Characteristics and Survival of Malignant Cardiac Tumors: A 40-Year Analysis of >500 Patients
Abstract
Background—
The aim of this study was to investigate the incidence, histopathology, demographics, and survival associated with primary malignant cardiac tumors (PMCTs).
Methods and Results—
We queried the Surveillance, Epidemiology and End Results (SEER) 18 registry from the National Cancer Institute for all PMCTs diagnosed from 1973 to 2011. We describe PMCT histopathology and incidence, comparing characteristics and survival of these patients with those of patients with extracardiac malignancies of similar histopathology. From a total of 7 384 580 cases of cancer registered in SEER, we identified 551 PMCTs (0.008%). The incidence of PMCT diagnosis is 34 cases per 100 million persons and has increased over time (25.1 in 1973–1989, 30.2 in 1990–1999, and 46.6 in 2000–2011). Most patients are female (54.1%) and white (78.6%) with median age at diagnosis of 50 years. The most common PMCTs are sarcomas (n=357, 64.8%), followed by lymphomas (n=150, 27%) and mesotheliomas (n=44, 8%). Most patients are diagnosed with tissue sample (96.8%). Although use of chemotherapy is not documented in SEER, 19% of patients received radiation and 44% had surgery. After a median follow-up of 80 months, 413 patients had died. The 1-, 3-, and 5-year survival rates were 46%, 22%, and 17% and have improved over the eras, with 1-, 3-, and 5-year survival rates of 32%, 17%, and 14% for 1973 to 1989 and 50%, 24%, and 19% for 2000 to 2011 (P=0.009). Cardiac sarcomas and mesotheliomas are the most lethal PMCTs, with 1-, 3-, 5-year survival rates of 47%, 16%, and 11% and of 51%, 26%, and 23% compared with 59%, 41%, and 34% for lymphomas, respectively (log rank test P<0.001). Patients with cardiac lymphomas and sarcomas are younger and have worse survival than patients with extracardiac disease of similar histopathology (P<0.001).
Conclusions—
PMCTs are extremely rare and continue to be associated with poor prognosis. Over the past 5 decades, the incidence and survival of patients diagnosed with PMCT appear to have increased. Compared with those with extracardiac cancers of similar histopathology, patients with PMCTs are often younger and have worse survival.
Introduction
Primary malignant cardiac tumors (PMCTs) are extremely rare neoplasms of varying histopathology that originate within cardiac structures and display biologically aggressive behavior.1–3 Because most practitioners may see only a handful of such cases in their lifetime, the accumulated experience on this subject has been collated and summarized in multiple extensive literature reviews.1,4 Nevertheless, the core knowledge of PMCTs has continued to come from single-center studies consisting of surgical case series and autopsy reports.2,4–7 Because of the relatively small numbers and significant referral bias of these reports, the incidence of PMCTs remains unclear, their histology incompletely defined, and treatment ineffectual, and prognosis is thought to be universally poor.
Clinical Perspective on p 2402
We therefore sought to better understand PMCTs by using the largest cancer registry in the United States.
Methods
We conducted a retrospective analysis of all PMCTs in the Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) from 1973 to 2011. We used the 18-registry research data with Hurricane Katrina–affected Louisiana cases, November 2013 submission (1973–2011 varying), from the National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Surveillance Systems Branch, released in April 2013. SEER 18 captures cancer data from 18 cancer registries in the United States: Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco–Oakland, Seattle–Puget Sound, Utah, Los Angeles and San Jose–Monterey, Rural Georgia, the Alaska Native, greater California, Kentucky, Louisiana, New Jersey, and greater Georgia. The data collection and reporting for the SEER are described elsewhere.8
All data were extracted from the registry with SEER*STAT version 8.2.1 from the surveillance research program of the Division of Cancer Control and Population Sciences, National Cancer Institute (Calverton, MD) on March 1, 2014. We used the following selection criteria: case selection (site and morphology. primary site – labeled) = ‘C38.0-Heart’. We included only patients with known age who were actively followed up and had tumors with malignant behavior. Our search was limited to cases within the research database. We excluded patients with either death certificate only or autopsy report only (However, no patients were excluded on the basis of these criteria). The study cutoff date was defaulted to December 2010.
We used code II, IX, and XII (a.5) for lymphomas, sarcomas, and mesotheliomas, respectively. We performed subgroup analyses based on age groups (pediatrics, ≤18 years versus adults, >18 years of age) and histological type [viz angiosarcoma, selected with International Classification of Childhood Cancer code IX (d.8)] and by era of diagnosis year (1973–1989, 1990–1999, 2000–2011). Data from SEER*STAT were imported into IBM SPSS version 19 (2010) for statistical analyses. All categorical variables were presented as frequencies and percentages. When appropriate, mean (SD) and median (25th, 75th percentiles) were presented for continuous data variables. Survival curves were formulated with Kaplan-Meier methods. All tumors were selected with the use of the International Classification of Childhood Cancer site recode (International Classification of Diseases 0–3/World Health Organization 2008). Per SEER guidelines, histopathologic data are entered on the basis of the most recent available diagnosis, and the registry does not contain information on the method used for histological sampling, whether biopsy, excision, or autopsy.
Incidence data were calculated with rate sessions within the SEER*STAT program. For the incidence calculations, we used the SEER 9 (1973–2011) based on November 2013 submission. This registry pulls data from following cancer registries: Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco–Oakland, Seattle–Puget Sound, and Utah. Age-adjusted incidence was standardized to the US 2000 standard-million population (19 age groups). Age-adjusted rates for incidence were calculated by summing the products of the age-specific rate (for each 5-year age group [0–4 years, 5–9 years, etc]) and multiplying by the fraction of the 2000 US population in each age range. We calculated the incidence by era of diagnosis and by histology.9
We used χ2 to compare categorical data. Independent t tests were used to compare means when normally distributed, and nonparametric tests (Mann-Whitney) were used if data were not normally distributed. The Kaplan-Meier method was used to present survival, and the log-rank test was used for all survival differences throughout the article. Median survival (25th, 75th percentile) is presented, taking into account censoring. We compared characteristics and survival of cardiac tumors with those of noncardiac tumors of a similar histopathological type (based on International Classification of Childhood Cancer classifications). In all tests, values of P<0.05 were considered statistically significant.
Results
Epidemiology
Of 7 384 580 cases of cancer in patients with known age registered in SEER, we identified 551 PMCTs (0.008%). The majority (298, 54.1%) of patients were female with a median age at diagnosis of 50 years (25th, 75th percentiles, 35, 67 years). Most patients were white (433, 78.6%), followed by black (57, 10.3%; Table 1). A histogram of age at diagnosis is shown in Figure 1. The majority of tumors were sarcomas (n=357, 64.8%), followed by lymphomas (150, 27.0%) and mesotheliomas (44, 8.0%; Table 2). There were 27 pediatric patients (4.9%): 19 with sarcoma, 7 with lymphoma, and 1 with mesothelioma.
Variable | |
---|---|
Age, y | 50 (35, 67) |
Era of diagnosis, n (%) | |
1973–1989 | 91 (16.5) |
1990–1999 | 93 (16.9) |
2000–2011 | 367 (66.6) |
Race, n (%) | |
White | 433 (78.6) |
Black | 57 (10.3) |
Other | 59 (10.7) |
Unknown | 2 (0.4) |
Sex, n (%) | |
Female | 298 (54.1) |
Male | 253 (45.9) |
History of malignancy, n (%) | 68 (12.3) |
Diagnostic confirmation, n (%) | |
Histology | 497 (90.2) |
Cytology | 36 (6.5) |
Clinical | 5 (0.9) |
Direct visualization | 2 (0.4) |
Microscopy, not otherwise specified | 1 (0.2) |
Radiography only | 9 (1.6) |
Unknown | 1 (0.2) |
Radiation, n (%) | |
Yes | 105 (19.1) |
No | 429 (77.9) |
Unknown | 11 (2.0) |
Surgery, n (%) | |
Surgery | 240 (43.6) |
No surgery | 242 (43.9) |
Unknown | 75 (13.6) |
Surgery and radiation | 56 (10.2) |
Values are median (25th, 75th percentiles) when appropriate.
Histopathology (WHO 2008 Groups) | n | % |
---|---|---|
Sarcoma | 357 | 64.8 |
IX(d.8) Blood vessel tumors | 161 | 29.2 |
IX(e) Unspecified soft tissue sarcomas | 77 | 14 |
IX(d.6) Leiomyosarcomas | 31 | 5.6 |
IX(b.1) Fibroblastic and myofibroblastic tumors | 30 | 5.4 |
IX(a) Rhabdomyosarcomas | 23 | 4.2 |
IX(d.7) Synovial sarcomas | 12 | 2.2 |
IX(d.5) Fibrohistiocytic tumors | 10 | 1.8 |
IX(d.11) Miscellaneous soft tissue sarcomas | 9 | 1.6 |
IX(d.4) Liposarcomas | 3 | 0.5 |
IX(b.2) Nerve sheath tumors | 1 | 0.2 |
Lymphoma | 150 | 27.2 |
II(b.2) Mature B-cell lymphomas except Burkitt lymphoma | 109 | 19.8 |
II(b.4) Non-Hodgkin lymphomas, not otherwise specified | 15 | 2.7 |
II(e) Unspecified lymphomas | 12 | 2.2 |
II(a) Hodgkin lymphomas | 6 | 1.1 |
II(b.3) Mature T-cell and NK-cell lymphomas | 3 | 0.5 |
II(c) Burkitt lymphoma | 2 | 0.4 |
II(b.1) Precursor cell lymphomas | 2 | 0.4 |
II(d) Miscellaneous lymphoreticular neoplasms | 1 | 0.2 |
Mesothelioma | 44 | 8 |
NK indicates natural killer; PCMT, primary malignant cardiac tumor; and WHO, World Health Organization.

The calculated age-adjusted incidence was 34 cases per 100 million persons. Since 1973, the incidence has increased over 3 eras (per 100 million persons): 25.1 in 1973 to 1989, 30.2 in 1990 to 1999, and 46.6 in 2000 to 2011. The incidence was higher in male than in female patients (38.2 versus 30.0 per 100 million persons). Cause-specific analysis shows that the incidence of both lymphomas (2.8, 10.3, and 15.8) and sarcomas (16.8, 17.1, and 29.2) has increased, whereas that of mesothelioma has decreased (5.5, 2.8, and 1.5; Figure 2).

Most patients were diagnosed by tissue samples (96.8%). Although chemotherapy data are not available in SEER, 19.1% of patients received radiation, and 43.6% of patients had surgery. Overall, 10.2% underwent both surgery and radiation as a part of their treatment.
Overall Survival
Survival data were available for 516 patients (93.6%). At a median follow-up of 80 months (25th, 75th percentiles, 33, 119 months), 413 patients had died. Median survival was 10 months (25th, 75th percentiles, 1, 29 months) with 1-, 3- and 5-year survival rates of 46%, 22%, and 17% (Figure 3). Survival improved over the study period from 1-, 3-, and 5-year rates of 32%, 17%, and 14% in 1973 to 1989 to 50%, 24%, and 19% in 2000 to 2011 (P=0.009; Figure 4). Pediatric patients had better survival than adults, with 1, 3, and 5-year survival rate of 71%, 47%, and 47% versus 44%, 21%, and 16% (P<0.001; Figure I in the online-only Data Supplement) Cardiac sarcomas have worse survival, with 1-, 3-, and 5-year survival of 47%, 16%, and 11% compared with lymphoma survival of 59%, 41%, and 34%, respectively (log-rank P<0.001). Survival analysis reveals that >80% of the patients die within 20 months of diagnosis.


Specific Histological Types
Sarcomas
Cardiac sarcomas represented 0.3% of all sarcomas, with a median age at diagnosis of 45 years (25th, 75th percentiles, 32, 59 years). The most common histopathological type was angiosarcoma (43.4%), followed by leiomyosarcoma (6.4%) and rhabdomyosarcoma (4.5%). Cardiac angiosarcomas had slightly worse survival than other types of cardiac sarcomas, with 1-, 3- and 5-year survival rates of 39%, 9%, and 8% versus 47%, 21%, and 14% (P=0.045). There were no statistically significant differences in cardiac sarcoma survival over the 3 eras, with 1-, 3-, and 5-year survival of 9%, 11%, and 6% in 1973 to 1989; 24%, 10%, and 6% in 1990 to 1999; and 31%, 11%, and 8% in 2000 to 2011 (P=0.173).
Compared with those with extracardiac sarcomas, patients with cardiac sarcomas were younger (46.1 versus 52.8 years; P=0.001), more likely to be female (47.1% versus 40.8%; P=0.02), less likely to have previous history of malignancy (7.6% versus 12.7%; P=0.005), and more likely to have surgical resection (60.4% versus 26.2%; P<0.001; Table 3). Median survival was 9.0 months (25th, 75th percentiles, 1.2, 21 months). Patients with cardiac sarcomas had worse survival than those with extracardiac sarcomas (log-rank P<0.001; Figure 5A).
Sarcomas | Lymphomas | Mesotheliomas | |||||||
---|---|---|---|---|---|---|---|---|---|
C (n=357) | NC (n=105 597) | P | C (n=150) | NC (n=439 341) | P | C (n=44) | NC (n=15 873) | P | |
Mean±SD age at diagnosis, y | 46.1±18.9 | 52.8±20.7 | 0.001* | 62.8±20.2 | 61.8±18.5 | 0.11 | 54.1±17.9 | 70.2±12.3 | <0.001* |
Male sex, % | 52.9 | 59.2 | 0.02* | 57.6 | 54.3 | 0.45 | 45.5 | 77.6 | <0.001* |
Race, % | 0.001* | 0.002* | 0.001* | ||||||
White | 77.5 | 81.7 | 82.0 | 84.0 | 77.3 | 91.8 | |||
Black | 11.7 | 12.2 | 5.0 | 9.6 | 15.9 | 4.9 | |||
Other minorities | 10.8 | 6.1 | 12.9 | 6.6 | 6.8 | 3.3 | |||
History of malignancy, % | 7.6 | 12.7 | 0.005* | 18.0 | 13.7 | 0.14 | 22.7 | 17.7 | 0.43 |
Treatment, % | |||||||||
Surgery | 59.4 | 67.5 | <0.001* | 16.5 | 24.9 | 0.06 | 31.8 | 24.0 | <0.001* |
Radiation | 23.1 | 26.5 | 0.064 | 15.1 | 22.1 | 0.77 | 9.1 | 12.1 | 0.98 |
C indicates cardiac primary; and NC, noncardiac primary.
*
Significant.

Lymphomas
Cardiac lymphomas accounted for 0.03% of all lymphomas, with a median age at diagnosis of 67 years (25th, 75th percentiles, 50, 79 years). The most common histopathological type was diffuse B-cell lymphoma (60.6%). There was a trend toward improved survival for cardiac lymphomas over the 3 eras, with 1-, 3-, and 5-year survival of 63%, 38%, and 38% in 1973 to 1989; 38%, 23%, and 19% in 1990 to 1999; and 62%, 46%, and 38% in 2000 to 2011 (P=0.087).
Compared with extracardiac lymphomas, patients with cardiac disease were less likely to be black (5.0% versus 9.6%; P=0.002), but there was no difference in age, sex, or history of previous malignancy. There was a nonsignificant trend toward fewer surgeries in patients with cardiac lymphomas (16.5% versus 24.9%; P=0.06) but no difference in use of radiation therapy (Table 3). Median survival for cardiac lymphomas was 23 months (25th, 75th percentiles, 5, 120 months). Compared with extracardiac lymphomas, cardiac lymphomas had worse survival (log-rank P<0.001; Figure 5B).
Mesotheliomas
Pericardial mesotheliomas represented 0.3% of all mesotheliomas, with a median age at diagnosis of 53 years (25th, 75th percentiles, 40, 70 years). Median survival of patients diagnosed with pericardial mesothelioma was 2 months (25th, 75th percentiles, 0, 12 months), with 1-, 3- and 5-year survival rates of 26%, 14%, and 9%. There was no statistically significant difference in survival for cardiac sarcoma over the 3 eras, with 1- year survival of 25% in 1973 to 1989, 20% in 1990 to 1999, and 7% in 2000 to 2011 (log-rank P=0.338).
Compared with extracardiac mesotheliomas, patients with pericardial mesotheliomas were younger (mean age, 54.1 versus 70.2 years; P<0.001), less likely to be male (45.5% versus 77.6%; P<0.001), and more likely to be blacks and other minorities (15.9% versus 4.9% and 6.8% versus 3.3%, respectively; P=0.001). Patients with cardiac mesotheliomas were more likely to have surgery (31.8% versus 24.0%; P<0.001) but had similar use of radiation therapy (Table 3). Cardiac or extracardiac location of mesothelioma did not appear to affect prognosis (P=0.06; Figure 5C).
Discussion
This study reports the characteristics of PMCTs using data amassed over 5 decades from a large-scale national registry. In it, we confirm the rarity and lethality of PMCTs and offer insight into their epidemiology, histopathology, demographics, and outcomes. Because we have studied numbers 20-fold larger than in existing reports, we have debunked previous misconceptions and shed light on unknown aspects of PMCTs.
The premortem diagnosis of PMCTs is much more uncommon than previously reported. In unselected autopsy reports, benign and malignant tumors were found in 0.021% of deaths.10 Of these, malignant cardiac tumors were even less common, representing 5.1% to 28.7% of all heart tumors in small series.2 Our study shows that clinically apparent PMCTs have an estimated prevalence of 34 cases per 100 million persons, >100 times lower than previous estimates. This discrepancy may be explained partially by the possibility that many of the autopsy-discovered tumors may have been incidentalomas rather than clinically significant tumors. Indeed, in a Spanish series, one quarter of all cardiac tumors were incidental findings.11 In addition, SEER includes only patients diagnosed with cancer before death, not postmortem findings. Although PMCTs commonly present with dyspnea, chest pain, palpitations, and edema,11–13 they can also remain clinically silent until causing ventricular arrhythmias13 and sudden cardiac death,14 thus escaping inclusion in SEER. Nevertheless, more in line with our findings, a recent study in Grosseto’s county in Italy (1998–2011) estimated the incidence of PMCTs at ≈130 per 100 million persons.15
Over the study period, the incidence of PMCTs appears to have increased, driven by a higher frequency of lymphomas and sarcomas. This increase may reflect better premortem diagnostic capabilities brought about by developments in cardiac imaging such as echocardiography, computed tomography, and magnetic resonance imaging, which were not widely available in the first decades of the study period. The incidence of cardiac lymphomas mirrors that of non-Hodgkin lymphoma in the general population, which peaked in the 1980s and 1990s but has remained stable16 since 2000 because of improvements in HIV management. Conversely, there has been a steady decrease in the incidence of pericardial mesotheliomas as a result of less common asbestos exposure.17
We confirm that PMCTs can present at any age with a peak incidence in the fifth decade of life, affect predominantly whites, and have a slight female predilection, consistent with previous reports.11,12,18–21 The reasons for age distribution, racial preference, and slight female preponderance cannot be gleaned from this study. We can speculate, however, that women receive more chest radiation for breast cancer22,23 and that blacks have less access to medical care than whites24; however, there may also be genetic and environmental factors that cannot be inferred from this study.
We also report and shed light on histopathological subtypes of PMCTs and their frequencies. For example, whereas we confirm that sarcomas are indeed the most common PMCT, we demonstrate that lymphomas affect the heart 10 times more frequently than previously thought. For example, a previous single-center surgical series reported only 10 lymphomas (6.9%) of 143 malignant cardiac tumors,2 likely a result of referral bias because lymphomas typically are chemoresponsive and not treated surgically. Therefore, whereas lymphomas were previously believed to represent 1.3% to 2% of all cardiac tumors,2,4 in our series, they accounted for 27% of all PMCTs. In addition, although a systematic literature analysis25 of 197 cardiac lymphomas in 2010 reported a male:female ratio of 1.94, we show more balanced sex distribution, not different from what is seen in extracardiac lymphomas. Although non-Hodgkin lymphoma has a strong tendency to involve the myocardium, with up to 20% of patients with non-Hodgkin lymphoma having evidence of myocardial involvement at autopsy,26 immunosuppressed patients (transplant recipients, those with HIV, etc) typically present with primary cardiac lymphoma without extracardiac involvement.2 In fact, 41% of all patients with primary cardiac lymphomas are immunocompromised and have universally poor survival.25 Previous reports show that diffuse large B-cell lymphomas have a predilection for the right side of the heart (92% had involvement of right atrium or right ventricle) and usually present with dyspnea, constitutional symptoms, pain and arrhythmias.25,27–29 About 90% of patients with diffuse large B-cell lymphomas receive a anthracycline-based regimen, with high treatment-related mortality.25 Historically, ≈28% of patients are treated with surgery and 20% with radiation, slightly higher than what we found at 16.5% and 15.1%, respectively.25
We also investigated the incidence of different subtypes of sarcomas. In the largest previous series of 143 cases of malignant cardiac tumors, angiosarcomas were most common at 23.1%, followed by leiomyosarcoma at 20.3% and rhabdomyosarcoma at 4.2%.2 Our data show similar distributions of angiosarcoma (25.8%) and rhabdomyosarcoma (2.6%) but a much lower prevalence of leiomyosarcoma (3.7%). The predominance of angiosarcoma was also reported previously by researchers in Italy (28.6%),18 the Mayo Clinic (41%),19 and the British Columbia Registry.20 In contradistinction, a single study from Germany reported the predominance of undifferentiated sarcoma,20 which may suggest either regional variances in histological distribution or differences in histological classifications across the eras. Whereas we found no sex predilection for cardiac sarcomas, we note low use of surgery (43.6%), and radiation (19.1%). This may suggest that these patients have advanced disease at presentation and may not be surgical or radiation candidates or, alternatively, are treated predominantly with chemotherapy and are not captured in the SEER database. Additionally, sarcomas have been reported to present at later stages of life and are difficult to diagnose.4 In contrast, we show here that patients with cardiac sarcomas present at a younger age than those with extracardiac disease.
We investigated for the first time demographic differences between patients with cardiac and extracardiac disease of similar histopathology. We found that patients with cardiac sarcomas and pericardial mesotheliomas are significantly younger than those with extracardiac disease of similar histology. Although the reason for this is unclear, it may be related to lead-time bias with earlier clinical presentation because of cardiac-related symptoms or pre-existing risk factors for early development of these cardiac malignancies. For example, because radiation has been implicated in some cases of sarcomas30 and other cancers,31 it is possible that survivors of childhood cancers who received radiation to the chest are at higher risk of developing cardiac sarcomas. Another possibility is that cardiac sarcomas are associated with gene mutations32,33 that predispose patients to develop these cancers at an earlier age. Interestingly, we also found ethnic differences between cardiac and extracardiac diseases across all histopathology groups. Cardiac lymphomas and sarcomas are more prevalent in minority groups, whereas mesotheliomas are more common in blacks. The reasons for this observation remain speculative and could be related to genetic predisposition,34 risk factors,35 or environmental exposures.36
Lastly, we performed extensive survival analyses among multiple subtypes of PMCTs and among those with cardiac versus extracardiac disease. We found that, despite the overall poor prognosis of PMCTs across all histopathology types, survival appears to have improved slightly over the past 5 decades. Because lymphoma treatment and rates of cure have improved dramatically during this period,37 the overall increased survival of PMCTs may be attributable to that alone. However, it may also be possible that survival has improved because of earlier diagnosis of PMCTs as a result of more common use of cardiac imaging. Incidental detection of these tumors when echocardiography is performed for other reasons might lead to earlier treatment with better outcomes than in the past when diagnosis relied predominantly on the presence of symptoms. In contrast, the paucity of advances in the treatment of sarcomas and mesotheliomas and the low use of surgery and radiation likely explain their worse survival. Because most of these patients are treated at large academic centers where radiation and surgical expertise are adequate,19,21 the underuse of these options probably reflects poor patient candidacy.
Overall, <50% of patients with PMCTs are alive by the end of the first year, with a sharp decrease in survival for sarcoma and mesothelioma patients. As expected, we found that overall survival from a real-world registry is slightly worse than at high-volume tertiary centers. For example, the median overall survival was 12 months in 32 patients with PMCTs at the Mayo Clinic (1975–2007)19 compared with 10 months in our series. However, our reported survival of sarcomas is much better than previously published reports11 (1-year survival, 47% versus 20%). Most probably, the modest improvement in observed overall survival of patients with PMCTs is driven by better treatment outcomes of lymphoma and sarcoma patients.
Another unique aspect of this study is that we provide survival comparisons between cardiac and extracardiac malignancies stratified by histopathology. We show that cardiac sarcomas and lymphomas have significantly worse survival compared with similar cancers of extracardiac origin, suggesting that any cardiac involvement, whether primary or metastatic, carries worse prognosis. It further implies that patients with extracardiac malignancies of histopathology types that affect the heart more commonly such as angiosarcomas and diffuse large B-cell lymphoma may need to be screened for cardiac involvement with echocardiography,38 cardiac magnetic resonance imaging,39 or cardiac positron emission tomography40 at diagnosis. This likely does not apply to mesotheliomas because they have similarly poor survival regardless of location.
In summary, we confirm that PMCTs are rare and currently have limited treatment options, leading to poor patient survival. There may be opportunities to better understand these tumors and their survival differences in the context of cancer genomics. Minimally invasive diagnostic techniques or circulating tumor assays may be necessary for early diagnosis and may eventually inform treatment decisions. Diagnostic and therapeutic clinical trials and locally directed approaches should be incorporated into future treatment considerations.
Limitations
Despite being the largest of its kind, this study has multiple important limitations. It is based on a national registry, which, although extensive, lacks fundamental information that severely limits our results and conclusions. In addition, although SEER is frequently used as a research tool, the quality and accuracy of its data collection cannot be ascertained and are prone to human error and inaccuracy. Furthermore, because the data in this study were collected over 5 decades and analyzed retrospectively, there are confounding factors that cannot be avoided despite adjustments. For example, histopathological classifications and diagnostic and treatment modalities most likely do not reflect modern practices3 and can therefore confound estimates of survival and incidence of PMCT types. Specifically, determination of histopathological type is confounded by the many reclassifications of PMCTs that have occurred since the 1970s, making inferences about PMCT subtype incidence less reliable. Therefore, it is possible that the increase in PMCTs and different subtypes that we report more accurately reflects an increased incidence in the diagnosis of PMCTs than of the actual disease. Unfortunately, because the SEER registry does not include data on chemotherapy and other treatment modalities, we have no information on the role of chemotherapy on specific histopathological types. Similarly, granular clinical information cannot be gleaned by this study such as method of diagnosis, clinical presentation, location of cardiac tumors, and most common method of histological sampling (biopsy, excision, or autopsy). In addition, we can offer no insight into details of surgery or radiation therapy. Lastly, the lack of information on mode of death also limits our understanding of the natural history of PMCTs and potentially confounds survival analyses. Whereas no other data source will likely be able to provide such high numbers of PMCT patients, small case series will remain the only source of more granular information on this subject.
Conclusions
Cardiac sarcomas, lymphomas, and mesotheliomas are the most common PMCTs but remain extremely rare and associated with dismal prognosis. Over the past 5 decades, the incidence and survival of patients diagnosed with PMCT appear to have increased. Compared with those with extracardiac cancers of similar histopathology, patients with PMCTs are often younger and have worse survival.
CLINICAL PERSPECTIVE
Primary malignant cardiac tumors are extremely rare and lethal neoplasms that most practitioners may encounter only a handful of times in their lifetime. Until now, knowledge about these tumors has remained incomplete because it has been compiled from case reports and small surgical and autopsy series and summarized in multiple reviews. In this article, we attempt to shed light on unknown aspects of primary malignant cardiac tumors by using the National Cancer Institute’s Surveillance, Epidemiology and End Results Program database, the largest cancer registry in the United States. We show that the incidence of diagnosed primary malignant cardiac tumors in the United States is about 34 cases per 100 million people and has doubled over the past 5 decades. The most common histopathological types are sarcomas, lymphomas, and mesotheliomas, and the average age at diagnosis is ≈50 years, with a slight predilection for women. Overall, more than half of patients die within 1 year of diagnosis, although survival has slowly and modestly increased since the 1970s. Finally, we found that mortality is highest among patients with mesotheliomas and sarcomas and lowest among those with lymphomas, and compared with those with extracardiac disease of the same histopathological type, patients with primary malignant cardiac tumors have worse survival.
Supplemental Material
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Received: 10 March 2015
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Published online: 14 October 2015
Published in print: 1 December 2015
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