ORIGINAL ARTICLE
Surgical and Pathology Findings of Primary Malignant Cardiac Tumors:an eleven year experience(*)
Salvatore Esposito, MD; Lucio Agozzino, MD; Manuela Agozzino, MD, Franco Covino, MD; Pasquale Sante, MD, FECTS; Flavio Cerasuolo, MD; Attilio Renzulli, MD, FECTS; Mourizio Cotrufo, MD, FECTS
*Department of Pathology, 2nd University of Naples and °Department of Cardiothoracic Sciences,
V. Monaldi Hospital , Naples, Italy
Progress in cardiac imaging techniques allowed earlier diagnosis of malignant
cardiac tumors.
Between January 1978 and June 1999, 75 cases of
primary heart tumours were surgically excised,
8 of them (10.67%) were malignant.
They came from 4 males and 4 females, and with
age ranging from 3 weeks to 70 years (mean 29);
3 tumours came from 3 infants (<1 year);
the others developed in adult patients. All patients
survived the surgical excision but died during
the follow-up period.
The histotypes were: 3 rhabdomyosarcomas (RMS),
2 malignant fibrous histiocytomas (MFH), 1 immature
malignant intrapericardial teratoma, 1 fibrosarcoma
and 1 mesothelioma.
Among the 3 RMS, 2 were pleomorphic RMS (in the
adult patients), located respectively in both
atria and in the left ventricle and infiltrating
the anterior papillary muscle;
one (in a newborn) was an embryonal RMS of the
anterior left ventricular wall spreading in the
pericardium. MFH recurred twice in both patients;
one patient died of post-operative complications
after the second recurrence while the other patient
died of heart failure 84 months after the first
surgery.
Also immature malignant intrapericardial teratoma
recurred 2 months after the surgery; the newborn
died of post-operative complications such as the
newborn with fibrosarcoma.
The mesothelioma occurred in an adult patient
who died 5 months after the surgery.
Despite complete surgical resection, which is
initially successful, recurrence of tumor occurs
and late mortality is still very high (100%).
Our experience over a ten-year period confirms:
a) the difficult differential diagnosis between
primary sarcomas of the heart with other masses
including secondary tumours and b) the relatively
low incidence of heart malignancies in adults
(10.95%) versus a higher incidence in childhood
(37.5%). (Heart Views. 2001;2(2): 63-68) © 2001
Hamad Medical Corporation.
Key Words:
malignant primary heart tumour
heart sarcomas malignant
fibrous histiocytoma
heart rhabdomyosarcoma
Improvement in cardiac imaging techniques (echocardiography, angiocardiography,
computed tomography and RMN) has considerably
increased the number of patients with a primary
cardiac tumor referred for surgical excision.
Diagnosis was made at autopsy until a few decades
ago and was the main concern at necropsy to pathologists
(1) Surgical therapy is curative in all benign
tumours and in some tumours with low grade malignancy.
Heart transplantation has been reported for the
treatment of malignant tumours with no extracardiac
metastases (2).
The role of the pathologist nowadays is to perform:
a) morphological and histopathological examination
of surgical specimens; b) cytological examination
of pericardial effusion; c) histological examination
of biopsies from intracardiac masses; d) morphological
and histological examination of the explanted
heart.
Primary malignant tumors of the heart are relative
rare (3,4).
They account for about 25% in some autopsy studies
and 3.5% of surgical studies (5) and they are
frequently misdiagnosed as myxoma (3).
Rhabdomyosarcoma (RMS) is the most frequent malignant
tumour of the heart after angiosarcoma (1,4),
while malignant fibrous histiocytoma (MFH) is
relatively rare (6).
Intrapericardial teratoma is the most frequent
tumor in children (3). We reviewed our 11 year-experience
of cardiac pathology in order to establish the
incidence of malignant cardiac tumours and their
prognosis.
Eight of 75 primary heart tumours (10.67%) surgically excised from January 1978 to June 1999
at the Department of Cardiothoracic Sciences, 2nd University of Naples, and studied at our Institution, were malignant.
The histotypes were: 3 rhabdomyosarcomas (RMS), 2 malignant fibrous histiocytomas (MFH),
1 immature malignant intrapericardial teratoma,
1 fibrosarcoma and 1 mesothelioma (Table 1).
Tissues for light microscopy were fixed in formalin and embedded in paraffin.
Sections were stained with hematoxylin-eosin, periodic acid-Schiff (PAS), Weigert’s stain for elastic fibres, Alcian-PAS, Alcian Weigert stain for elastic fibres, von Kossa’s stain, Wilder’s reticulum, Masson’s and van Gieson’s trichrome and phosphotungstic-acid-hematoxylin stain (PTAH).
Tumor histotype was established also by immuno-histochemistry, using a large panel of antibodies, through avidin-biotin peroxidase method, against factor VIII-related antigen, desmin, myoglobin, muscle-specific actin, myosin, vimentin, a-1 antitrypsin, trypsin and lysozima.
RESULTS
Of the 3 rhabdomyosarcomas, one was a multiple tumour involving both atria (a 70 year-old woman admitted with clinical
diagnosis of multiple myxoma, who died 14 months after surgical operation); and one was in the left ventricle (Fig.1a),
|
Fig. 1 Histology findings of Rabdomiosarcoma: high-density proliferation of pleomorphic anaplastic cells with large and vesicular nuclei with well-defined nucleoli are shown |
infiltrating the anterior papillary muscle (a 23 year-old man who died 72 months after surgery with lung, bone and kidney metastases).
The third one was in the pericardium (a 28 day-old newborn who died during the post-operative course).
N
|
Tumours |
Sex |
Age |
Site |
Recurrence |
Outcome |
1
2
3
4
5
6
7
8 |
ERMS
RMS
RMS
MFI
MFI
MIT
PSM
FBS |
M
M
F
M
F
F
F
M |
27days
23 years
70 years
28 years
57 years
1 month
51 years
21 days |
Pericardium
Left ventricle
Left and
right atrium
Left atrium
Left atrium
Pericardium
Pericardium
Right atrium |
-
-
-
2
2
1
-
- |
Died
Died
Died
Died
Died
Died
Died
Died |
|
ERMEmbryonic
Rhabdomyosarcoma MIT Malignant Immature Teratoma
RMS Rhabdomyosarcoma PSM Pseudosarcomatous Mesothelioma
MFI Malignant Fibrous Histiocytoma FBS
Fibrosarcoma
The tumour size ranged from 3 to 5 cm.; they
were oval and similar in appearance to myxoma
with a soft consistency and a myxoid aspect.
At histology, the tumours excised in adult patients
were pleomorphic rhabdomyosarcomas characterized
by high-density proliferation of pleomorphic anaplastic
cells (Fig. 1) with large and vesicular nuclei
with well-defined nucleoli.
At times, cross-striations were evident in PTAH
stains. Immunohistochemical stains showed focal
and diffuse positivity (>50%) for myoglobin, myosin
and vimentin anti-sera.
The newborn’s tumour was an embryonal rhabdomyosarcoma
characterized by higher cellularity and abundant
mucoid intercellular material. PTAH and immunohistochemical
stains were negative.
One MFH was located in the left atrium and infiltrated the atrial wall (57 year-old female);
the other was in the left atrium (28 year-old male) (Fig. 2) In this patient, preoperative echocardiography is shown in Fig 3 The tumour recurred twice in both patients.
|
Fig. 2 Speciment of Hystocitoma surgically resected in a 28 year old male |
The female’s tumor recurred 18 months and 39 months after surgery; she died
after the third operation due to post-operative
complications.
The autopsy showed no metastases or residual tumour
in the heart. The male’s tumor, despite complete
excision which required mitral valve replacement,
recurred 23 months and 53 months after surgery.
This patient died while in the waiting list for
heart transplantation.
He died 84 months following the first operation
due to heart failure and tumor recurrence.
Both tumors were solid and ovoidal in shape, with
a myxoid aspect.
|
Fig.3 Preoperative echocardiographic evaluation through a transesophageal approach in the case shown in Fig 2.A mass attached on the atrial side of the anterior leaflet of the mitral valve is shown.In order to achieve complete tumor excission mitral valve was replaced with a tilting disc prosthesis |
They were composed of plump spindle cells with abundant cytoplasm and pointed ends that formed fascicles and had a focal storiform pattern.
The nuclei of the spindle cells were elongated with blunt ends and somewhat vesicular chromatin.
Many contained large eosinophilic nucleoli.
<>BR Polygonal cells with similar appearing cytoplasm and nuclei were also present in the tumour, either in small nests or mixed with spindle cells;
these cells somewhat resembled histiocytes.
Some inflammatory cells (lymphocytes, granulocytes) were intermingled.
Sparse multinucleated and bizarre giant cells were also observed. Mitoses averaged 10x10 high power field (HPF). They were observed mostly in the stromal cells and rarely in the giant cells.
No muscle-type cross-striations were identified on hematoxylin-eosin or PTAH.
On immunohistochemical study there was diffuse positivity for vimentin, a-1 antitrypsin and trypsin.
There was also focal positivity for lysozima, whereas there was no reactivity for muscle cell markers.
A 4 week-old female newborn was admitted with respiratory distress.
Chest radiography revealed marked cardiac enlargement and echocardiography disclosed a large pericardial effusion and dense layers of echoes (measuring 3 x 3 cm.) in the region of the anterior wall of the right ventricle and great vessels.
At surgery, there was a soft myxomatous mass (10 x 7 cm.), closely attached to the anterior wall of right ventricle. The mass was solid with some microcystic areas.
The tumour recurred two months later and the patient was readmitted with congestive heart failure. At surgery, a soft, solid, myxomatous mass similar to the previous tumor adhered to the anterior wall of the right ventricle invading the left pleural space was found. Complete excision of the recurrent tumor was performed. Postoperative course was complicated by right pneumothorax which was drained.
The patient was discharged home but she died on the 9th post-operative day of sudden death. Parents denied permission for autopsy.
At histology, the tumour showed differentiated tissues such as epidermoid or bronchial cysts, mature cartilage, bronchial glands, smooth or striated muscle and cerebral cortical parenchyma with well-differentiated glial and neuronal cells.
Immature tissue consisting of immature cartilage, undifferentiated mesenchyma, nests and cords of embryonic neuroephitelium with ependymal-like or neuroblastic rosettes (Fig 4) and lumina resembling retinal anlage were also observed; in the immature neurephitelial zones there was high mitotic activity.
Some embryoid bodies were also evident .
The recurrence was similar to the first mass, with the exception of the presence of adenocarcinoma-like zones and embryoid bodies.
|
Fig. 4 Undifferentiated mesenchyma, nests
and cords of embryonic neuroephitelium with
ependymal-like or neuroblastic rosettes
are shown
|
A 3 week-old male newborn was admitted with cyanosis and respiratory distress.
Echocardiography showed a mass attached to the anterior wall of the right atrium.
The post-operative clinical course was complicated by respiratory failure and the baby died on the 12th post-operative day.
At surgery, there was a compact elastic mass with calcifications. At histology, findings were consistent with fibrosarcoma with spindle-shaped cells that were arranged
haphazardly or in broad bundles or fascicles; a parallel arrangement of collagen and reticulin fibers was associated.
Foci of necrosis and high mitotic activity were present.
A 51-year old female was admitted with respiratory distress, dyspnea, dizziness and headaches; echocardiography disclosed a large pericardial effusion and dense layers of echoes in the pericardium; computed tomography showed a mass in the pericardium shifting the heart posteriorly. At surgery, a solid calcific mass (Fig 5) attached to the pericardium was excised.
|
Fig. 5 Speciment of Mesothelioma surgically resected |
|
Fig. 6 Histology of mesothelioma showed
spindle-shaped cells and of osteoclast-like
multinucleated giant cells; mitoses were
numerous,moderate pleomorphism and nuclear
atypia were observed
|
The patient unfortunately died suddenly 5 months later at home.
No metastases or residual heart tumour were found at autopsy.
At histology, the tumour consisted of spindle-shaped cells and of osteoclast-like multinucleated giant cells; mitoses were numerous (Fig 6) and there were moderate pleomorphism and nuclear atypia.
Rimming of osteoid spicules by appositional osteoblasts was seen.
Von Kossa’s stain showed diffuse calcific deposits in the tumour.
Immunohistochemical positivity for keratin was focal and scanty.
The diagnosis was mesothelioma with areas of bone-metaplasia.
Primary malignant tumours are relatively rare in the heart (1, 7).
The rhabdomyosarcoma is the most frequent malignant tumour after angiosarcoma (8) and sometimes it is multiple (3).
These tumours frequently give distant metastases (6), and as a result, surgical therapy fails.
In our cases, the tumours were surgically excised because the clinical diagnosis was myxoma in the adult patients and intrapericardial teratoma in the newborn.
Both adult patients died with diffuse extracardiac metastases, while the newborn died of post-operative complications; no distant metastases were found at the autopsy.
MFH is a well-known malignant tumour of the soft tissue and bone, but it is rarely found in other regions (8).
Heart MFHs are very rare; a recent review of the literature reported 11 cases (6).
MFH is an aggressive tumor which infiltrates the pericardium or the myocardium and is capable of giving distant metastases (9,10).
In our cases, MFHs recurred twice without extracardiac metastases.
One patient died in the post-operative course after the third operation and the autopsy showed no metastasis or residual tumour in the heart.
The other patient died of heart failure 84 months after the first surgery.
While the macroscopic aspect of MFH is similar to myxoma, both tumours grow as polypoid intracavitary masses with myxoid aspect, but unlike myxoma, MFH frequently infiltrates the myocardium (11).
The mixture of spindle cells arranged in a storiform pattern, polygonal cells resembling histiocytes, and malignant giant cells, is typical of the entity known as pleomorphic MFH (11).
Generally, it is difficult to find true histiocytic cells in the tumour (11).
On the other hand, Davies (12) has argued that any cardiac sarcoma which contains giants cells should be called a rhabdomyosarcoma, despite the absence of demonstrable cross-striations or other resemblances to muscle tumours.
While rhabdomyosarcomas are almost invariably highly aggressive tumours, the behaviour of MFH is less predictable.
Features such as mitotic index and cellular pleomorphism, which are useful in predicting the behaviour of many sarcomas, do not appear to be correlate with prognosis in this type of tumour (11).
In our cases, as in other reports (6), cardiac MFH recurred but failed to give distant metastases, so surgical excision was useful (2).
Intrapericardial malignant teratomas in infancy are rare (13,14).
Immature mediastinal teratomas are very rare and account for only 1% of mediastinal tumours (15).
Our case was a predominantly solid teratoma exhibiting both mature and immature tissues.
The embryonic tissue was more abundant in the recurrence. It consisted mostly of immature tissue neuroepithelium or other histological features of malignancy, such as increased cellularity, frequent mitoses and atypical nuclei.
Well defined histologic grades have been established for grading ovarian teratomas and that are linked with their eventual outcome.
The presence of immature neuroepithelium or other primitive tissue and mitotic activity is correlated with a poor diagnosis.
Metastatic capability has been found to correlate with the amount of immature neuroepithelium present.
A similar grading system, based on quantitative and qualitative assessment of the neuroectodermal component, has been formulated for sacrococcygeal tumors, but their correlation with prognosis is not as good as in the ovary (10,16).
The most unfavourable prognosis is linked to the presence of embryonal adenocarcinoma or yolk sac tumour areas (17).
Fibrosarcoma is an infiltrative tumour which occurs with equal frequency on the left and right side of the heart (3).
Microscopically, it consists of spindle-shaped cells, with elongated but blunt-ended nuclei, and tapering cytoplasm.
Pleomorphism and anaplasia are generally minimal, but mitoses are frequent.
Spindle cells are arranged haphazardly or in broad bundles or fascicles. MFH has fibrosarcomatous areas, often identical to differentiated fibrosarcoma, but a storiform or whorled pattern of the spindle cells and the presence of giant cells differentiate MFH from fibrosarcoma.
Surgical excision is not feasible and patients die generally post-operatively (3); our patient also died during the post-operative course.
Malignant mesothelioma is frequent in the pleura but more rare in the pericardium (3).
Histologically, it may be epithelial, spindle-cell or sarcomatoid and mixed.
Our case resembles sarcomatoid mesothelioma. In some features, it must be differentiated from extraskeletal osteosarcoma, which is very rare in the heart and generally intracavitary.
On the other hand, metaplastic bone and/or cartilage may occur in mesothelioma as in fibrosarcoma (3). The scanty positivity for keratin did not aid to differentiate the two tumours.
The mortality rate is high in malignant cardiac tumours and as a result, unlike myxoma, the role of the surgeon and pathologist is to achieve the longest remission of the disease.
Nevertheless, the majority of malignant heart tumors have high grade of local invasiveness but rarely give metastases.
Therefore, earlier diagnosis and preoperative staging with modern techniques of cardiac imaging can allow complete tumor excision and long-term diagnosis.
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