Pericardial tumours
Solitary fibrous tumour 8815/1
Malignant mesothelioma 9050/3
Germ cell tumours
Metastatic pericardial tumours
__________
1
Morphology code of the International Classification of Diseases for Oncology (ICD-O) {6} and the Systematized Nomenclature of Medicine (http://snomed.org).
Behaviour is coded /0 for benign tumours, /3 for malignant tumours, and /1 for borderline or uncertain behaviour.
Epidemiology that determine clinical features {737}. carditis may also result from tumour infil-
The estimated frequency of cardiac Large tumours may be relatively silent, tration.
tumours ranges from 0.0017-0.33% whereas small tumours in a critical loca- Rarely, tumours such as myxoma, cause
{2165}. In a review of 22 autopsy-based tion may give rise to devastating clinic systemic symptoms, including anorexia,
series of primary cardiac tumours a fre- consequences. weight loss, fatigue and malaise which
quency of 0.021% was identified among Left atrial tumours, especially those that may mimic a variety of systemic disor-
731,309 patients {1656}. In one 20-year are mobile or pedunculated, may lead to ders {356,737,1774,2077}. Interestingly,
(1972-1991) review of 12,485 autopsy systemic embolism involving the coro- they may also cause haematologic
cases, there was a 0.056% incidence of nary, cerebral and peripheral circulations abnormalities, including anemia, poly-
primary tumours and a 1.23% incidence {737,1568,2077}, resulting in myocardial cythemia, leukocytosis, thrombocytosis
of secondary tumours {1116}. However, infarction, stroke or ischemic viscera or and elevated sedimentation rate {1225}.
these data may have a high referral bias limbs. Left atrial tumours may also inter- Tumour production of mediators, includ-
and may not reflect population-based fere with mitral valve function resulting in ing interleukins, has been reported
incidence rates {2079}. At the Mayo mitral stenosis or regurgitation. Cardiac {1774}.
Clinic, the autopsy incidence of primary murmurs and a characteristic tumour
cardiac tumours from 1915 to 1931 was “plop” may be auscultated. Valve dys- Imaging
0.05%, but more than tripled to 0.17% function manifests as left-sided heart fail- Primary tumours of the heart and peri-
between 1954 and 1970 {2165}; again, ure with shortness of breath, orthopnea, cardium may be detected as an abnor-
referral bias may have played a role in paroxysmal nocturnal dyspnoea, pul- mal finding on a chest radiogram or
this change. monary edema, fatigue, cough, and another imaging test obtained for an
When most cardiac tumours were diag- chest pain {356}. unrelated reason. Once detected car-
nosed at autopsy, myxomas and sarco- Intramural left ventricular tumours may diac imaging is needed to define (1)
mas were reported at a similar frequency. be asymptomatic or present with a mass tumour location, extent and boundaries;
With the utilization of cardiopulmonary effect. With protrusion into the cavity, (2) relationships with adjacent key car-
bypass and surgical excision, the report- hemodynamic compromise may result diac structures such as valves and coro-
ed frequency of myxomas as opposed to {1225}. Local extension of the tumour nary arteries; (3) tumour type; and (4)
cardiac sarcomas has increased sub- may cause conduction or coronary artery presence and degree of functional
stantially {249,1568}. In a review of surgi- compromise with chest pain, myocardial impairment. The main non-invasive imag-
cal series, cardiac myxomas constitute infarction, arrhythmia, heart block or sud- ing modalities for evaluating primary car-
77% of surgically excised tumours, and den death {356,737,1225,1791}. diac tumours each have advantages and
cardiac sarcomas, 10% {249}. Right atrial or right ventricular tumours disadvantages. They are often used
In children, cardiac tumours are not com- may result in right heart failure from atri- together in a complementary manner for
mon and most are benign {249}. The oventricular or pulmonary outflow diagnosis and surgical planning.
most common pediatric tumours include obstruction, resulting in peripheral
rhabdomyomas, fibromas, myxomas, edema, hepatomegaly, ascites, short- Echocardiography
and teratomas {249,356}. ness of breath, syncope and sometimes, The primary advantage of echocardiog-
Secondary cardiac tumours, either sudden death {737}. If the tumours inter- raphy is that it has the best spatial and
metastatic or by direct invasion, outnum- fere with valve function they may result in temporal resolution and provides excel-
ber primary cardiac neoplasms {1116}. A regurgitation or stenosis {1791}. lent anatomic and functional information
review of 3,314 autopsies found a 2.9% Right-sided cardiac tumours may {492,705,1070,1162,2104,2215}. It is the
frequency of metastatic tumours involv- embolize to the lungs and present as pul- optimal imaging modality for small mass-
ing the heart {12}. The most common pri- monary emboli with chest pain, pul- es (<1 cm) or masses arising from
mary sites are lung, breast, and cuta- monary infarction and haemoptysis valves. A second major advantage of
neous melanoma. {1634,1791}. Chronic embolization may echocardiography is the ability to image
also mimic chronic thromboembolic dis- velocities with Doppler, which allows for
Clinical features ease with signs and symptoms of pul- assessment of presence, degree, and
Cardiac neoplasms may cause a variety monary hypertension. location of obstructions to blood flow or
of signs and symptoms {1225,1791, Pericardial tumours may cause chest valve regurgitation. Echocardiography is
2079}. The clinical presentation depends pain typical of pericarditis {1225,1568}. typically the modality used for the initial
on the size of the tumour and its anatom- The tumours may be haemorrhagic and evaluation of cardiac tumours and may
ic location. Growth rate, friability, and cause pericardial effusion and tampon- be the only diagnostic test required in
invasiveness are also important factors ade {1634}. However, constrictive peri- some patients. Disadvantages include
Introduction 251
suboptimal image quality in patients with Fig. 4.01 Classification of Tumours of Soft Tissue
poor acoustic windows, inability to image Parameters of the grading system for sarcomas of and Bone {590}. The concept of grading
extent of disease outside of the medi- the Féderation Nationale des Centres de Lutte sarcomas was first introduced in 1977
Contre le Cancer (FNCLCC).
astinum, and relatively low soft tissue {1712}. Several grading systems have
contrast, which limits detection of tumour Tumour differentiation since been proposed which have shown
infiltration and characterization of tumour Score 1: Sarcomas closely resembling to correlate with prognosis {412,1247,
tissue. Also, intravenous contrast agents normal adult mesenchymal tissue 1418,2031,2070}. The two most impor-
are not routinely used with echocardiog- (e.g., low-grade leiomyosarcoma). tant parameters in non-cardiac soft tis-
raphy, which limits the ability to charac- Score 2: Sarcomas for which histological sue seem to be the mitotic index and
terize tumour vascularity. typing is certain (e.g., Myxoid extent of tumour necrosis {1793,2031,
Fibrosarcoma) 2070}. Most pathologists recognize three
Score 3: Undifferentiated, angiosarcoma
Magnetic Resonance Imaging (MRI) grades of malignancy: G1, low grade;
The primary advantage of MRI is its G2, intermediate grade; and G3, high
Mitotic count
excellent soft tissue contrast which Score 1: 0-9 mitoses per 10 HPF* grade. Some use a 4-tiered system.
makes it the most sensitive modality for Score 2: 10-19 mitoses per 10 HPF The two most widely used systems are
detection of tumour infiltration. MRI has Score 3: ≥20 mitoses per 10 HPF those of the NCI (U.S. National Cancer
more manipulable imaging parameters Institute) {412,413} and the FNCLCC
than other imaging modalities. Because Tumour necrosis (Fédération Nationale des Centres de
of this, MRI is the best modality for char- Score 0: No necrosis Lutte Contre le Cancer) {387-389,748,
acterizing tumour tissue {1003,1768, Score 1: <50% tumour necrosis 2031}.
1831,2156}. For example, a T2-weighted Score 2: ≥50% tumour necrosis According to the methodology defined in
standard or fast spin echo sequence dis- 1984 {412} and refined in 1999 {413}, the
Histologic grade
tinguishes tumours with high water con- NCI system uses a combination of histo-
Grade 1: Total score 2,3
tent, such as haemangioma, from Grade 2: Total score 4,5
logic type, cellularity, pleomorphism and
tumours with low water content, such as Grade 3: Total score 6, 7, 8 mitotic rate for attributing grade 1 or 3.
fibroma. A third advantage of MRI is the All the other types of sarcomas are clas-
ability to characterize tumour vascularity Modified from Trojani et al {2031}. sified as either grade 2 or grade 3
with intravenous contrast. Though not as *A high-power field (hpf) measures 0.1734mm2 depending on the amount of tumour
flexible as echocardiography, MRI does necrosis, with 15% necrosis as the
allow assessment of wall motion and threshold for separation of grade 2 and
assessment of velocities through large tissue contrast and ability to characterize grade 3 lesions.
vessels. This allows for characterization tumour infiltration and tumour type is less The FNCLCC system is based on a score
of ventricular function, inflow or outflow than that of MRI. Intravenous contrast obtained by evaluating three features:
obstruction and valve regurgitation. The can provide information about tumour tumour differentiation, mitotic rate and
primary disadvantage of MRI is long vascularity, an advantage CT shares with amount of tumour necrosis {2031}. A
examination times, which translates into MRI. CT may be used as an adjunct to score is attributed independently to each
the need for sedation in children, and the both echocardiography and MRI. parameter and the grade is obtained by
need for reliable ECG gating. MRI should adding the three attributed scores.
be considered when the tissue type, Cardiac Catheterization Tumour differentiation is highly depend-
exact location, or the relationships of the This is seldom required for diagnosis of ent on histologic type and subtype. The
tumour with neighbouring structures are cardiac tumours, but may be performed reproducibility of this system has been
not completely defined by echocardiog- in adults to exclude coronary artery dis- tested by 15 pathologists: the crude pro-
raphy or when surgical resection of the ease. Angiography provides indirect and portion of agreement was 75% for tumour
tumour is considered. nonspecific imaging based on filling grade, but only 61% for histologic type
defects within the cardiac chambers and {748}.
Computed Tomography (CT) displacement of the coronary arteries Because of the limitations and pitfalls of
ECG gated CT scans with the latest gen- {347,1840}. Two exceptions are worth grading, the following guidelines have
eration of multidetector scanners or with noting. First, endomyocardial biopsy for been suggested to improve reliablility:
electron beam scanners are also very tissue typing may be considered in > Grading should be used only for
useful for cardiac imaging {65,275}. In selected patients. Second, selective untreated primary soft tissue sarcomas.
many ways, the advantages and disad- coronary angiography is helpful when > Grading should be performed on rep-
vantages of CT are intermediate between planning surgical resection of an resentative and well-processed material.
those of echocardiography and MRI. intramyocardial tumour. > Grading is not a substitute for a histo-
Modern CT scanners have excellent spa- logic diagnosis and does not differentiate
tial resolution, which is better than that of Tumour grading and staging benign and malignant lesions. Before
MRI, but not as high echocardiograpy. Given the low frequency of malignant grading a soft tissue lesion, one must be
CT has better soft tissue contrast than cardiac tumours, there is no grading sure that one is dealing with a true sar-
echocardiography, and can be used to scheme specifically referring to malig- coma and not a pseudosarcoma.
definitively characterize fatty content and nant heart tumours. This volume uses the > Parameters of grading must be carefully
calcifications; however, the overall soft criteria published in the recent WHO evaluated, particularly the mitotic rate.
Introduction 253
Benign tumours with myocyte B.M. Shehata
A.P. Burke
R. Virmani
T. Geva
differentiation H. Tazelaar
C.R. Patel
G. Tornambene
D.J. Radford
Rhabdomyoma in any location in the heart, but are more be identified as early as 21 weeks by
common in the ventricles. In patients with ultrasound {863}. The tumours may
Definition tuberous sclerosis, tumours are usually cause infant respiratory distress, con-
A benign tumour of the cardiac myocyte, multiple (> 90%) and can consist of gestive heart failure, or low cardiac out-
which can be solitary or multiple. The numerous miliary nodules measuring less put. Right-sided tumours that cause
cells typically contain large glycogen than 1 mm; in this instance, the term obstruction may cause cyanosis, or fea-
filled vacuoles. “rhabdomyomatosis” has been used. The tures suggestive of tetralogy of Fallot or
most common locations are the left ven- pulmonary stenosis {41,583}. Left-sided
ICD-O code 8900/0 tricle and ventricular septum, although tumours may present as subaortic
30% will have atrial wall or right ventricu- obstruction, or hypoplastic left heart syn-
Epidemiology lar involvement {1602}. In contrast to drome {2068}. Rarely they can be asso-
Cardiac rhabdomyoma is commonly patients with tuberous sclerosis, approxi- ciated with structural cardiac defects
associated with tuberous sclerosis, an mately 50% of sporadic rhabdomyomas {2113}. Patients with “rhabdomyomato-
autosomal dominant disorder with a high occur singley. sis” or diffuse microscopic involvement
mutation rate. It involves multiple organs of the myocardium may present as
including brain, kidney, pancreas, retina Clinical features though they have a cardiomyopathy.
and skin. In autopsy series, patients with Signs and symptoms Spontaneous regression is a common
tuberous sclerosis have a 30% incidence Rhabdomyomas are the most common feature {1254,1840}.
of cardiac rhabdomyoma {571}. tumours in the pediatric age group. They Electrocardiographic abnormalities will
However, the actual incidence is likely are also the tumours most commonly vary depending on location, but evi-
higher since series that have evaluated diagnosed during the prenatal period by dence of ventricular hypertrophy and ST-
patients with echocardiography have foetal echocardiography. Intrauterine as T wave abnormalities consistent with
found an incidence between 40% and well as sudden death after birth has ischemia and/or strain are common. The
86% {119,492,777}. The presence of been attributed to these tumours. conduction abnormalities consist of bun-
multiple cardiac rhabdomyomas prena- Clinical and hemodynamic findings are dle branch block, preexcitation, and first
tally may be the earliest manifestation of related to the number, position, and size to third degree atrioventricular block.
tuberous sclerosis. of the tumours. For instance large intra-
mural or intracavitary tumours may Imaging
Localization obstruct valvular orifices, or occlude At echocardiography rhabdomyomas
Rhabdomyomas are firm, white, well-cir- intracavitory spaces {1254}. Foetal dys- appear as homogeneous, well-circum-
cumscribed lobulated nodules that occur rhythmias or non-immune hydrops may scribed echogenic masses in the ventric-
ular myocardium, possibly protruding
into the ventricular cavity. Although
uncommon, extensive rhabdomyomas
can be associated with ventricular dys-
function. Given that the finding of multi-
ple cardiac masses is diagnostic of rhab-
domyoma, especially in patients with
tuberous sclerosis, and that the tumours
are not infiltrative, echocardiography
usually provides adequate information
for diagnosis and clinical management. If
there is question of tumour type or of
tumour invasion, MRI or CT may be used
to further define the tumours. At MRI,
rhabdomyomas appear as well-circum-
scribed masses with signal characteris-
A B tics similar to that of normal myocardium
Fig. 4.01 Rhabdomyoma. A Echocardiogram of an infant who presented with supraventricular tachycardia. {155,737,1003}. Compared with the sig-
There are multiple rhabdomyomas. These eventually regressed and the arrhythmias resolved. nal from uninvolved myocardium, the
B Echocardiographic imaging from the apical chamber view, showing multiple cardiac rhabdomyomas masses are hypointense on post-
involving the left (LV) and right (RV) ventricles. gadolinium imaging. At CT, rhabdomy-
Immunoprofile
Immunohistochemical studies document
the striated muscle characteristics of
rhabdomyoma cells, which express myo-
A B globin, desmin, actin, and vimentin.
Tumour cells do not express cell prolifer-
ation markers such as Ki-67 and PCNA,
indicating that the lesions are more likely
hamartomas as opposed to neoplasms
{248}.
Electron microscopy
By electron microscopy, the cells resem-
ble altered myocytes. They possess
abundant glycogen, small and sparse
C D mitochondria, and cellular junctions
Fig. 4.02 Cardiac rhabdomyoma. A Multiple rhabdomyomas in an infant with tuberous sclerosis complex resembling intercalated disks surround
(courtesy of William D. Edwards, M.D.). B Intraoperative photograph. The tumour nearly fills the ventricu- the cell periphery. In contrast, the inter-
lar cavity, and is glistening and polypoid. C Stillborn child with a ventricular rhabdomyoma. D Subaortic calated disks of differentiated myocytes
rhabdomyoma in an 5 months old child. are located exclusively at the poles of the
cell. Intercalated discs and myofibrils or
collections of Z band material are pres-
omas also appear as multiple nodules, cially in sporadic cases. In one series of ent. Rarely one may observe there primi-
which may be hyper or hypoattenuating 14 cases, the range was 0.3-9.0 cm, with tive T-tubules. Leptomeric fibers close to
compared to normal myocardium. With a mean of 3.4 cm {248}. They most often the sarcolemma may also be identified.
MRI or CT, the rest of the body can be occur in the ventricle, but can be found
imaged for signs of tuberous sclerosis. in the atria, at the cavoatrial junction and Differential diagnosis
However, because rhabdomyoma has on the epicardial surface. Large tumours The diagnosis of cardiac rhabdomyoma
many imaging features similar to normal may obliterate and distort a ventricular in infants and young children is straight-
myocardium, echocardiography, MRI, cavity. forward. In patients with multiple non-cal-
and CT may be complementary as rhab- cifying masses, especially with other
domyomas that are not visible by one Histopathology manifestations of tuberous sclerosis
modality may be visible on another {737}. Cardiac rhabdomyomas are well-demar- complex, a tissue diagnosis is unneces-
cated nodules of enlarged cardiac sary. However, because the tumours
Macroscopy myocytes with cleared cytoplasm. In have been shown to regress with age
Single or multiple, they are well-circum- some cells, strands of eosinophilic cyto- and multiple biopsies do not allow for
scribed, non-capsulated white or grey plasm stretch from a central nucleus to evaluation of the morphologic changes
white nodules which may vary in size the cell membrane giving rise to cells that characterize this process, the rela-
from millimeters to several centimeters. that resemble a spider (“spider cells”). tionship between persistent rhabdomy-
Tumours can become quite large, espe- The majority of cells show vacuolization omas and so-called adult rhabdomy-
A B
Fig. 4.03 Rhabdomyoma. A The subendocardium shows a poorly demarcated area of cellular vacuolization. Fig. 4.04 Cardiac rhabdomyoma with classic spider
B A higher magnification note "spider" cells, several vacuolated tumor cells, and cells with abundant cell.
eosinophilic cytoplasm , which is more typical for rhabdomyomas in older children.
Rhabdomyoma 255
omas and hamartomas is not clear. In the be continued until the arrhythmias or The female preponderance is 3:1. In
rare examples of rhabdomyomas in older tumours regress. If drugs fail to control approximately 5% of cases there seems
children, there is often a paucity of spider arrhythmias, surgical resection is indicat- to be a familial tendency.
cells, resulting in a tumour with some ed. When a tumour is causing intracar-
characteristics of adult rhabdomyomas, diac obstruction, surgery is necessary Clinical features
but without the proliferative activity. {180,525,538,1289}. Histiocytoid cardiomyopathy is an
Hamartoma of mature cardiac myocytes, arrhythmogenic disorder; 70% of pub-
which, like rhabdomyoma, is a non-prolif- lished cases the patients present with a
erative hamartomatous lesion, occurs in Histiocytoid cardiomyopathy spectrum of arrhythmias and electrical
adults. These tumours lack circumscrip- disturbances including: paroxysmal atrial
tion and spider cells. Definition tachycardia, atrial fibrillation, ventricular
Histiocytoid cardiomyopathy is a rare, fibrillation, ventricular tachycardia, pre-
Genetic alterations but distinctive arrhythmogenic disorder mature atrial contractions, premature
The familial form of tuberous sclerosis, caused by a neoplastic or hamartoma- ventricular contractions, Wolff-Parkinson-
which is present in up to 50% of patients tous proliferation of cardiac cells with White syndrome, and right or left bundle
with cardiac rhabdomyoma, exhibits some Purkinje cell characteristics. branch block.
autosomal dominant inheritance. Two Approximately 20% of patients present
disease genes have been identified: Synonyms as sudden death and often such cases
TSC-1 at chromosome 9q34, and TSC-2 Purkinje cell hamartoma, arachnocytosis have been misclassified as Sudden
at chromosome 16p13 {1613}. The TSC- of the myocardium, infantile cardiomy- Infant Death Syndrome (SIDS). Other
1 gene encodes hamartin, and TSC-2 opathy, infantile xanthomatous cardio- infants experience flu-like symptoms pre-
tuberin, proteins involved in tumour sup- myopathy, oncocytic cardiomyopathy, ceding or accompanying the cardiac
pression. Loss of heterozygosity is often focal lipid cardiomyopathy, isolated car- manifestations. The majority of patients
found at these loci in tumours from diac lipidosis, infantile cardiomyopathy (95%) display cardiomegaly, but may
patients with tuberous sclerosis. The pre- with histiocytoid changes, myocardial or also have a number of associated anom-
cise roles of TSC-1 and TSC-2 in the conduction system hamartoma, foamy alies, including cardiac malformation
development of cardiac tumours and myocardial transformation, and congeni- (16%): ventricular and atrial septal
regulation of embryonic and neonatal tal cardiomyopathy. defects, hypoplastic left heart syndrome;
cardiomyocyte growth remain to be elu- and endocardial fibroelastosis. Extra-
cidated. Epidemiology cardiac anomalies occur in 17% of
Histiocytoid cardiomyopathy occurs pre- patients including corneal opacities,
Treatment and Prognosis dominantly in the first two years of life; microcephaly, cataract, aphakia, hydro-
Rhabdomyomas have a natural history of 20% of cases are diagnosed in the first cephalus, agenesis of the corpus callo-
spontaneous regression {204,556,1840}. month, 60% in the first year, and less sum, cleft palate, laryngeal web, and lin-
However, serious symptoms may precip- than 3% after two years of life. The preva- ear skin defect. Combined cardiac and
itate the need for surgical resection. lence of this disease may be higher than extracardiac anomalies occur in 4%, and
When arrhythmias are the presenting the reported cases would suggest, since 7% show extracardiac histiocytoid cells
symptom, treatment with anti-arrhythmic some cases are undoubtedly diagnosed in exocrine and endocrine glands {1794}.
drugs is commenced. If control is as Sudden Infant Death Syndrome
achieved by that means, then drugs can (SIDS).
A B
Fig .4.05 Histiocytoid cardiomyopathy. A Gross picture of the heart, showing multiple histiocytoid nodules in the aortic valve leaflets, endocardium, and papillary
muscles (arrows). B Macroscopic photograph of a heart demonstrating the left ventricle and portion of the mitral valve. Note pale tan endocardial nodules at the
level of the annulus.
Etiology may show a mottled appearance with able size, scattered desmosomes, inter-
Many theories of the etiopathogenesis irregular ill-defined yellowish-tan areas. calated discs, and leptometric fibers.
have been proposed, including viral
infection, myocardial ischemia, toxic Histopathology Differential diagnosis
exposure, and metabolic disorders such Histiocytoid cardiomyopathy lesions The disease has been confused with mito-
as glycogen storage disease, cardiac appear as multifocal, ill-defined islands chondrial cardiomyopathy. However, there
lipidosis, and various mitochondrial of large polygonal cells with granular are major gross, light microscopic, and
myopathies. However, the clinical, gross, eosinophilic cytoplasm, small round to ultrastructural differences between the two
microscopic, and ultrastructural findings oval shaped nuclei containing occasion- diseases. Mitochondrial cardiomyopathy
show clear differences between the al nucleoli. The cytoplasmic appearance shows no discrete nodules as present in
above-mentioned disorders and histiocy- is due to extensive accumulation of mito- histiocytoid cardiomyopathy. Additionally,
toid cardiomyopathy. The clinical presen- chondria. The cells are distributed along in mitochondrial cardiomyopathy, all
tation (arrhythmia), the distribution of his- the bundle branches of the conduction myocytes are affected, but to a variable
tiocytoid cells, and their ultrastructural system. The sinoatrial and atrioventricu- degree, whereas in histiocytoid cardiomy-
and immunohistochemical characteris- lar nodes are involved in 28% of cases; opathy, only focal areas of the heart are
tics, all point to the cardiac conduction however, these areas are not sampled involved, but the affected cells are affect-
system as playing a key role. The primi- routinely {1794}. ed totally. The ultrastructural changes in
tive Purkinje cells of the developing heart histiocytoid cardiomyopathy cells consist
show a striking resemblance to histiocy- Immunoprofile of increased numbers of mitochondria with
toid cells. Both types of cells show strong Histiocytoid cardiomyopathy cells react and without structural changes and
positivity for cholinesterase by frozen with anribodies to desmin, myoglobin, reduced myofibrils. In mitochondrial car-
section histochemistry and for neutral myosin, and muscle specific actin. There diomyopathy, the mitochondria are consis-
lipids with the Sudan Black stain. is no expression of macrophage or histi- tently abnormal in a varitey of ways. They
Cholinesterase is present only in the con- ocyte antigens (CD68, CD69, MAC 387, are enlarged, show variation in size and
duction tissue of the heart; it is not pres- LN3, HAM-56). The cells also fail to react shape, contain occasional glycogen parti-
ent in contractile myocytes {1794}. with antibodies to vimentin and cytoker- cles, and have cristae which are
atin (CAM-5.2), whereas S-100 protein increased in number and on cross section,
Macroscopy reactivity is variable. Cell proliferation are arranged in a concentric circular fash-
Single or multiple subendocardial yellow- markers (Ki-67 and MIB-1) are usually ion (like growth rings of a tree) surrounding
tan nodules or plaques ranging from 1- negative {682,1713}. occasional dense bodies.
15 mm may be seen in both ventricles,
the septum, and on all four cardiac Electron microscopy Genetic susceptibility
valves. Although these nodules are main- Ultrastructurally, the cells of histiocytoid Familial recurrence of histiocytoid car-
ly seen beneath the endocardium follow- cardiomyopathy show poorly developed diomyopathy in 5% of cases has led to
ing the distribution of the bundle branch- intercellular junctions. Their cytoplasm several proposals of a genetic mecha-
es of the conduction system, they can contains a superabundance of swollen nism. The female preponderance of
also be seen in the inner myocardium mitochondria with disorganized cristae cases suggests an X-linked mutation
and subepicardial areas. Lesions may be and dense membrane bounded gran- causing prenatal lethality in the homozy-
grossly inapparent as nodules, but multi- ules, which push the diminished myofib- gous male {168,234,1898}. A female
ple cross sections of the myocardium rils to the periphery of the cell. The cyto- infant with “oncocytic cardiomyopathy”
plasm also contains lipid droplets of vari- and microphthalmia with linear skin
Adult cellular rhabdomyoma tures distinguish these tumours from tumours, the absence of tumour necro-
other cardiac tumours with muscle differ- sis, mitotic figures, myogenin expression,
Definition entiation. and the presence of a well-defined
Adult cellular rhabdomyoma is a benign pseudocapsule help to distinguish it from
neoplasm of striated myocytes. A similar Histopathology rhabdomyosarcoma.
tumour frequently occurs in the head and These tumours are histologically distinct
neck region (extracardiac rhabdomy- from cardiac rhabdomyomas, and are Histogenesis
oma). composed of tightly packed, round to The lesion is believed to be a true neo-
polygonal cells with eosinophilic, finely plasm of striated muscle origin.
ICD-O code 8904/0 granular cytoplasm, occasional vacuoles
and occasional spider cells. Conversely, Somatic genetics
Epidemiology cardiac rhabdomyomas are composed Due to the rarity of these lesions, molec-
The adult form of extracardiac rhab- of large cells with clear cytoplasm con- ular and genetic characterization has not
domyoma occurs primarily in the head taining abundant glycogen and many been undertaken. In extracardiac rhab-
and neck region of men and women over spider cells. domyoma, a reciprocal translocation
40 years. Four cases of “extracardiac” between chromosomes 15 and 17 and
rhabdomyomas have been described in Differential diagnosis abnormalities of the long arm of chromo-
the heart {241,2226}. In contrast to congenital rhabdomyomas, some 10 have been described {680}.
adult cellular rhabdomyomas occur in
Clinical features and localization adults, demonstrate evidence of cellular Prognosis and predictive factors
Three of the four reported cases of adult proliferation e.g. by expression of Ki-67 The prognosis of adult cellular rhab-
cellular rhabdomyoma have occurred in antigen, and contain relatively few vac- domyoma is unknown, but presumed to
the atria, and all have occurred in adults uolated or spider cells. Unlike hamar- be benign, based on the biologic behav-
from 35-55 years of age. Common to any toma of mature cardiac myocytes, the iour of extracardiac rhabdomyomas in
heart tumour, the mode of presentation is tumours are well circumscribed, and adults. Late recurrences have been
often electrical disturbance such as although not as frequent as in congential described in extracardiac rhabdomyoma
supraventricular tachycardia or nonsus- rhabdomyoma, some vacuolated cells {680}.
tained ventricular tachycardia. The are usually present. Furthermore, the dis-
masses may be identified incidentally. organized masses of myofilaments char-
acteristic of hamartoma of mature car-
Macroscopy diac myocytes are not seen. Rhabdo-
They range in size from 2–5 cm. The myosarcoma shares some features with
tumours are soft, bulging, tan to brown adult cellular rhabdomyoma. Despite the
and have a pseudocapsule. These fea- evidence of cell proliferation in the latter
Imaging
At echocardiography carciac myxomas
typically appear as a mobile mass
attached to the endocardial surface by a
stalk, usually arising from the fossa
ovalis. Myxomas with this appearance
can be confidently diaganosed by
A B echocardiography and further imaging is
not necessary {1298}. In fact, because
Fig. 4.10 Cardiac myxoma. A Long axis MRI view of the left ventricle demonstrating a well-circumscribed
myxoma (T) centered in the left atrium. The inferior portion of the mass abuts the tricuspid valve. B The the tumours are usually small and
mass seen in the previous figure (T) originates from the atrial septum and is best demonstrated on the axial mobile, myxomas are typically better
view. The right-sided effusion and consolidation (E) are unrelated to the myxoma (the patient had metasta- defined by echocardiography than by
tic malignant melanoma, with an incidental cardiac myxoma). either MRI or CT, because echocardiog-
Histopathology
The myxoma cells may be arranged
C D singly, in cords, or in vasoformative ring
structures {245,361,1625}. The cells can
be elongated, fusiform or stellate. They
contain modest amounts of eosinophilic
cytoplasm. Nuclei are oval, round, or
elongated and mitoses are very rare.
Myxoma cells have a tendency to form
primitive or differentiated vessels, reflect-
ed in expression of endothelial markers.
Less myxoid stroma often forms a halo
around the vascular formations.
E F
The stroma contains variable amounts of
Fig. 4.11 Cardiac myxoma. A This incidental finding at autopsy is a sessile smooth surfaced mass attached
proteoglycans, collagen and elastin. It
to the endocardium of the let atrium at the level of the oval fossa. Note the relationship to the mitral valve,
which may often become partly obstructed in patients with left atrial myxoma, resulting in pulmonary hyper-
shows strong reactivity with alcian blue,
tension. B Myxoma of the left atrium, with typical localization at the fossa ovalis. C Cut surface of a papil- resistant to predigestion by hyaluro-
lary myxoma of the left atrium. D Papillary myxoma with necrosis, left atrium. E Left atrial myxoma after nidase. The vessels within the tumour are
resection. F Left atrial myxoma with an old and recent haemorrhages. thin-walled and lack pericytes. Occa-
sionally, cavernous vascular spaces con-
taining blood or proteinaceous material
raphy has the best spatial and temporal Multiple tumours occurring at sites other are encountered. Thick walled blood ves-
resolution. If the narrow stalk is not visi- than fossa ovalis and ventricles are gen- sels with prominent muscular walls are
ble, the diagnosis cannot be made by erally found in the inherited form of car- present predominantly at the base of
echocardiography and further imaging, diac myxoma. Very rarely, cardiac myxo- tumour and in the stalk. Extravasated red
usually MRI, is necessary to show the mas have also been documented to cells, foci of recent and organizing
tumour’s margins and to exclude tumour occur on valves and chordae tendineae. haemorrhage and hemosiderin deposi-
infiltration. At MRI and CT myxoma tion are frequent. Hemosiderin is seen
appears as an intracavitary heteroge- The external appearance, consistency, free within the stroma, within histiocytes
neous, lobular mass. As with echocardio- size and weight are extremely variable. and myxoma cells. Variable numbers of
graphy, if the narrow stalk is visible, myx- They may be as small as a few millime- lymphocytes, plasma cells, macro-
oma can be diagnosed by MRI or CT ters and as large as 14 cm in diameter. phages, dendritic cells, and mast cells
{66}. The weight ranges from 2-250 gm. Tiny may be present.
cardiac myxomas may be totally asymp- Gamna-Gandy bodies as seen in chron-
Macroscopy tomatic and discovered incidentally at ic venous congestion of the spleen may
Cardiac myxomas are intracavitary surgery for another purpose or autopsy. be encountered infrequently. Calcifi-
masses that occur most often in the left Larger ones are either sessile or pedun- cation and metaplastic bone formation
atrium {361}. They arise from the endo- culated, but the site of attachment is may also occur. The latter are more fre-
cardium of the atrial septum near the always discrete and usually in the region quent in right atrial myxomas. The sur-
fossa ovalis in 85-90% of cases. Most of of the fossa ovalis. Occasionally, the face is usually composed of a single
the remainder are located in the right atri- stalk may be long, resulting in free mobil- layer of flattened cells, but multilayering
um. Rarely, they arise in the ventricles. ity of the tumour within the atrial cavity. and tufting may occur.
Immunoprofile
E F
The cells are cytokeratin negative, vari-
Fig. 4.12 Cardiac myxoma. A Numerous rudimentary vessels. B Three stages of rudimentary vessels.
ably S-100 positive, and variably positive
C A primitive endothelial marker, CD34 is often present within the central areas of the vascular structures
for smooth muscle and endothelial mark- formed by cardiac myxoma. D Cardiac myxoma glands with PAS-positive-diastase resistant material con-
ers e.g. CD 34 and CD31 {362,1269, sistent with mucus. E Cardiac myxoma with complex glands whose cells show moderate cytologic atypia.
1625,2013}. Calretinin is expressed in F Cytokeratin 7 staining of a cardiac myxoma with heterologous components.
about 75% of cardiac myxomas {16}.
Histogenesis
Some years ago myxomas were consid- histochemical properties of myxoma diac manifestations: abnormal skin pig-
ered nothing more than organised throm- cells {15,16}. On the other hand, car- mentation (lentigines and blue nevi), cal-
bi. Their neoplastic nature is supported diomyocyte-specific transcription factor cifying Sertoli-Leydig testicular tumours,
by the presence of chromosomal abnor- mRNAs have been recently found in RNA cutaneous myxomas, myxoid breast
malities {489}, abnormal DNA content extracted from myxoma lysates, suggest- fibroadenomas, pigmented adrenal corti-
{1226} and the presence of microsatellite ing cardiomyogenic differentiation in cal hyperplasia, pituitary hyperactivity,
instability {1853}. The presence of het- myxoma cells and a possible origin in psammomatous melanotic schwannoma
erologous elements, however, still sug- cardiomyocite progenitor cells {1037}. and thyroid tumours {295}. Familial myx-
gest to some that they may be reactive or omas are estimated to account for 7% of
hamartomatous {1925}. The origin of Genetic susceptibility atrial myxomas {299}, are more often
myxoma cells is unclear. They are Although most myxomas are sporadic, multiple, recurrent and right sided, as
thought to arise from subendothelial some have been associated with the compared to sporadic myxomas. The
vasoformative reserve cells or primitive myxoma complex {295,483}. This auto- affected patients are also younger, most
cells which reside in the fossa ovalis and somal dominat syndrome has been presenting at 20-30 years of age
surrounding endocardium. The minute reported under the acronyms NAME {530,1133,1544}.
endocardial structures described by (nevi, atrial myxoma, myxoid neurofibro-
Prichard {1618} do not seem to corre- ma, ephelides), LAMB (lentigines, atrial Somatic genetics
spond to the hypothetical subendothelial myxoma, mucocutaneous myxomas, The chromosomal patterns of sporadic
pluripotential vasoformative reserve cells blue nevi), and more recently as Carney cardiac myxoma are characterised by
from which the myxomas would arise, syndrome {295,299,530}. This syndrome extensive intratumour heterogeneity. In
because they do not share the immuno- includes cardiac myxomas and extracar- the seventeen cases published to date,
C D
Fig. 4.14 Papillary fibroelastoma. A Location at the aortic valve. B Movat pentachrome stain demonstrating an incidental papillary fibroelastoma on the surface of
the valve. In this example, there is little elastic tissue within the papillae. C Papillary fibroelastoma showing multiple fronds with prominent elastic tissue cores
(elastic van Gieson). D Fibroelastic papilloma with young vegetations.
Definition also enhance brightly with contrast vessel. This lobular or grouped arrange-
Haemangiomas (angiomas) are benign administration {1003}. At CT the tumors ment of vessels is helpful for distinguish-
tumours composed predominantly of are usually circumscribed, low attenua- ing these benign from malignant vascu-
blood vessels. The histologic classifica- tion, heterogeneous and also enhance lar proliferations. Mast cells and factor
tion includes those composed of multiple brightly with contrast administration. XIII-positive interstitial cells are a consis-
dilated thin-walled vessels (cavernous {737}. The circumscribed, non-infiltrative tent feature.
type), smaller vessels resembling capillar- appearance of haemangioma, particular- Intramuscular cardiac haemangioma has
ies (capillary type), and dysplastic mal- ly on MRI which is most sensitive to tis- superficial resemblance to arteriovenous
formed arteries and veins (arterio-venous sue infiltration, can be used to suggest malformation, with the presence of het-
haemangioma, cirsoid aneurysm). Car- that the neoplasm is benign, but a spe- erogeneous vessel types, including mus-
diac haemangiomas often have com- cific diagnosis cannot be made with cularized arteries, veins, and capillaries.
bined features of cavernous, capillary and imaging. In contrast to capillary haemangioma,
arteriovenous haemangiomas, and many they are infiltrative lesions and occur
contain fibrous tissue and fat. These fea- Localization within the myocardium. They are histo-
tures are reminiscent of intramuscular The most frequent locations are the later- logically identical to intramuscular hae-
haemangiomas of skeletal muscle. al wall of the left ventricle (21%), the mangiomas within skeletal muscle, and
anterior wall of the right ventricle (21%), may possess, in addition to the vessels,
ICD-O code 9120/0 the interventricular septum (17%) and fat and fibrous tissue. Because of the lat-
occasionally, the right ventricular outflow ter features, some intramuscular cardiac
Clinical features tract {226}. haemangiomas are misclassified as lipo-
Most cardiac haemangiomas are discov- mas or fibrolipomas.
ered incidentally but patients may pres- Macroscopy Cavernous haemangiomas are com-
ent with dyspnoea on exertion, arrhyth- The tumours are often large and gross posed of large dilated vascular spaces.
mias, right-sided heart failure, pericardi- appearance depends on the size of the They tend to infiltrate the myocardium.
tis, pericardial effusion, and failure to vascular spaces in the tumour. The cap- The lining cells are bland and flattened
thrive. Patients may have associated illary type is frequently slightly raised and mitotically inactive.
vascular syndomes e.g. Kasabach- from the endocardial sruface and
Merritt {675}. appears red to purple. Intramuscular Genetic susceptibility
types will appear infiltrative. Cavernous Genetic susceptibility to cardiac hae-
Imaging haemangiomas are usually large and are mangiomas has not been identified.
At echocardiography, haemangiomas also poorly circumscribed. Extracardiac haemangiomas occur in a
are usually hyperechoic, circumscribed, variety of contexts. They may be single
and intracavitary solitary masss. At MRI, Histopathology sporadic lesions or multiple lesions that
hemaniogmas may be intermediate to Capillary haemangiomas are composed are components of complex genetic syn-
high on T1 weighted images, often are of nodules of small capillary-size vessels, dromes. Capillary haemangiomas occur
very intense on T2 weighted images, and each of which is subserved by a “feeder” in up to 10% of live births and are the
most frequent tumour in newborns
{1409}. When these tumours occur in the
absence of associated syndromes, they
may represent manifestations of an auto-
somal dominant mendelian trait (OMIM
#602089) {7}. Linkage analyses {224,
2101} of multiplex kindreds affected by
hereditary capillary haemangiomas have
identified loci on chromosome 5 (q31-
q33 and q13-q22) that appear to contain
as yet unidentified causal disease
A B genes.
Fig. 4.15 Cardiac haemangioma. A MRI of right atrial haemangioma in a newborn who underwent partial A wide array of complex syndromes,
surgical resection of the tumor. ECG-triggered breath-hold T2-weighted fast spin echo sequence shows a such as von Hippel Lindau syndrome
markedly hyperintense signal from the tumor (arrow). B Echocardiographic imaging of cardiac haeman- (OMIM #193300) and SC phocomelia/
gioma involving the interventricular septum in a 7-year-old boy. Roberts syndrome (OMIM #269000), that
Somatic genetics
Specific genes have been associated
with two disorders involving arteriove-
nous malformations. Mutations in the Fig. 4.16 Haemangioma. This lesion has some features of arteriovenous malformation, with a non-uniform
gene on chromosome 9p21 encoding the collection of thick walled arteries, dilated veins and capillaries. In addition, there is fat and fibrous tissue,
endothelial cell-specific receptor tyrosine as ooccasionally seen in an intramuscular haemangioma.
kinase TIE2 cause the autosomal domi-
nant Bean or “Blue rubber-bleb nevus”
syndrome (OMIM #112200) and familial
multiple cutaneous and mucosal venous
malformations (OMIM#600195) {2084}. At
least some cases of hereditary cerebral
cavernous malformations (OMIM
#116860) are caused by mutations in the
chromosome 7q21-q22 Krev interaction
trapped-1, KRIT-1, gene {1110}. KRIT1
normal binds to RAP1A, a Ras GTPase,
and the disease causing mutations
appear to disrupt these interactions.
Other genetic loci for this disorder have
been identified at chromosomes 17p15-
p13 and 3q25.2-q27 and remain to be
studied. The genetic and clinical relation-
ship of this disorder to hereditary neuro-
cutaneous angioma (OMIM #106070) is
unclear.
Syndromic associations
Fig. 4.17 Haemangioma. This tumor shows a relatively uniform population of capillary type vessels with vari-
The majority of cardiac haemangiomas
able degrees of dilatation. The myxoid background may suggest myxoma, but other features of myxoma are
are sporadic, without evidence of extrac-
absent, and the vessels are mature.
ardiac vascular lesions. Rarely, there
may be extracardiac haemangiomas of
the gastrointestinal tract and port-wine
stain of the face. Giant cardiac haeman-
giomas can result in thrombosis and
coagulopathies (Kasabach-Merritt syn-
drome) {239,675}.
Haemangioma 267
Benign tumours with myofibroblastic E. Dulmet
A.P. Burke
V. T. de Montpréville
C.T. Basson
differentiation T. Geva
H. Kamiya
G. Watanabe
P.A. Araoz
H. Tazelaar
Epidemiology Imaging
Most cardiac fibromas are discovered in At echocardiography fibromas typically
B
children and often before one year of age appear as a large, well-circumscribed, Fig. 4.19 Cardiac fibroma. A The tumour fills the left
{737,1944}. Prenatal diagnosis with solitary mass in the septum or ventricular ventricular cavity, which is obliterated. The right
ventricle and tricuspid valve are on the left.
sonography is possible {121,134,538}. free wall {1010,1242} and in some cases
B Cardiac fibroma with prominent whorled sur-
However, cases are also reported in may be confused with hypertrophic car- face.
adults {307} and even as an incidental diomyopathy {66}. The tumors are fre-
finding in the elderly {2093}. There is no quently very large and may cause
sex predominance. The incidence is very obstruction, which can be assessed by enhanced imaging usually demonstrates
low with only about 200 cases reported colour Doppler. MRI likewise shows a a hypoperfused tumour core. CT also
to date. large, solitary, homogeneous myocardial shows a large, solitary, ventricular mass,
mass centered in the ventricles {1003, which is usually low attenuation on CT.
Localization 1215,1660}. Because of the fibrous Unlike other imaging modalities CT may
The most common site of cardiac fibro- nature of the tumour, the signal intensity detect calcification which is a helpful fea-
ma is the ventricular septum, but the free is often less than that of adjacent unin- ture in making a confident diagnosis.
walls of the left and right ventricle are volved myocardium, and contrast- {66}. Overall, the imaging finding of a
A B C
Fig. 4.18 Cardiac fibroma. A Left ventricular fibroma in a 6-month-old infant. A. ECG-triggered breath-hold proton-density fast spin echo MRI with double inversion
recovery sequence in the axial plane showing a large inhomogeneous mass involving the left ventricular free wall. B MRI of left ventricular fibroma in a 6-months-
old infant. Post-gadolinium imaging shows enhancement of the uninvolved myocardium and the tumour’s periphery. Note the hypoperfused tumor core.
C Echocardiogram of an infant with a large right ventricular fibroma causing right ventricular outflow tract obstruction.
Immunoprofile
Tumour cells express vimentin and
smooth muscle actin, both in cellular and
fibrous lesions. They do not express
desmin, CD34 or S-100 protein.
Reacitivity for markers of proliferation,
are much more frequent in cellular
tumours than in the fibrous ones {451}.
Somatic genetics
A clonal translocation has been
A described in cell cultures of a subepicar-
dial fibroma resected from an infant.
Cytogenetic analysis in this tumor
showed a clonal reciprocal translocation,
46,XY,t(1;9)(q32;q22),inv(9)(p11q12)c
{572}.
Genetic susceptibility
Approximately 3% of patients with Gorlin
syndrome have cardiac fibromas {418,
547,716}. Gorlin syndrome (or nevoid
basal cell carcinoma syndrome) is an
autosomal dominant disorder character-
ized by generalized body overgrowth,
jaw keratocysts, developmental abnor-
malities of the skeleton, and a predispo-
sition to neoplasms, specifically cardiac
fibroma. Gorlin syndrome results from
germline mutations in the PTC gene,
which maps to chromosome 9q22.3 and
B is homologous to the Drosophila patched
Fig. 4.20 Cardiac fibroma. A Fibroma infiltration into adjacent myocardium. B Calcifications in a fibrous
(ptc) gene {756}. The ptc gene encodes
lesion from a 19-year-old patient.
a transmembrane protein in Drosophila
that represses the Hedgehog signaling
solitary, very large, hypovascular mass in a bundles. They are not encapsulated and pathway to control cell fate, growth, and
child is suggestive of a cardiac fibroma. extend into the surrounding myocardium. development {756,893}. These data sug-
Even in grossly circumscribed cases, gest that the PTC gene not only functions
Macroscopy entrapped myocytes can often be seen as a tumour suppressor gene, but also
They are typically rounded masses that deep within the tumours, far from the plays a critical role in development.
are fibrous, white and whorled, reminis- gross margins {244,451}. The fibroma However, the precise role of the PTC
cent of uterine leimyomas. The margin cells have oval or tapered nuclei without gene in myocardial cell growth and dif-
may be either circumscribed or infiltra- nucleoli. Their cytoplasm is pale. These ferentiation and its role in the develop-
tive. In some cases, fibromas are mas- cells are associated with abundant col- ment of cardiac fibroma remains to be
sive and can obliterate ventricular cavi- lagenous stroma, which increases with defined {2077}.
ties. They are nearly always mural, the age of the patient. Cellular lesions are Associated hydrocephalus, cleft lip and
although polypoid endocardial based observed in infants during their first palate, and Sotos syndrome (megalen-
lesions have been reported. Most occur months of life, while fibromas in older cephaly with gigantism) have been
singly. The mean diameter is 5 cm. patients contain large amounts of colla- reported {446,1242}.
gen. Mitoses and foci of extramedullary
Histopathology haematopoiesis may be present in cellu- Prognosis and predictive factors
Fibromas are composed of bland-looking lar tumours {451}. Calcification is The cardiac fibroma is benign, but its
spindle cells forming loose intersecting observed in lesions from patients of all nature of slow but continuous growth
Treatment
Operative intervention is usually required
{451,615,2071}. When the tumour proves
unresectable, heart transplantation is an
option {731,2071}. However, favourable
late results even after incomplete exci-
sion have been reported {132,307,1880}.
Inflammatory myofibroblastic
tumour
Definition Fig. 4.21 Inflammatory myofibroblastic tumour of the left ventricle. Plump spindle cells are arranged in a
Inflammatory myofibroblastic tumour is haphazard fashion and focally surround myocytes. A modest chronic inflammatory cell infiltrate including
composed of myofibroblasts accompa- plasma cells is also present.
nied by a variable number of inflammato-
ry cells including lymphocytes, macro-
phages, plasma cells and eosinophils. inflammatory myofibroblastic tumour has 100 protein and p53. It is unknown if
been reported in a patient with systemic ALK-1 expression is diagnostically useful
ICD-O code 8825/1 vasculitis and another tumour regressed in cardiac inflammatory myofibroblastic
spontaneously. tumours as is the case with extracardiac
Synonyms tumours.
Plasma cell granuloma, inflammatory Macroscopy
pseudotumour and possibly inflammato- Inflammatory myofibroblastic tumours of Differential diagnosis
ry fibrosarcoma the heart are large lesions, measuring up In contrast to fibromas, inflammatory
to 8 cm {451}. Grossly, they tend to have myofibroblastic tumours are endocardial
Epidemiology relatively narrow attachments to the lesions, and there is often organizing fib-
These tumours are very rare in the heart, endocardium and project into the ven- rin thrombus on the surface. In addition
and only small series and case reports tricular lumen. the tumours are more histologically vari-
appear in the literature. able, the spindle cells are larger than in
Histopathology fibromas and the cells often have nucleoli.
Localization Inflammatory myofibroblastic tumor is
Although there is a predilection for the composed of spindled myofibroblasts, Prognosis and predictive factors
ventricles, especially the right ventricular fibroblasts, chronic inflammatory cells The biologic behavior of inflammatory
outflow tract, any site in the heart may be and sometimes eosinophils. Various myofibroblastic tumour is that of a low-
involved {1177}. combinations of these cell types make grade lesion with the propensity for recur-
these tumours quite variable from one rence, but overt malignancy is rare. No
Clinical features case to another Occasional mitoses and case of metastases arising from cardiac
Signs and symptoms foci of necrosis may be present. inflammatory myofibroblastic tumour has
There are no specific signs or symptoms been reported.
related to cardiac inflammatory myofi- Immunoprofile
broblastic tumour, as these are related to The tumour cells strongly express actin
location within the heart. One cardiac and vimentin, but not desmin, CD34, S-
Definition
Benign tumour composed of mature,
white adipocytes.
Epidemiology
Cardiac lipoma is rare and found in fewer
than 1 in 10,000 autopsies {1116}.
Lipomas generally account for only 0.5-
3% of excised heart tumours {121,573,
952,1257,1672}. Higher estimates of up
to 10% of heart tumours are likely be-
cause lipomatous hypertrophy, a sepa-
rate entity, has been included
{1257,1628}. Lipomas occur in children,
but account for less than 2% of heart
Fig. 4.23 Lipomatous hypertrophy. Lipomatous hypertrophy of atrial septum. Note the multivacuolated
tumours similar to the relative incidence
adipocytes which can mimic liposarcoma.
in adults {134}.
Definition in advanced years occurs, the congeni- valves. Tumour cells occur in nests or
Congenital multicystic tumour or rest tal nature is not proved in all. Evidence line the variably sized cystic spaces.
located at the base of the atrial septum in that limited cell proliferation occurs in Cells can interdigitate with myocytes
the region of the atrioventricular node. some cases may explain presentation within the inferior septum, resulting in
Lining cells may be derived from primi- later in life, and patients may live for degenerative changes within the
tive endoderm. decades with complete heart block {64}. myocytes. Cells may be cuboidal, transi-
tional, squamoid or show sebaceous dif-
ICD-O code 8454/0 Localization ferentiation. Multilayering may occur
By definition they occur adjacent to the along the cyst walls {240,1157,1189}.
Synonyms atrioventricular node. Similar lesions
Mesothelioma of atrioventricular node, have not been described elsewhere in Immunohistochemistry
lymphangioma, endothelioma, inclusion the body. The cells strongly express cytokeratin,
cyst, Tawarian node, benign mesothe- epithelial membrane antigen, carcinoem-
lioma of Mahaim, endodermal rest, con- Clinical features bryonic antigen and B72.3. Cells may
genital polycystic tumour of atrioventricu- Two-thirds of patients present with com- also express calcitonin and serotonin.
lar node, intracardiac endodermal het- plete heart block, 15% with lesser {465,523,1173,1345}.
erotopia. degress of atrioventricular block, and
10% with sudden death without docu- Electron microscopy
Epidemiology mented history of heart block {240}. The Two cells types are characteristic. Within
The mean age at presentation is 38 years remainder are incidental findings in new- the solid nests, cells have well formed
(range birth- 78 years) and women are borns and infants with structural heart basement membrane, cytoplasmic
more frequently affected than men defects. Only rarely are atrioventricular tonofilaments and desmosomes. Cells
(approximately 3:1). One patient with nodal tumours detected in patients with lining the spaces are also connected by
long standing heart block survived to normal sinus rhythm. Most tumours have desmosomes, have short microvilli and
age 95, at which time the diagnosis was first been diagnosed at autopsy but in may contain electron dense material
made at autopsy {64}. vivo diagnosis has been reported {102}. {240}.
A B C
Fig. 4.24 Cardiac angiosarcoma. A CT section at the level of the aortic valve demonstrates a soft tissue mass completely filling the right atrium. B Cardiac angiosar-
coma arising in right atrioventricular groove, forming a papillary right atrial mass. Note the extensive pericardial involvement. C Metastatic angiosarcoma to the
lung, forming multiple haemorrhagic subpleural nodules (courtesy of Dr. William D. Edwards).
Pleomorphic malignant fibrous In a recent review, 81% of 47 cases were majority occur in the left atrium, where
histiocytoma (MFH) / left atrial {1508}. The other reported loca- they most often present like cardiac myx-
Undifferentiated pleomorphic tions included the pericardial space (3 omas, they more commonly arise along
sarcoma cases), right ventricle/ pulmonary valve the posterior wall in comparison to the
(3 cases), right atrium (1 case), and left septum {1056,1142,1526}.
Definition ventricle (1 case) {1508}. Although the
Malignant fibrous histiocytoma or undif-
ferentiated plemorphic sarcoma is high-
grade malignancy showing fibroblastic
or myobroblastic differentiation and
areas of marked cellular pleomorphism.
Malignant fibrous histiocytomas and
fibrosarcomas represent a broad spec-
trum of mesenchymal tumours and the
degree of cellular pleomorphism is the
major distinguishing feature.
ICD-O code
Malignant fibrous A B
histiocytoma 8830/3
Synonym
Malignant fibrous histiocytoma is now
regarded as synonymous with undiffer-
entiated pleomorphic sarcoma, as many
tumours formerly classified as MFH have
been found to have evidence of myo-
genic or other more specific differentia-
tion.
C D
Epidemiology
Malignant fibrous histiocytoma, as histor-
ically defined, is the second most com-
mon malignant cardiac sarcoma in adults
and, if considered with all undifferentiat-
ed sarcomas represents the most com-
mon sarcoma. There is no gender
predilection and the mean age is around
45 years (range, 20-80 years). Rare
cases have been reported in infants. E F
Fig. 4.29 Malignant fibrous histiocytoma (pleomorphic undifferentiated sarcoma). A In this example, there
Localization is a myxoid background and a prominent vascular pattern reminiscent of myxoid malignant fibrous histio-
Malignant fibrous histiocytoma tends to cytoma found in soft tissue. B Malignant fibrous histiocytoma arising in left atrium where it initially mim-
be located in the left atrium of the heart, icked a cardiac myxoma. Note mitotic activity. C Note pleomorphic growth pattern. D Malignant fibrous
most commonly the posterior wall and / histiocytoma with osseous differentiation (osteosarcoma). Note formation of the mature bone trabeculae.
or interatrial septum {1056,1142,1526}. E Osteoid formation. F Cartilagenous differentiation.
Localization
Fibrosarcomas are most common in the
left atrium, but have been reported to
arise in all chambers. Fibrosarcomas
may also infiltrate the pericardial space,
thus mimicking mesothelioma {1034}.
Clinical features
The clinical features of fibrosarcomas
have not been well-delineated from relat-
ed cardiac sarcomas such as malignant
fibrous histiocytoma (undifferentiated Fig. 4.31 Embryonal rhabdomyosarcoma predenting as small cell undifferentiated tumor with cellular areas
pleomorphic sarcoma) as the classifica- concentrated towards the surface.
tion of these lesions has not been stan-
dardized in large series. As with other
sarcomas, signs and symptoms vary phasic synovial sarcoma, inflammatory Rhabdomyosarcoma
depending on the location of the tumour. myofibroblastic tumours and localized
Because most occur on the left side of fibrous tumours, and for the myxoid vari- Definition
the heart, signs and symptoms related to ant, other myxoid sarcomas (MFH, Rhabdomyosarcoma is a malignant
pulmonary congestion, mitral stenosis leiomyosarcoma, etc.) and cardiac myx- tumour with striated muscle differentiation.
and pulmonary vein obstruction are most oma. The latter is generally distinguished
frequent. Rarely, cardiac fibrosarcoma by the presence of myxoma cells, abun- ICD-O code 8900/3
may present with metastases in the dant organizing hemorrhage, and
lungs, lymph nodes, skin, and kidney. absence of mitotic figures and high cel- Epidemiology
lularity. Fibromas are easily distinguished Rhabdomyosarcoma is a very rare sub-
Macroscopy from typical fibrosarcoma by lack of cel- type of cardiac sarcoma. In the past,
Fibrosarcoma typically presents as a soft lularity and abundant collagen. before immunohistochemical documen-
polypoid tumour projecting into the tation of tumour histogenesis was routine,
chamber from whose walls they arise. Prognosis and predictive factors it was stated that a large proportion of
They have a gross appearance similar to See discussion on treatment of maligant cardiac sarcomas were rhabdomyosar-
MFH {329}, but haemorrhage, necrosis, fibrous histiocytoma. There is no proven comas. However, in more recent series,
and variegation are less common. difference in prognosis between cardiac the proportion is less than 5% {250}, and
fibrosarcoma and malignant fibrous histi- in one recent series of cardiac sarcomas
Histopathology ocytoma as demonstrated in a meta- with rigorous immunohistochemical doc-
Fibrosarcoma of adult type is composed analysis using actuarial methods {249}. umentation, none of 24 was classified as
of spindle shaped cells arranged in rhabdomyosarcoma {509}.
sweeping fascicles that are often
arranged at angles to one another result- Localization
ing in a “herringbone” pattern. The nuclei Rhabdomyosarcomas occur anywhere in
are usually elongate with tapered ends the heart. Approximately 50% occur in
and darkly staining. Mitotic activity is the atria, and 50% in the ventricles. The
variable. In the myxoid variant tumour frequency of ventricular involvement is
cells spindling is less pronounced and greater than other cardiac sarcomas.
cells may take on a stellate or ovoid con- Contrary to sarcomas with fibro- or myofi-
figuration. However in all types pleomor- broblastic differentiation, they are not
phism is minimal and prominent vascu- usually intracavitary tumours, but are
larity is absent. more often mural.
Differential diagnosis Fig. 4.32 Embryonal rhabdomyosarcoma with rhab- Clinical features
The differential diagnosis for the typical domyoblasts containing abundant eosinophilic Cardiac rhabdomyosarcomas are usual-
variant of fibrosarcoma includes mono- cytoplasm. ly of the embryonal variant and, there-
fore, occur most frequently in children genin greatly facilitates the diagnosis been detected in cardiac rhabdomyosar-
and young adults; it is the most common {1630}. Desmin is also useful in docu- coma {662}.
primary cardiac malignancy in children. menting muscular differentiation.
The mean age at presentation is approx- Alveolar rhabdomyosarcoma, character- Treatment
imately 20 years, compared to 40-50 ized by a collagenous stroma and a Surgery
years of age for other subtypes of car- paucity of rhabdomyoblasts, has been Surgical resection of the tumour is usual-
diac sarcoma. Rhabdomyosarcoma is described in the heart generally as a ly indicated even if it is considered as
more likely than other primary cardiac metastatic lesion.Sarcoma botryoides, palliative to relieve obstruction to cardiac
sarcomas to involve the valves. The clin- with characteristic grape-like structures blood flow and to clarify the diagnosis
ical presentation, as with other cardiac and a so-called cambium layer, a form of {301,470,952}. Total orthotopic heart
tumours, depends on the cardiac loca- embryonal rhabdomyosarcoma, has also transplantation may offer relatively long-
tion. been described in the heart {760}. term survival {67,701,733} if there are no
distant metastases.
Macroscopy Differential diagnosis
Cardiac rhabdomyosarcomas are bulky, The differential diagnosis includes other Chemotherapy
invasive tumours that may be grossly cardiac sarcomas, especially undifferen- Although the outcome of chemotherapy
mucoid or gelatinous, similar to cardiac tiated lesions and metastatic small round on cardiac rhabdomyosarcoma has not
myxoma, or soft and necrotic, with varie- cell tumours in children and young been fully studied, due to the rarity of the
gation and heterogeneity. They usually adults. Immunohistochemical stains are tumour, there have been advances in the
arise within the myocardium and are less vital in identifying rhabdomyoblasts. treatment of soft tissue rhabdomyosarco-
likely than sarcomas with myofibroblastic Adult cellular rhabdomyomas, in contrast ma {423,529, 1194,1749} with a three-
or fibroblastic differentiation to be endo- to rhabdomyosarcoma, lack significant year progression-free survival of approx-
cardial based, luminal tumours. mitotic activity, necrosis, and do not imately 65%. Neoadjuvant chemotherapy
express myogenin. may optimize a surgical approach
Tumour spread and staging {1749}.
Sites of metastatic spread are, in order of Electron microscopy
descending frequency: lungs, regional The diagnostic features are thick and thin Radiotherapy
lymph nodes, central nervous system, filaments reminiscent of normal striated Adjuvant radiotherapy is commonly
gastrointestinal tract, kidney, adrenals, muscle. Internal A and I banding may or mandatory to preclude local relapse or to
thyroid, ovary, bone and pancreas. may not be present, but Z-bands are fre- optimize the results of a surgical
quently well formed. Plentiful glycogen approach. However radiotherapy may be
Histopathology granules and abundant mitochondria are used preoperatively to decrease tumor
Cardiac rhabdomyosarcomas are almost also present. Tumour nuclei are lobulat- size and allow surgical resection.
exclusively embryonal. Embryonal rhab- ed, containing variable amounts of con-
domyosarcoma is small cell neoplasm densed chromatin. Occasionally, several Prognosis and predictive factors
with variable numbers of PAS-positive grids must be examined before rhab- Specific prognostic microscopic features
rhabdomyoblasts (tadpole or strap domyoblasts are identified. have not been devised for cardiac rhab-
cells). Well-differentiated embryonal domyosarcomas. However, grading is
rhabdomyosarcoma has numerous tad- Somatic genetics similar for other subtypes of cardiac sar-
pole-shaped rhabdomyoblasts. Nuclear At exon 1 of K-ras, a mutation at the first comas, and includes an assessment of
staining with antibodies against myo- base of codon 13 (G to A transition) has mitotic activity and necrosis {509}. The
Rhabdomyosarcoma 279
A B
Fig. 4.34 Synovial sarcoma. A The tumour is highly cellular and composed predominantly of spindled cells. The epithelial areas may be difficult to discern on rou-
tine stains. B Immunohistochemical stain demonstrating expression of pancytokeratin in islands of epithelial cells.
prognosis is poor, with recurrence and oriented at sharp angle or 90° to one 300,400,1466}. The true incidence has
eventual metastasis with death of the another. Inconstant characteristic fea- probably been underestimated, as
patient within months the rule {1944}. The tures include the presence of cytoplas- molecular studies can now confirm the
mean survival rarely exceeds 12 months. mic glycogen and perinuclear vacuoles. diagnosis in the monophasic variant,
Pleomorphic and giant cells may be which is the most common form in the
present. Zones of necrosis and mitotic heart. An association between cardiac
Leiomyosarcoma figures are generally plentiful. Usual synovial sarcoma and asbestos expo-
immunohistochemical markers of neo- sure has been reported {1144}.
Definition plastic cells are smooth muscle alpha
A malignant tumour composed of cells actin and desmin. Alpha actin also Localization
with distinct smooth muscle features. shows numerous normal little vessels in There is a predilection for the atria and
the tumour tissue. There may occasional- pericardial surfaces.
ICD-O code 8890/3 ly be aberrant expression of cytokeratin
and epithelial membrane antigen. Clinical features
Epidemiology Demonstration of smooth muscle cell Clinical symptoms may arise from
Cardiac leiomyosarcoma is uncommon, derivation virtually confirms malignancy, obstruction, embolism, and tamponade.
representing less 10% of cardiac sarco- as leiomyomas remain undescribed in
mas. There is no sex predilection, and this location. Macroscopy
most occur in patients between 40 and Synovial sarcomas are bulky, infiltrative
50 years of age. Treatment and prognosis tumours that are typically firm and white.
Treatment consists of surgical excision, Necrosis or hemorrhage may be present.
Clinical features almost always incomplete. This may
Dyspnoea is the main clinical feature. allow some patients several months of Histopathology
Sometimes patients present with chest symptom free survival, typically less than The classic lesion is biphasic, but the
pain, cough, atrial arrythmias, or haemo- one year. Chemotherapy and radiation monomorphic variant is especially com-
ptysis. therapy may provide palliation. mon in the heart. The spindle component
resembles a fibrosarcoma, but alternating
Macroscopy cellular and oedematous areas are typi-
Most of them are located in the left atrium Synovial sarcoma cal. The spindle cells are small, compact,
(posterior wall) and invade pulmonary and often infiltrated by sparse mononu-
veins or mitral valve. But, tumours can Definition clear lymphoid cells. The epithelioid cells
arise elsewhere, including the right atri- Synovial sarcoma is a biphasic tumour form clusters and nests, and occasional-
um and ventricle, or pulmonary valve or composed of spindled and epithelioid ly larger gland–like spaces which may
trunk. The tumours tend to be firm, fleshy, areas, characterized by X;18 chromoso- show branching. Immunohistochemically,
grey and sessile. They may present as mal translocations. cytokeratin and epithelial membrane anti-
multiple intra-cavitary nodules. gen are strongly expressed in the epithe-
ICD-O code 9040/3 lioid cells. Staining for these markers in
Histopathology the spindle cells may be very focal.
Leiomyosarcoma is composed of com- Epidemiology Spindle cells express vimentin and occa-
pact bundles of spindle cells that pos- Synovial sarcomas account for approxi- sionally smooth muscle actin. The cells
sess blunt-ended nuclei and are often mately 5% of cardiac sarcomas {173, do not express CD34.
Differential diagnosis differential diagnosis. Unlike mesothe- either of two genes, SSX1 or SSX2, at
Distinction of synovial sarcoma from lioma, solitary fibrous tumour is generally Xp11.2. This rearrangement of genes
mesothelioma, another biphasic tumour, lower-grade, usually expresses CD34 produces a chimeric SS18 /SSX tran-
can usually be made on the basis of antigen, is less cellular and tends to have script, which could be implicated in
tumour location (mesotheliomas do not alternating hyper- and hypocellular areas. tumourigenesis {375}. The SS18/SSX
occur within the atria) and growth pattern transcripts can be specific markers of
(synovial sarcoma is usually a circum- Somatic genetics synovial sarcoma that can be detected
scribed solitary lesion while mesothe- Cytogenetically the reciprocal transloca- by the reverse transcriptase-polymerase
lioma tends to grow diffusely over the tion t(X;18)(p11.2;q11.2) is seen in more chain reaction (RT-PCR). The transcripts
pericardium. Additionally, the spindle cell than 90% of soft tissue synovial sarco- can be identified in almost all synovial
areas of synovial sarcoma tend to be rel- mas {1330}. This is considered to be the sarcomas when there is adequate
atively monomophic. The X;18 transloca- primary cytogenetic abnormality and tumour RNA {837}. This molecular diag-
tion may be confirmed on formalin fixed, specific for synovial sarcomas. nostic method also can be applied to
paraffin embedded tissues and has a The breakpoints of the t(X;18) have been paraffin-embedded tissue {747}.
high degree of sensitivity and specificity cloned, and it has been shown that this
{1506}. Reactivity for calretinin has been translocation results in fusion of SS18
described in both mesothelioma and syn- gene (previously described as SYT or
ovial sarcoma, and is not helpful in the SSXT) at the chromosome 18q11.2 to
Definition a predisposing factor. However, the heart may be the only findings. In additon to
Primary cardiac lymphoma (PCL) is an is an uncommon site for immunodeficien- echocardiography, MRI, and CT, nuclear
extra-nodal lymphoma involving only the cy-related lymphoma. Most PCL arise in medicine techniques may be useful pro-
heart and/or the pericardium. A less immunocompetent patients. The median cedures for the non-invasive assessment
restrictive definition includes small sec- age of the reported cases is 62 years of cardiac lymphomas. Gallium-67
ondary lesions elsewhere, with the vast (range, 5-90 years) with a male-to-female uptake is non-specific, though a marked
bulk of the tumour arising in the heart. It ratio of 3:1. accumulation in the heart without extrac-
is clinically defined as a lymphoma pre- The clinical course is generally short, ardiac uptake can suggest the diagnosis
senting as cardiac disease with the bulk with a mean survival of 7 months (range, of PCL {1680}.
of the tumour being intra-pericardial. 0-48 months).
Cardiac involvement by disseminated Diagnostic approach
non-Hodgkin lymphoma should be Clinical features When pericardial effusion is present its
excluded. Signs and symptoms drainage may have both palliative and
The clinical course is generally acute in diagnostic purposes. Lymphoma cells
Epidemiology onset. There is no pathognomonic clini- may be detected in serous fluid in up to
PCL is an uncommon malignancy, cal presentation and patients are gener- 88% of cases {308}.
accounting for 1.3% of primary cardiac ally investigated because of chest pain, When cytology is not available, the diag-
tumours and 0.5% of extranodal lym- pericardial effusion, refractory heart fail- nosis of PCL is usually assessed by
phomas {249,273,1679}. The published ure, arrhythmia, or lightheadness and explorative thoracotomy with cardiac
series account for about 80 cases, while syncope due to a myxoma-like intracav- mass biopsy. Recently, less invasive pro-
cardiac involvement in disseminated itary mass {308}. Superior vena cava cedures have been performed, such as
lymphoma has been documented in obstruction {363}, multiple pulmonary transoesophageal echocardiography
nearly 20% of autopsy cases {1280}. The emboli and infarction {1832} and hyper- (TEE) guided percutaneous intracardiac
appearance of PCL in patients with AIDS trophic cardiomyopathy {266} have also biopsy {46,947}.
{1736} and in a kidney recipient {1667} been reported as initial diagnosis in
suggests that immunodeficiency may be patients with PCL. Complete atrio-ven- Macroscopy
tricular block may be the major clinical PCL may arise in either atrium or ventri-
presentation {1416}. cle. Usually the tumour is large, infiltrat-
ing myocardium and extending into the
Imaging right atrium and ventricle in the form of
Because the gross pathologic features of multiple intracavitary polypoid nodules,
primary cardiac lymphoma are variable, which may eventually obliterate the cavi-
the imaging findings are variable. ties. The right atrium is involved in more
Cardiac lymphomas most commonly than 2/3 of patients. The pericardium is
manifest as circumscribed, nodular usually thickened by white-greyish
masses in the myocardium, often with an tumour infiltration. Pericardial effusion,
associated pericardial effusion. These which is generally massive, may be iso-
findings are usually well seen at echocar- lated (12.5% of cases) or associated with
diography, MRI, and CT. Lymphoma may a heart mass (near half of cases) {737}.
also manifest as an ill-defined, infiltrative
mass, in which case, they are typically Cytology
best depicted with MRI because of its A diagnostic cytologic sample sample is
superior soft tissue contrast {66}. Internal obtained in less than 20% of primary car-
imaging features and contrast enhance- diac lymphomas (PCL) {1680}. It may be
ment patterns are very variable with car- difficult to differentiate PCL from benign
diac lymphomas. Lymphomas may have reactive lymphocytosis by cytology
high or low signal on MRI, may have sim- alone. Immunocytochemical staining
ilar attenuation as muscle or lower atten- {1724}, cytogenetic studies {1} and poly-
uation than muscle on CT, and may show merase chain reaction {964} have been
increased, or decreased contrast performed successfully to confirm the
Fig. 4.36 Cardiac lymphoma. Mulitofocal masses enhancement. In some cases, pericar- lymphoid lineage and detect the pres-
involving both atria and ventricular walls. dial effusion or pericardial thickening ence of a monoclonal population.
Definition tumor; haematogenously; via lymphatics; and there is less frequent infiltration of
Malignant cardiac neoplasm with a non- and rarely by intracavitary extension from epi- and endocardium.
pericardial or myocardial primary site. the inferior vena cava or pulmonary Leukemic and lymphomatous infiltrates
Metastatic tumors that infiltrate myocardi- veins. Lymphatic spread is generally are typically widespread, involving the
um are frequently accompanied by peri- accompanied by involvement and epicardium (61%), and myocardium dif-
cardial metastases, especially in the enlargement of pulmonary hilar or medi- fusely. The left ventricle is involved in
cases of carcinomas, which additionally astinal lymph nodes. Haematogenous 55%, and right atrium in 54% of cases.
involve mediastinal lymph nodes. spread is characterized by myocardial Sarcomatous deposits are found within
involvement. the myocardium (50%), pericardium
Epidemiology Epithelial malignancies typically spread (33%), or both myocardium and peri-
In a series of 133 surgically resected car- to the heart by lymphatics. Melanoma, cardium (17% of cases). Valvular metas-
diac tumors, 14% were metastatic sarcomas, leukemia and renal cell carci- tases are uncommon {764}.
{1411}. In a recent review, cardiac noma metastasize to the heart by a Osteosarcoma, liposarcoma, leiomyosar-
metastases were present in 12% of haematogenous route. Melanomas, renal coma, unclassifiable sarcomas, rhab-
autopsies performed for widespread tumours, including Wilms’ tumour and domyosarcoma, neurofibrosarcoma, syn-
malignancy {12}. Primary tumors in renal cell carcinoma, adrenal tumours, ovial sarcoma, and maligant fibrous histi-
decreasing order of frequency include liver tumours, and uterine tumours are ocytoma have been reported to involve
carcinomas of the lung, lymphomas, car- the most frequent intracavitary tumours. the heart secondarily.
cinomas of the breast, leukemia, carcino- Metastatic cardiac tumours affect the
mas of the stomach, malignant right side of the heart in 20-30% of Pathologic findings
melanoma, hepatocellular carcinoma cases, the left side in 10-33% of cases, Metastatic deposits may be diffuse,
and carcinomas of the colon. The follow- and show bilateral or diffuse involvement multinodular, or consist of a single domi-
ing tumors have an especially high rate in approximately 30-35% of cases. The nant mass. Especially with carcinomas,
of cardiac metastasis if the incidence of endocardium or chamber cavities are there may be diffuse studding and thick-
the primary tumor is considered: involved in 5% of cases {1398}. The most ening of the pericardial surfaces. This
leukemia, melanoma, thyroid carcinoma, common epithelial malignancies to pattern can grossly be confused with
extracardiac sarcomas, lymphomas, metastasize to the heart are carcinomas mesothelioma, or benign fibrosing peri-
renal cell carcinomas, carcinomas of the of the breast and lung. In most cases carditis. The tumour burden in the heart
lung and carcinomas of the breast. there is pericardial involvement with is the highest with melanoma, as com-
These tumors all had a greater than 15% superficial myocardial infiltration. The pared to any other malignancy.
rate of cardiac metastasis in a large valves and endocardium are usually Carcinomatous spread in the myocardi-
autopsy study {1398}. spared. Generally, the heart is not the um is frequently most prominent in
The rate of cardiac involvement by only organ involved, and metastatic subepicardial lymphatics, whereas
metastatic disease has not appeared to deposits are usually present in extracar- melanomas, sarcomas, renal cell carci-
change over a 14-year period, indicating diac sites. nomas and lymphoid neoplasms form
that current treatment modalities may not The myocardium is involved in virtually intramyocardial interstitial tumours. The
have a significant effect on the rate of 100% of cases of metastatic melanoma, histopathologic distinction between pri-
metastatic malignancy to the heart. mary and metastatic sarcoma may be
impossible upon surgical resection of a
Clinical features cardiac tumour. Most sarcomas metasta-
The cardiac location of the tumor greatly tic to the heart cause symptoms at their
affects the signs and symptoms. These primary site before cardiac symptoms
can include symptoms related pericar- are evident, however {764}. Although pri-
dial effusions, arrhythmias, or congestive mary sarcomas of the heart are uncom-
heart failure. Obstruction of the mitral or mon, extracardiac sarcomas presenting
aortic valve may cause syncope. Involve- as cardiac metastases are even rarer.
ment of the right heart and tricuspid
valves may give rise to right-sided failure.
Localization
Malignancies spread to the heart by Fig. 4.38 Metastases of a large cell carcinoma of
direct extension, usually from mediastinal the lung in the heart.
Fig. 4.40 Localized fibrous tumor of the mesothelium is identical in appearance to those of the pleura. Note
the spindle cell growth with prominent vascularity and variable cellularity.
Prognosis and predictive factors patients with mesothelioma who have no Immunoprofile
The prognosis is generally good, known exposure history. The immunohistochemical profile of peri-
although recurrences and local spread cardial mesothelioma is similar to that of
have been reported. Criteria for malig- Clinical features pleural mesothelioma. Expression of
nancy of pleural tumours include necro- Signs and symptoms mesothelial antigens, such as calretinin,
sis and a mitotic count of greater than 4 The mean age of patients with pericardial and cytokeratins 5/6 are helpful in the
per 10 high powered fields, but the appli- mesothelioma is about 45 years, with a diagnosis, as are negative reactions for
cability of these criteria to tumours in the wide age range, including elderly, older adenocarcinoma markers, such as carci-
heart and pericardium is unknown. children and young adults. The initial noembryonic antigen.
course is usually related to pericardial
effusions. Tamponade may eventually Electron microscopy
Malignant mesothelioma occur {1202}. Ultrastructurally, mesothelioma cells from
epithelioid areas contain branched,
Definition Imaging bushy microvilli. Cytoplasmic tonofibrils
Malignant mesothelioma arises from Echocardiography usually shows peri- are present in approximately 50% of
mesothelial cells or demonstrates cardial effusions and may show pericar- tumours. Asbestos bodies may be identi-
mesothelial differentiation. The definition dial thickening. However, because peri- fied within pericardial mesothelioma, but
of primary pericardial mesothelioma stip- cardium is at the periphery of the field of are of no diagnostic utility.
ulates that there is no tumour present view obtainable with echocardiography,
outside the pericardium, with the excep- MRI or CT are usually necessary. MRI Differential diagnosis
tion of lymph node metastases. and CT usually demonstrate pericardial The distinction between mesothelioma
fluid as well as pericardial thickening and pleural-based lung adenocarcinoma
ICD-O code 9050/3 and/or pericardial masses {737}. can be quite difficult, and is generally
based on immunohistochemical findings.
Epidemiology Macroscopy Distinction from reactive mesothelial cell
Mesothelioma of the pericardium repre- Malignant mesotheliomas of the peri- proliferations may also be difficult; in
sents approximately 0.7% of malignant cardium can form bulky nodules that fill comparison to reactive pleural mesothe-
mesotheliomas {831}. As with mesothe- the pericardial cavity. The tumour can lial proliferations, reactive pericardial
liomas in other sites, the incidence may also spread diffusely over the pericardial mesothelial cells may be more deeply
be increasing, due to the latency surface and completely encase the “invasive”. Reactive stromal cells may
between asbestos exposure and tumour heart. They can further encircle the great also often attain bizarre and pleomorphic
development {1074}. vessels and may obstruct the venae shapes, confusing the histopathologic
cavae. picture. Other malignancies that may be
Etiology confused with mesothelioma include
Like pleural mesotheliomas, a large pro- Histopathology pericardial-based angiosarcoma, which
portion of mesotheliomas of the peri- Malignant mesotheliomas of the peri- may elicit a prominent mesothelial
cardium are induced by asbestos {1074}. cardium resemble pleural mesothe- response, malignant solitary fibrous
Iatrogenically induced pericardial liomas. Although the majority are of the tumour and synovial sarcoma.
mesotheliomas have been reported epithelioid type, forming tubules, papil- Immunohistochemistry is invaluable in
decades after exposure to pericardial lary structures, and cords of infiltrating such circumstances. Mesothelioma lacks
dusting with asbestos and fibreglass as cells that can incite a desmoplastic the X;18 translocation of synovial sarco-
a treatment for angina pectoris. response, the sarcomatous variant is ma.
Therapeutic radiation for breast cancer also common. Variants similar to those
and mediastinal lymphoma has also described in the pleura may also be seen Prognosis and predictive factors
been implicated in rare patients. in the pericardium e.g. microcystic, ade- The prognosis of pericardial mesothe-
However, there remains a subset of nomatoid, deciduoid {1649,1802}. lioma is poor. Fifty per cent of patients