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Recurrent Cardiac Intimal (Spindle Cell) Sarcoma of the Left Atrium
Recurrent Cardiac Intimal (Spindle Cell) Sarcoma of the Left Atrium Zhe Li, MD, Tyken Hsieh, MD, and Ali Salehi, MD
P
RIMARY CARDIAC TUMORS are roughly 100 to 1,000 times rarer than secondary cardiac neoplasms. About 75% of primary cardiac tumors are benign and 25% malignant. Rarer still is primary spindle cell sarcoma of the heart, with only a handful of cases reported in the literature. Prognosis generally is poor because the role of chemotherapy in this setting remains ill defined, and complete surgical tumor resection often proves to be challenging if not utterly unfeasible because of the tumor’s anatomic location. The authors report a unique case of resection of recurrent primary cardiac intimal spindle cell sarcoma. CASE REPORT A 46-year-old previously healthy man who presented to the local hospital with progressive shortness of breath and diminished exercise tolerance was found on a chest computed tomography (CT) scan to have an 8 ⫻ 4.5 ⫻ 3-cm mass in his left atrium. A transthoracic echocardiogram was interpreted as showing a left atrial mass that was mobile and protruding into the left ventricle and noted that it was “like a myxoma, though its attachment is not visualized.” He was taken to the operating room with the initial diagnosis of left atrial myxoma, but upon surgical inspection of the left atrium, it was noted that the appearance of the tumor was more suggestive of malignancy. Biopsy results confirmed the surgeon’s suspicion; pathologic examination revealed high-grade spindle cell sarcoma. The bulk of the tumor was removed at that time although with positive margins. The patient then was treated with chemotherapy for 4 months but did not receive radiation therapy. Surveillance magnetic resonance imaging (MRI) scans performed at 6 months and 10 months after surgery were negative for evidence of new tumor growth. However, only 2 months after the last negative surveillance scan (12 months after the initial tumor resection), the patient reported experiencing recurrent shortness of breath and fatigue with exercise. A chest radiograph revealed a suspicious shadow occupying the aortopulmonary window, suggesting a mass in the left atrium (Fig 1).
Fig 1. A posterior-anterior chest radiograph showing a tumor mass in the left atrial region, occupying the aortopulmonary window.
Fig 2. Preoperative contrast-enhanced MRI showing a large left atrial filling defect, with extension into the left-sided pulmonary veins. RV, right ventricle; LV, left ventricle.
Repeat MRI then showed a recurrent mass within the left atrium measuring 4.7 ⫻ 3.5 ⫻ 4.3 cm with extension into the left pulmonary veins (Fig 2). Nuclear lung perfusion studies showed that the right lung received 92.5% of the total lung perfusion, whereas the left lung received 7.5% (Fig 3). The patient then was referred to the authors’ institution for repeat left atrial tumor resection and possible left pneumonectomy, with the intent of a curative resection. After the induction of anesthesia in the operating room, standard arterial and venous access were obtained for cardiopulmonary bypass (CPB), and a transesophageal echocardiographic (TEE) examination was performed. Transesophageal echocardiography showed a large spherical mass, measuring 3.9 ⫻ 4.4 cm and occupying nearly the entire left atrium and partially invading the right upper pulmonary vein (Figs 4-6). Blood flow was absent in both the left upper and lower pulmonary veins. The mean transmitral inflow pressure gradient was approximately 5 mmHg, which was consistent with mild-to-moderate mitral stenosis (Fig 7 and Video 1 [supplementary video is available online]). The preoperative CT angiogram was re-examined, and partial tumor invasion of the right-sided pulmonary veins was noted (Fig 8). After establishing CPB, the surgeon visually confirmed tumor involvement in both the left and
From the Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA. Address reprint requests to Ali Salehi, MD, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Suite 3325, Los Angeles, CA 90095. E-mail: [email protected] © 2012 Elsevier Inc. All rights reserved. 1053-0770/2701-0001$36.00/0 doi:10.1053/j.jvca.2011.07.027 Key words: secondary cardiac tumor, spindle cell sarcoma, pulmonary vein, transesophageal echocardiography
Journal of Cardiothoracic and Vascular Anesthesia, Vol 27, No 1 (February), 2013: pp 103-107
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Fig 5. A midesophageal 5-chamber view in diastole, with magnification of the left atrial mass measuring 3.93 ⴛ 4.45 cm. RA, right atrium; RV, right ventricle; LV, left ventricle.
Fig 3. A technetium-99m bilateral lung perfusion scan (upper panel: anterior view; lower panel: posterior view) showing predominance of pulmonary blood flow (as indicated by scintigraphic density) to the right lung, with minimal residual left lung perfusion.
Fig 4. A midesophageal 5-chamber transesophageal echocardiographic view showing tumor nearly filling the left atrium. RA, right atrium; RV, right ventricle; LV, left ventricle.
Fig 6. A midesophageal view with magnification of the left atrium showing invasion of the right upper pulmonary vein (bracket) by tumor (arrow) from the left atrium.
Fig 7. Transmitral spectral Doppler tracing showing a mean pressure gradient of 5 mmHg, which is consistent with mild-to-moderate mitral stenosis.
CARDIAC INTIMAL SARCOMA
Fig 8. An axial computed tomography scan with intravenous contrast. The left atrial tumor mass creates a large filling defect and is shown invading/obstructing the left pulmonary veins while partially invading the right. Only a narrow rivulet of contrast from the right pulmonary veins can be appreciated coursing past the tumor.
right pulmonary veins, and the patient was thus deemed unsuitable for left pneumonectomy because of high morbidity without the assurance of surgical cure. Any visible tumor was debulked as much as possible (Fig 9), from both the left posterior atrial wall and the left and right pulmonary veins. On repeat TEE examination, blood flow was visualized from all 4 pulmonary veins. Partial stenosis of the RUPV was evident but not flow limiting. A 2- to 3-mm-thick pedicle to which the atrial mass had been attached was still present in the left atrial posterior wall. The patient was weaned successfully from CPB and transferred to the intensive care unit. He was extubated the following day and discharged home on postoperative day 4. A postoperative MRI showed patent left- and right-sided pulmonary veins, and a CT angiogram showed restored perfusion to the left lung (Figs 10 and 11). The patient currently is active and undergoing radiation and chemotherapy. Pathologic tissue analysis consisting of hematoxylin and eosin staining, immunohistochemical profiling, and karyotyping was consistent with intimal sarcoma.
Fig 9. Intraoperative photographs. (Left panel) A tumor mass visualized in situ through the left atrial incision. (Right panel) The excised tumor. (Color version of figure is available online.)
105
Fig 10. Contrast-enhanced MRI performed 7 months postoperatively, showing patent left and right pulmonary veins.
DISCUSSION
In this report, the authors described the presentation of an extremely rare cardiac lesion, recurrent intracardiac intimal spindle cell sarcoma. Cardiac spindle cell sarcomas have been reported in the great vessels, pulmonary veins, and right atrium, but their occurrence in the left atrium has only been reported twice before in the literature.1,2 Histologically, spindle cell sarcoma is composed of tightly packed spindleshaped cells arranged in long fascicles. As is typically observed in intimal spindle cell sarcoma, this patient’s tumor showed complex karyotypes encompassing the 12q13-14 region (MDM2 gene). By contrast, the more common angiosarcomas are composed of well-to-moderately well-differentiated cells showing well-formed vascular channels and papillary structures and form tumors that are irregular with points of focal necrosis, often accompanied by pericardial effusion. The differential diagnosis also includes synovial sarcoma, but the tissue specimen did not show translocation of X;18 as is characteristic (and diagnostic) of synovial sarcoma (Appendix 1).
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LI, HSIEH, AND SALEHI
Fig 11. A CT angiogram performed 7 months postoperatively, showing robust left lung blood flow.
Primary cardiac tumors are highly unusual, and their frequency has been estimated to be 0.02% based on the results of autopsy series.3 Primary cardiac sarcomas affect adults (mean age 41 years at presentation) and are extremely rare in infants and children. Little is known regarding the etiology of primary cardiac tumors. However, cases occurring because of radiation have been described.3 Dyspnea is the most common presenting complaint. These are highly aggressive lesions with the mean survival of affected patients being 3 months to 1 year although survival of up to 11 years has been reported.2 Chemotherapy and radiation therapy have limited benefit.4 Although aggressive surgery can offer dramatic palliation of symptoms caused by valvular and/or vascular obstruction, local recurrence and metastasis occur frequently and early, usually within 1 year.3 Such was the case with the patient presented here. He remained tumor free on surveillance scans and was asymptomatic until almost exactly 1 year after his initial tumor-debulking surgery. Although surgery with negative margins is the only mainstay of therapy, complete tumor resection is possible in fewer than half of patients. In 1 recent study, only 65% of patients planned for surgery based on preoperative imaging studies could undergo actual complete resection.4 Imaging modalities for preoperative assessment of affected patients include cardiac MRI, CT, ventilation-perfusion scanning, transthoracic echocardiography, and TEE.
As this case shows, information gleaned from preoperative transthoracic echocardiography and intraoperative TEE can reveal findings that are strongly suggestive of (consistent with) malignancy, define the extent of tumor involvement/spread, and influence surgical planning. Benign cardiac tumors, such as atrial myxomas, tend to arise from the interatrial septum and often have a stalk-like base with well-demarcated margins and usually do not invade the pulmonary veins.5 Malignant tumors, in contrast, often form broad-based atrial masses with poorly defined margins, are usually found in nonseptal locations, and can be associated with tumor infiltration into the pulmonary veins.2 This was a young, otherwise healthy patient who presented to a community hospital with acute decompensation in his health. It was clear that the cardiac tumor was the cause of his symptoms, and the preliminary transthoracic echocardiogram suggested myxoma, which is cured easily by surgical resection. However, a left atrial tumor without a clear attachment to the interatrial septum should raise concern for a malignancy or at least prompt the consideration of masses other than myxoma. Furthermore, myxomas are more typically slow growing, leading to more chronic symptomatology, whereas this patient’s rapidly progressive symptoms should have been suggestive of a more aggressive tumor. In this patient’s case, initial preoperative studies revealed obstruction of the left-sided pulmonary veins only, and, thus, the patient was scheduled for a left pneumonectomy in addition to left atrial tumor resection in hopes of a completely curative surgery. However, intraoperative TEE examination, surgical exposure, and reassessment of the CT angiogram confirmed tumor infiltration of both left and right pulmonary veins, suggesting a further-advanced tumor than was suspected initially. The left pneumonectomy then was abandoned with the surgery changed to palliative debulking. In conclusion, the authors wish to emphasize that patients with intracardiac tumors need careful preoperative assessment to distinguish benign masses (such as atrial myxoma) from highly malignant tumors that require the most aggressive surgical and oncologic treatment tolerable at the time of initial presentation. Atypical presentation of a cardiac mass on echocardiography, MRI, or CT angiography, plus a rapidly progressive clinical picture, should alert the physician to a possibility of a more aggressive or malignant process. Given the highly aggressive nature of the tumor described, every effort should be made to achieve negative margins at initial surgical resection and adjunct chemotherapy and radiation therapy considered at the earliest opportunity to achieve the best prognosis.
REFERENCES 1. Cho GJ, Hai JK, Kang JS: Primary cardiac sarcoma in pregnancy: A case report. J Korean Med Sci 21:940-943, 2006 2. Modi A, Lipvinicius A, Haw M, et al: Prolonged survival with left atrial spindle cell sarcoma. Interact Cardiovasc Thorac Surg 8:703-704, 2009
3. Gupta A: Primary cardiac sarcomas. Expert Rev Cardiovasc Ther 6:1295-1297, 2008 4. Grebenc M, Rosado de Christenson M, Burke A, et al: Primary cardiac and pericardial neoplasms: Radiologic-pathologic correlation. Radiographics 20:1073-1103, 2000
CARDIAC INTIMAL SARCOMA
5. Burke AP, Cowan D, Virmani R: Primary sarcomas of the heart. Cancer 69:387-395, 1997 APPENDIX 1. SURGICAL PATHOLOGY REPORT
FINAL DIAGNOSIS: (A) LEFT INFERIOR PULMONARY VEIN THROMBUS (EXCISION): Organizing thrombus. (B) RIGHT INFERIOR PULMONARY VEIN TUMOR (EXCISION): Consistent with intimal sarcoma, high grade (see comment). (C) SOFT-TISSUE TUMOR OBSTRUCTING LEFT ATRIUM (EXCISION): Consistent with intimal sarcoma, high grade (see comment). NOTE: Imaging studies have been reviewed. Discussion: Given the location, hematoxylin and eosin appearance, and immunohistochemical profile, the most appropriate diagnosis is intimal sarcoma.
MICROSCOPIC EXAMINATION Sections from Part B show a cellular proliferation of predominantly bland-appearing spindle cells in a collagenous background with focal areas of less cellularity. The cells have oval to elongated to somewhat wavy nuclei, dispersed chromatin, inconspicuous nucleoli, and scant fibrillary eosinophilic cytoplasm. Occasional dark, larger, and hyperchromatic cells are present. Rare mitoses are noted and estimated at approximately 10 per 10 HPF (40⫻). Sections from Part C reveal a proliferation of spindle cells arranged in fascicles and storiform patterns in a fibrocollagenous background containing fine vasculatures. Focally, there are less cellular areas. Most of the spindle cells have elongated nuclei, dispersed chromatin, inconspicuous nucleoli, and scant fibrillary eosinophilic cytoplasm. However, some of these cells are moderately-to-markedly pleomorphic with large hyperchromatic nuclei and irregular nuclear contours. Mitoses are brisk and estimated at 14 per 10 HPF. Necrosis is inconspicuous.
GENERAL IMMUNOHISTOCHEMISTRY REPORT FIXATIVE: Formalin ANTIBODY/PROBE: RESULT/COMMENT CD34 negative S100 negative Desmin negative Smooth muscle actin positive (patchy) Microsatellite analysis weak positive (scattered) Pankeratin negative Caldesmon negative
GROSS DESCRIPTION
107
A. Part A, labeled “L inferior pulmonary vein thrombosis,” consists of multiple small fragments of tubular shaped and irregularly shaped blood clots. This aggregate measures 2.8 ⫻ 2.7 ⫻ 0.7 cm. There is a tubular segment of clot with possible attached vessel wall, measuring 0.2 ⫻ 0.9 ⫻ 0.4 cm. Representative sections of the specimen are submitted in cassette A1 and the more intact segment with possible vessel wall placed in cassette A2. B. Part B, labeled “R inferior pulmonary vein tumor,” consists of a roughly oval, pink-gray tumor mass that measures 1.5 ⫻ 0.9 ⫻ 0.7 cm. The superficial surface of this mass is covered by membranous material, with multiple areas of irregularities. This specimen is unoriented. The entire external surface is inked green. The tumor is then serially sectioned to reveal homogeneously yellow pearl white cut surfaces. The entire specimen is placed in cassette B1. C. Part C, labeled “spindle cell sarcoma obstructing left atrium,” consists of multiple irregularly shaped fragments of pink-white, somewhat gelatinous/membranous soft tissue. The aggregate measures 6.6 ⫻ 6.0 ⫻ 3.2 cm. Within this tumor mass are multiple areas of hemorrhage. No obvious necrosis is present. Sectioning reveals homogeneously, yellow-white cut surfaces. Representative sections are placed in cassette C1-C9. Samples are submitted for cytogenetic studies and also placed in glutaraldehyde for possible electron microscopy studies.
CYTOGENETICS REPORT CLINICAL INDICATION: CHROMOSOME SCREENING FOR ANOMALIES ANALYSIS Metaphases counted: 8 Colonies counted: N/A Metaphases analyzed: 8 Banding technique: GPG Metaphases karyotyped: 4 Banding Resolution: 400
KARYOTYPE 63-133, -X, -Y, del1 (p22), add3 (q21), -4, add5 (q35), -10, add10 (q22);add11 (q23), del12 (p11.2p11.2), Tas13,13 (q34; q34), -16, ⫹18, add19 (p13), ⫹7-14mar, ⬃30dmin[cp8] INTERPRETATION A complete analysis was not possible because of a low mitotic index. The 8 cells available for analysis revealed an abnormal male karyotype with clonal abnormalities. The abnormal cells (8/8) exhibited a highly complex composite karyotype with multiple numerical and structural abnormalities described above, up to 14 marker chromosomes and approximately 30 double minutes; all these features are characteristic of high-grade tumor. Complex karyotypes and double minutes encompassing the 12q13-14 region (MDM2 gene) are typically observed in intimal sarcoma. This result is compatible with the diagnosis of high-grade intimal sarcoma.
P
RIMARY CARDIAC TUMORS are roughly 100 to 1,000 times rarer than secondary cardiac neoplasms. About 75% of primary cardiac tumors are benign and 25% malignant. Rarer still is primary spindle cell sarcoma of the heart, with only a handful of cases reported in the literature. Prognosis generally is poor because the role of chemotherapy in this setting remains ill defined, and complete surgical tumor resection often proves to be challenging if not utterly unfeasible because of the tumor’s anatomic location. The authors report a unique case of resection of recurrent primary cardiac intimal spindle cell sarcoma. CASE REPORT A 46-year-old previously healthy man who presented to the local hospital with progressive shortness of breath and diminished exercise tolerance was found on a chest computed tomography (CT) scan to have an 8 ⫻ 4.5 ⫻ 3-cm mass in his left atrium. A transthoracic echocardiogram was interpreted as showing a left atrial mass that was mobile and protruding into the left ventricle and noted that it was “like a myxoma, though its attachment is not visualized.” He was taken to the operating room with the initial diagnosis of left atrial myxoma, but upon surgical inspection of the left atrium, it was noted that the appearance of the tumor was more suggestive of malignancy. Biopsy results confirmed the surgeon’s suspicion; pathologic examination revealed high-grade spindle cell sarcoma. The bulk of the tumor was removed at that time although with positive margins. The patient then was treated with chemotherapy for 4 months but did not receive radiation therapy. Surveillance magnetic resonance imaging (MRI) scans performed at 6 months and 10 months after surgery were negative for evidence of new tumor growth. However, only 2 months after the last negative surveillance scan (12 months after the initial tumor resection), the patient reported experiencing recurrent shortness of breath and fatigue with exercise. A chest radiograph revealed a suspicious shadow occupying the aortopulmonary window, suggesting a mass in the left atrium (Fig 1).
Fig 1. A posterior-anterior chest radiograph showing a tumor mass in the left atrial region, occupying the aortopulmonary window.
Fig 2. Preoperative contrast-enhanced MRI showing a large left atrial filling defect, with extension into the left-sided pulmonary veins. RV, right ventricle; LV, left ventricle.
Repeat MRI then showed a recurrent mass within the left atrium measuring 4.7 ⫻ 3.5 ⫻ 4.3 cm with extension into the left pulmonary veins (Fig 2). Nuclear lung perfusion studies showed that the right lung received 92.5% of the total lung perfusion, whereas the left lung received 7.5% (Fig 3). The patient then was referred to the authors’ institution for repeat left atrial tumor resection and possible left pneumonectomy, with the intent of a curative resection. After the induction of anesthesia in the operating room, standard arterial and venous access were obtained for cardiopulmonary bypass (CPB), and a transesophageal echocardiographic (TEE) examination was performed. Transesophageal echocardiography showed a large spherical mass, measuring 3.9 ⫻ 4.4 cm and occupying nearly the entire left atrium and partially invading the right upper pulmonary vein (Figs 4-6). Blood flow was absent in both the left upper and lower pulmonary veins. The mean transmitral inflow pressure gradient was approximately 5 mmHg, which was consistent with mild-to-moderate mitral stenosis (Fig 7 and Video 1 [supplementary video is available online]). The preoperative CT angiogram was re-examined, and partial tumor invasion of the right-sided pulmonary veins was noted (Fig 8). After establishing CPB, the surgeon visually confirmed tumor involvement in both the left and
From the Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA. Address reprint requests to Ali Salehi, MD, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Suite 3325, Los Angeles, CA 90095. E-mail: [email protected] © 2012 Elsevier Inc. All rights reserved. 1053-0770/2701-0001$36.00/0 doi:10.1053/j.jvca.2011.07.027 Key words: secondary cardiac tumor, spindle cell sarcoma, pulmonary vein, transesophageal echocardiography
Journal of Cardiothoracic and Vascular Anesthesia, Vol 27, No 1 (February), 2013: pp 103-107
103
104
LI, HSIEH, AND SALEHI
Fig 5. A midesophageal 5-chamber view in diastole, with magnification of the left atrial mass measuring 3.93 ⴛ 4.45 cm. RA, right atrium; RV, right ventricle; LV, left ventricle.
Fig 3. A technetium-99m bilateral lung perfusion scan (upper panel: anterior view; lower panel: posterior view) showing predominance of pulmonary blood flow (as indicated by scintigraphic density) to the right lung, with minimal residual left lung perfusion.
Fig 4. A midesophageal 5-chamber transesophageal echocardiographic view showing tumor nearly filling the left atrium. RA, right atrium; RV, right ventricle; LV, left ventricle.
Fig 6. A midesophageal view with magnification of the left atrium showing invasion of the right upper pulmonary vein (bracket) by tumor (arrow) from the left atrium.
Fig 7. Transmitral spectral Doppler tracing showing a mean pressure gradient of 5 mmHg, which is consistent with mild-to-moderate mitral stenosis.
CARDIAC INTIMAL SARCOMA
Fig 8. An axial computed tomography scan with intravenous contrast. The left atrial tumor mass creates a large filling defect and is shown invading/obstructing the left pulmonary veins while partially invading the right. Only a narrow rivulet of contrast from the right pulmonary veins can be appreciated coursing past the tumor.
right pulmonary veins, and the patient was thus deemed unsuitable for left pneumonectomy because of high morbidity without the assurance of surgical cure. Any visible tumor was debulked as much as possible (Fig 9), from both the left posterior atrial wall and the left and right pulmonary veins. On repeat TEE examination, blood flow was visualized from all 4 pulmonary veins. Partial stenosis of the RUPV was evident but not flow limiting. A 2- to 3-mm-thick pedicle to which the atrial mass had been attached was still present in the left atrial posterior wall. The patient was weaned successfully from CPB and transferred to the intensive care unit. He was extubated the following day and discharged home on postoperative day 4. A postoperative MRI showed patent left- and right-sided pulmonary veins, and a CT angiogram showed restored perfusion to the left lung (Figs 10 and 11). The patient currently is active and undergoing radiation and chemotherapy. Pathologic tissue analysis consisting of hematoxylin and eosin staining, immunohistochemical profiling, and karyotyping was consistent with intimal sarcoma.
Fig 9. Intraoperative photographs. (Left panel) A tumor mass visualized in situ through the left atrial incision. (Right panel) The excised tumor. (Color version of figure is available online.)
105
Fig 10. Contrast-enhanced MRI performed 7 months postoperatively, showing patent left and right pulmonary veins.
DISCUSSION
In this report, the authors described the presentation of an extremely rare cardiac lesion, recurrent intracardiac intimal spindle cell sarcoma. Cardiac spindle cell sarcomas have been reported in the great vessels, pulmonary veins, and right atrium, but their occurrence in the left atrium has only been reported twice before in the literature.1,2 Histologically, spindle cell sarcoma is composed of tightly packed spindleshaped cells arranged in long fascicles. As is typically observed in intimal spindle cell sarcoma, this patient’s tumor showed complex karyotypes encompassing the 12q13-14 region (MDM2 gene). By contrast, the more common angiosarcomas are composed of well-to-moderately well-differentiated cells showing well-formed vascular channels and papillary structures and form tumors that are irregular with points of focal necrosis, often accompanied by pericardial effusion. The differential diagnosis also includes synovial sarcoma, but the tissue specimen did not show translocation of X;18 as is characteristic (and diagnostic) of synovial sarcoma (Appendix 1).
106
LI, HSIEH, AND SALEHI
Fig 11. A CT angiogram performed 7 months postoperatively, showing robust left lung blood flow.
Primary cardiac tumors are highly unusual, and their frequency has been estimated to be 0.02% based on the results of autopsy series.3 Primary cardiac sarcomas affect adults (mean age 41 years at presentation) and are extremely rare in infants and children. Little is known regarding the etiology of primary cardiac tumors. However, cases occurring because of radiation have been described.3 Dyspnea is the most common presenting complaint. These are highly aggressive lesions with the mean survival of affected patients being 3 months to 1 year although survival of up to 11 years has been reported.2 Chemotherapy and radiation therapy have limited benefit.4 Although aggressive surgery can offer dramatic palliation of symptoms caused by valvular and/or vascular obstruction, local recurrence and metastasis occur frequently and early, usually within 1 year.3 Such was the case with the patient presented here. He remained tumor free on surveillance scans and was asymptomatic until almost exactly 1 year after his initial tumor-debulking surgery. Although surgery with negative margins is the only mainstay of therapy, complete tumor resection is possible in fewer than half of patients. In 1 recent study, only 65% of patients planned for surgery based on preoperative imaging studies could undergo actual complete resection.4 Imaging modalities for preoperative assessment of affected patients include cardiac MRI, CT, ventilation-perfusion scanning, transthoracic echocardiography, and TEE.
As this case shows, information gleaned from preoperative transthoracic echocardiography and intraoperative TEE can reveal findings that are strongly suggestive of (consistent with) malignancy, define the extent of tumor involvement/spread, and influence surgical planning. Benign cardiac tumors, such as atrial myxomas, tend to arise from the interatrial septum and often have a stalk-like base with well-demarcated margins and usually do not invade the pulmonary veins.5 Malignant tumors, in contrast, often form broad-based atrial masses with poorly defined margins, are usually found in nonseptal locations, and can be associated with tumor infiltration into the pulmonary veins.2 This was a young, otherwise healthy patient who presented to a community hospital with acute decompensation in his health. It was clear that the cardiac tumor was the cause of his symptoms, and the preliminary transthoracic echocardiogram suggested myxoma, which is cured easily by surgical resection. However, a left atrial tumor without a clear attachment to the interatrial septum should raise concern for a malignancy or at least prompt the consideration of masses other than myxoma. Furthermore, myxomas are more typically slow growing, leading to more chronic symptomatology, whereas this patient’s rapidly progressive symptoms should have been suggestive of a more aggressive tumor. In this patient’s case, initial preoperative studies revealed obstruction of the left-sided pulmonary veins only, and, thus, the patient was scheduled for a left pneumonectomy in addition to left atrial tumor resection in hopes of a completely curative surgery. However, intraoperative TEE examination, surgical exposure, and reassessment of the CT angiogram confirmed tumor infiltration of both left and right pulmonary veins, suggesting a further-advanced tumor than was suspected initially. The left pneumonectomy then was abandoned with the surgery changed to palliative debulking. In conclusion, the authors wish to emphasize that patients with intracardiac tumors need careful preoperative assessment to distinguish benign masses (such as atrial myxoma) from highly malignant tumors that require the most aggressive surgical and oncologic treatment tolerable at the time of initial presentation. Atypical presentation of a cardiac mass on echocardiography, MRI, or CT angiography, plus a rapidly progressive clinical picture, should alert the physician to a possibility of a more aggressive or malignant process. Given the highly aggressive nature of the tumor described, every effort should be made to achieve negative margins at initial surgical resection and adjunct chemotherapy and radiation therapy considered at the earliest opportunity to achieve the best prognosis.
REFERENCES 1. Cho GJ, Hai JK, Kang JS: Primary cardiac sarcoma in pregnancy: A case report. J Korean Med Sci 21:940-943, 2006 2. Modi A, Lipvinicius A, Haw M, et al: Prolonged survival with left atrial spindle cell sarcoma. Interact Cardiovasc Thorac Surg 8:703-704, 2009
3. Gupta A: Primary cardiac sarcomas. Expert Rev Cardiovasc Ther 6:1295-1297, 2008 4. Grebenc M, Rosado de Christenson M, Burke A, et al: Primary cardiac and pericardial neoplasms: Radiologic-pathologic correlation. Radiographics 20:1073-1103, 2000
CARDIAC INTIMAL SARCOMA
5. Burke AP, Cowan D, Virmani R: Primary sarcomas of the heart. Cancer 69:387-395, 1997 APPENDIX 1. SURGICAL PATHOLOGY REPORT
FINAL DIAGNOSIS: (A) LEFT INFERIOR PULMONARY VEIN THROMBUS (EXCISION): Organizing thrombus. (B) RIGHT INFERIOR PULMONARY VEIN TUMOR (EXCISION): Consistent with intimal sarcoma, high grade (see comment). (C) SOFT-TISSUE TUMOR OBSTRUCTING LEFT ATRIUM (EXCISION): Consistent with intimal sarcoma, high grade (see comment). NOTE: Imaging studies have been reviewed. Discussion: Given the location, hematoxylin and eosin appearance, and immunohistochemical profile, the most appropriate diagnosis is intimal sarcoma.
MICROSCOPIC EXAMINATION Sections from Part B show a cellular proliferation of predominantly bland-appearing spindle cells in a collagenous background with focal areas of less cellularity. The cells have oval to elongated to somewhat wavy nuclei, dispersed chromatin, inconspicuous nucleoli, and scant fibrillary eosinophilic cytoplasm. Occasional dark, larger, and hyperchromatic cells are present. Rare mitoses are noted and estimated at approximately 10 per 10 HPF (40⫻). Sections from Part C reveal a proliferation of spindle cells arranged in fascicles and storiform patterns in a fibrocollagenous background containing fine vasculatures. Focally, there are less cellular areas. Most of the spindle cells have elongated nuclei, dispersed chromatin, inconspicuous nucleoli, and scant fibrillary eosinophilic cytoplasm. However, some of these cells are moderately-to-markedly pleomorphic with large hyperchromatic nuclei and irregular nuclear contours. Mitoses are brisk and estimated at 14 per 10 HPF. Necrosis is inconspicuous.
GENERAL IMMUNOHISTOCHEMISTRY REPORT FIXATIVE: Formalin ANTIBODY/PROBE: RESULT/COMMENT CD34 negative S100 negative Desmin negative Smooth muscle actin positive (patchy) Microsatellite analysis weak positive (scattered) Pankeratin negative Caldesmon negative
GROSS DESCRIPTION
107
A. Part A, labeled “L inferior pulmonary vein thrombosis,” consists of multiple small fragments of tubular shaped and irregularly shaped blood clots. This aggregate measures 2.8 ⫻ 2.7 ⫻ 0.7 cm. There is a tubular segment of clot with possible attached vessel wall, measuring 0.2 ⫻ 0.9 ⫻ 0.4 cm. Representative sections of the specimen are submitted in cassette A1 and the more intact segment with possible vessel wall placed in cassette A2. B. Part B, labeled “R inferior pulmonary vein tumor,” consists of a roughly oval, pink-gray tumor mass that measures 1.5 ⫻ 0.9 ⫻ 0.7 cm. The superficial surface of this mass is covered by membranous material, with multiple areas of irregularities. This specimen is unoriented. The entire external surface is inked green. The tumor is then serially sectioned to reveal homogeneously yellow pearl white cut surfaces. The entire specimen is placed in cassette B1. C. Part C, labeled “spindle cell sarcoma obstructing left atrium,” consists of multiple irregularly shaped fragments of pink-white, somewhat gelatinous/membranous soft tissue. The aggregate measures 6.6 ⫻ 6.0 ⫻ 3.2 cm. Within this tumor mass are multiple areas of hemorrhage. No obvious necrosis is present. Sectioning reveals homogeneously, yellow-white cut surfaces. Representative sections are placed in cassette C1-C9. Samples are submitted for cytogenetic studies and also placed in glutaraldehyde for possible electron microscopy studies.
CYTOGENETICS REPORT CLINICAL INDICATION: CHROMOSOME SCREENING FOR ANOMALIES ANALYSIS Metaphases counted: 8 Colonies counted: N/A Metaphases analyzed: 8 Banding technique: GPG Metaphases karyotyped: 4 Banding Resolution: 400
KARYOTYPE 63-133, -X, -Y, del1 (p22), add3 (q21), -4, add5 (q35), -10, add10 (q22);add11 (q23), del12 (p11.2p11.2), Tas13,13 (q34; q34), -16, ⫹18, add19 (p13), ⫹7-14mar, ⬃30dmin[cp8] INTERPRETATION A complete analysis was not possible because of a low mitotic index. The 8 cells available for analysis revealed an abnormal male karyotype with clonal abnormalities. The abnormal cells (8/8) exhibited a highly complex composite karyotype with multiple numerical and structural abnormalities described above, up to 14 marker chromosomes and approximately 30 double minutes; all these features are characteristic of high-grade tumor. Complex karyotypes and double minutes encompassing the 12q13-14 region (MDM2 gene) are typically observed in intimal sarcoma. This result is compatible with the diagnosis of high-grade intimal sarcoma.