:87-90. 5. Lantz DA, Dougherty TH, Lucca MJ. Primary angiosarcoma of the heart causing cardiac rupture. Am Heart J 1989;118:186188. 6. Thompson DS, Westaby S, Lincoln JCR. Ventricular haemangioendothelioma diagnosed in life. Br Heart J 1977;39:462-465. 7. Yang HT, Wasielewski JF, Lee W, Lee E, Paik YK. Angiosarcoma of the heart: ultrastructural study. Cancer 1981;47:7280. 8. Bennett MT, Weber PM, Killebrew ET. Primary angiosarcoma of the heart detected by technetium-labeled erythrocyte cardiac imaging. Cancer 1982;49:2587-2590. 9. Sorlie D, Myhre ESP, Stalsberg H. Angiosarcoma of the heart: unusual presentation and survival after treatment. Br Heart J 1984;51:94-97~ 10. Janigan DT, Husain A, Robinson NA. Cardiac angiosarcomas: a review and a case report. Cancer 1986;57:852-859. 11. Wakely PE. Angiosarcoma of the heart in an adolescent. Arch Pathol Lab Med 1987;111:472-475. 12. Dichek DA, Holmvang G, Fallon JT, et al. Angiosarcoma of the heart: three-year survival and follow-up by nuclear magnetic resonance imaging. Am Heart J 1986;115:1323-1324. 13. Keohane ME, Lazzam C, Halperin JL, Strauchen JA, Ergin MA. Angiosarcoma of the left atrium mimicking myxoma: case report. Hum Pathol 1989;20:599-601. 14. Putnam JB, Sweeney MS, Colon R, Lanza LA, Frazier OH, Cooley DA. Primary cardiac sarcomas. Ann Thorac Surg 1991;51: 906-910. 15. Herrmann MA, Shankerman RA, Edwards WD, Shub C, Schaff HV. Primary cardiac angiosarcoma: a clinicopathologic study of six cases. J Thorac Cardiovasc Surg 1992;103:655-664. 16. Flipse TR, Tazelaar HD, Holmes DR. Diagnosis of malignant cardiac disease by endomyocardial biopsy, Mayo Clin Proc 1990; 65:1415-1422. 17. Adachi K, Tanaka H, Toshima H, Morimatsu M. Right atrial angiosarcoma diagnosed by cardiac biopsy. Am Heart J 1988;115: 482-485.