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Metastatic malignant melanoma manifesting as an intracardiac mass
Cardiovascular Pathology 19 (2010) 153 – 157
Original Article
Metastatic malignant melanoma manifesting as an intracardiac mass Angela Wood a , Svetomir N. Markovic b,d , Patricia J.M. Best c , Lori A. Erickson a,d,⁎ a
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA b Department of Oncology, Mayo Clinic, Rochester, MN, USA c Department of Cardiology, Mayo Clinic, Rochester, MN, USA d The Melanoma Study Group, Mayo Clinic, Rochester, MN, USA
Received 29 October 2008; received in revised form 9 December 2008; accepted 19 December 2008
Abstract Introduction: Antemortem diagnoses of intracardiac metastases are uncommon. Metastatic melanoma shows a propensity for cardiac involvement, but cardiac involvement by melanoma is rarely identified clinically due to a paucity of cardiac symptoms. Methods: The surgical pathology files of Mayo Clinic were searched for cases of metastatic melanoma presenting or manifesting as an intracardiac mass. The lesions were evaluated pathologically for diagnoses. Clinical information was obtained by chart review. Results: Seven patients, four female and three male (age 31 to 79 years), were identified. No patient had a history of metastatic melanoma. All patients presented with dyspnea and symptoms of outflow obstruction. Echocardiography or CT revealed an intracardiac mass (four atrial, three ventricular). Six cases involved the right side of the heart and one involved the left ventricle. Five of the seven patients had a history of malignant melanoma, but none had a history of metastases when they presented with cardiac symptoms. In four cases, the history of primary melanoma was remote, occurring 7, 9, 13, and 28 years prior to the discovery of their cardiac mass. One patient had no history of melanoma, and no primary melanoma was ever identified. One patient had a history of a benign melanocytic lesion biopsied 2 years before, but retrospective review showed malignant melanoma. Conclusions: Melanoma is known to have an unpredictable and prolonged course. Neoplastic involvement of the heart should be considered in patients with cardiac symptoms when a documented malignancy exists, no matter how remote. © 2010 Elsevier Inc. All rights reserved. Keywords: Heart; Cardiac; Melanoma
1. Introduction Metastases to the heart are much more common than primary cardiac tumors [1,2]. The incidence of cardiac metastases is unknown, but ranges from 1.6% [3] to 18.3 % [4] of patients with malignancies. In a large series of 18,751 autopsies from the University of Trieste, Trieste, Italy, malignancy was noted in 7289 patients, of whom 622 (9.1%) had cardiac metastases [5]. Cardiac metastases usually occur in the setting of disseminated disease and are usually diagnosed postmortem. Of 662 patients with cardiac No funding was received in support of our study. ⁎ Corresponding author. Division of Anatomic Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel.: +1 507 284 1199. E-mail address: [email protected] (L.A. Erickson). 1054-8807/08/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2008.12.010
metastases, only in 10 cases was the heart the only site of metastasis [5]. The incidence of cardiac metastases is based primarily on autopsy studies, as cardiac metastases are often unrecognized in the clinical setting [5–8]. Although any tumor can potentially metastasize to the heart, malignant melanoma appears to have a particular propensity for cardiac involvement [3,9,10]. In an autopsy series of 70 patients with metastatic malignant melanoma, cardiac metastases were identified in 45 (64%) patients [10]. Other tumors showing a propensity for cardiac metastases include mesothelioma, lung carcinoma, and breast adenocarcinoma [5], while others found lung, lymphoma, breast, leukemia, stomach, liver, and colon malignancies to be common [11]. Cardiac metastases from malignant melanoma are usually multiple with numerous small metastases throughout the heart [10], but intracardiac tumifactive melanoma metastases
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Table 1 Clinicopathologic features of seven patients with malignant melanoma manifesting as an intracardiac mass Case Age/sex Tumor location Size (cm) Prior history of melanoma 1
72/M
Right atrium
6
2
65/M
Right ventricle
8
3
79/F
Right atrium
5
4
31/F
Right atrium
7.6
5
50/F
Left ventricle
6 7
65/F 59/M
Right ventricle Right atrium
10 9.5 5
Subsequent findings and follow-up
None. No primary melanoma was ever identified.
Metastases to skin, gallbladder, brain. Died of disease 7 years after cardiac metastasis. Skin biopsy 2 years prior benign, rereviewed Lung metastases. Died of disease 2 years after 5-mm deep melanoma. cardiac metastasis. 13 years prior had Stage 1 melanoma on skin of left knee. Brain metastases. Died of disease 4 months after Negative lymph node dissection. cardiac metastasis. 2 years prior had an ulcerated 3-mm deep melanoma on Mediastinal and bone metastases. Died of disease skin of back while pregnant. 4 months after cardiac metastasis. Toe amputation 9 years prior. Review of pathology showed Patient lost to follow-up. spindle amelanotic melanoma. 28 years prior had melanoma skin of left shoulder. Died of disease 6 months after cardiac metastasis. 7 years prior melanoma skin of left temple (1.2 mm deep). Bladder, brain, lymph node, liver metastases. Died of disease 2 years after cardiac metastasis.
M, male; F, female.
have been reported [2,12,13]. Antemortem identification of cardiac melanoma metastases is rare due to a paucity of cardiac symptoms [8,10]. We present seven cases of metastatic malignant melanoma presenting or manifesting as an intracardiac mass, initially identified as a result of cardiac symptoms, and diagnosed antemortem. 2. Materials and methods Formalin-fixed, paraffin-embedded tissues from seven patients with malignant melanoma forming a single intracardiac mass were identified from the surgical pathology files at the Mayo Clinic in Rochester, MN, from 1986 to 2000. In all seven patients, the diagnosis was made antemortem. Mayo Clinic Institutional Review Board approval was obtained. Hematoxylin and eosin-stained sections were evaluated for verification of diagnosis in all cases. Immunoperoxidase studies including S100, Melan A, and HMB-45 were used to confirm the diagnosis. Clinical history and follow-up information were obtained by chart review. 3. Results Clinical and follow-up information is presented in Table 1. Three men and four women, ranging in age from 31 to 79 years (mean age 60 years), were identified with a cardiac mass antemortem. No patient had a history of metastatic melanoma when their cardiac mass was discovered. A primary cardiac tumor (myxoma) was suspected clinically in the majority of cases. Six cases demonstrated an intracardiac mass of the right side of the heart (four atrial and two ventricular). One case involved the left ventricle. Five patients had a history of malignant melanoma, but none
had a history of metastases when they presented with cardiac symptoms. In four cases, the history of primary melanoma was remote, occurring seven or more years prior to identification of the cardiac mass (7, 9, 13, and 28 years prior). No patient was known to have metastases before the cardiac findings. One patient had no history of malignant melanoma whatsoever, and no primary melanoma was ever identified. One patient had a history of a melanocytic lesion biopsied 2 years before and interpreted as benign. Retrospective review of that specimen showed malignant melanoma. Follow-up data was available in six of seven cases, all of whom died of disease. In each case, the intracardiac tumor was a large, bulky lesion ranging in size from 5 to 10 cm (mean, 7 cm). The patients presented with dyspnea or substernal pressure and were found to have an intracardiac mass by echocardiogram or CT scan. Surgical resection or biopsy was performed in all cases and the diagnosis of malignant melanoma was confirmed by histopathologic review of the tumor in all cases (Fig. 1). All seven tumors were composed of large, atypical epithelioid cells with mitotic activity. Five of the seven metastases (Cases 2, 4, 5, 6, and 7) were amelanotic, while pigment was identified in the cardiac metastases in two cases (Cases 1 and 3).
4. Discussion The majority of metastases to the heart occur in the setting of disseminated disease and are often identified at autopsy. However, none of the seven patients in this series had a history of metastatic melanoma when their cardiac metastasis was discovered, and all of the cases were diagnosed antemortem with surgical biopsy or resection of the
Fig. 1. Photomicrographs of the histologic features of intracardiac malignant melanoma metastases. (A) Case 1: metastatic malignant melanoma with epithelioid cells and prominent melanocytic pigmentation. (B) Case 2 showing prominent mitotic figures. (C) Case 3 showing malignant melanoma involving the endocardium and myocardium. (D) Case 4: metastatic melanoma without pigment (amelanotic). (E) Case 5: biopsy of intracardiac melanoma, clinically unresectable. (F) Case 5: intracardiac melanoma metastasis with epithelioid cells without pigmentation. (G) Case 7: malignant melanoma with necrosis in the lower left portion of the photomicrographs. (H) Example of S100 immunostaining in the intracardiac metastatic melanoma.
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metastasis. One of the two had a cutaneous melanocytic lesion reviewed that was retrospectively diagnosed as melanoma after the cardiac melanoma metastases were identified. No primary melanoma was ever identified in the other patient with no prior history of melanoma. Malignant melanoma involving the heart with no known primary has been reported [14–16], but is an exceptionally rare event. Theoretically, melanoma could be primary in the heart, but it is more likely that a primary was elsewhere (cutaneous or mucosal) or was either never discovered or regressed. In an autopsy study of 662 patients with cardiac metastases from a variety of tumors including malignant melanoma, only in 10 cases was the heart the only site of metastasis, and none of these was from malignant melanoma [5]. Melanoma metastases to the heart can involve any structure, but the right atrium is the most common site [10,15,17–25]. In this study, the right atrium was also the most common site, involved in four of the seven cases. The other three cases showed involvement of the right ventricle (two cases) and the left ventricle (one case). Intracavitary right atrial metastases have been suggested to occur due to diffusion along the inferior vena cava reaching the right atrium and producing an intracavitary lesion [5]. None of the patients in this study presented with left atrial tumors, but melanoma metastases to the left atrium have been reported [26], including a case of melanoma of the esophagus metastasizing to the left atrium [27]. Metastases in the left atrium are seen more commonly in patients with lung carcinoma whose tumors are thought to embolize through the venous circulation of the lungs [5]. Melanoma metastases to the heart can involve any cardiac area, but most involve the myocardium [12]. In an autopsy study which identified cardiac metastases in 162 patients (8.4%) with malignancy, a particularly high frequency of myocardial involvement was noted in melanoma (45%), urinary tract tumors (60%), and lung squamous cell carcinomas (62%), while breast cancer (73%), lung small cell carcinoma (74%), lung adenocarcinoma (82%), and mesothelioma (100%) showed the highest frequency of metastases to the pericardium [28]. Overall, the pericardium and epicardium are more often affected by metastases, but myocardium appears to more often show involvement by melanoma and lymphoma [9]. Endocardial involvement appears uncommon [9], but endocardial metastases of melanoma, renal cell carcinoma, Wilm's tumor, and hepatocellular carcinoma have been reported [5,29]. Endocardial metastases are often associated with tumors with a vascular growth pattern. Tumors can spread to the heart by direct contiguous extension, through the blood or lymphatic system, and by transvenous extension through the inferior vena cava or the pulmonary veins [1,5]. Intracardiac tumifactive metastases, as in the seven cases reported here, are thought to be a result of invasion from the bloodstream with subsequent intracavitary lodging. Diffusion of tumor cells from within the myocardium to the endocardium is also possible, but less likely.
Cardiac metastases from malignant melanoma usually occur without clinical manifestations [10]. As the majority of cardiac metastases are identified in the setting of disseminated disease during postmortem examination, it is reasonable that the cardiac metastases detected antemortem are usually symptomatic. All seven of the patients in this study had symptoms including fatigue, chest pain, substernal pressure on exertion dyspnea, exertional dyspnea, orthopnea, leg edema, or weakness which led to their subsequent cardiac evaluation and identification of intracavitary cardiac mass on echochardiogram (six cases) or CT (one case). A pericardial effusion was identified by echocardiogram in Case 5 for which the patient underwent pericardiocentesis which was bloody, but no malignant cells were identified cytologically. Pericardial effusion has been reported to cause impairment of cardiac function in approximately 30% of cases [1]; thus the pericardial effusion may have accounted for some of the patient's cardiac symptoms. However, she did not experience complete resolution of cardiac symptoms, and a subsequent echocardiogram revealed the left ventricular mass. Five of the seven patients had a history of a primary cutaneous malignant melanoma, but in four of these patients the history was remote, occurring seven or more years (7, 9, 13, and 28 years, respectively) before the cardiac metastasis was discovered. Interestingly, none of the seven patients had any history of previous melanoma metastases when their cardiac metastasis was discovered. The reason for the apparent propensity of malignant melanoma for the heart is unknown. Although the remote history of the primary melanoma appears unusual, there have been a few cases in the literature in which patients presented with cardiac involvement more than 20 years after diagnosis of their primary tumor [12,23,30,31]. However, unlike the patients in this study, some of the patients in the literature with a remote history of melanoma were known to have metastatic disease at other sites before their cardiac tumor was identified [12,23]. Thus, cardiac metastases are a possible etiology for patients with cardiac symptoms even if their history of primary malignant melanoma is remote and they have no history of metastatic melanoma. All six patients for whom follow-up was available died of disease. The average time from diagnosis of the intracardiac tumifactive melanoma metastasis until death from disease was 2 years (range, 4 months to 7 years). Although the prognosis is poor for patients with metastatic malignant melanoma, surgery may be useful to palliate symptoms and prevent death from cardiac complications [12]. In conclusion, we report seven unusual cases of metastatic melanoma presenting or manifesting as an intracardiac mass. Each patient exhibited symptoms attributable to cardiac etiology including dyspnea, fatigue, chest pain, or decreased exercise tolerance. Associated cardiac abnormalities were identified on electrocardiogram and echocardiogram, and the diagnosis of malignant melanoma was confirmed by histopathologic evaluation in all cases. Although sympto-
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matic cardiac involvement by malignant melanoma appears to be rare, malignant melanoma may cause symptomatic involvement of the heart due to intracardiac metastasis even when the history of a primary melanoma is remote and there is no other history of metastasis. References [1] Chiles C, Woodard PK, Gutierrez FR, Link KM. Metastatic involvement of the heart and pericardium: CT and MR imaging. Radiographics 2001;21:439–49. [2] Lobo A, Lewis JF, Conti CR. Intracardiac masses detected by echocardiography: case presentations and review of the literature. Clin Cardiol 2000;23:702–8. [3] Klatt EC, Heitz DR. Cardiac metastases. Cancer 1990;65:1456–9. [4] Hanfling SM. Metastatic cancer to the heart. Review of the literature and report of 127 cases. Circulation 1960;22:474–83. [5] Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiac metastases. J Clin Pathol 2007;60:27–34. [6] Savoia P, Fierro MT, Zaccagna A, Bernengo MG. Metastatic melanoma of the heart. J Surg Oncol 2000;75:203–7. [7] Sheldon R, Isaac D. Metastatic melanoma to the heart presenting with ventricular tachycardia. Chest 1991;99:1296–8. [8] Lustig V, Vlasveld LT, Bakker RH, Schreuder JE, Mooi WJ, ten Bokkel Huinink WW. Intracardiac metastases, report of three cases. Neth J Med 1991;38:29–32. [9] MacGee W. Metastatic and invasive tumours involving the heart in a geriatric population: a necropsy study. Virchows Arch A Pathol Anat Histopathol 1991;419:183–9. [10] Glancy DL, Roberts WC. The heart in malignant melanoma. A study of 70 autopsy cases. Am J Cardiol 1968;21:555–71. [11] Abraham KP, Reddy V, Gattuso P. Neoplasms metastatic to the heart: review of 3314 consecutive autopsies. Am J Cardiovasc Pathol 1990;3: 195–8. [12] Gibbs P, Cebon JS, Calafiore P, Robinson WA. Cardiac metastases from malignant melanoma. Cancer 1999;85:78–84. [13] Malouf JF, Thompson RC, Maples WJ, Wolfe JT. Diagnosis of right atrial metastatic melanoma by transesophageal echocardiographicguided transvenous biopsy. Mayo Clin Proc 1996;71:1167–70. [14] Basarici I, Demir I, Yilmaz H, Altekin RE. Obstructive metastatic malignant melanoma of the heart: imminent pulmonary arterial occlusion caused by right ventricular metastasis with unknown origin of the primary tumor. Heart Lung 2006;35:351–4. [15] Bossert T, van Son JA, Autschbach R, Mohr FW. Resection of a right atrial metastatic melanoma with unknown origin of primary tumor. Eur J Cardiothorac Surg 1999;15:373–5.
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[16] Qu G, Kaur JS, Seward JB. Metastatic melanoma presenting as cardiac mass and hemobilia. Am J Med Sci 2003;325:157–9. [17] Vetto JT, Heelan RT, Burt M. Malignant melanoma metastatic to the right atrium: an asymptomatic solitary metastasis diagnosed incidentally by magnetic resonance imaging. J Thorac Cardiovasc Surg 1992; 104:843–4. [18] Ozer N, Yavuz B, Atalar E. Recurrent syncope in a case of metastatic malignant melanoma–an unusual presentation of an uncommon disease. Eur J Echocardiogr 2006;7:233–4. [19] Merer DM, Dutcher JP, Mercando A, Brodman R, Suhrland MJ, Bhandari A, Zimmerman D, Mitchell MS, Wiernik PH. Case report: clinical findings and successful resection of melanoma metastatic to the right atrium. Cancer Invest 1994;12:409–13. [20] Marti G, Galve E, Huguet J, Soler Soler J. Cardiac metastases of malignant melanoma mimicking sick sinus syndrome. Rev Esp Cardiol 2004;57:589–91. [21] Gosalakkal JA, Sugrue DD. Malignant melanoma of the right atrium: antemortem diagnosis by transvenous biopsy. Br Heart J 1989;62: 159–60. [22] Gaudree L, Chabrun A, Corbi P, Levillain P, Herpin D. Intracardiac metastasis of malignant melanoma. Literature review and case report. Arch Mal Coeur Vaiss 2000;93:1339–42. [23] Chen RH, Gaos CM, Frazier OH. Complete resection of a right atrial intracavitary metastatic melanoma. Ann Thorac Surg 1996;61: 1255–7. [24] Chrissos DN, Stougiannos PN, Mytas DZ, Katsaros AA, Andrikopoulos GK, Kallikazaros IE. Multiple cardiac metastases from a malignant melanoma. Eur J Echocardiogr 2008;9:391–2. [25] Prabhakar G, Vasilakis A, Hill RC, Cruzzavala JL, Graeber GM, Gustafson RA, Murray GF. Right atrial metastatic melanoma in a patient with transient ischemic attacks. Ann Thorac Surg 1998;65: 844–6. [26] Canver CC, Lajos TZ, Bernstein Z, DuBois DP, Mentzer Jr RM. Intracavitary melanoma of the left atrium. Ann Thorac Surg 1990;49: 312–3. [27] Chello M, Marchese AR, Panza A, Mastroroberto P, Di Lello F. Primary malignant melanoma of the oesophagus with a left atrial metastasis. Thorax 1993;48:185–6. [28] Silvestri F, Bussani R, Pavletic N, Mannone T. Metastases of the heart and pericardium. G Ital Cardiol 1997;27:1252–5. [29] Bryant J, Vuckovic G. Metastatic tumors of the endocardium: report of three cases. Arch Pathol Lab Med 1978;102:206–8. [30] Hanley PC, Shub C, Seward JB, Wold LE. Intracavitary cardiac melanoma diagnosed by endomyocardial left ventricular biopsy. Chest 1983;84:195–8. [31] Mindell SM, Chernick AW, Sugarman MH, Zirkin RM, Bloom RE. Right ventricular metastatic melanoma 27 years after resection of the primary tumor. Cancer 1989;63:1237–9.
Original Article
Metastatic malignant melanoma manifesting as an intracardiac mass Angela Wood a , Svetomir N. Markovic b,d , Patricia J.M. Best c , Lori A. Erickson a,d,⁎ a
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA b Department of Oncology, Mayo Clinic, Rochester, MN, USA c Department of Cardiology, Mayo Clinic, Rochester, MN, USA d The Melanoma Study Group, Mayo Clinic, Rochester, MN, USA
Received 29 October 2008; received in revised form 9 December 2008; accepted 19 December 2008
Abstract Introduction: Antemortem diagnoses of intracardiac metastases are uncommon. Metastatic melanoma shows a propensity for cardiac involvement, but cardiac involvement by melanoma is rarely identified clinically due to a paucity of cardiac symptoms. Methods: The surgical pathology files of Mayo Clinic were searched for cases of metastatic melanoma presenting or manifesting as an intracardiac mass. The lesions were evaluated pathologically for diagnoses. Clinical information was obtained by chart review. Results: Seven patients, four female and three male (age 31 to 79 years), were identified. No patient had a history of metastatic melanoma. All patients presented with dyspnea and symptoms of outflow obstruction. Echocardiography or CT revealed an intracardiac mass (four atrial, three ventricular). Six cases involved the right side of the heart and one involved the left ventricle. Five of the seven patients had a history of malignant melanoma, but none had a history of metastases when they presented with cardiac symptoms. In four cases, the history of primary melanoma was remote, occurring 7, 9, 13, and 28 years prior to the discovery of their cardiac mass. One patient had no history of melanoma, and no primary melanoma was ever identified. One patient had a history of a benign melanocytic lesion biopsied 2 years before, but retrospective review showed malignant melanoma. Conclusions: Melanoma is known to have an unpredictable and prolonged course. Neoplastic involvement of the heart should be considered in patients with cardiac symptoms when a documented malignancy exists, no matter how remote. © 2010 Elsevier Inc. All rights reserved. Keywords: Heart; Cardiac; Melanoma
1. Introduction Metastases to the heart are much more common than primary cardiac tumors [1,2]. The incidence of cardiac metastases is unknown, but ranges from 1.6% [3] to 18.3 % [4] of patients with malignancies. In a large series of 18,751 autopsies from the University of Trieste, Trieste, Italy, malignancy was noted in 7289 patients, of whom 622 (9.1%) had cardiac metastases [5]. Cardiac metastases usually occur in the setting of disseminated disease and are usually diagnosed postmortem. Of 662 patients with cardiac No funding was received in support of our study. ⁎ Corresponding author. Division of Anatomic Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel.: +1 507 284 1199. E-mail address: [email protected] (L.A. Erickson). 1054-8807/08/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2008.12.010
metastases, only in 10 cases was the heart the only site of metastasis [5]. The incidence of cardiac metastases is based primarily on autopsy studies, as cardiac metastases are often unrecognized in the clinical setting [5–8]. Although any tumor can potentially metastasize to the heart, malignant melanoma appears to have a particular propensity for cardiac involvement [3,9,10]. In an autopsy series of 70 patients with metastatic malignant melanoma, cardiac metastases were identified in 45 (64%) patients [10]. Other tumors showing a propensity for cardiac metastases include mesothelioma, lung carcinoma, and breast adenocarcinoma [5], while others found lung, lymphoma, breast, leukemia, stomach, liver, and colon malignancies to be common [11]. Cardiac metastases from malignant melanoma are usually multiple with numerous small metastases throughout the heart [10], but intracardiac tumifactive melanoma metastases
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Table 1 Clinicopathologic features of seven patients with malignant melanoma manifesting as an intracardiac mass Case Age/sex Tumor location Size (cm) Prior history of melanoma 1
72/M
Right atrium
6
2
65/M
Right ventricle
8
3
79/F
Right atrium
5
4
31/F
Right atrium
7.6
5
50/F
Left ventricle
6 7
65/F 59/M
Right ventricle Right atrium
10 9.5 5
Subsequent findings and follow-up
None. No primary melanoma was ever identified.
Metastases to skin, gallbladder, brain. Died of disease 7 years after cardiac metastasis. Skin biopsy 2 years prior benign, rereviewed Lung metastases. Died of disease 2 years after 5-mm deep melanoma. cardiac metastasis. 13 years prior had Stage 1 melanoma on skin of left knee. Brain metastases. Died of disease 4 months after Negative lymph node dissection. cardiac metastasis. 2 years prior had an ulcerated 3-mm deep melanoma on Mediastinal and bone metastases. Died of disease skin of back while pregnant. 4 months after cardiac metastasis. Toe amputation 9 years prior. Review of pathology showed Patient lost to follow-up. spindle amelanotic melanoma. 28 years prior had melanoma skin of left shoulder. Died of disease 6 months after cardiac metastasis. 7 years prior melanoma skin of left temple (1.2 mm deep). Bladder, brain, lymph node, liver metastases. Died of disease 2 years after cardiac metastasis.
M, male; F, female.
have been reported [2,12,13]. Antemortem identification of cardiac melanoma metastases is rare due to a paucity of cardiac symptoms [8,10]. We present seven cases of metastatic malignant melanoma presenting or manifesting as an intracardiac mass, initially identified as a result of cardiac symptoms, and diagnosed antemortem. 2. Materials and methods Formalin-fixed, paraffin-embedded tissues from seven patients with malignant melanoma forming a single intracardiac mass were identified from the surgical pathology files at the Mayo Clinic in Rochester, MN, from 1986 to 2000. In all seven patients, the diagnosis was made antemortem. Mayo Clinic Institutional Review Board approval was obtained. Hematoxylin and eosin-stained sections were evaluated for verification of diagnosis in all cases. Immunoperoxidase studies including S100, Melan A, and HMB-45 were used to confirm the diagnosis. Clinical history and follow-up information were obtained by chart review. 3. Results Clinical and follow-up information is presented in Table 1. Three men and four women, ranging in age from 31 to 79 years (mean age 60 years), were identified with a cardiac mass antemortem. No patient had a history of metastatic melanoma when their cardiac mass was discovered. A primary cardiac tumor (myxoma) was suspected clinically in the majority of cases. Six cases demonstrated an intracardiac mass of the right side of the heart (four atrial and two ventricular). One case involved the left ventricle. Five patients had a history of malignant melanoma, but none
had a history of metastases when they presented with cardiac symptoms. In four cases, the history of primary melanoma was remote, occurring seven or more years prior to identification of the cardiac mass (7, 9, 13, and 28 years prior). No patient was known to have metastases before the cardiac findings. One patient had no history of malignant melanoma whatsoever, and no primary melanoma was ever identified. One patient had a history of a melanocytic lesion biopsied 2 years before and interpreted as benign. Retrospective review of that specimen showed malignant melanoma. Follow-up data was available in six of seven cases, all of whom died of disease. In each case, the intracardiac tumor was a large, bulky lesion ranging in size from 5 to 10 cm (mean, 7 cm). The patients presented with dyspnea or substernal pressure and were found to have an intracardiac mass by echocardiogram or CT scan. Surgical resection or biopsy was performed in all cases and the diagnosis of malignant melanoma was confirmed by histopathologic review of the tumor in all cases (Fig. 1). All seven tumors were composed of large, atypical epithelioid cells with mitotic activity. Five of the seven metastases (Cases 2, 4, 5, 6, and 7) were amelanotic, while pigment was identified in the cardiac metastases in two cases (Cases 1 and 3).
4. Discussion The majority of metastases to the heart occur in the setting of disseminated disease and are often identified at autopsy. However, none of the seven patients in this series had a history of metastatic melanoma when their cardiac metastasis was discovered, and all of the cases were diagnosed antemortem with surgical biopsy or resection of the
Fig. 1. Photomicrographs of the histologic features of intracardiac malignant melanoma metastases. (A) Case 1: metastatic malignant melanoma with epithelioid cells and prominent melanocytic pigmentation. (B) Case 2 showing prominent mitotic figures. (C) Case 3 showing malignant melanoma involving the endocardium and myocardium. (D) Case 4: metastatic melanoma without pigment (amelanotic). (E) Case 5: biopsy of intracardiac melanoma, clinically unresectable. (F) Case 5: intracardiac melanoma metastasis with epithelioid cells without pigmentation. (G) Case 7: malignant melanoma with necrosis in the lower left portion of the photomicrographs. (H) Example of S100 immunostaining in the intracardiac metastatic melanoma.
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metastasis. One of the two had a cutaneous melanocytic lesion reviewed that was retrospectively diagnosed as melanoma after the cardiac melanoma metastases were identified. No primary melanoma was ever identified in the other patient with no prior history of melanoma. Malignant melanoma involving the heart with no known primary has been reported [14–16], but is an exceptionally rare event. Theoretically, melanoma could be primary in the heart, but it is more likely that a primary was elsewhere (cutaneous or mucosal) or was either never discovered or regressed. In an autopsy study of 662 patients with cardiac metastases from a variety of tumors including malignant melanoma, only in 10 cases was the heart the only site of metastasis, and none of these was from malignant melanoma [5]. Melanoma metastases to the heart can involve any structure, but the right atrium is the most common site [10,15,17–25]. In this study, the right atrium was also the most common site, involved in four of the seven cases. The other three cases showed involvement of the right ventricle (two cases) and the left ventricle (one case). Intracavitary right atrial metastases have been suggested to occur due to diffusion along the inferior vena cava reaching the right atrium and producing an intracavitary lesion [5]. None of the patients in this study presented with left atrial tumors, but melanoma metastases to the left atrium have been reported [26], including a case of melanoma of the esophagus metastasizing to the left atrium [27]. Metastases in the left atrium are seen more commonly in patients with lung carcinoma whose tumors are thought to embolize through the venous circulation of the lungs [5]. Melanoma metastases to the heart can involve any cardiac area, but most involve the myocardium [12]. In an autopsy study which identified cardiac metastases in 162 patients (8.4%) with malignancy, a particularly high frequency of myocardial involvement was noted in melanoma (45%), urinary tract tumors (60%), and lung squamous cell carcinomas (62%), while breast cancer (73%), lung small cell carcinoma (74%), lung adenocarcinoma (82%), and mesothelioma (100%) showed the highest frequency of metastases to the pericardium [28]. Overall, the pericardium and epicardium are more often affected by metastases, but myocardium appears to more often show involvement by melanoma and lymphoma [9]. Endocardial involvement appears uncommon [9], but endocardial metastases of melanoma, renal cell carcinoma, Wilm's tumor, and hepatocellular carcinoma have been reported [5,29]. Endocardial metastases are often associated with tumors with a vascular growth pattern. Tumors can spread to the heart by direct contiguous extension, through the blood or lymphatic system, and by transvenous extension through the inferior vena cava or the pulmonary veins [1,5]. Intracardiac tumifactive metastases, as in the seven cases reported here, are thought to be a result of invasion from the bloodstream with subsequent intracavitary lodging. Diffusion of tumor cells from within the myocardium to the endocardium is also possible, but less likely.
Cardiac metastases from malignant melanoma usually occur without clinical manifestations [10]. As the majority of cardiac metastases are identified in the setting of disseminated disease during postmortem examination, it is reasonable that the cardiac metastases detected antemortem are usually symptomatic. All seven of the patients in this study had symptoms including fatigue, chest pain, substernal pressure on exertion dyspnea, exertional dyspnea, orthopnea, leg edema, or weakness which led to their subsequent cardiac evaluation and identification of intracavitary cardiac mass on echochardiogram (six cases) or CT (one case). A pericardial effusion was identified by echocardiogram in Case 5 for which the patient underwent pericardiocentesis which was bloody, but no malignant cells were identified cytologically. Pericardial effusion has been reported to cause impairment of cardiac function in approximately 30% of cases [1]; thus the pericardial effusion may have accounted for some of the patient's cardiac symptoms. However, she did not experience complete resolution of cardiac symptoms, and a subsequent echocardiogram revealed the left ventricular mass. Five of the seven patients had a history of a primary cutaneous malignant melanoma, but in four of these patients the history was remote, occurring seven or more years (7, 9, 13, and 28 years, respectively) before the cardiac metastasis was discovered. Interestingly, none of the seven patients had any history of previous melanoma metastases when their cardiac metastasis was discovered. The reason for the apparent propensity of malignant melanoma for the heart is unknown. Although the remote history of the primary melanoma appears unusual, there have been a few cases in the literature in which patients presented with cardiac involvement more than 20 years after diagnosis of their primary tumor [12,23,30,31]. However, unlike the patients in this study, some of the patients in the literature with a remote history of melanoma were known to have metastatic disease at other sites before their cardiac tumor was identified [12,23]. Thus, cardiac metastases are a possible etiology for patients with cardiac symptoms even if their history of primary malignant melanoma is remote and they have no history of metastatic melanoma. All six patients for whom follow-up was available died of disease. The average time from diagnosis of the intracardiac tumifactive melanoma metastasis until death from disease was 2 years (range, 4 months to 7 years). Although the prognosis is poor for patients with metastatic malignant melanoma, surgery may be useful to palliate symptoms and prevent death from cardiac complications [12]. In conclusion, we report seven unusual cases of metastatic melanoma presenting or manifesting as an intracardiac mass. Each patient exhibited symptoms attributable to cardiac etiology including dyspnea, fatigue, chest pain, or decreased exercise tolerance. Associated cardiac abnormalities were identified on electrocardiogram and echocardiogram, and the diagnosis of malignant melanoma was confirmed by histopathologic evaluation in all cases. Although sympto-
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matic cardiac involvement by malignant melanoma appears to be rare, malignant melanoma may cause symptomatic involvement of the heart due to intracardiac metastasis even when the history of a primary melanoma is remote and there is no other history of metastasis. References [1] Chiles C, Woodard PK, Gutierrez FR, Link KM. Metastatic involvement of the heart and pericardium: CT and MR imaging. Radiographics 2001;21:439–49. [2] Lobo A, Lewis JF, Conti CR. Intracardiac masses detected by echocardiography: case presentations and review of the literature. Clin Cardiol 2000;23:702–8. [3] Klatt EC, Heitz DR. Cardiac metastases. Cancer 1990;65:1456–9. [4] Hanfling SM. Metastatic cancer to the heart. Review of the literature and report of 127 cases. Circulation 1960;22:474–83. [5] Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiac metastases. J Clin Pathol 2007;60:27–34. [6] Savoia P, Fierro MT, Zaccagna A, Bernengo MG. Metastatic melanoma of the heart. J Surg Oncol 2000;75:203–7. [7] Sheldon R, Isaac D. Metastatic melanoma to the heart presenting with ventricular tachycardia. Chest 1991;99:1296–8. [8] Lustig V, Vlasveld LT, Bakker RH, Schreuder JE, Mooi WJ, ten Bokkel Huinink WW. Intracardiac metastases, report of three cases. Neth J Med 1991;38:29–32. [9] MacGee W. Metastatic and invasive tumours involving the heart in a geriatric population: a necropsy study. Virchows Arch A Pathol Anat Histopathol 1991;419:183–9. [10] Glancy DL, Roberts WC. The heart in malignant melanoma. A study of 70 autopsy cases. Am J Cardiol 1968;21:555–71. [11] Abraham KP, Reddy V, Gattuso P. Neoplasms metastatic to the heart: review of 3314 consecutive autopsies. Am J Cardiovasc Pathol 1990;3: 195–8. [12] Gibbs P, Cebon JS, Calafiore P, Robinson WA. Cardiac metastases from malignant melanoma. Cancer 1999;85:78–84. [13] Malouf JF, Thompson RC, Maples WJ, Wolfe JT. Diagnosis of right atrial metastatic melanoma by transesophageal echocardiographicguided transvenous biopsy. Mayo Clin Proc 1996;71:1167–70. [14] Basarici I, Demir I, Yilmaz H, Altekin RE. Obstructive metastatic malignant melanoma of the heart: imminent pulmonary arterial occlusion caused by right ventricular metastasis with unknown origin of the primary tumor. Heart Lung 2006;35:351–4. [15] Bossert T, van Son JA, Autschbach R, Mohr FW. Resection of a right atrial metastatic melanoma with unknown origin of primary tumor. Eur J Cardiothorac Surg 1999;15:373–5.
157
[16] Qu G, Kaur JS, Seward JB. Metastatic melanoma presenting as cardiac mass and hemobilia. Am J Med Sci 2003;325:157–9. [17] Vetto JT, Heelan RT, Burt M. Malignant melanoma metastatic to the right atrium: an asymptomatic solitary metastasis diagnosed incidentally by magnetic resonance imaging. J Thorac Cardiovasc Surg 1992; 104:843–4. [18] Ozer N, Yavuz B, Atalar E. Recurrent syncope in a case of metastatic malignant melanoma–an unusual presentation of an uncommon disease. Eur J Echocardiogr 2006;7:233–4. [19] Merer DM, Dutcher JP, Mercando A, Brodman R, Suhrland MJ, Bhandari A, Zimmerman D, Mitchell MS, Wiernik PH. Case report: clinical findings and successful resection of melanoma metastatic to the right atrium. Cancer Invest 1994;12:409–13. [20] Marti G, Galve E, Huguet J, Soler Soler J. Cardiac metastases of malignant melanoma mimicking sick sinus syndrome. Rev Esp Cardiol 2004;57:589–91. [21] Gosalakkal JA, Sugrue DD. Malignant melanoma of the right atrium: antemortem diagnosis by transvenous biopsy. Br Heart J 1989;62: 159–60. [22] Gaudree L, Chabrun A, Corbi P, Levillain P, Herpin D. Intracardiac metastasis of malignant melanoma. Literature review and case report. Arch Mal Coeur Vaiss 2000;93:1339–42. [23] Chen RH, Gaos CM, Frazier OH. Complete resection of a right atrial intracavitary metastatic melanoma. Ann Thorac Surg 1996;61: 1255–7. [24] Chrissos DN, Stougiannos PN, Mytas DZ, Katsaros AA, Andrikopoulos GK, Kallikazaros IE. Multiple cardiac metastases from a malignant melanoma. Eur J Echocardiogr 2008;9:391–2. [25] Prabhakar G, Vasilakis A, Hill RC, Cruzzavala JL, Graeber GM, Gustafson RA, Murray GF. Right atrial metastatic melanoma in a patient with transient ischemic attacks. Ann Thorac Surg 1998;65: 844–6. [26] Canver CC, Lajos TZ, Bernstein Z, DuBois DP, Mentzer Jr RM. Intracavitary melanoma of the left atrium. Ann Thorac Surg 1990;49: 312–3. [27] Chello M, Marchese AR, Panza A, Mastroroberto P, Di Lello F. Primary malignant melanoma of the oesophagus with a left atrial metastasis. Thorax 1993;48:185–6. [28] Silvestri F, Bussani R, Pavletic N, Mannone T. Metastases of the heart and pericardium. G Ital Cardiol 1997;27:1252–5. [29] Bryant J, Vuckovic G. Metastatic tumors of the endocardium: report of three cases. Arch Pathol Lab Med 1978;102:206–8. [30] Hanley PC, Shub C, Seward JB, Wold LE. Intracavitary cardiac melanoma diagnosed by endomyocardial left ventricular biopsy. Chest 1983;84:195–8. [31] Mindell SM, Chernick AW, Sugarman MH, Zirkin RM, Bloom RE. Right ventricular metastatic melanoma 27 years after resection of the primary tumor. Cancer 1989;63:1237–9.