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Nodular fibroelastosis (Fibroelastic hamartoma) A tumorous malformation of the heart
Case Reports Nodular Fibroelastosis (Fibroelastic Hamartoma) A Tumorous Malformation
of the Heart*
GORDON M. FOLGER, JR., M.D. and HANS J. PETERS, M.D.1. Augusta,
Georgia
RIMARY tumors of the ventricular myocardium are uncommon lesions that may arise from a wide variety of cell types. Regarded until recently as pathologic curiosities, these bizarre abnormalities should now be considered important clinical entities. Adequate clinical descriptions, however, are found in a surprisingly small number of the reported cases, with few cases diagnosed before death. In the case described in this report, the diagnosis was established before death, and pathologic study indicated a tumorous malformation, principally of the left ventricle, which we believe to be a specific congenital myocardial entity.
The family cousin had
P
CASE
history revealed that a maternal second undergone surgical removal of a brain
tumor and two maternal
uncles were institutionalized
for
neuropsychiatric disorders. Physical examination on admission revealed a small, poorly developed infant, who was pale and tachypneic. Length was 61 cm. (twenty-fifth percentile), weight 4.7 kg. (below third percentile), pulse 160,’ min., respirations 60 to 80/min. and blood pressure 75/50 mm. Hg. The heart was enlarged to the anterior axillary line, and a prominent left ventricular impulse was felt laterally. A systolic thrill was palpable in the left axilla. The first and second heart
sounds were normal,
but a prominent
third
sound
was audible over the entire precordium. A grade 3/6 to-and-fro murmur with presystolic accentuation was heard; it was sharply localized to the left axilla. Except for its location, this murmur had the characteristics of the murmurs of combined mitral in-
REPORT
A white female infant was admitted to the teaching hospital of the Medical College of Georgia at age 4 months with signs of congestive heart failure. The chid was born to a gravida 3, para 3, 39 year old woman after an uncomplicated term pregnancy. Birth weight was 3,550 gm. A heart murmur heard at birth was initially attributed to anemia secondary to proved Rh factor incompatibility. In the neonatal period, the child was noted to tire easily when bottle-fed although she had no difficulty taking solid foods. Weight gain was poor. Rapid breathing had been present from birth. At age 3 months, she became noticeably worse and was unable to suck for more than brief periods before becoming exhausted. Frequent episodes of crying, interpreted by the mother as expressions of pain, had occurred.
sufficiency
and
stenosis.
Moist
rales
were
heard
throughout both lung fields. The liver was enlarged to below the umbilicus and did not pulsate. Pitting edema of the lower limbs was present. Laboratory Studies: Hemoglobin was 11.8 gm.%, hematocrit 37% and white blood cell count 7,300 per cu mm. with a normal differential count. The uncorrected erythrocyte sedimentation rate was 15 mm./hr. Urinalysis was normal. Routine blood chemistry values, including the transaminases and lactic dehydrogenase, were all within normal limits. The electrocardiogram (Fig. l), taken before digitalization, revealed a sinus rhythm, biatrial hypertrophy, left ventricular hypertrophy and unusual T
* From the Department of Pediatrics, the Hemodynamic Research Unit and the Department Medical College of Georgia, Eugene Tahnadge Memorial Hospital, Augusta, Ga. 30902. This in part by Grant No. HE-07266 from the National Institutes of Health. t Present address: Director of Laboratories, Saint Francis Hospital, Columbus, Ga. Address for reprints: Gordon M. Folger, Jr., M.D., Department of Pediatrics, Medical College Talmadge Memorial Hospital, 1120-15th St., Augusta, Ga. 30902.
420
THE
AMERICAN
of Pathology, the study was supported
JOURNAL
of Georgia,
Eugene
OF CARDIOLOGY
Nodular
wave changes that resembled those seen with left Ventricular ventricular strain rather than &hernia. activation was normal. Widening of the QRS complexes occurred after inscription of the initial segment This of the complex derived from the left ventricle. terminal slowing was particularly striking when contrasted with the normal intrinscicoid deflection, thus suggesting impairment of conduction in the more peripheral aspects of the left ventricle. The vectorcardiogram (Helm system, Fig. 2) further illustrated this slowing of conduction after normal initial inscription of the loop. Chzst roentgenograms (Fig. 3) revealed massive enlargement of the heart. The heart shadow extended superiorly in the frontal projection, thereby obscuring completely the vascular pedicle. Oblique views revealed enlargement of the left atrium and left ventricle. The pulmonary vascularity was normal, but there was a noticeable increase in the pulmonary venous pattern. At fluoroscopy, cardiac pulsation was greatly reduced. A radioisotope scan of the heart employing human albumin tagged with I I31 showed the entire lower segment of the ventricular shadow to be noncavitary (Fig. 4). The cardiac blood pool had an unusual contour and was elevated superiorly and to the right. During cardiac catheterization, pressures were elevated to 40 mm, Hg systolic in the right ventricle and pulmonary artery. Right atrial and right ventricular Passage of the end-diastolic pressures were normal. catheter across a patent foramen ovale revealed elevated left atrial pressures. The left ventricle was entered by advancing the catheter laterally toward the left axilla instead of in the inferior direction usually taken. A diastolic gradient of 8 to 10 mm. Left venHg was recorded across the mitral valve. tricular systolic pressure was normal, but the enddiastolic pressure was elevated. Cardiac output was no shunts were present. Recurrent episodes low; VOLUME
21,
MARCH
1968
421
Fibroelastosis
FIG.
1.
Abow,
electrocardiogram
(see
text 1.
of supraventricular tachycardia occurred during this study. Left atria1 and ventricular cineangiocardiography (Fig. 5) revealed, as had the cardiac scan, the presence of a large mass filling the major portion of the left ventricle, displacing it superiorly and to the right, with its apex pointing toward the left axilla. No contraction of the inferior border of the left ventricle could be seen, and only the superiorly displaced free wall demonstrated contractility. Mitral insufficiency was apparent. The left atrium was displaced to the right. Right ventricular cineangiocardiography (Fig. 6) showed a distorted chamber displaced to the right. Both great vessels arose unusually far to the right but maintained their usual relationship. The results of these studies conjrmed the diagnosis of a tumor of the wall of the left ventricle. A rhabdomyosarcoma was considered the most likely in view of the F ( 1041
H
5
h -/ !,, Ilm" ,l1 /'I ,',-: ' ' / ‘O \
40
2. Aboue, vectorcardiogram. With the exception of the prominent voltage increase, most notable is the presence of terminal slowing involving the posteriorly directed (left ventricular) forces. Numerals indicate time in milliseconds and direction of inscription.
FIG.
422
Folger and Peters
child’s progressive deterioration. The history of neuropsychiatric disorders in several family members suggested the possibility of a cardiac rhabdomyoma associated with tuberous sclerosis. Information now available about these persons does not reveal this abnormality. Surgical Findings: An exploratory cardiotomy was performed. When the chest was opened, the heart action was identical to that seen angiographically; the entire inferior aspect of the heart was firm and noncontractile. However, the superiorly displaced left ventricular free wall and the medially located right ventricle displayed active contraction. The mass comprising the bulk of the heart was pale, firm and solid. When the right ventricle was opened, its lumen was found to be small. The interventricular septum was involved by the tumor, which, due to its extent, was not resectable. The child withstood the operation surprisingly well. After her discharge, her general condition remained essentially unchanged, and intractable heart failure persisted despite active measures. The frequent episodes of protracted crying with apparent pain continued. She died during her third hospital admission at age 7 months.
FIG.
3.
Abor~c,
frontal chrf
radroi’rm
(SW
tcstj
AUTOPSY
The heart was enlarged and weighed 240 gm. A large, firm, white tumor occupied most of the apex. The lumen of the right ventricle was narrowed by the tumor, which occupied the posterior part of the interventricular septum. The right atrium was dilated. The left ventricle, greatly reduced and compressed by the tumor, had a hook-like configuration, and the aortic outflow tract was in a nearly horizontal position (Fig. 7). The left auricle was dilated. The tumor measured approximately 8 cm. in greatest dimension and spread out to the lateral walls of both the right and the left ventricle. It was well demarcated grossly from the surrounding myocardium, but several smaller independent nodules were present within the myocardium. The largest mass extended to the endocardial surface of the left ventricle and had several central foci of cystic necrosis. Microscopic examination (Fig. 8A) revealed the tumor to be fibrous, composed of slender cells having pale staining nuclei and eosinophilic cytoplasmic granules. It was not nearly so sharply demarcated from the surrounding myocardium as had been assumed from its gross appearance. No capsule separated the tumor from the normal myocardium. Occasional cardiac muscle bundles extended into the tumor. Nowhere was a transition from muscle fiber to tumor observed. The myocardium bordering the tumor was atrophied. Trichrome stain revealed, in addition to fibrous tissue, abundant collagen, which was seen to surround vessels and to extend along them occasionally to the endocardium. This unusual connective tissue when stained with picro-Sirius-red and resorcin-fuchsin appeared as immature collagen
FIG. 4. Below, radioisotope scan of heart. The blood pool indicated by the area of activity superiorly and to the right by the noncavitary cupying the left inferior area.
THE
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intracardiac is displaced portion oc-
OF CARDIOLOGY
Nodular
Fibroelastosir
FIG. 5. Cineangiocardiogram.r. Above left, left atria/. Single cineangiographic frame, frontal projection with selective injection into the left atrium (L.4). The left atrium is enlarged and displaced somewhat to the right. The left ventricle (LV) is small and lies lateral to the left atrium. The mitral valve, indicated by the arrows, is tilted upward, its orifice directed laterally. The inferior portion of the heart fails to opacify. The aorta (AO) arises to the right with more obliquity than is normal. App. = left atria1 appendage. Above right, left ventricular. Single cineangiographic frame, left anterior oblique projection with selective injection into the left ventricle. The cavity of the left ventricle is reduced to a slit-like crescent by the nonopacified mass inferior to it. FIG. 6. At right, right ventricular cineangiogram. Single cineangiographic frame, frontal projection with selective injection into the right ventricle (RV). The right ventricle is displaced superiorly and compressed from below. The origin of the pulmonary artery (PA) is prominently displaced to the right.
similar to that seen in endocardial fibroelastosis (Fig. 8B). Mitotic figures were not seen, and no evidence for a true neoplastic process could be found. The remainder of the gross and microscopic autopsy findings failed to reveal any other pertinent lesions. VOLUME
21,
MARCH
1968
Tumor tissue enzyme studies performed by Dr. J. B. Sidbury, Jr., at Duke University Medical Center revealed no increase in the content of glycogen, phosphoglucomutase, phosphorylase, maltase, or amylo-1, 6 glucosidase.
424
Folger
and
Peters
FIG. ?. Gross aj$eara?~e of the tumor. The heart is opened from
the apex. The tumor is apparent in the interventricular septum, and the entire apex is obliterated. The left ventricle (LV)
is compressed to a narrow
slit,
and distortion of the right ventricle (RV) is also seen. Arrow indicates the left ventricular outflow area.
DISCUSSION
This case represents a condition of the myocardium which clearly required differentiation from other forms of primary myocardial disease. Congestive heart failure had developed early in infancy. The clinical findings indicating a mitral valvular abnormality suggested endocardial fibroelastosisl and anomalous origin of the left coronary artery.2 The electrocardiogram, which was not characteristic for either lesion, suggested, in addition, the diagnosis of asymmetrical hypertrophy of the heart.3 A tumor was considered, and the similarity in the clinical course to the case of rhabdomyosarcoma of the left ventricle reported by Engle and Glenn4 led to the consideration of this possibility. Review of our findings and a comparison with previously recognized examples of fibrous ventricular tumors taken as a group is revealing. Although such tumors are found more commonly in childhood, they have been encountered throughout a wide age range. Of the previously reported 39 cases, 29 were in patients under age 6 years, 27 of these in patients under 3 years.5-11 Sudden death without recognized premonitory signs was the most common single feature; it occurred in one fourth
of the cases, often after some form of physical effort.‘** In those patients with definite symptoms occurring before the terminal episode, dyspnea appeared to predominate. g,i2-i4 Chest pain and episodes of pallor and coldness suggesting arrhythmia or coronary insufficiency have also been noted.1°J2J3 The physical findings, although no more specific, appear more uniform. In most instances, the heart was significantly enlarged, with chest asymmetry obvious in some.12J4-16 Systolic murmurs, generally nonspecific in nature, were usual, although not constant, findings. 6fg~12~14,16 The first and second heart sounds were routinely unaltered; a prominent diastolic sound was occasionally detected. Clinical Diagnosis: Although the diagnosis of this malformation ultimately depends on the angiographic findings,sJ4J7 it is apparent that it may be suspected from the more routine clinical studies. Several electrocardiographic features deserve comment. Foremost among these is the terminal delay pattern best seen in the QRS complexes recorded from the left precordial leads. This finding was demonstrated in all but 2 reported instances of this anomaly in which electrocardiography was THE
AMERICAN
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OF CARDIOLOGY
Nodular
FIG. 8. At right, low-power photo micrographs of the tumor. A, he matoxylin and eosin stain. A fibroelastic stroma comprises the bulk of the tumor. Arrows indicate myocardial fibers included within the stroma. (X 10, reB, resorcinduced by 97&) fuchsin stain. The elastic component of the tumor is repreented as darkly staining material. Myocardial fibers are seen within the stroma (arrow). (X 10, reduced by ‘I?(.)
VOLUME
21, MARCH1968
Fibroelastosis
425
426
Folger and Peters
performed and, together with the voltage and ST-T changes seen, constitutes the principal electrocardiographic feature.Y.14-16 However, similar voltage and ST-T aberrations may also be found in other c&diomyopathies, thus leaving the terminal delay pattern as a possible specific clue to the clinical diagnosis of this type of myocardial tumor. The vectorcardiogram furthe? documents this feature. Review of the published chest radiograms suggests that, in addition to the cardiac enlargement usually present,‘,‘” aIs.17 a squared-off configuration of the ventricular shadow is a frequent finding and may suggest the diagnosis.8J4J5 Isotopic scanning of the heart has not, to our knowledge, been previously employed in the identification of myocardial tumors, although Folger and co-workers3 reported employing this study with another space-occupying abnormality, asymmetrical hypertrophy of the heart. This case, as well as the present case, clearly demonstrates that any cavity-reducing lesion will cause alteration in and diminution of the intracavitary blood pool, and in this respect will be diagnostic. Surgical i~esection of left ventricular tumors is feasible and has been successfully carried out.9J4J7 In our patient, the involved area was so extensive as to preclude removal. Nevertheless, thorough surgical exploration is indicated in all proved cases. Pathogenesis: The incidence of this specific malformation is difficult to ascertain. Of the 39 cases of fibrous ventricular tumors previously reported, at least 17 appear to conform histologically to the classification of tumorous malformations within the myocardium of which the present case is representative.6-13J5--22 This condition appears to represent proliferation of fibrous tissue rather than a true fibroma, as ascertained by the histologic appearance of absence of a distinct capsule in any area and presence of myocardial fibers within the proliferation. Using special staining technics for connective tissue employing picro4irius-red,23 detailed histologic examination of the tumor in this case was performed. This method revealed multiple areas within the tumor in which the tissue closely resembled that seen lining the endocardial surface in endocardial fibroelastosis, thus suggesting an etiologic relation between the two conditions. Several investigators have used the term fibroelastic hamartoma to describe the appearance of this tissue.1g-21 Nodu-
lar fibroelastosis better describes this condition, which probably has as its origin the supporting tissue found within the ll+ocardiunl and is the result of an abnormal proliferation during cardiogenesis. We assume that such 17) pcrplastic connective tissue within the myocardiutu proliferates M ith the developing m)-ocardial fibers in the embryonic heart and ceases with cessation of myocardial fiber growth. Examples of this process rl:ay be found in the cardiac “fibromas” that are occasionaIl)seen in the rnyocardium of the elderly.‘” The ttltimate size of the tumor probably depends on both the extent and propensity for abnormal proliferation of the tissue. In view of the present findings, inclusion of this abnormality in the group of primary cardiomyopathies seems indicated. Further experience may substantiate our observations, thus allowing clinical diagnosis to be made with the degree of accuracy presently attainable in these other myocardial disorders. SUMMARY
A tumorous malformation, i.e., nodular fibroelastosis of the left ventricle and interventricular septum of the heart, is described. A relation between the tissue composing the mass and that seen with endocardial fibroelastosis is postulated. The clinical and laboratory findings bear distinct similarities to those of previously reported cases and suggest specificity for this type of malformation. Inclusion of this abnormality in the group of cardiomyopathies is recommended. ACKNOWLEDGMENT We thank Dr. Holde Puchtler for performing interpreting the special stains used in the study pathologic material.
and of the
REFERENCES J. H. et al. Endocardial fibroelastosis. A clinical and anatomic study of 47 patients with emphasis on its relationship to mitral insufficiency. CirEulation, 30: 759, 1964. 2. NOREN, G. R. et al. Anomalous origin of the left coronary artery from the pulmonary trunk with special reference to the occurrence of mitral insufficiency. Circulation, 30: 171, 1964. 3. FOLGER, G. M., JR., HARPER, D. T., JR. and MEHRIZI, A. Asymmetrical hypertrophy of the heart in childhood. Report of 3 cases. J. Pediat., 67: 204, 1965. 1. MOLLER,
Y
THE
AMERICANJOURNALOFCARDIOLOGY
Nodular 4. ENGLE: Xi. A. and GLENN, F. Primary malignant tumor of the heart in infancy. Case report and review of the subject. Pediatrics, 15: 562, 1955. 5. PRICHARD, R. W. Tumors of the heart. Review of the subject and report of one hundred and fifty cases. Arch. Path., 51 : 98, 1951. 6. BIGELOIY. X. H., KLINGER, S. and WRIGHT, A. W. Primary tumors of the heart in infancy and early childhood. Cancer, 7: 549, 1954. 7. FREEMAN, J. A., GEER, J. C., RANDALL, W. S., JR. and PALFREY, W. G. Intramural fibroma of the heart. Am. J. Clin. Path., 39: 374, 1963. 8. HOEN, ~2. G. and ELLIS, E. J. Intramural fibroma of the heart. Am. J. Cardiol., 17: 579, 1966. 9. GEHA, :\. S., WEIDMAN, W. H., SOULE, E. H. and M~GooN, D. C. Intramural ventricular cardiac fibroma. Successful removal in two cases and review of the literature. Circulation, 36: 427, 1967. 10. CLAY, R. D. and SHORTER, R. G. Intramural fibroma of the heart. J. Path. Back, 74: 163, 1957. 11. .\LBERS, J. T. H.: Atlas der pathologischen Anatomic fuer Praktische Aerate, p. 215. Bonn, 1833. Henry u. Cohen. 12. VALLEDOR, T. et al. Fibroma of the heart. Case report. Dis. Chest, 37: 698, 1960. 13. BOYETTE, D. P. and FOUSHEE, J. H. S. Cardiac libroma of the interventricular septum in a newborn infant. Case report. North Carolina M. J., 14.
21:544,1960. EDLUND, S. and
the heart. Report dinnr,., 46: 59, 1957.
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21,
MARCH
K. of a case.
HOLMDAHL,
1968
Primary tumour of Acta paediat. scan-
Fibroelastosis 15.
16.
427
U. and STANFIELD, M. H. 21 cast of fibroma of the left ventricle in a child of 4 years. Arch. Es. Childhood, 30: 187, 1955. MCCUE, C. M., HENNINGAR, G. R., DAVIS, E. and RAY, J. Congenital subaortic stenosis caused by a iibroma of the left ventricle. Pediatrics, 16: 372,
JAMES,
1955. 17.
PARKS, F. R., JR., ADAMS, F. and LONGMIRE, \1’. I’., Successful excision of a left ventricular JR. hamartoma. Report of a case. Circulation, 26: 1316,
1962.
18. JERNSTROM, P. and CREMIN, J. Il. Intramural fibroma of the heart. Am. J. Clin. Path., 32: 250, 19.
1959. SYMEONIDIS,
fibro-elastoesen Herzfibrom). 20.
21.
383,1938. NAEVE, W.
fibro-elastoeser Herzfibrom). FROBOESE, C. des kindlichen
22.
59,1955. PALLSTHY,
23.
128,1965. SWEAT, F.,
A.
and LINZBACH, A. J. Ueber die Hamartien des Myokards (Sag. Virchows Arch. path. Anat., 302:
Ploetzlicher Tod eines Saeuglings bei Harmartie des Myokards (Sag. Kinderarztl. Praxis, 23: 304, 1955. Grosses angeborenes Elastofibrom Herzmuskels. Arch. Kinderh., 151:
G. and T~TH, J. Primaere Herzgeschwulst eines neugeborenen mit Symptomen eines angeborenen Vitiums ( fibroma pseudomyxomatosum cordis). Helvet. paediat. acta, 20: PUCHTLER, H. and ROSENTHAL, Sirius red FSBA as a stain for connective Arch. Path., 78: 69, 1964.
S.
tissue.
I.
of the Heart*
GORDON M. FOLGER, JR., M.D. and HANS J. PETERS, M.D.1. Augusta,
Georgia
RIMARY tumors of the ventricular myocardium are uncommon lesions that may arise from a wide variety of cell types. Regarded until recently as pathologic curiosities, these bizarre abnormalities should now be considered important clinical entities. Adequate clinical descriptions, however, are found in a surprisingly small number of the reported cases, with few cases diagnosed before death. In the case described in this report, the diagnosis was established before death, and pathologic study indicated a tumorous malformation, principally of the left ventricle, which we believe to be a specific congenital myocardial entity.
The family cousin had
P
CASE
history revealed that a maternal second undergone surgical removal of a brain
tumor and two maternal
uncles were institutionalized
for
neuropsychiatric disorders. Physical examination on admission revealed a small, poorly developed infant, who was pale and tachypneic. Length was 61 cm. (twenty-fifth percentile), weight 4.7 kg. (below third percentile), pulse 160,’ min., respirations 60 to 80/min. and blood pressure 75/50 mm. Hg. The heart was enlarged to the anterior axillary line, and a prominent left ventricular impulse was felt laterally. A systolic thrill was palpable in the left axilla. The first and second heart
sounds were normal,
but a prominent
third
sound
was audible over the entire precordium. A grade 3/6 to-and-fro murmur with presystolic accentuation was heard; it was sharply localized to the left axilla. Except for its location, this murmur had the characteristics of the murmurs of combined mitral in-
REPORT
A white female infant was admitted to the teaching hospital of the Medical College of Georgia at age 4 months with signs of congestive heart failure. The chid was born to a gravida 3, para 3, 39 year old woman after an uncomplicated term pregnancy. Birth weight was 3,550 gm. A heart murmur heard at birth was initially attributed to anemia secondary to proved Rh factor incompatibility. In the neonatal period, the child was noted to tire easily when bottle-fed although she had no difficulty taking solid foods. Weight gain was poor. Rapid breathing had been present from birth. At age 3 months, she became noticeably worse and was unable to suck for more than brief periods before becoming exhausted. Frequent episodes of crying, interpreted by the mother as expressions of pain, had occurred.
sufficiency
and
stenosis.
Moist
rales
were
heard
throughout both lung fields. The liver was enlarged to below the umbilicus and did not pulsate. Pitting edema of the lower limbs was present. Laboratory Studies: Hemoglobin was 11.8 gm.%, hematocrit 37% and white blood cell count 7,300 per cu mm. with a normal differential count. The uncorrected erythrocyte sedimentation rate was 15 mm./hr. Urinalysis was normal. Routine blood chemistry values, including the transaminases and lactic dehydrogenase, were all within normal limits. The electrocardiogram (Fig. l), taken before digitalization, revealed a sinus rhythm, biatrial hypertrophy, left ventricular hypertrophy and unusual T
* From the Department of Pediatrics, the Hemodynamic Research Unit and the Department Medical College of Georgia, Eugene Tahnadge Memorial Hospital, Augusta, Ga. 30902. This in part by Grant No. HE-07266 from the National Institutes of Health. t Present address: Director of Laboratories, Saint Francis Hospital, Columbus, Ga. Address for reprints: Gordon M. Folger, Jr., M.D., Department of Pediatrics, Medical College Talmadge Memorial Hospital, 1120-15th St., Augusta, Ga. 30902.
420
THE
AMERICAN
of Pathology, the study was supported
JOURNAL
of Georgia,
Eugene
OF CARDIOLOGY
Nodular
wave changes that resembled those seen with left Ventricular ventricular strain rather than &hernia. activation was normal. Widening of the QRS complexes occurred after inscription of the initial segment This of the complex derived from the left ventricle. terminal slowing was particularly striking when contrasted with the normal intrinscicoid deflection, thus suggesting impairment of conduction in the more peripheral aspects of the left ventricle. The vectorcardiogram (Helm system, Fig. 2) further illustrated this slowing of conduction after normal initial inscription of the loop. Chzst roentgenograms (Fig. 3) revealed massive enlargement of the heart. The heart shadow extended superiorly in the frontal projection, thereby obscuring completely the vascular pedicle. Oblique views revealed enlargement of the left atrium and left ventricle. The pulmonary vascularity was normal, but there was a noticeable increase in the pulmonary venous pattern. At fluoroscopy, cardiac pulsation was greatly reduced. A radioisotope scan of the heart employing human albumin tagged with I I31 showed the entire lower segment of the ventricular shadow to be noncavitary (Fig. 4). The cardiac blood pool had an unusual contour and was elevated superiorly and to the right. During cardiac catheterization, pressures were elevated to 40 mm, Hg systolic in the right ventricle and pulmonary artery. Right atrial and right ventricular Passage of the end-diastolic pressures were normal. catheter across a patent foramen ovale revealed elevated left atrial pressures. The left ventricle was entered by advancing the catheter laterally toward the left axilla instead of in the inferior direction usually taken. A diastolic gradient of 8 to 10 mm. Left venHg was recorded across the mitral valve. tricular systolic pressure was normal, but the enddiastolic pressure was elevated. Cardiac output was no shunts were present. Recurrent episodes low; VOLUME
21,
MARCH
1968
421
Fibroelastosis
FIG.
1.
Abow,
electrocardiogram
(see
text 1.
of supraventricular tachycardia occurred during this study. Left atria1 and ventricular cineangiocardiography (Fig. 5) revealed, as had the cardiac scan, the presence of a large mass filling the major portion of the left ventricle, displacing it superiorly and to the right, with its apex pointing toward the left axilla. No contraction of the inferior border of the left ventricle could be seen, and only the superiorly displaced free wall demonstrated contractility. Mitral insufficiency was apparent. The left atrium was displaced to the right. Right ventricular cineangiocardiography (Fig. 6) showed a distorted chamber displaced to the right. Both great vessels arose unusually far to the right but maintained their usual relationship. The results of these studies conjrmed the diagnosis of a tumor of the wall of the left ventricle. A rhabdomyosarcoma was considered the most likely in view of the F ( 1041
H
5
h -/ !,, Ilm" ,l1 /'I ,',-: ' ' / ‘O \
40
2. Aboue, vectorcardiogram. With the exception of the prominent voltage increase, most notable is the presence of terminal slowing involving the posteriorly directed (left ventricular) forces. Numerals indicate time in milliseconds and direction of inscription.
FIG.
422
Folger and Peters
child’s progressive deterioration. The history of neuropsychiatric disorders in several family members suggested the possibility of a cardiac rhabdomyoma associated with tuberous sclerosis. Information now available about these persons does not reveal this abnormality. Surgical Findings: An exploratory cardiotomy was performed. When the chest was opened, the heart action was identical to that seen angiographically; the entire inferior aspect of the heart was firm and noncontractile. However, the superiorly displaced left ventricular free wall and the medially located right ventricle displayed active contraction. The mass comprising the bulk of the heart was pale, firm and solid. When the right ventricle was opened, its lumen was found to be small. The interventricular septum was involved by the tumor, which, due to its extent, was not resectable. The child withstood the operation surprisingly well. After her discharge, her general condition remained essentially unchanged, and intractable heart failure persisted despite active measures. The frequent episodes of protracted crying with apparent pain continued. She died during her third hospital admission at age 7 months.
FIG.
3.
Abor~c,
frontal chrf
radroi’rm
(SW
tcstj
AUTOPSY
The heart was enlarged and weighed 240 gm. A large, firm, white tumor occupied most of the apex. The lumen of the right ventricle was narrowed by the tumor, which occupied the posterior part of the interventricular septum. The right atrium was dilated. The left ventricle, greatly reduced and compressed by the tumor, had a hook-like configuration, and the aortic outflow tract was in a nearly horizontal position (Fig. 7). The left auricle was dilated. The tumor measured approximately 8 cm. in greatest dimension and spread out to the lateral walls of both the right and the left ventricle. It was well demarcated grossly from the surrounding myocardium, but several smaller independent nodules were present within the myocardium. The largest mass extended to the endocardial surface of the left ventricle and had several central foci of cystic necrosis. Microscopic examination (Fig. 8A) revealed the tumor to be fibrous, composed of slender cells having pale staining nuclei and eosinophilic cytoplasmic granules. It was not nearly so sharply demarcated from the surrounding myocardium as had been assumed from its gross appearance. No capsule separated the tumor from the normal myocardium. Occasional cardiac muscle bundles extended into the tumor. Nowhere was a transition from muscle fiber to tumor observed. The myocardium bordering the tumor was atrophied. Trichrome stain revealed, in addition to fibrous tissue, abundant collagen, which was seen to surround vessels and to extend along them occasionally to the endocardium. This unusual connective tissue when stained with picro-Sirius-red and resorcin-fuchsin appeared as immature collagen
FIG. 4. Below, radioisotope scan of heart. The blood pool indicated by the area of activity superiorly and to the right by the noncavitary cupying the left inferior area.
THE
AMERICAN
JOURNAL
intracardiac is displaced portion oc-
OF CARDIOLOGY
Nodular
Fibroelastosir
FIG. 5. Cineangiocardiogram.r. Above left, left atria/. Single cineangiographic frame, frontal projection with selective injection into the left atrium (L.4). The left atrium is enlarged and displaced somewhat to the right. The left ventricle (LV) is small and lies lateral to the left atrium. The mitral valve, indicated by the arrows, is tilted upward, its orifice directed laterally. The inferior portion of the heart fails to opacify. The aorta (AO) arises to the right with more obliquity than is normal. App. = left atria1 appendage. Above right, left ventricular. Single cineangiographic frame, left anterior oblique projection with selective injection into the left ventricle. The cavity of the left ventricle is reduced to a slit-like crescent by the nonopacified mass inferior to it. FIG. 6. At right, right ventricular cineangiogram. Single cineangiographic frame, frontal projection with selective injection into the right ventricle (RV). The right ventricle is displaced superiorly and compressed from below. The origin of the pulmonary artery (PA) is prominently displaced to the right.
similar to that seen in endocardial fibroelastosis (Fig. 8B). Mitotic figures were not seen, and no evidence for a true neoplastic process could be found. The remainder of the gross and microscopic autopsy findings failed to reveal any other pertinent lesions. VOLUME
21,
MARCH
1968
Tumor tissue enzyme studies performed by Dr. J. B. Sidbury, Jr., at Duke University Medical Center revealed no increase in the content of glycogen, phosphoglucomutase, phosphorylase, maltase, or amylo-1, 6 glucosidase.
424
Folger
and
Peters
FIG. ?. Gross aj$eara?~e of the tumor. The heart is opened from
the apex. The tumor is apparent in the interventricular septum, and the entire apex is obliterated. The left ventricle (LV)
is compressed to a narrow
slit,
and distortion of the right ventricle (RV) is also seen. Arrow indicates the left ventricular outflow area.
DISCUSSION
This case represents a condition of the myocardium which clearly required differentiation from other forms of primary myocardial disease. Congestive heart failure had developed early in infancy. The clinical findings indicating a mitral valvular abnormality suggested endocardial fibroelastosisl and anomalous origin of the left coronary artery.2 The electrocardiogram, which was not characteristic for either lesion, suggested, in addition, the diagnosis of asymmetrical hypertrophy of the heart.3 A tumor was considered, and the similarity in the clinical course to the case of rhabdomyosarcoma of the left ventricle reported by Engle and Glenn4 led to the consideration of this possibility. Review of our findings and a comparison with previously recognized examples of fibrous ventricular tumors taken as a group is revealing. Although such tumors are found more commonly in childhood, they have been encountered throughout a wide age range. Of the previously reported 39 cases, 29 were in patients under age 6 years, 27 of these in patients under 3 years.5-11 Sudden death without recognized premonitory signs was the most common single feature; it occurred in one fourth
of the cases, often after some form of physical effort.‘** In those patients with definite symptoms occurring before the terminal episode, dyspnea appeared to predominate. g,i2-i4 Chest pain and episodes of pallor and coldness suggesting arrhythmia or coronary insufficiency have also been noted.1°J2J3 The physical findings, although no more specific, appear more uniform. In most instances, the heart was significantly enlarged, with chest asymmetry obvious in some.12J4-16 Systolic murmurs, generally nonspecific in nature, were usual, although not constant, findings. 6fg~12~14,16 The first and second heart sounds were routinely unaltered; a prominent diastolic sound was occasionally detected. Clinical Diagnosis: Although the diagnosis of this malformation ultimately depends on the angiographic findings,sJ4J7 it is apparent that it may be suspected from the more routine clinical studies. Several electrocardiographic features deserve comment. Foremost among these is the terminal delay pattern best seen in the QRS complexes recorded from the left precordial leads. This finding was demonstrated in all but 2 reported instances of this anomaly in which electrocardiography was THE
AMERICAN
JOURNAL
OF CARDIOLOGY
Nodular
FIG. 8. At right, low-power photo micrographs of the tumor. A, he matoxylin and eosin stain. A fibroelastic stroma comprises the bulk of the tumor. Arrows indicate myocardial fibers included within the stroma. (X 10, reB, resorcinduced by 97&) fuchsin stain. The elastic component of the tumor is repreented as darkly staining material. Myocardial fibers are seen within the stroma (arrow). (X 10, reduced by ‘I?(.)
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Folger and Peters
performed and, together with the voltage and ST-T changes seen, constitutes the principal electrocardiographic feature.Y.14-16 However, similar voltage and ST-T aberrations may also be found in other c&diomyopathies, thus leaving the terminal delay pattern as a possible specific clue to the clinical diagnosis of this type of myocardial tumor. The vectorcardiogram furthe? documents this feature. Review of the published chest radiograms suggests that, in addition to the cardiac enlargement usually present,‘,‘” aIs.17 a squared-off configuration of the ventricular shadow is a frequent finding and may suggest the diagnosis.8J4J5 Isotopic scanning of the heart has not, to our knowledge, been previously employed in the identification of myocardial tumors, although Folger and co-workers3 reported employing this study with another space-occupying abnormality, asymmetrical hypertrophy of the heart. This case, as well as the present case, clearly demonstrates that any cavity-reducing lesion will cause alteration in and diminution of the intracavitary blood pool, and in this respect will be diagnostic. Surgical i~esection of left ventricular tumors is feasible and has been successfully carried out.9J4J7 In our patient, the involved area was so extensive as to preclude removal. Nevertheless, thorough surgical exploration is indicated in all proved cases. Pathogenesis: The incidence of this specific malformation is difficult to ascertain. Of the 39 cases of fibrous ventricular tumors previously reported, at least 17 appear to conform histologically to the classification of tumorous malformations within the myocardium of which the present case is representative.6-13J5--22 This condition appears to represent proliferation of fibrous tissue rather than a true fibroma, as ascertained by the histologic appearance of absence of a distinct capsule in any area and presence of myocardial fibers within the proliferation. Using special staining technics for connective tissue employing picro4irius-red,23 detailed histologic examination of the tumor in this case was performed. This method revealed multiple areas within the tumor in which the tissue closely resembled that seen lining the endocardial surface in endocardial fibroelastosis, thus suggesting an etiologic relation between the two conditions. Several investigators have used the term fibroelastic hamartoma to describe the appearance of this tissue.1g-21 Nodu-
lar fibroelastosis better describes this condition, which probably has as its origin the supporting tissue found within the ll+ocardiunl and is the result of an abnormal proliferation during cardiogenesis. We assume that such 17) pcrplastic connective tissue within the myocardiutu proliferates M ith the developing m)-ocardial fibers in the embryonic heart and ceases with cessation of myocardial fiber growth. Examples of this process rl:ay be found in the cardiac “fibromas” that are occasionaIl)seen in the rnyocardium of the elderly.‘” The ttltimate size of the tumor probably depends on both the extent and propensity for abnormal proliferation of the tissue. In view of the present findings, inclusion of this abnormality in the group of primary cardiomyopathies seems indicated. Further experience may substantiate our observations, thus allowing clinical diagnosis to be made with the degree of accuracy presently attainable in these other myocardial disorders. SUMMARY
A tumorous malformation, i.e., nodular fibroelastosis of the left ventricle and interventricular septum of the heart, is described. A relation between the tissue composing the mass and that seen with endocardial fibroelastosis is postulated. The clinical and laboratory findings bear distinct similarities to those of previously reported cases and suggest specificity for this type of malformation. Inclusion of this abnormality in the group of cardiomyopathies is recommended. ACKNOWLEDGMENT We thank Dr. Holde Puchtler for performing interpreting the special stains used in the study pathologic material.
and of the
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THE
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Nodular 4. ENGLE: Xi. A. and GLENN, F. Primary malignant tumor of the heart in infancy. Case report and review of the subject. Pediatrics, 15: 562, 1955. 5. PRICHARD, R. W. Tumors of the heart. Review of the subject and report of one hundred and fifty cases. Arch. Path., 51 : 98, 1951. 6. BIGELOIY. X. H., KLINGER, S. and WRIGHT, A. W. Primary tumors of the heart in infancy and early childhood. Cancer, 7: 549, 1954. 7. FREEMAN, J. A., GEER, J. C., RANDALL, W. S., JR. and PALFREY, W. G. Intramural fibroma of the heart. Am. J. Clin. Path., 39: 374, 1963. 8. HOEN, ~2. G. and ELLIS, E. J. Intramural fibroma of the heart. Am. J. Cardiol., 17: 579, 1966. 9. GEHA, :\. S., WEIDMAN, W. H., SOULE, E. H. and M~GooN, D. C. Intramural ventricular cardiac fibroma. Successful removal in two cases and review of the literature. Circulation, 36: 427, 1967. 10. CLAY, R. D. and SHORTER, R. G. Intramural fibroma of the heart. J. Path. Back, 74: 163, 1957. 11. .\LBERS, J. T. H.: Atlas der pathologischen Anatomic fuer Praktische Aerate, p. 215. Bonn, 1833. Henry u. Cohen. 12. VALLEDOR, T. et al. Fibroma of the heart. Case report. Dis. Chest, 37: 698, 1960. 13. BOYETTE, D. P. and FOUSHEE, J. H. S. Cardiac libroma of the interventricular septum in a newborn infant. Case report. North Carolina M. J., 14.
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Primary tumour of Acta paediat. scan-
Fibroelastosis 15.
16.
427
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S.
tissue.
I.