Aota Path. Jap. 26(5): 603-610, 1976
ATRIAL MYXOMA ASSOCIATED WITH MULTIPLE HAMARTOMAS
Hiroshi KANEKO*,Takeshi MUROHASHI**, Akira KATANO***, Haruto H6~6,***and Shinobu ISHIKAWA***
* Dept. of Pathology, Nagaoka Red Cross Hospital, Nagaoka ** Dept. of Internal Med., Nagaoka Red Cross Hoapital *** Dept. of Pathology, School of Medicine, Niigata University, Niigata (Received on Jan. 9, 1976)
A case of cardiac myxoma associated with renal angiofibrolipomas, renal medullary fibromas, thyroid adenoma and jejunal polyp was presented. So f a r as we know, the combined form of cardiac myxoma and renal hamartoma has not been hitherto reported. The combination of these various complications may suggest the relationships of tuberous sclerosis, Cowden disease, lymphangiomatosis among others. Besides it is noteworthy that the three of them, i.e. cardiac myxoma, renal angiofibrolipomas and thyroid adenoma, presented considerable atypism at the same time. As to the Nstogenesis of cardiac myxoma, this case may be in accord with the hamartoma theory. ACTA PATH. JAP. 26: 603-610, 1976.
Introduction There are three main theories concerning the pathogenesis of cardiac myxoma. The first is of thrombogenous origin that myxoma must be considered as an organized endocardia1 thrombuslQ. The second is of neoplastic origin that the neoplastic nature of cardiac myxoma has been confirmed by some reports of malignant m y ~ o m a . ~ ~ ~ , ~ , 1 8 ~ 1 ~ On the other hand, there is the hamartoma theory.1~517 This paper is in agreement with the theory that cardiac myxoma may belong to the group of hamartoma, and is discussed taking into account the pertinent literature. Case Repmt
Pdient: 62 years old housewife. Family history: Her father died of diabetes mellitus a t 48 years of age, and her mother of heart disease a t the age of 61 years. Her elder brother died of rectal carcinoma a t 61 years of age. Anamnesis: Hypertension, 160190, was pointed out 5-6 years before around that time arthralgia of both knee joints appeared repeatedly. &T I% 55% @, 58 3% MA, 25111 B Mailing Address: Hiroshi Kaneko, M.D., Dept. of Path., Nagaoka Red Cross Hospital, 2-6-1 Nissekicho, Nagaokaahi, 940, Japan. 603
604
Acta Path. Jap.
ATRIAL MYXOHA WITH HAMARTOHAS
Status praesm: In December, 1972, a fever of 38°C occurred. The fever appeared and disappeared frequently. In January, 1973, anemia was pointed out. In July edema was found in the face and shins. On July 25 the patient visited the author's hospital. Blood pressure, 132192. Pulse rate, l2O/min., arrhythmic. The area of cardiac dullness was enlarged on both sides. Systolic murmur was heard a t the apex. The results of routine laboratory examinations are shown in Table 1. I n addition, urine protein, 60 mg/dl, sugar (-). Chest roentgenography revealed the shadow of the heart enlarged to the left and right. Cardiothoracic ratio, 65%. The pulmonary markings were intensified. Electrocardiography (ECG) revealed sinus tachycardia, ventricular extrasystole, left atrial loading, T inversion of 111, aVp and Vl-3. Phonocardiography exhibited the enhancement of I sound, musical-sound-like systolic murmur at the apex, and splitting of I1 sound, but no diastolic murmur. PSP was 13x115 min. and 10%/30 min. C, 198 mg/dl, C, 80. Antinuclear antibody, positive weakly. Wassermann (-).
~
~
Table 1. Luboratory Finding8 ~
~
_
July. '73 WBC RBC ( x 104) Hb (g/dl) ESR (mm/lh.) ASLO Antistreptokinase
CRP
7900 362 9.7 98 625
5900
sao
1400 146
9.9 106 833 6130 S+ a360 1180 37
a80
!Z90
64a940
M LDH Al. P.
Aug.-Oct.
12.6 31
9.0 47 986
_
'73
-
Sep. '74
19000 439 10.3 1 60 640
S+ 1480 780 140 1990 6.0 60
a48
Course of disease after a d m i s s k : The patient suffered from a fever in the order of 37°C. She was given the diagnosis of rheumatic fever with mitral valvular disease. The fever disappeared after therapy. In August, ESR became 5 mm/l h. from 33 mm. Moreover, cardiac murmur, reversed T wave and others were ameliorated. She was discharged temporarily on Jan. 19, '74. Since the beginning of September, pronounced anorexia and edema had been persistent. Hematemesis was seen on September 9 and the patient was admitted to the author's hospital again on the following day. The h d i n g s of ECG and chest X-ray had exacerbated again. Na 131 mEq/dl, K 3.7, C1 93.7. Urea N 46 mg/dl. She was suspected of suffering from cardiac insufficiency and received treatment. As a result, diuresis occurred, and electrolytes showed improvement. On September 18, speech disorder and facial paralysis on the left side appeared suddenly. It was unknown whether tetraplegia occurred simultaneously. Dyspnea became exacerbated and death occurred on September 24.
26(5j: 1976
H. M E K O r l al.
605
Histopathological Findings There was a large, global, 7 by 6 by 5.5 cm sized tumor almost completely occupying the lumen of the left atrium of the heart (Fig. 1). It was localized at the lower margin just below the fossa ovalis. A slender fibrous stalk which measured about 1 cm in diameter was present at the base of the tumor. The supeficial portion of the polypoid mass was in places whitish and firm, but in greater part gelatinous, glistening and soft. The cut-surface of the tumor similarly was mottled with gelatinous, hematomatous and organized thrombotic tissues.
Microscopical Jindings : So-called myxoma cells had a medium-sized nucleus rather rich in chromatin and considerably abundant cytoplasm. Various findings were obtained from them according to their location. Some cells presented an endothelioma-like proliferation and pericyte-like arrangement, some cells showing a glandular structure demonstrated an outstanding secretion in their cytoplasm Fig. Cut-sdam of the left (Fig. 2) (weakly positive for mucicarmine myxoma from the lower marginal region just below the fossa ovalis. and alcian blue, positive PAS and positive metachromasia as examined with toluidine blue). Myxoma cells were a h scattered cellularly in the interstitial tissue and formed giant cells occasionally. A great number of histiocytes were seen in the interstitial tissue. I n some areas they contained a number of granules strongly positive for PAS. In others they were positive for hemosiderin and strongly positive for Sudan 111. In some part on the surface of this myxoma hyperplasia of the cells exhibiting a strong atypism was seen medullarly (Fig. 3). They had an enlarged nucleus with hyperchromatism containing 3 or 4 nucleoli occasionally. Electron microscopic observations: The tumor was examined after formalin fixation. We observed various types and degrees of differentiation of the myxoma cells, smooth muscle cells, endothelial cells, histiocytes among others, containing iron, fat and myelin-like substances. Besides marked secretory granules (Fig. 4) were seen in some cells covering the inner surface of the gland-like arrangement probably corresponding to that in Fig. 2. In the wall of blood vessel-like structure, the cells of two types which were thought to present both-sided differentiation from the smooth muscle cells to the myxoma cell and endothelial cell were observed (Figs. 6 , 6 and 7). The left kidney had two white subcapsular tumors about 0.6 and 1.0 cm, in
606
A
m YYXOMA WITH HAXARTOhUS
Fig. 2. Glandular structure of the myxoma showing high secretory activity. magnification x 200. Fig. 3. Marked atypism of the myxoma cells. H.E. Original mag. x 400.
Acta Path. Jap.
H.E. Original
diameter respectively. Microscopically angiofibrolipomas in which large hyperchromatic cells were scattered were detected in both tumors (Fig. 8). Two fibromas were also seen in the medulla. The right kidney had no tumors, but presented multiple old infarcts as in the left kidney. The thyroid gland had two nodular colloid goiters up to 7 mm in diameter and a small adenoma (Fig. 9) in the left lobe which showed marked papillary proliferation. The jejunum had a mucosal polyp 7 mm in diameter. Moreover, there was a tendency of thrombus and infarct formation throughout the body. A number of thrombi partially organized were seen in the lung and the Fig. 4. The cells containing mucinous substance in the apical cytoplasm have many microvilli projections facing the lumen. This figure is probably compatible with Fig. 2. Original magg. x 2000. Fig. 5. The cells on the top show pericyte-like arrangement. The cells at the lower half lining the vascular structure are thought to have both-sided findings of smooth muscle cell and endothelial cell. Original mag. x 2000. Fig. 6. High power view of the lining cells shown on the lower half of Fig. 5. Original mag. x 4000. Fig. 7. The cell on the top seems to show the differentiation to the myxoma cell resembling pericyte shown in Fig. 6, hevhg character of smooth muscle cell. The endothelial cell at the bottom with tight junotione. Original mag. x 7000.
26(5): 1976
H. KAliEKO s l
at.
607
608
ATRIAL M Y X O U WITH HAMARTOBUS
Acta Path. Jap.
Fig. 8. Angiofibrolipoma of the kidney. H.E. Original mag. x 40. Fig. 9. Papillary edenome of the thyroid. H.E. Original mag. x 40.
auricles of the heart. As a result, a large hemorrhagic infarction was found in the iniddle lobe of the right lung. In addition to the kidney, the spleen contained old infarcts.
Discua& Opinions have been divided as to the origin of cardiac myxoma, as mentioned previously. It is generally accepted that this myxoma is a sort of tumor a little different from the usual neoplasm. Attention should be paid to the occurrence of complications with this myxoma. REESl4 reported a case of cardiac myxoma complicated with severe general lentiginosis. It has been known that lentiginosis may concur gastrointestinal polyposis, It has a h been suggested that lentiginosis may well be related to phacomatosis. NASSER~~ found multiple cystic bone lesions of unknown etiology in a case of cardiac myxoma. It has been reported that bone cyst is observed in Cowden disease, which is to be mentioned below. Furthermore, there are some reports on cardiac myxoma complicated with fibroadenoma of the breast.W6 These reports coinciding with various interesting complications seem to be very important in discussing the histogenesis of cardiac myxoma if we can regard these complications as hamartoma. So far as the literatures are concerned, no reports have been made on a case of cardiac myxoma combined with hamartoma of the kidney. In the case presented
26(5): 1976
H. m E 0
el
al.
609
here, two angiofibrolipomas and two fibromas were found in the kidney. It has been presumed up to date that the occurrence of renal hamartoma is almost restricted to the case of tuberous sclerosis which is a representative disease of phacomatosis. Therefore, it is a very important finding that renal hamartoma occurred in a case other than tuberous sclerosis. It is a well-known fact that the hamartomas in the case of tuberous sclerosis can develop in the main organs all over the body. In short, as complications of cardiac myxoma, various types of hamartoma have been observed. Discussion will be made on Cowden disease and lymphangiomyomatosis as two representative diseases of multiple hamartoma syndrome. Cowden disease is one in which fibrocystic breast tumor, thyroid tumor, gastrointestinal polyposis, anomaly of the nervous system, fibroma, angioma, lipoma and bone cyst are seen, in addition to changes of the skin.4,WS It should be noted that these various hamartomatous changes indicate the essential nature of this disease itself, rather than complications with this disease, and that they are strikingly simdar to the complications of cardiac myxoma. Lymphangiomyomatosis is a disease in which lymphangioma appears in the retroperitoneum and mediastinum. It is known to be complicated with cystic lesions of the lung, renal angiomyolipoma and tuberous sclerosis.11 In the case presented here, the concurrence of thyroid adenoma and jejunal polyp was observed in addition to the presence of renal hamartomas. These disorders are included in the complications of the diseases of myxoma and multiple hamartoma syndrome mentioned previously. Case reports have been published on the malignant changes of cardiac myxoma. I n the case presented here, such changes considered to be sufficiently malignant were noticed in some part of the superficial region of the cardiac myxoma. Moreover, changes thought to be slightly malignant or regarded as hamartoblastoma were recognjzed in the renal angiofibrolipomas. The thyroid adenoma also showed atypisni slightly. These changes which exhibited atypism a t the same time will lend support to the presumption that these tumors including the myxoma may have developed on the same basis. Reports have been made on the connatals, sibling? and familial* cases of cardiac myxoma. This fact will lend support to the hamartoma theory on the origin of this myxoma. In conclusion, it is presumed that cardiac myxoma may be classified into the group of multiple hamartoma syndrome. Ackmwledgemnt: The authors wish to thank Dr. T. EBE for his advice and help on the electronmicroscopic observations.
References 1. ECE, H.: Zur Frage der gutartigen Endocardtumoren. Beitr. Pathol. 102: 554-559, 1939. 2. FISHER, E.R. et al.: Evidence in support of the neoplastic nature of cardiac myxoma. Am. Heart J. 60: 630-640, 1960.
3. FLENKER, H.: Connatal endocardia1 myxoma. Case report and pathogenesis. Virchows.
610
ATRIAL MYXOYA WITH HAMARTOMAS
Acta Path. Jap.
4.
Arch. Pathol. Anat. 356: 363-358, 1972. GENTRY,W.C.JR.et al.: Multiple hamartoma syndrome (Cowden disease). Arch. Dermatol.
5.
Haam, H.P.: Zur Tumornatur der Endocardmyxome. Zentralbl. Allg. Pathol. 114: 534-
109: 521626, 1974.
638, 1971. 6.
H u m , D. et d.: Pulmonary hypertension due to myxoma of the right atrium. Am. Heart J. 68: 227-235, 1964. 7. HIPYDOBN, W.H. et al.: Atrial myxoma in siblings. J. Thorac. Cardiovasc. Surg. 65: 484486, 1973. 8.
HUEBSOEU", H.: Zur R a g e der sog. Herzmyxome.
Verh. Dtsch. Ges. Pathol. 28:
162-165, 1935.
9. KLEID,J.J. et d.: Familial atrial myxoma. Am. J. Cardiol. 32: 361-364, 1973. LLOYD, K.M. et al.: Cowden's diaeeee: A possible new symptom complex with multiple s p t e m involvement. Ann. Inhrn. Med. 58: 138-142, 1973. 11. MONTHWORTH, W.J. et al.: Angiomyolipomas in a case of lymphangiomyomatosis syndrome: Relationships to tuberous sclerosis. Cancer. 34: 317-321, 1974. 12. NASSER, W.K. et al.: Clinical and pathological fmtures in nine c m . Am. Heart J. 83:
10.
694-704, 1972. 13. ~ ( I H A R D R.W.: , Tumors of the heart. Arch. Pathol. 51: 98-128, 1951. 14. RHBS,J.R. et d.: Lentiginosia and left atrial myxoma. Br. Heart J. 35: 874-876, 1973. 15. Ropm, C.L. et al.: Atrial myxoma associated with fibroadenomes of the breast. Mo. Med. 62: 113-116, 1965. 16. RUTKAI,P.: Endocardmyxome mit Embolien. Zentrdbl. Allg. Pathol. 104: 381-383, 1963. 17. V A O ~ KR.: , Des intrakardiale Hamartoblestom. Zentralbl. Allg. Pathol. 104: 383-391, 1963. 18. WEARY,P.E. et al.: The multiple hamartoma syndrome (Cowden's diaeese). Arch. Dermatol. 106: 682490, 1972. 19. ZOLL~QER, H.U.: Pathologieche Anatomie. Bd. 11. Stuttgart: Thieme. 1909. Cited from 5.
ATRIAL MYXOMA ASSOCIATED WITH MULTIPLE HAMARTOMAS
Hiroshi KANEKO*,Takeshi MUROHASHI**, Akira KATANO***, Haruto H6~6,***and Shinobu ISHIKAWA***
* Dept. of Pathology, Nagaoka Red Cross Hospital, Nagaoka ** Dept. of Internal Med., Nagaoka Red Cross Hoapital *** Dept. of Pathology, School of Medicine, Niigata University, Niigata (Received on Jan. 9, 1976)
A case of cardiac myxoma associated with renal angiofibrolipomas, renal medullary fibromas, thyroid adenoma and jejunal polyp was presented. So f a r as we know, the combined form of cardiac myxoma and renal hamartoma has not been hitherto reported. The combination of these various complications may suggest the relationships of tuberous sclerosis, Cowden disease, lymphangiomatosis among others. Besides it is noteworthy that the three of them, i.e. cardiac myxoma, renal angiofibrolipomas and thyroid adenoma, presented considerable atypism at the same time. As to the Nstogenesis of cardiac myxoma, this case may be in accord with the hamartoma theory. ACTA PATH. JAP. 26: 603-610, 1976.
Introduction There are three main theories concerning the pathogenesis of cardiac myxoma. The first is of thrombogenous origin that myxoma must be considered as an organized endocardia1 thrombuslQ. The second is of neoplastic origin that the neoplastic nature of cardiac myxoma has been confirmed by some reports of malignant m y ~ o m a . ~ ~ ~ , ~ , 1 8 ~ 1 ~ On the other hand, there is the hamartoma theory.1~517 This paper is in agreement with the theory that cardiac myxoma may belong to the group of hamartoma, and is discussed taking into account the pertinent literature. Case Repmt
Pdient: 62 years old housewife. Family history: Her father died of diabetes mellitus a t 48 years of age, and her mother of heart disease a t the age of 61 years. Her elder brother died of rectal carcinoma a t 61 years of age. Anamnesis: Hypertension, 160190, was pointed out 5-6 years before around that time arthralgia of both knee joints appeared repeatedly. &T I% 55% @, 58 3% MA, 25111 B Mailing Address: Hiroshi Kaneko, M.D., Dept. of Path., Nagaoka Red Cross Hospital, 2-6-1 Nissekicho, Nagaokaahi, 940, Japan. 603
604
Acta Path. Jap.
ATRIAL MYXOHA WITH HAMARTOHAS
Status praesm: In December, 1972, a fever of 38°C occurred. The fever appeared and disappeared frequently. In January, 1973, anemia was pointed out. In July edema was found in the face and shins. On July 25 the patient visited the author's hospital. Blood pressure, 132192. Pulse rate, l2O/min., arrhythmic. The area of cardiac dullness was enlarged on both sides. Systolic murmur was heard a t the apex. The results of routine laboratory examinations are shown in Table 1. I n addition, urine protein, 60 mg/dl, sugar (-). Chest roentgenography revealed the shadow of the heart enlarged to the left and right. Cardiothoracic ratio, 65%. The pulmonary markings were intensified. Electrocardiography (ECG) revealed sinus tachycardia, ventricular extrasystole, left atrial loading, T inversion of 111, aVp and Vl-3. Phonocardiography exhibited the enhancement of I sound, musical-sound-like systolic murmur at the apex, and splitting of I1 sound, but no diastolic murmur. PSP was 13x115 min. and 10%/30 min. C, 198 mg/dl, C, 80. Antinuclear antibody, positive weakly. Wassermann (-).
~
~
Table 1. Luboratory Finding8 ~
~
_
July. '73 WBC RBC ( x 104) Hb (g/dl) ESR (mm/lh.) ASLO Antistreptokinase
CRP
7900 362 9.7 98 625
5900
sao
1400 146
9.9 106 833 6130 S+ a360 1180 37
a80
!Z90
64a940
M LDH Al. P.
Aug.-Oct.
12.6 31
9.0 47 986
_
'73
-
Sep. '74
19000 439 10.3 1 60 640
S+ 1480 780 140 1990 6.0 60
a48
Course of disease after a d m i s s k : The patient suffered from a fever in the order of 37°C. She was given the diagnosis of rheumatic fever with mitral valvular disease. The fever disappeared after therapy. In August, ESR became 5 mm/l h. from 33 mm. Moreover, cardiac murmur, reversed T wave and others were ameliorated. She was discharged temporarily on Jan. 19, '74. Since the beginning of September, pronounced anorexia and edema had been persistent. Hematemesis was seen on September 9 and the patient was admitted to the author's hospital again on the following day. The h d i n g s of ECG and chest X-ray had exacerbated again. Na 131 mEq/dl, K 3.7, C1 93.7. Urea N 46 mg/dl. She was suspected of suffering from cardiac insufficiency and received treatment. As a result, diuresis occurred, and electrolytes showed improvement. On September 18, speech disorder and facial paralysis on the left side appeared suddenly. It was unknown whether tetraplegia occurred simultaneously. Dyspnea became exacerbated and death occurred on September 24.
26(5j: 1976
H. M E K O r l al.
605
Histopathological Findings There was a large, global, 7 by 6 by 5.5 cm sized tumor almost completely occupying the lumen of the left atrium of the heart (Fig. 1). It was localized at the lower margin just below the fossa ovalis. A slender fibrous stalk which measured about 1 cm in diameter was present at the base of the tumor. The supeficial portion of the polypoid mass was in places whitish and firm, but in greater part gelatinous, glistening and soft. The cut-surface of the tumor similarly was mottled with gelatinous, hematomatous and organized thrombotic tissues.
Microscopical Jindings : So-called myxoma cells had a medium-sized nucleus rather rich in chromatin and considerably abundant cytoplasm. Various findings were obtained from them according to their location. Some cells presented an endothelioma-like proliferation and pericyte-like arrangement, some cells showing a glandular structure demonstrated an outstanding secretion in their cytoplasm Fig. Cut-sdam of the left (Fig. 2) (weakly positive for mucicarmine myxoma from the lower marginal region just below the fossa ovalis. and alcian blue, positive PAS and positive metachromasia as examined with toluidine blue). Myxoma cells were a h scattered cellularly in the interstitial tissue and formed giant cells occasionally. A great number of histiocytes were seen in the interstitial tissue. I n some areas they contained a number of granules strongly positive for PAS. In others they were positive for hemosiderin and strongly positive for Sudan 111. In some part on the surface of this myxoma hyperplasia of the cells exhibiting a strong atypism was seen medullarly (Fig. 3). They had an enlarged nucleus with hyperchromatism containing 3 or 4 nucleoli occasionally. Electron microscopic observations: The tumor was examined after formalin fixation. We observed various types and degrees of differentiation of the myxoma cells, smooth muscle cells, endothelial cells, histiocytes among others, containing iron, fat and myelin-like substances. Besides marked secretory granules (Fig. 4) were seen in some cells covering the inner surface of the gland-like arrangement probably corresponding to that in Fig. 2. In the wall of blood vessel-like structure, the cells of two types which were thought to present both-sided differentiation from the smooth muscle cells to the myxoma cell and endothelial cell were observed (Figs. 6 , 6 and 7). The left kidney had two white subcapsular tumors about 0.6 and 1.0 cm, in
606
A
m YYXOMA WITH HAXARTOhUS
Fig. 2. Glandular structure of the myxoma showing high secretory activity. magnification x 200. Fig. 3. Marked atypism of the myxoma cells. H.E. Original mag. x 400.
Acta Path. Jap.
H.E. Original
diameter respectively. Microscopically angiofibrolipomas in which large hyperchromatic cells were scattered were detected in both tumors (Fig. 8). Two fibromas were also seen in the medulla. The right kidney had no tumors, but presented multiple old infarcts as in the left kidney. The thyroid gland had two nodular colloid goiters up to 7 mm in diameter and a small adenoma (Fig. 9) in the left lobe which showed marked papillary proliferation. The jejunum had a mucosal polyp 7 mm in diameter. Moreover, there was a tendency of thrombus and infarct formation throughout the body. A number of thrombi partially organized were seen in the lung and the Fig. 4. The cells containing mucinous substance in the apical cytoplasm have many microvilli projections facing the lumen. This figure is probably compatible with Fig. 2. Original magg. x 2000. Fig. 5. The cells on the top show pericyte-like arrangement. The cells at the lower half lining the vascular structure are thought to have both-sided findings of smooth muscle cell and endothelial cell. Original mag. x 2000. Fig. 6. High power view of the lining cells shown on the lower half of Fig. 5. Original mag. x 4000. Fig. 7. The cell on the top seems to show the differentiation to the myxoma cell resembling pericyte shown in Fig. 6, hevhg character of smooth muscle cell. The endothelial cell at the bottom with tight junotione. Original mag. x 7000.
26(5): 1976
H. KAliEKO s l
at.
607
608
ATRIAL M Y X O U WITH HAMARTOBUS
Acta Path. Jap.
Fig. 8. Angiofibrolipoma of the kidney. H.E. Original mag. x 40. Fig. 9. Papillary edenome of the thyroid. H.E. Original mag. x 40.
auricles of the heart. As a result, a large hemorrhagic infarction was found in the iniddle lobe of the right lung. In addition to the kidney, the spleen contained old infarcts.
Discua& Opinions have been divided as to the origin of cardiac myxoma, as mentioned previously. It is generally accepted that this myxoma is a sort of tumor a little different from the usual neoplasm. Attention should be paid to the occurrence of complications with this myxoma. REESl4 reported a case of cardiac myxoma complicated with severe general lentiginosis. It has been known that lentiginosis may concur gastrointestinal polyposis, It has a h been suggested that lentiginosis may well be related to phacomatosis. NASSER~~ found multiple cystic bone lesions of unknown etiology in a case of cardiac myxoma. It has been reported that bone cyst is observed in Cowden disease, which is to be mentioned below. Furthermore, there are some reports on cardiac myxoma complicated with fibroadenoma of the breast.W6 These reports coinciding with various interesting complications seem to be very important in discussing the histogenesis of cardiac myxoma if we can regard these complications as hamartoma. So far as the literatures are concerned, no reports have been made on a case of cardiac myxoma combined with hamartoma of the kidney. In the case presented
26(5): 1976
H. m E 0
el
al.
609
here, two angiofibrolipomas and two fibromas were found in the kidney. It has been presumed up to date that the occurrence of renal hamartoma is almost restricted to the case of tuberous sclerosis which is a representative disease of phacomatosis. Therefore, it is a very important finding that renal hamartoma occurred in a case other than tuberous sclerosis. It is a well-known fact that the hamartomas in the case of tuberous sclerosis can develop in the main organs all over the body. In short, as complications of cardiac myxoma, various types of hamartoma have been observed. Discussion will be made on Cowden disease and lymphangiomyomatosis as two representative diseases of multiple hamartoma syndrome. Cowden disease is one in which fibrocystic breast tumor, thyroid tumor, gastrointestinal polyposis, anomaly of the nervous system, fibroma, angioma, lipoma and bone cyst are seen, in addition to changes of the skin.4,WS It should be noted that these various hamartomatous changes indicate the essential nature of this disease itself, rather than complications with this disease, and that they are strikingly simdar to the complications of cardiac myxoma. Lymphangiomyomatosis is a disease in which lymphangioma appears in the retroperitoneum and mediastinum. It is known to be complicated with cystic lesions of the lung, renal angiomyolipoma and tuberous sclerosis.11 In the case presented here, the concurrence of thyroid adenoma and jejunal polyp was observed in addition to the presence of renal hamartomas. These disorders are included in the complications of the diseases of myxoma and multiple hamartoma syndrome mentioned previously. Case reports have been published on the malignant changes of cardiac myxoma. I n the case presented here, such changes considered to be sufficiently malignant were noticed in some part of the superficial region of the cardiac myxoma. Moreover, changes thought to be slightly malignant or regarded as hamartoblastoma were recognjzed in the renal angiofibrolipomas. The thyroid adenoma also showed atypisni slightly. These changes which exhibited atypism a t the same time will lend support to the presumption that these tumors including the myxoma may have developed on the same basis. Reports have been made on the connatals, sibling? and familial* cases of cardiac myxoma. This fact will lend support to the hamartoma theory on the origin of this myxoma. In conclusion, it is presumed that cardiac myxoma may be classified into the group of multiple hamartoma syndrome. Ackmwledgemnt: The authors wish to thank Dr. T. EBE for his advice and help on the electronmicroscopic observations.
References 1. ECE, H.: Zur Frage der gutartigen Endocardtumoren. Beitr. Pathol. 102: 554-559, 1939. 2. FISHER, E.R. et al.: Evidence in support of the neoplastic nature of cardiac myxoma. Am. Heart J. 60: 630-640, 1960.
3. FLENKER, H.: Connatal endocardia1 myxoma. Case report and pathogenesis. Virchows.
610
ATRIAL MYXOYA WITH HAMARTOMAS
Acta Path. Jap.
4.
Arch. Pathol. Anat. 356: 363-358, 1972. GENTRY,W.C.JR.et al.: Multiple hamartoma syndrome (Cowden disease). Arch. Dermatol.
5.
Haam, H.P.: Zur Tumornatur der Endocardmyxome. Zentralbl. Allg. Pathol. 114: 534-
109: 521626, 1974.
638, 1971. 6.
H u m , D. et d.: Pulmonary hypertension due to myxoma of the right atrium. Am. Heart J. 68: 227-235, 1964. 7. HIPYDOBN, W.H. et al.: Atrial myxoma in siblings. J. Thorac. Cardiovasc. Surg. 65: 484486, 1973. 8.
HUEBSOEU", H.: Zur R a g e der sog. Herzmyxome.
Verh. Dtsch. Ges. Pathol. 28:
162-165, 1935.
9. KLEID,J.J. et d.: Familial atrial myxoma. Am. J. Cardiol. 32: 361-364, 1973. LLOYD, K.M. et al.: Cowden's diaeeee: A possible new symptom complex with multiple s p t e m involvement. Ann. Inhrn. Med. 58: 138-142, 1973. 11. MONTHWORTH, W.J. et al.: Angiomyolipomas in a case of lymphangiomyomatosis syndrome: Relationships to tuberous sclerosis. Cancer. 34: 317-321, 1974. 12. NASSER, W.K. et al.: Clinical and pathological fmtures in nine c m . Am. Heart J. 83:
10.
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