sign in sign up
<<
Home , Giant cell

J Clin Pathol: first published as 10.1136/jcp.39.11.1209 on 1 November 1986. Downloaded from

J Clin Pathol 1986;39:1209-1216

Acute idiopathic interstitial myocarditis: case report with special reference to morphological characteristics of giant cells

M TANAKA, R ICHINOHASAMA, Y KAWAHARA, Y ESAKI,* K HIROKAWA,t K OKISHIGE,j Y TANAKAt From the Pathological Anatomical Services, Tokyo Metropolitan Hiroo General Hospital, and the *Tokyo Metropolitan Geriatric Hospital, the tDepartment of Pathology, Tokyo Metropolitan Institute of Gerontology, and the 4Oume Municipal General Hospital, Tokyo, Japan

SUMMARY Necropsy findings of an acute fatal case of idiopathic interstitial myocarditis were reported. The patient was a 33 year old housewife who had acute cardiac failure on the sixteenth day after the onset of the disease. Necropsy showed important pathological changes confined to the heart. Both ventricles were affected by confluent with an ill defined patchy appearance. Histologically these lesions consisted of round cells, , and myogenic giant cells. The findings were compatible with those of interstitial myocarditis associated with a prolif- eration of giant cells. Both atriums were also affected to a minor extent, detectable only by histological examination. Electron microscopy and cytochemistry showed that most giant cells noted in the lesion showed myofibrils and primary lysosomes in the cytoplasm. Giant cells were positive for myoglobin. copyright. Though the origin of the giant in this disorder has been emphasised in a recent report, these cytological results suggest that giant cells observed in the cardiac granulomatous lesions of this case were mainly myogenic in origin.

disorders are known to induce Careful review of these reported cases showed that Various infectious http://jcp.bmj.com/ granulomatous lesions in the myocardium, which are nearly half were probably cardiac .5 Char- associated with the appearance ofgiant cells. ' 2 These acteristic giant cells observed in acute idiopathic inter- disorders are not necessarily fatal, and some cases can stitial myocarditis may originate from degenerating be cured. An acute idiopathic form ofinterstitial myo- myocardial cells and myocardial interstitial carditis, a rare primary disorder of the heart, is often histiocytes,' their origin, however, is still somewhat fatal and is accompanied by extensive degeneration controversial. Filamentous materials resembling and necrosis of the myocardium and a like degenerated myofibrils detectable ultrastructurally in lesion consisting of round cell infiltration, these cells6 were interpreted either as degenerating on September 28, 2021 by guest. Protected histiocytosis, and eosinophilia. A proliferation of myofibrils of the myocardial cell7 or phagocytised giant cells ofboth histiocytic and myogenic type, with myofibrils of .8'-I Histochemically, the a certain variation in number according to the case, is lysosomal activity of these giant cells did not help to also often noted in this disorder.' 2 The important distinguish their origin.10 A recent immuno- change is confined to the heart and has been named as histochemical study showed the presence of anti- either isolated or idiopathic interstitial myocarditis. macrophage and anti-Leu 3a (anti-T cell) antigens in Because of the unique morphology of its myocardial giant cells and suggested that they originated from granulomatous lesion, the disorder is commonly macrophages.'0 referred to as giant cell myocarditis. About 40 cases of This paper adds a further case to the reported cases an acute idiopathic form ofgiant cell myocarditis have of acute idiopathic interstitial myocarditis and been reported worldwide.34 presents evidence for the myogenic origin of giant cells, particularly on the basis of their ultrastructural Accepted for publication 27 May 1986 and immunohistological characteristics. 1209 J Clin Pathol: first published as 10.1136/jcp.39.11.1209 on 1 November 1986. Downloaded from

1210 Tanaka, Ichinohasama, Kawahara, Esaki, Hirokawa, Okishige, Tanaka Case report showed first degree A-V block (PQ interval 0-26 sec- onds), disturbance of intraventricular conduction CLINICAL HISTORY (QRS 009 seconds), and low voltage. Changes in A 33 year old Japanese housewife had been healthy serum enzyme activities were unimportant: creatine and had no history of allergic reaction to commonly phosphokinase 107 IU/i (normal range = 24-170), prescribed drugs. She had no history of recent travel glutamic-oxaloacetic transaminase 28 IU/I (normal abroad. Her husband and two children were all range: 0-40), glutamic pyruvic transaminase 16 IU/I healthy. In September 1984 she felt discomfort in the (normal range: 0-35), except for slightly raised lactate espigastric region after breakfast. On a visit to a dehydrogenase activities (751 Wroblewski units, nor- neighbouring hospital, cardiomegaly and arrhythmia mal range: 100-450). Data on peripheral were pointed out. She then developed syncope for five showed (red blood cells 481 x 104, white cells 7600, minutes when she went upstairs at home. She was haemoglobin concentration 11-2 g/dl, haematocrit immediately taken to a local hospital. Electro- 33-5%, 16-1 x 104) and serum (rheumatic cardiography showed an increase in S-T segment in II, factor test negative, Treporema pullidum hae- III, aVf and V1-2, premature atrial contraction, and magglutination test negative, C-reactive protein 1+) premature ventricular contraction and sinus tachy- showed no clinically important changes. Tests for cardia (120/minute). Digitalis and lidocaine were tuberculin and Kveim reactions and estimations of ineffective. She was transferred to Oume Municipal antibody titres for viruses were not performed. Pri- General Hospital. On admission, her physical condi- mary myocardial disease was suspected clinically, and tion was as follows: body temperature 36-7°C; cardiac the patient was conservatively treated by furosemide rate 96/minute; respiratory rate 14/minute; blood (80 mg/day) and dopamine (4-5 ug/kg/minute). Right pressure 90/70 mm Hg. Congestion of both lungs and pneumothorax occurred and a continuous drainage enlarged cardiothoracic ratio (67%) were found on was carried out. The pneumothorax improved four chest radiography. Central venous pressure was days later. Ventricular tachycardia (150/minute) then slightly raised (17cm water). An electron cardiogram appeared and bradycardia followed (40/minute). Her copyright. http://jcp.bmj.com/ on September 28, 2021 by guest. Protected

Fig I Cross section of ventricles. Note slight to moderate Fig 2 Low power view ofpart ofleft ventricle showing dilatation ofbilateral ventricles with diffuse thinning of difusely distributed patchy granulomas (*). Changes are myocardium. No focal necrosis is observed. important at external myocardial layer adjacent to epicardialfatty tissue. Endocardial side is at the bottom. (Azan stain.) x 8. J Clin Pathol: first published as 10.1136/jcp.39.11.1209 on 1 November 1986. Downloaded from

Case report of acute idiopathic interstitial myocarditis 1211 blood pressure became unmeasurable. A transient up to a rice grain size, which were vaguely bordered pacemaker was inserted but she died on September 21, and appeared greyish-white in colour, were spread 1984, 16 days after the onset of the disease. diffusely and occupied about one third to a half of bilateral ventricle volumes (figs 1 and 2). Overall, Pathology neither scars nor necrotic foci were detectable in the myocardium. Necropsy was carried out two and a half hours after Histologically patchy lesions were noted through- death. Notable pathological changes were confined to out the myocardium and consisted of granulomas of the heart. No clinically important changes were various sizes spread extensively through both ventri- observed in other viscera. cles (figs 2-4), the left atrium slightly, and the right The heart weighed 320 g. There was a small amount atrium only at the appendage. The disease in both of pericardial effusion (60 ml) without apparent signs ventricles manifested itself more noticeably in the of pericarditis. Both ventricles were moderately myocardium of the epicardial side; the epicardial dilated. The volume ofthe cardiac chambers was mea- tissue was only partially affected (fig2). Papillary sured by a clay moulding method, and the data muscles of both ventricles were affected. No granu- obtained were as follows: left ventricle 57 8 ml; right lomatous lesions were noted in the chorda tendinae ventricle 72-9 ml; left atrium 28-1 ml; right atrium and cardiac valves. Major cellular Clements found in 49-7 ml. The wall thickness of the heart was at the low the granulomatous lesions were small to medium sized limit of the normal range: left ventricle 8-0 mm; right lymphocytes and histiocytes (figs 3 and 4). A mod- ventricle 2 0-2-5 mm. The circumference of the val- erate number of eosinophils and plasma cells were vula annuli was within the normal range. No abnor- also noted, but almost no . Multinucleated mality was found in any cardiac valve. Both coronary giant cells of 25-90 x 10-20 gm in size, having up to arteries showed minimal sclerosis. A bean sized fresh 20 nuclei were found throughout the granulomatous thrombus was attached to the endocardium ofthe left foci, particularly at the periphery where a close con- ventricular apex. On the cut surface, patchy lesions of tact to undamaged myocardial cells was speculated. In copyright. http://jcp.bmj.com/ on September 28, 2021 by guest. Protected 40

(D'V * ;7t w 4'8+

{~~~Pw ~i &"~. ,- Fig 3 General view ofgranulomatous changes observed Fig 4 Granulomatous changes consisted of round cells, adjacent. to degenerating myocardial cells (right upper fibroblasts, and giant cells (arrow). Giant cells are corner). Details of cellular reaction in marked area of this commonly seen at parallel to degenerating myocardial cells picture are shown in fig4. (Haematoxylin and eosin.) (*). (Haematoxylin and eosin.) x 185. x 155. J Clin Pathol: first published as 10.1136/jcp.39.11.1209 on 1 November 1986. Downloaded from

1212 Tanaka, Ichinohasama, Kawahara, Esaki, Hirokawa, Okishige, Tanaka granulomatous foci atrophy, swelling, and degener- Neither granulomatous lesions nor angitis were ation of muscle fibres were common (figs 3 and 4). found in other organs. A 2 x 1 cm sized scar was Proliferation of fibroblasts and capillaries and new found in the right apex of the lung (230:310 g) (weight deposition ofcollagen were evident. Neither of left lung 230 g, right lung 310 g); focal lympho- nor neuritis was noted. cytosis was also noted. Organising pneumonia of right

*?- v.e

p.,g a v b.. 1''~~~~~ kxt copyright.

Figs 5-7 Three types of multinuclear giant cells distinguished by nuclear position. Figs 5 and 6 were taken from haematoxylin and eosin stained sections, andfig 7 was taken from immunohistochemically stained section (PAP method, myoglobin.) x 820. http://jcp.bmj.com/

Fig 5 Elongated type which often communicates with degenerating muscle cells. Fig 6 Giant cell with centrally located multiple nuclei. Fig 7 Giant cell with circularly arranged multiple nuclei. Myoglobin is weakly positive in upper part of the cytoplasm ofgiant cell. on September 28, 2021 by guest. Protected Table 1 Immunohistochemical differences ofgiant cells shown by PAP method

Types ofgiant cells (incidence in %) I 11 III Sarcoidosis Langhans' type type Touton type Myoglobin* (A) 52 24 22 6 () () (-) (-) (B) 32 8 14 10 (C) 16 0 10 6 Lysozyme* (A) 8 0 4 4 (+ +) (+ + +) (+)(-) (B) 42 6 26 10 (C) 50 20 18 12 IgG** ( + + M( ++ )+ H +) IgA** (++F- (+M- (++ () +F- IgM** (+)-(-) (+M- (+ + () (F- Sources of reagents: *DakoPatts Inc, **Boehringerwerke. A, B, and C (A =' definitely positive, B = faintly positive, C = negative), staining intensity = (-) negative, (+) weakly positive, (+ +) moderately positive, (+ + +) strongly positive. J Clin Pathol: first published as 10.1136/jcp.39.11.1209 on 1 November 1986. Downloaded from

Case report of acute idiopathic interstitial myocarditis 1213 copyright. http://jcp.bmj.com/ on September 28, 2021 by guest. Protected

Fig 8 Low power view of multinucleated giant cell ofelongated type. Cell was preserved poorly due to cadaverous change. Parts of cytoplasm, (square) and (arrow) were further enlarged and are shown in figs 9 and 10, respectively. (Lead citrate and uranyl acetate.) x 1960. Fig 9 Higher magnification of cytoplasmic portion ofgiant cell shown in fig8. Myofibrils (Mf) in cytoplasm are shown. Mb: cell membrane. x 8480. Fig 10 Dense structure of cytoplasm consisting of condensed (degenerating) myofibrils (Mf). M = mitrochondria. x 17000. J Clin Pathol: first published as 10.1136/jcp.39.11.1209 on 1 November 1986. Downloaded from

1214 Tanaka, Ichinohasama, Kawahara, Esaki, Hirokawa, Okishige, Tanaka segment 5 of the lung was also noted. Slight Table 2 Immunohistochemical markers ofgiant cells eosinophilia was noted in the muscle layer of the gas- shown by ABC method tric antrum. Numerous fibrin thrombi in the liver Reactions (960 g) and a small number of pulmonary vessels sug- Markers gested that disseminated intravascular Antihuman rabbit might have occurred at the final stage. a I -antichymotrypsin' (+ + )( +) a I -antitrypsin' (+ +)-(+) CEA' (-) Desmin' (-) CHARACTERISTICS OF GIANT CELLS Factor Vlll' (-) Morphological characteristics in histology Most Ferritin' (-) giant cells observed in myocardial granulomas of this Fibronectin2 (-) Immunoglobulin' (+ (-) case resembled either foreign body or myogenic giant Keratin' (-) cells. Their positions seemed to parallel those of the Lactoferin' (-) muscle cells (fig 4). Three types of giant cells were Lysozyme' (+ )( ) distinguished in the granulomas: type I-giant cells Myoglobin3 S-100 protein4 (-) with elongated cytoplasm either arranged in parallel Actin IgG (chicken)5 or connecting directly with muscle fibres (fig 5); type II-giant cells with centrally arranged multiple nuclei Antihuman mouse (monoclonal) Myosin6 (fig 6); and type III-giant cells with circularly Vimentin7 (-) arranged multiple nuclei (fig 7). Table 1 shows a rough Sources of reagents: 1. DakoPatts Inc; 2. ZYM: Zymed Laboratory estimation of their incidence in 100 giant cells. With Inc, USA; 3. CPL: Cappel Laboratory Inc, USA; 4. Dr Matsuda, periodic acid Schiff stain the cytoplasm of giant cells Department of Pathology, Yamagata University; 5. BTI: Biological Technologies Inc, USA; 6. Dr Nishikawa, Department of Pathology, seemed to be rather pink. Lipofuscin granules, which Tokyo Women's Medical College, Japan; 7. LBS: Labsystem Oy, could suggest a myogenic origin for the giant cells, Finland. were often noted at the paranuclear area. Electron microscopy (figs 8-10) The tissue was poorly preserved due to cadaverous changes. Multi- complex (ABC) methods (table 2). Myoglobin, nucleated giant cells (fig8), however, with elongated lysozyme, IgG, IgA and IgM were examined using the copyright. cytoplasm (about 80,um in length) that contained PAP method (table 1). For controls, various types of myofibrils (fig 9) were easily detected. Giant cells were giant cells obtained from the following cases were located adjacent to degenerating muscle fibres, which examined: cardiac sarcoidosis (woman aged 21) for appeared condensed and osmiophilic (fig 10). sarcoid giant cells; tuberculous lymphadenitis (man Myofibrils of degenerating muscle cells extended aged 27) for Langhans' giant cells; a tissue adjacent to occasionally into the cytoplasm of neighbouring giant oesophageal cancer (man aged 48) for foreign body cells closely attached to a thin membrane of compli- giant cells; and a pulmonary cryptococcosis tissue cated infoldings (an intercalated disc), suggesting a (man aged 56) for giant cells of the Touton type. http://jcp.bmj.com/ myogenic origin. Filamentous materials of 12-5 to Myoglobin was definitely positive in over 50% of the 25 nm in thickness, with a sparse density, were also giant cells observed in the present case, in contrast to seen in the cytoplasm of the giant cell. Occasionally the negative reaction ofgiant cells ofthe control cases. more than a pair of centrioles were found in the cyto- Halfofthe giant cells ofthe present case were negative plasm near the nuclei, suggesting that the giant cell for lysozyme. A similar tendency was noted in foreign was formed either by an impaired cytoplasmic body giant cells. Giant cells of both and

division or cell fusion. There were two types of gran- sarcoidosis were strongly positive for the lysozyme on September 28, 2021 by guest. Protected ules, one consisting of highly osmiophilic granules of reaction. Reactions to IgG, IgA, and IgM scarcely 100 to 200 nm in diameter found in mitochondria, and differed in giant cells of this case and of the controls. the other consisting oflow osmiophilic granules of200 Sixteen cellular markers, including both myoglobin to 500 nm in diameter with a halo in the cytoplasm. and lysozyme that had been studied by the PAP The second type may have been the primary lysosome. method, were analysed using the ABC method (table Most rounded form giant cells showed ultrastructural 2). In this study reactions to both myoglobin and characteristics similar to those of the elongated form, lysozyme showed a similar pattern as had been noted except that numerous lysosomes, both primary and with the PAP method. Giant cells of the present case secondary types, were found in the cytoplasm of some were often equally positive in a l-antichymotrypsin cells which had a few filamentous materials. and a l-antitrypsin, suggesting that some of the giant Immunohistochemistry (tables 1 and 2) Paraffin cells of the present case were of the macrophage ori- embedded tissues were examined by both peroxidase- gin. The importance of the rest of the markers tested antiperoxidase (table l) and avidin-biotin-peroxidase was inconclusive and may serve only for a reference. J Clin Pathol: first published as 10.1136/jcp.39.11.1209 on 1 November 1986. Downloaded from

Case report of acute idiopathic interstitial myocarditis 1215 Discussion already been considered.' 214 Although a myogenic origin for giant cells is favoured, both foreign body Acute idiopathic interstitial myocarditis, a diffuse and Langhans' type giant cells have also been sug- type of Fiedler's myocarditis,"l 12 has been dis- gested.'4 19 The morphological grounds for the myo- tinguished from other forms of myocarditis observed genic origin of giant cells are as follows: (i) parallel in systemic disorders, including sarcoidosis, infec- position of giant cells and muscle fibres; (ii) a direct tious, toxic, and allergic diseases.Because of the pres- contact between giant cells and muscle cells'7 18 20 21. ence of occasional multinucleated giant cells in the (iii) the presence of a smooth transition from a giant myocardial lesions of this disease,'3 the term isolated cell to a muscle cell; (iv) myofibrils in the cytoplasm of giant cell myocarditis is often applied, particularly in giant cells6 22 23 24; (v) lipofuscin granules in the cyto- western reports. As the appearance of giant cells is plasm of giant cells.'3 These criteria have been drawn related to non-specific myocardial lesions and is less from data obtained during regeneration ofthe skeletal common in acute idiopathic interstitial myocarditis muscle after injury.423 Some argue that the latter the term giant cell myocarditis has not been used in three criteria are related to .'0 18 this report. We morphologically classified the giant cell of this The pathogenesis of this disease is unknown,'4 but case into three types. The type I giant cell satisfies all viral have been speculated.'5 The acute morphological citeria stated above and thus can be fatal course of a case of an isolated cardiac lesion, regarded as a myogenic type. Though giant cells ofthe compatible histologically with interstitial myocarditis, two other types also satisfy the criteria for the myo- led to the final diagnosis. No granulomatous foci, genic origin, the type II giant cells resemble foreign which would suggest sarcoidosis, were detected in sys- body giant cells. Morphological differences were seen temic organs examined both grossly and histologi- between the type III giant cell and giant cells observed cally. Looking at the available pathological in tuberculosis and sarcoidosis. The myogenic origin anatomical data, our case resembles Friedler's myo- of most giant cells observed in our case was further carditis reported by Parrish'6 and giant cell myo- confirmed ultrastructurally and immuno- carditis reported by Suganuma et all7; more extensive histochemically. An electron microscopical exam- myocardial disease was reported in the former case. ination showed a close association between In general, the term "giant cell myocarditis" is degenerated muscle fibres and the cytoplasm of the copyright. loosely applied to granulomatous myocardial lesions giant cell, confirming earlier an observation made by associated with the appearance of giant cells: any Pyun et al.6 The presence of myoglobin was shown granulomatous lesion that affects the myocardium immunohistochemically in over 50% of giant cells in can expect to form giant cells.'4 18 The appearance of our case, suggesting that most of the giant cells were giant cells in myocardial ganulomatous lesions is pos- of myogenic origin. sibly related to a reparatory process ofdamaged myo- Recently immunocytochemical methods have been cardial cells. Intervention of macrophages of both applied to define the macrophage nature of giant cells local (histiocytes) and blood () origin, with observed in interstitial myocarditis.'0 Although not http://jcp.bmj.com/ certain variations in numbers, reflecting the stage of tested in this study, Theaker etal'0 showed two the disease, may occur. different antimacrophage antibodies (EMB 11 and In an earlier stage giant cells originating from KB 90) in giant cells using a monoclonal antibody degenerated or regenerating myocardial cells, or both, method. They reported that both desmin and Ki 67 may predominate, in contrast to specimens of a later were negative in giant cells, except for a positive Ki 67 stage, in which macrophages may be obserVed more reaction in the nuclei of lymphocytes and mono-

commonly following an advanced reparative process. nuclear . Lysozyme activity was nearly on September 28, 2021 by guest. Protected It is likely that the controversial problem of the origin absent in our case, which agrees with the findings of of giant cells in interstitial myocarditis is related, at most other cases reported,7 810 except that a positive least in a part, to morphological differences between reaction was noted in one case.9 This case may be granulomatous lesions, relating to the repair stage of regarded as specific, as the giant cells of this case the disease. The presence of giant cells in granu- showed no elongated forms (type I of our case), no lomatous lesions of the myocardium thus does not transitional forms to muscle cells, and a negative cyto- suggest any definitive pathogenesis. Rather, the chemical reaction to myosin and creatine phos- topography ofthe granuloma, which is confined to the phokinase. Negative lysozyme activity, however, does heart, may be more reliable and specific to define the not completely exclude a histiocytic origin for giant disorder. cells, because some macrophages are known to appear The origin of giant cells is one of the most popular negatively.25 Cellular immunity is required to induce topics concerning interstitial myocarditis. Both myo- the lysozyme activity.8 Perhaps the positive lysozymal genic and macrophage origins for giant cells have activity noted in that case9 was related to underlying J Clin Pathol: first published as 10.1136/jcp.39.11.1209 on 1 November 1986. Downloaded from

1216 Tanaka, Ichinohasama, Kawahara, Esaki, Hirokawa, Okishige, Tanaka immunological abnormality caused by chronic active 8 Ohno T, Tamaki N, Motoki K, Yamamoto K, Seki K. An autopsy case report of giant cell myocarditis with mediastinal hepatitis with positive antinuclear antibody. lymphnode involvement. Shinzo 1983;15:91-6. 9 Rabson AB, Schoen FJ, Warhol MJ, Mudge GH, Collins Jr JJ. We express our gratitude for the excellent technical Giant cell myocarditis after mitral valve replacement: case re- help of the following technologists in the preparation port and studies of the nature of giant cells. Hum Pathol 1984;15:585-7. of the histological, immunochemical, and electron10 Theaker JM, Gatter KC, Heryet A, Evans DJ, McGee JO'D. microscopical specimens used in this study: Y Ootani Giant cell myocarditis: evidence for the macrophage origin of and Y Hirahara of the Clinical Pathology Service, giant cells. J Clin Pathol 1985;38:160-4. Oume Municipal General Hospital; Mr I Sakuma and11 Jarcho S. Fiedler on acute interstitial myocarditis (1899)-I. Am Mrs Y Suzuki, the Pathological J Cardiol 1973;32:221-3. Anatomical Service, 12 Jarcho S. Fielder on acute interstitial myocarditis (1899)-1l. Am Tokyo Metropolitan Hiroo Hospital. We also J Cardiol 1973;32:716-8. acknowledge valuable advice and comments for case13 Whitehead R. Isolated myocarditis. Br Heart J 1965;27:220-30. analysis from Dr S Otsu, Yokufiikai Geriatric Hospi- 14 McAllister HA, Ferrans VJ. Granulomas of the heart and blood vessels. In: Loauhin HL, ed. Pathology of granuloma. New tal, Tokyo, and Professor Morie Sekiguchi, the Heart York: Raven Press, 1983:75-123. Institute of Tokyo Women's Medical College, and Dr15 Sekiguchi M, Hiroe M, Take M, Hirosawa K. Clinical and histo- Y Matsui, Japan Red Cross Medical Center, Tokyo. pathological profile of sarcoidosis of the heart and acute idio- We are indebted to Professor T Kasajima and Dr T pathic myocarditis. Concepts through a study employing endomyocardial . II. Myocarditis. Jpn Cire J 1980; Nishikawa, Second Department of Pathology, Tokyo 44:264-73. Women's Medical College, for their kind help in 16 Parrish JA. Fiedler's myocarditis. Br Heart J 1965;27:458-61. immunohistochemical studies (ABC method) of the 17 Suganuma T, Okada M, Sakai Y, Fujiwara M. An autopsy case giant cells of this case. We also thank associate Pro- of giant cell myocarditis. Shinshuu Igakkai Zasshi 1975; fessor J Patrick Barron of St Marianna 23:149-55. University 18 Dilling NV. Giant-cell myocarditis. J Pathol Bacteriol 1956; School of Medicine for his revision of the manuscript. 71:295-300. 19 Sekiguchi M, Numao Y, Imai M, Furuie T, Mikami R. Clinical and histopathological profile of sarcoidosis of the heart and acute idiopathic myocarditis. Concept through a study employ- References ing endomyocardial biopsy. I. Sarcoidosis. Jpn Circ J

1980;44:249-63. copyright. 1 Pomerance A, Davies MJ. The pathology of the heart. Oxford: 20 Langston JD, Wagman GF, Dickenman RC. Granulomatous Blackwell Scientific Publications, 1975. myocarditis and myositis associated with thymoma. Archives of 2 Becker AE. Myocarditis. In: Silver MD, ed. Cardiovascular Pathology 1959;68:367-73. pathology. Vol 1. New York: Churchill-Livingstone, 1983: 21 Boeson K, Hansen BF. A case ofgiant cell myocarditis. Acta Med 469-88. Scand 1981;210:521-2. 3 Palmer HP, Michael IE. Giant-cell myocarditis with multiple 22 Peison B, Lowenstein EC. Giant-cell myocarditis. /VY State J Med organ involvement. Arch Intern Med 1965;116:444-7. 1973:73:259-63. 4 Davies MJ, Pomerance A, Teare RD. Idiopathic giant cell 23 Shimada N, Ishihara Y, Kojima A, Moriyasu K. Three cases of myocarditis-a distinct clinico-pathological entity. Br Heart J granulomatous myocarditis with giant cells. Acta Pathol Jpn 1975;37:192-5. 1967;17:503- 5. 5 Ooneda G, Mitomo H, Kato K, Kanai H, Yoshimoto T. Myo- 24 Tesluk H. Giant cell versus granulomatous myocarditis. Am J http://jcp.bmj.com/ cardial sarcoidosis (giant cell myocarditis). Report of a case Clin Pathol 1956;26:1326-33. with autopsy and a study on the nature of asteroid bodies. 25 Mason DY, Taylor CR. The distribution of muramidase Transactiones Societatis Pathologicae Japonicae 1957; (lysozyme) in human tissues. J Clin Pathol 1975;28:124-32. 46:838-54. 6 Pyun KS, Kim YH, Katzenstein RE, Kikkawa Y. Giant cell myocarditis. Light and electron microscopic study. Archives of Pathological Pathology 1970;90:181-8. Requests for reprints to: Dr M Tanaka, 7 Tubbs RR, Sheibani K, Hawk WA. Giant cell myocarditis. Arch Anatomical Service, Tokyo Metropolitan Hiroo General Ebisu, Shibuya-ku, Tokyo 150, Japan. Pathol Lab Med 1980;104:245-6. Hospital, 2-34 on September 28, 2021 by guest. Protected