GIANT CELL MYOCARDITIS IN ASSOCIATION WITH DRUG-INDUCED SKIN ERUPTION

A case of giant cell myocarditis In a 19-year-old woman is presented. She had high fever, vomiting, epigastralgia, cardiomegaly, and disseminated papular erythema probably due to anti-epileptic agents. At autopsy, giant cell myocarditis and the myositis of the systemic skeletal muscles were found. To our knowledge, no case of giant cell myocarditis in association with drug-induced skin eruption was reported. This is a rare case of giant cell myocarditis.     

Giant cell myocarditis associated with lymphoma: an immunocytochemical study.

A case of giant cell myocarditis in a patient with non-Hodgkin's lymphoma is reported. To our knowledge, this is a previously unrecorded association and supports the hypothesis that the aetiology of giant cell myocarditis is related to a changed immune state. Immunohistochemical investigation of this case with a panel of monoclonal antibodies against a range of leucocyte and muscle antigens supports the view that the giant cells have a histiocytic rather than a myogenic origin.     

Mitral stenosis together with a giant cell myocarditis limited to the left atrium

A case is described in which mitral stenosis was associated with a giant cell myocarditis; the latter lesion was, however, localized to the left atrium. A quite high proportion of reported cases of giant cell myocarditis have occurred in association with rheumatic heart disease. The nature of this relationship is discussed and it is concluded that, in such cases, the giant cell reaction may represent an unusual myocardial response to rheumatic fever.     

Hyperacute graft rejection during heart transplantation for giant cell myocarditis: A case report

We report the case of a patient with giant cell myocarditis who was bridged to transplantation with mechanical circulatory support and developed a fatal perioperative hyperacute rejection. The patient had received abundant transfusions that had raised her anti-HLA antibody titers. The cross-match test was positive. No pre-transplantation immunosuppressive therapy had been administered given concomitant infection. The severity and acuteness of the rejection in this case likely reflect the combined effect of preformed anti-HLA antibodies in the context of an active organ-specific immune process at the time of transplantation. This case raises the questions of the need for intensive immunosuppressive therapy before transplantation in giant cell myocarditis and of the management of patients with positive cross-match in the context of a giant cell myocarditis.     

IgG anti-cardiomyocyte antibodies in giant cell myocarditis

Giant cell myocarditis, a rare, fatal, and poorly understood cause of myocarditis, requires pathological examination for diagnosis. It is considered to be an autoimmune disease and is frequently associated with other conditions, in particular thymoma and myasthenia gravis. The typical patient with giant cell myocarditis is young and has severe, progressive congestive cardiac failure that is unresponsive to standard medical therapy and ultimately requires cardiac transplantation. Hence giant cell myocarditis is the most dangerous form of myocarditis. Here we report an unusual presentation of giant cell myocarditis, which mimicked acute myocardial infarction in an elderly woman with myasthenia gravis and a previous diagnosis of thymoma. This patient had evidence of anti-myocyte antibodies, consistent with an autoimmune mechanism.     

Phenotypic analysis of infiltrating cells in human myocarditis. An immunohistochemical study in paraffin-embedded tissue

To define the cellular subpopulations that infiltrate the heart in human myocarditis, formaldehyde-fixed, paraffin-embedded sections from 18 hearts with histologically proved myocarditis were examined immunohistochemically. Disease was classified on routine stains as follows: mixed mononuclear cell (7 cases), granulomatous (3), giant cell (1), rheumatic (2), and fungal (5) myocarditis, respectively. On immunohistochemical examination, T-lymphocyte and macrophage predominance was found in nearly every case, except in fungal myocarditis, in which polymorphonuclear leukocytes and macrophages prevailed. In contrast, B lymphocytes and natural killer cells were conspicuously absent, regardless of histologic classification. Giant cells in giant cell myocarditis and in the Aschoff lesions of rheumatic carditis expressed macrophage, but not myocyte, antigens, suggesting derivation along macrophage lineage. Immunohistochemical data obtainable in paraffin-embedded tissues supplement the study of myocarditis, providing information potentially relevant to immunopathogenesis, natural history, and therapy.     

Survival outcomes of patients with giant cell myocarditis bridged by ventricular assist devices

Giant cell myocarditis is a highly lethal disorder characterized by rapidly progressive congestive heart failure. The aim of this study was to describe the clinical course of patients with giant cell myocarditis who received a ventricular assist device. Patients with giant cell myocarditis were identified from the Multicenter Giant cell Myocarditis Registry. Bridging to cardiac transplantation in the giant cell myocarditis patients who received a ventricular assist device was compared with bridging in the general population of heart failure patients, as reported in the literature. Median posttransplantation survival for patients with giant cell myocarditis who received and did not receive ventricular assist devices was calculated by the Kaplan-Meier method and compared with use of the log-rank test. Nine patients with giant cell myocarditis who received ventricular assist devices were identified. Seven patients survived to transplantation, four were alive 30 days posttransplantation, and two survived to 1 year. The rate of successful bridging to transplantation in seven of nine patients (78%) is similar to that reported for other ventricular assist device recipients. Posttransplantation survival of 57% (4 of 7) at 30 days and 29% (2 of 7) at 1 year was significantly lower compared with 93% 1-year survival of the 30 patients with giant cell myocarditis who did not receive ventricular assist devices before transplantation (p<0.001). Ventricular assist devices can be an effective bridge to transplantation for patients with heart failure caused by giant cell myocarditis. Although their posttransplantation survival was poor in our series, a few patients had long-term survival.     

A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction

It is suspected that autoimmune disease processes are involved in the pathogenesis of a part of giant cell myocarditis. However, evidence for autoimmunity has rarely been demonstrated in clinical investigations. In this study, we have demonstrated a new animal model of autoimmune myocarditis characterized by the appearance of multinucleated giant cells. Lewis rats were immunized twice with human cardiac myosin fraction in complete Freund's adjuvant. Cardiac myosin fraction was prepared from the ventricular muscle of human hearts. Three weeks after the first immunization, acute and severe myocarditis was elicited in all rats. This myocarditis was characterized by massive pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac muscle. Microscopically, there was marked cellular infiltration consisting of mononuclear cells, neutrophils, fibroblasts, and a considerable number of multinucleated giant cells. Extensive myocardial necrosis was also present. The heart weights increased from the third week to the fourth week and then gradually decreased. The titer of anti-myosin antibodies began to elevate from the second week and remained high until the sixth week. In the sixth week, inflammation became smoldering and the multinucleated giant cells disappeared. These findings indicate that the cardiac myosin fraction contains myocarditogenic antigen and that giant cell myocarditis can be induced by autoimmune involvement. To our knowledge, this is the first report of experimental giant cell myocarditis, which is closely similar to human giant cell myocarditis in its histology and clinical course.     

Giant cell myocarditis: evidence for the macrophage origin of the giant cells.

In order to elucidate the origin of giant cells in giant cell myocarditis a case has been studied immunohistologically using monoclonal antibodies against a variety of antigens, including those associated with muscle and macrophages. The results strongly suggest that the giant cells are derived from macrophages rather than the muscle cells.     

An autopsy case of giant cell myocarditis probably due to a non-steroidal anti-inflammatory drug

An autopsy case of giant cell myocarditis (GCM) in a 74-year-old woman is presented. She suffered from hepatic dysfunction, skin eruption and disseminated intravascular coagulation due to the side-effects of a non-steroidal anti-inflammatory drug. After admission, heart failure progressed rapidly, and the patient died suddenly. At autopsy, her heart was slightly enlarged and the heart muscle was thickened with many small whitish nodules. She was diagnosed with GCM because of the infiltration of multinuclear giant cells, histiocytes, eosinophils and lymphocytes into the heart. We did not find any similar lesions in any other organs. Giant cell myocarditis, the etiology of which is not defined, is a rare disease with unfavorable prognosis. This case suggests the possibility of drug-induced GCM.     

Giant cell myocarditis of the left atrium

Here we describe an unusual case of giant cell myocarditis (GCM) found in the left atrial appendage. Giant cell myocarditis is a rare entity in itself, while isolated left atrial GCM has only been reported on a few occasions. We describe a patient who underwent mitral valve replacement for rheumatic mitral stenosis and excision of a grossly abnormal, thickened, and enlarged left atrial appendage. Histological examination confirmed the presence of GCM.     

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

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 granulomas with an ill defined patchy appearance. Histologically these lesions consisted of round cells, histiocytes, eosinophils and myogenic giant cells. The findings were compatible with those of interstitial myocarditis associated with a proliferation 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. Though the macrophage origin of the giant cell 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.     

THREE CASES OF GRANULOMATOUS MYOCARDITIS WITH GIANT CELLS

Three autopsy cases of granulomatous myocarditis were presented, which showed numerous multinucleated giant cells and diffuse proliferation of collagenous tissue. The first case revealed limited lesions only in the myocardium and classified as isolated myocarditis. The second and third cases disclosed classical generalized sarcoidosis with emphasis of myocardial involvement. The interrelationship between these two entities was discussed. Giant cell myocarditis, a disease entity, should be differentiated from the myocardial manifestation of sarcoidosis. ACTA PATH.JAP. 17: 503–515, 1967     

Idiopathic giant cell myocarditis--a case report and review of literature

Idiopathic giant cell myocarditis (IGCM) is a rare clinicopathological entity which is usually known to cause in more than half the cases sudden death. The histological features are characteristic with a central area of myocardial necrosis and a rich cellular infiltration of lymphocytes with a few eosinophils, plasma cells, macrophages and multinucleated giant cells. We hereby report a case of IGCM in a 72 year old male with history of sudden death. This case is being presented for its rarity and a review of literature is made.     

心肌扩张型心脏病的病理形态特征及其临床意义

目的探讨单纯心壁病损造成的心脏扩张者的病理形态特征及其意义。方法收集2004年6月至2006年8月中国医学科学院北京协和医学院阜外心血管病医院60例心脏移植的受体心脏在离体后立即进行了肉眼观察、测量和摄影记录,并进行了全面的组织病理学观察。以其中40例单纯心壁病损造成的心脏扩张者进行临床-病理对照分析,并观察其形态特点。结果40例单纯心壁病损造成的心脏扩张者中21例（52．5％）为原发性扩张型心肌病,9例（22．5％）为致心律失常性右心室心肌病,6例（15．0％）为缺血性心肌病,其余的4例（10．0％）为局灶性心肌致密化不全、巨细胞性心肌炎和特异性心肌病中的酒精性心肌病和高血压性心肌病。40例中临床诊断与病理诊断不符15例（37．5％）,不相符率较高的依次为致心律失常性右心室心肌病（7／9）、缺血性心肌病（5／6）和巨细胞性心肌炎（1／1）。不相符的这几种病的原临床和影像学诊断都是扩张型心肌病。致心律失常性右心室心肌病、缺血性心肌病、心肌致密化不全和巨细胞性心肌炎都有特征性的病理形态表现,酒精性心肌病和高血压性心肌病等的病理诊断需要参考临床病史。该组病例没有观察到慢性心肌炎样病变发展成扩张型心肌病的形态学迹象。结论进行心脏移植病例受体心脏的病理学检查有利于提高心脏病的临床和影像诊断的正确率,病理形态检查是不可忽视的重要手段。     

Acute idiopathic interstitial giant cell myocarditis. A histological and immunohistological study of a case.

The Authors report on a case of acute idiopathic giant cell myocarditis, which occurred in a young man without previous history of immunodeficiency or tumours, and displayed a rapidly fatal clinical course. Autoptic examination showed diffuse damage to the myocardium, with myocytolysis, granuloma formation and abundant giant cell reaction. No significant changes were observed in the other organs and systems . Immunohistochemistry revealed that the giant cells strongly reacted with the antibody KP1--raised to the macrophage-associated antigen CD68--whereas they did not stain with the monoclonal against the muscle-specific marker desmin. In the light of their findings and previous reports in the literature, the Authors discuss the possible origin of giant cells, along with the pathogenesis of the condition.     

Immunohistochemical characterization of infiltrating mononuclear cells in the rat heart with experimental autoimmune giant cell myocarditis.

The pathogenesis of giant cell myocarditis remains unclear. Subsets of inflammatory infiltrating cells may reflect the pathogenesis and etiology of the disease. Therefore, we examined subsets of infiltrating mononuclear cells in the heart of the rat with experimental giant cell myocarditis. Lewis rats were immunized with cardiac myosin in Freund's complete adjuvant (FCA). Severe myocarditis characterized by congestive heart failure and multinucleated giant cells were elicited. The lesions were composed of predominant mononuclear cells, polymorphonuclear neutrophils and fragments of degenerated myocardial fibres. The subsets of infiltrating mononuclear cells were investigated using MoAbs against rat CD4+ T cell (W3/25), CD8+ T cell (CX8), B cell (OX33) and macrophage (OX42). By serial examination, bound immunoglobulin could only be found on degenerated myocardial fibres. In this model, most infiltrating mononuclear cells were composed of macrophages and CD4+ T cells. The frequencies of macrophages and CD4+ T cells were 73.7% and 13.8%, respectively. CD8+ T cells were scarce and B cells were rare in the lesions. The frequencies of CD8+ T cells and B cells were 4.5% and 0.4%, respectively. The dominance of macrophages and CD4+ T cells was the constant finding among the sites of the lesions and throughout the course of the disease. These characteristic subsets of infiltrating cells were in contrast to those of murine viral myocarditis which were mainly composed of natural killer (NK) cells and CD8+ T cells. Clarifying the subsets of infiltrating cells in myocarditis may contribute to differential diagnosis of myocarditis between viral and autoimmune types. From this study, the pathogenesis of experimental autoimmune giant cell myocarditis seemed to be closely related to CD4+ T cells and macrophages.     

An Autopsy Case of Giant Cell Myocarditis (Myocardial Sarcoidosis)

An autopsy case of the so-called giant cell myocarditis, which was understood to be sarcoidosis, the main lesion of which situated in the myocardium, was reported.
In the morphogensis of asteroid bodies, the protein moiety of lipoprotein was considered to participate. The theory that these bodies would be derivatives of elastin could not be supported.     

Giant cell myocarditis associated with silicone. An unusual case of biomaterials pathology discovered at autopsy using X-ray energy spectroscopic techniques

Silicones, used extensively in the fabrication of medical devices because they were presumed inert and biocompatible, are now well-recognized inducers of localized granulomatous inflammation. Silicones less commonly are also associated with more complex clinico-pathologic entities. In this communication, the authors present a case of a patient on chronic hemodialysis involving tubing probably fabricated from silicone rubber who died from a giant cell myocarditis associated with silicone rubber. This case is presented to expand the interpretive paradigm of human pathology and underscores the need for pathologists to consider medical-device associated phenomena in the differential diagnosis of clinical specimens.     

Giant cell myocarditis as a manifestation of drug hypersensitivity.

Adverse drug effects on the myocardium are often classified into toxic and hypersensitivity forms of myocarditis, each with distinct histologic findings. In contrast, giant cell myocarditis (GCM) is generally not associated with adverse drug reactions and has unique histopathologic features. We report four cases of adverse drug reactions in which the histologic findings were characteristic of GCM. The clinical recognition that GCM may be a manifestation of an adverse drug reaction is important, since the prognosis and treatment of this entity may be different from that of other forms of myocarditis.