1

Peter Tripp
The Heart of the Problem
Frequency and treatment of cancers of the heart and cancer related heart conditions.
Among all the rare types of cancers, cancer of the heart is one of the rarest. Primary tumors of the heart only occur at around .02%, while secondary tumors have 100 times higher incidence.1 As with all tumors, these tumors can be either benign or malignant, (though by definition, any and all secondary tumors found in the heart are malignant). An additional defining
characteristic of these tumors is if they stem from the connective tissue of the heart wall, or the
valves of the heart. In any case, due to the dangerous location, any kind of tumor in the heart can
be extremely dangerous. Malignant tumors have an excellent mode of transport for spreading
throughout the body, and even benign tumors can cause issues if they block blood flow, or break
and cause an embolism somewhere else in the body. Tumors may also break through the heart
wall and cause a cardiac tamponade.
Much like the tumors in the brain, tumors in the heart can become dangerous based purely on where they are located. Tumors in the atriums of the heart can block blood flow, and tumors in the wall of the heart may cause arrhythmia. Tumors that break the wall of the ventricle or
atrium can cause cardiac tamponade, a condition where fluid builds up in the pericardial sac that
surrounds the heart3. This condition will increase pressure on the heart, making it continuously
more difficult for the heart to properly function, and leading to issues such as chest pain, decreased oxygenation of the limbs, fainting, and other issues that may occur when the body is not
getting proper blood flow. As the pericardium has been found to be the most common location

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for secondary tumors, this is a very real threat to the heart4. One or more of these conditions can
occur form many of these cancers, making even benign tumors extremely dangerous.
The most common kind of primary tumors that are found in the heart are myxomas.2
Myxomas are benign myxoid tumors, and almost three quarters form in the left atrium of the
heart. While they do not present a threat of metastasizing throughout the body, they can cause a
myriad of complications anyway. Firstly, many of the myxomas found are with stalks, this allows
them to flow with the blood. If one forms in the atrium and grows to a large size, it could flow
with the blood through the left bicuspid valve and act as a plug to blood flow. This would be
heard through examinations as a secondary heart sound, and would be felt by the patient as the
flow of oxygen rich blood was impeded. A second issue that myxomas present is that some may
be formed brittle and easily broken. Should a piece be broken off, it may cause an embolism
within the body, leading to tissue death and blockage. If the tumor was on the right side of the
heart, then this embolism would take place in the lungs. Myxomas may be treatable with removable by heart surgery and chemotherapy.
Carney complex is a rare autosomal dominant disorder that elevates the risk of an individual having multiple reoccurring myxomas5. There is no treatment other than monitoring and
removing dangerous myxomas. The complex is thought to be caused by mutations of the gene
that codes for a subunit of protein kinase A. When the subunit is mutated, protein kinase A loses
its regulatory abilities, due to the mutated subunit being easily degradable. Without regulation,
protein kinase A causes cell growth rates to increase rapidly and form a myxoma. Another possible cause lies the the short arm of chromosome 2, however researchers have not isolated the gene
that may cause this5.

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Another type of primary, benign heart tumors are papillary fibroelastomas, the second
most common after myxomas. Like myxomas they are usually pedunculated and cause the majority of their problems via mechanical issues and emboli. However, unlike the myxomas which
prefer the heart wall, papillary fibroelastomas form on the valves of the atrium6. They generally
do not grow very large and are found more in older-age groups, making the decision to remove
them via surgery a controversial issue. Many of these papillary fibroelastomas do not cause serious issues like myxomas do, although they do present a greater risk of renal or coronary emboli
as they are generally more fixable than myxomas. The activation mechanism isnt very well understood for these kinds of tumors, but the leading theory is the microthrombus theory7. This
theory states that the tumor begins as a microthrombus which lands on the valve and serves as a
introduction point for the growth, which slowly grows over time. This means that these tumors
may be accumulated issues instead of congenital like myxomas7. These does make treatment a
bit easier since recurrence rates are low, although the issue of weighing the risks of surgery
comes up again.
Unlike the two classes of cardiac tumors previously discussed, rhabdomyomas form within the walls and cells of the heart. They are benign tumors of striated muscles fibers, and are
multiple tumors are often found in affected patients in infancy8. They do not metastasize
throughout the body, and many patients may be asymptomatic. However, they can present issues
if they grow near the electrical conduction of the heart. If this is the case, they can cause arrhythmia and palpitations. Also unlike the other two tumors, which generally present in the heart,
rhabdomyomas usually grow within the walls of the ventricle, and may block blood flow or prevent proper oxygenation of the body, if they grow too large. Fortunately these kinds of tumors

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tend to either maintain their size or decrease as time goes on. There is a large correlation between
patients with rhabdomyomas and with tuberous sclerosis.
Tubersous sclerosis is a condition where non-malignant tumors form in many place of the
body. In general, the organs most affected are the brain, eyes, kidney, skin, lungs, and the heart.
Like Carney complex it is autosomal dominant, and it also presents a varying degree of difference- no two patients have the same degree of severity. A study was done to see the extent of the
correlation between rhabdomyomas and tuberous sclerosis in childern, and of the fifteen children
shown to have rhabdomyomas, twelve had tuberous sclerosis9. Of the three that did not have
tuberous sclerosis, one was not screened for it, one had only a single rhabdomyoma, and the final
child had clear cranial and renal ultrasounds. The study went on to look at hospital-based data
and estimated that 60% of children under 18 with tuberous sclerosis present with rhabdomyomas.
The cause of tuberous sclerosis isnt clear, but it may be caused by loss of heterozygosity. A
study found that a tuberous sclerosis gene on chromosome 16p13.3 may function as a tumor suppressor gene, as allele loss on the chromosome was found in six out of eight tumors studied10.
Another benign primary tumor of the heart are the fibromas. Fibromas are connective tissue tumors from fibroblasts that can occur without any preference to age or sex. As with many
other kinds of benign tumor their problems stem from their size and location in the heart. They
are associated with Gorlins syndrome. Gorillas syndrome is an autosomal dominant disease in
which a mutation in the PTCH1 gene12. The PTCH1 gene is a tumor suppressor that produced a
protein called patched-1. Patched-1 is needed to act as a receptor for a protein called Sonic
Hedgehog. Until Sonic Hedgehog is attached to patched-1, patched-1 blocks cell growth and proliferation. When the PTCH1 gene is mutated and creates a mutated patched-1, the receptor loses

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the ability to stop cell growth and the Sonic Hedgehog ligand causes uncontrolled growth and
division. Gorlins syndrome can also be associated with a deletion on chromosome 912. Chromosome 9 holds the PTCH1 gene and a deletion called the 9q22.3 micro deletion causes the same
outcome as a mutated PTCH1 gene.
Moving on to malignant tumors, sarcomas are the most common malignant tumor and the
second most common primary tumor of the heart. Of these sarcomas, the most common are angiosarcomas, which tend to originate in the right atrium of the heart2. Due to blood flow, these
tumors can metastasize to the lungs. Lungs may metastases many tumors and the complex alveolar bed of capillaries forms a tight net that captures many tumor cells that pass through and provide good oxygenation and blood flow to these tumors. Cardiac tamponade and blocked blood
flow would also result from these tumors. While its not totally clear exactly what causes soft-tissue sarcomas, there has been a link to the HRAS gene mutation. Ras is an oncogene and the
HRAS gene mutation causes the ras gene to stay constantly active11.
Angiosarcomas can have very different appearances tumor to tumor. On a microscope
levels they are characterized by vascular channels of malignant cells. However some tumors may
also have areas of spindle cells or sheets of the anapestic rounds of spindle cells. The channels
can differ greatly in terms of size or shape and are lined with swollen multilayered epithelial
cells12. In general they do not metastasize much further from the body although they do have
extensive local growth. This local growth leads to many of the problems seen in other tumors,
such as cardiac tamponade, reduced blood flow, and issues with heart rhythms.

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The cytogenetics of angiosarcomas are poorly understood according to a 2010 study
that looked for distinctive features of angiosarcomas14. The study used immunohistochemistry,
array-based comparative genomic hybridization and bicolor fluorescence in situ hybridization
analyses to look at twenty-two cases. In secondary angiosarcomas it was found that high level
amplifications of MYC on chromosome 8 were a defining characteristic. The same was not
found in primary tumors, showing that the primary and secondary iterations of angiosarcomas
are genetically different.
Lymphomas may also occur as a primary malignant tumor. When occurring as a primary
tumor, they are often of a non-Hodgkins related type and involved only the heart and pericardium. They comprise of only 1% of cardiac primary tumors. B-cell and T-cell tumors have both
been found in the heart and there is mounting evidence for a connection to AIDS, immunosuppression and cardiac transplantation12. There are several proposed factors that may control the
growth of non-Hodgkins lymphomas, but as with many other kinds of tumors, a definite mechanism is unknown. The role viruses like the Epstein-Barr virus and herpesvirus 8, along with Bcell stimulation and immunodeficiency are seen as possible activators15.
Non-Hodgkins lymphomas can be classified as either small, non cleaved cell or diffuse,
large cell lymphoma. Burkitt lymphoma is an example of the small non cleaved cell type. In
AIDS patients with non cleaved, small cell, non-Hodgkins lymphomas, the Epstein-Barr virus is
found a third of the patients. This virus operates as an oncogene by chromosomal translocation. It
moves the gene code for c-Myc to a different chromosome to amplify production. This is the
cause of Burkitts lymphoma. The virus was also found in diffuse large cell lymphomas, but varied depending on the type of tumor.

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There are three kinds of diffuse, large cell lymphomas, centroblastic, immunoblastic, and
plasmablastic. In centroblastic, the Epstein-Barr virus was only found in a third of the patients.
like the small cell tumors. This jumps to 90% in patients with immunoblastic lymphomas. Immunoblastic lymphomas also express a protein labeled the latent membrane protein. In plasmablastic lymphomas, half of patients had the virus. This all points to AIDS being a contributing
factor as its resulting immunodeficiency opens the patients up for infection by multiple viruses.
When a virus like the Epstein-Barr or herpes 8 virus take advantage of this opportunity to infect
a patient, they mutate the genes within a cell. Should something like chromosomal translocation
occur, like in Burkitts lymphoma, then the c-Myc gene will begin amplifying cell growth. This
can cause extreme proliferation of the B-cells in a body, which resulting in a growth like a lymphoma.
As most primary tumors are rare in the heart, many malignant tumors do not start in the
heart but metastasize there, as is their nature. These tumors can come from any kind of cancer
that may metastasize to somewhere else in the body, although cancers of the central nervous system dont seem to be as common1. And as the heart is a common hub that all blood must filter
through it becomes a prime location for growth. Other organs that have intricate capillary beds,
such as the kidney and lungs, would also be able to capture a large amount of the tumor cells that
are in the blood.
The extra cardiac cancer that has the hight rate of metastases to the heart is melanomas,
followed by breast lung and throat cancers. These metastases usually present as multiple small
tumors, but variations may occur. The infecting cells can reach the heart through the lymph or
vascular systems. Should a tumor originate via the lymph system, it will likely grow on the peri-

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cardium, while blood borne tumors spread in the hearts muscle tissue. Tumors rarely metastasize
inside of the heart. Tumors may also spread via contact, as cancers of the bronchus or esophagus
tubes can grow to actually touch the heart, although these kinds of tumors usually spread via the
lymph system before they reach a large enough size to spread via contact.1.
Tumor cells using the lymphatic system for transport to the heart usually enter from the
thoracic cavity's lymph system before invading the myocardial system. This pathway is utilized
by carcinomas of lung and breast cancers the most. Most other cancers, like melanomas, lymphomas, and bone sarcomas use the cardiovascular system as transport for their cancer cells1.
Those tumor cells infect the myocardium of the heart, and sometimes the internal cavities. The
valves are rarely affect by metastases.
As with most metastases treatment for metastases must start with the tumor of origin,
otherwise reoccurrence is a very likely outcome. With heart metastases, and heart tumors in general, surgical procedures are a risky business as postoperative survival rates are low1. If the pericardium is effected pericardiocentesis, the surgery of draining fluid from the pericardium, should
be a top priority in cases of cardiac tamponade. This surgery has a better survival rate, although
rare complications like effusions into the thoracic cavity may occur. Cancer treatments may also
be administered to the pericardium via this surgery, an example of one used is 5-flurouracil1.
Some types of tumors occur more frequently in a non-human host. In dogs, a type of tumor called a chemodectoma, These tumors as usually benign and arise from chemoreceptors of
the aorta and carotid artery that are meant to monitor the blood16. Like the other tumors mentioned here, the real danger of a chemodectoma in the aorta arises from its ability to grow to size

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large enough to displace the trachea, causing respiratory issues, or squeeze the atria or vena cava
and reduce blood flow into the heart. In the carotid artery tumor occur at the split between the
internal and external arteries, cutting down on oxygenated blood flow to the brain. These tumors
may also metastasize to the lymph system, due to the proximity of the necks lymph nodes to the
point of origin for these tumors. As theses tumors are more common in breeds that have genetic
issues with respiration, like Boxers, it is thought that constantly low oxygen levels in the blood
spur the development of theses tumors.
To review, tumors of the heart are deadly more often due to the effect that tumor growth
has on the function of the heart, rather than a present danger of spreading to other parts of the
body, or being a common occurrence. Many kinds, such as papillary fibroelastomas and rhabdomyomas may be asymptomatic as they rarely present a clear and present danger to the patient,
and some may not even be worth the risk of surgery. Other cancers may metastasize to the heart
via the lymph system or through the blood, but this usually result in tumors in the muscle of the
heart, or on the pericardium, rarely within the ventricles or atriums of the hear, and even less frequently on the valves. These secondary tumors may also be asymptomatic, but can result in the
same issues that the cause the risk in primary tumors, such as cardiac tamponade, decreased
blood flow and disturbances in the hearts rhythm. Biochemical causes of these tumors follow the
same pathways as in other parts of the body with genetic issues like Carneys complex, viruses,
and gene mutations like the patched-1 gene, leading to the onset of these tumors.

1. Reyen, K., U. Kckeritz, and R. H. Strasser. "Annals of Oncology." Metastases to the

Heart.
Annals of Oncology, n.d. Web. 13 Dec. 2014.

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