Serial right ventricular endomyocardial biopsy in rapid-onset severe heart failure due to giant cell myocarditis.

Giant cell myocarditis (GCM) is a serious condition that warrants immediate diagnosis and treatment. It often presents as rapidly progressive heart failure and/or malignant ventricular arrhythmias. Here, we describe a 34-year-old patient with myasthenia gravis who presented with GCM 2 weeks after resection of a thymoma. A cardiac biopsy confirming the diagnosis was done within 3 days after admission. After institution of an aggressive immunosuppressive drug regimen, implantation of an implantable cardioverter defibrillator, and intensive cardiac rehabilitation, the patient recovered dramatically. In control biopsies after 4 weeks and 6 months, no more giant cells were found. We conclude that, in the case of nonischemic acute heart failure in young patients, a biopsy should be performed as soon as possible to prevent an unfavourable outcome of this often fatal disease.     

Metaplastic thymoma with myasthenia gravis presumably caused by an accumulation of intratumoral immature T cells: a case report

Among human neoplasms, thymomas are well known for their association with paraneoplastic autoimmune diseases such as myasthenia gravis. However, regarding rare metaplastic thymoma, only one case of an association with myasthenia gravis has been reported. Here, we present the second case of a 44-year-old woman with metaplastic thymoma associated with myasthenia gravis. In metaplastic thymoma, intratumoral terminal deoxynucleotidyl transferase-positive T-cells (immature T-cells) are generally scarce, while they were abundant in the present case. We believe that these immature T-cells could be related to the occurrence of myasthenia gravis.     

Thymic germinal centres in myasthenia gravis: a correlative study

The density of germinal centres in the thymic medulla in twenty-three cases of myasthenia gravis correlated inversely with age but did not correlate with sex, the duration of symptoms of myasthenia gravis, the presence of thymoma, or the result of tests for antibody to striated muscle and thymic epithelial cells.

The number of germinal centres formed in lymphoid tissues during an immune response in man is known to decrease with increasing age and this probably applies to autoimmune reactions. The inverse correlation of thymic germinal centres and age in myasthenia gravis is thus consistent with an autoimmune reaction occurring in the thymus in all cases of myasthenia gravis.

     

重症肌无力患者AchR-Ab、Titin-Ab的检测及其临床意义

目的 对重症肌无力患者血清乙酰胆碱受体抗体(AchR-Ab)、连接素抗体(Titin-Ab)进行检测,探讨其临床意义,为临床提供诊断、治疗的依据.方法 选取本院2013年1月至2014年12月收治的重症肌无力患者80例.依据胸部CT检查结果将患者分为伴胸腺瘤(MGT)组与不伴胸腺瘤(NTMG)组.测定各组患者外周血AchR-Ab与Titin-Ab的含量并统计阳性例数,探讨其用于诊断重症肌无力的价值及意义.结果 MG组AchR-Ab与Titin-Ab阳性率明显高于HC组,MGT组AchR-Ab与Titin-Ab阳性率明显高于NTMG组,全身型(Ⅱ～Ⅳ型)AchR-Ab与Titin-Ab阳性率明显高于眼睑型(Ⅰ型)组,差异具有统计学意义(P＜0.05).结论 AChR抗体作为临床使用最广泛的重症肌无力患者检测指标具有一定价值,Titin抗体是应用于重症肌无力患者合并胸腺瘤时敏感而特异的血清学指标,在重症肌无力患者中开展血清Titin抗体的测定对于胸腺瘤的诊断及判断预后具有重要的临床指导意义.     

重症肌无力患者抗Ryanodine受体抗体检测及其意义

本实验应用Westernblot分析 4 4例伴不同胸腺病理类型重症肌无力 (MG )患者血清中Ryanodine受体 (RyR )抗体特异性 ,同时应用ELISA法检测 1 6 9例伴不同胸腺病理类型MG血清中RyR抗体水平。结果显示在Westernblot法分析中 ,2 4例伴胸腺瘤重症肌无力 (MGT )患者血清中有 1 9例可见到RyR抗体阳性条带 ,2 0例非胸腺瘤重症肌无力 (NTMG )患者血清中仅1例可见RyR抗体阳性条带 ,2 5例非MG个体 (NMG )均未见RyR抗体阳性条带。MGT患者血清中RyR抗体阳性条带检出率明显高于NTMG和NMG组 (P <0 0 1 )。在ELISA法检测中 ,MGT组患者血清中RyR抗体水平明显高于NTMG组、其他神经系统疾病 (OND )组、正常对照 (NC )组 (P <0 0 1 ) ;5 9例MGT患者血清中 4 6例RyR抗体阳性 ,2 83例NTMG、OND、NC组检测血清中 1 9例RyR抗体阳性 ,ELISA法检测MGT患者血清中RyR抗体敏感性为 78% ,特异性为 93 3%。结果表明RyR抗体检测是诊断MGT特异性较高的实验室指标 ,具有重要的临床意义     

A case report of sclerosing thymoma of the anterior mediastinum: an exceedingly rare morphology

The morphology of thymoma is diverse, although 5 basic subtypes are recognized in the World Health Organization classification system. Sclerosing thymoma was first documented in 1994 and to date only 13 cases have been reported. Sclerosis itself is considered to be an ancient change and can occur in various histological subtypes. Herein, we present a case of a 62-year-old woman incidentally found to have an anterior mediastinal mass, 31 × 24 × 17 mm in size, without an associated autoimmune disease such as myasthenia gravis. The mass was finally diagnosed as sclerosing thymoma derived from type A thymoma. Intraoperative pathological examination using a limited amount of sample did not allow a definitive diagnosis of thymoma in this case. When dealing with fibrous lesions observed in limited samples such as biopsy and intraoperative frozen specimens, recognizing sclerosing thymoma is important since there are several disease entities accompanying fibrosis in the anterior mediastinum.     

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.     

血清CAE和Titin抗体检测对伴胸腺瘤重症肌无力诊断意义的比较

为评价CAE Ab和Titin Ab测定对诊断伴胸腺瘤重症肌无力 (MGT )的意义 ,采用酶联免疫吸附法 (ELISA )平行检测了6 5例MGT、 97例非胸腺瘤MG (NTMG )、 7例单纯性胸腺瘤 (NMGT )、 35例其他疾病患者 (OND )、 10 0例健康对照者 (NC )血清中的CAE Ab、Titin Ab水平。结果表明 ,MGT患者血清中CAE Ab、Titin Ab检测敏感性分别是 6 3 1%和 6 1 5 % (P >0 0 5 ) ;特异性分别是 75 3%和 91 8% (P <0 0 1)。MGT同一病理类型中的CAE Ab与Titin Ab之间阳性率比较无明显差异(P >0 0 5 )。由此可见CAE Ab、Titin Ab均可作为MGT术前诊断的重要参数 ,两者敏感性无明显差异 ,但Titin Ab特异性明显优于CAE Ab。     

Coexistence of myasthenia gravis and pemphigus foliaceus.

Myasthenia gravis and pemphigus are both considered to have an autoimmune basis. Although immunological and clinical studies have been performed on large numbers of patients with myasthenia gravis, the coexistence of myasthenia gravis and pemphigus foliaceus has rarely been described. We recently have the opportunity to study a 33-year-old female patient having both of these autoimmune diseases confirmed by various diagnostic methods. This rare coexistence of myasthenia gravis and pemphigus foliaceus has not been previously documented in Korea.     

Myasthenia gravis with thymoma and pure red blood cell aplasia

A case of myasthenia gravis with histopathologic confirmation of spindle cell thymoma and pure red blood cell aplasia is reported. This is the twelfth case in the literature in which a simultaneous occurrence of all three disorders, with documented thymic pathology, is noted. Immunologic observations in this patient include an elevated acetylcholine receptor antibody and antinuclear antibody titer, agglutination of mouse red blood cells when combined with the patient's serum, and lack of inhibition of binding of radioactive erythropoietin to mouse red cell receptors when combined with the patient's serum. Although both myasthenia with thymoma and pure red blood cell aplasia may have a common immunologic denominator, our findings in this case indicate that inhibition of erythropoiesis is unrelated to erythropoietin receptor blockade. An alternative hypothesis is offered based on defective T-cell function.     

Micronodular thymic carcinoma with lymphoid hyperplasia: a clinicopathological and immunohistochemical study of five cases

Five cases of an unusual variant of thymic carcinoma are described, which represent the counterpart of the so-called micronodular thymoma with lymphoid hyperplasia. The patients were three men and two women aged 42-78 years (mean 64 years). Three patients were asymptomatic and the tumors were found incidentally on chest radiographs performed for unrelated reasons. Two patients complained of dyspnea, chest pain and shortness of breath prompting further investigations. The tumors ranged in size from 3.2 to 10.0 cm and were described as infiltrative masses often invading adjacent structures. Prominent cystic changes were not identified. Histologically, the neoplasms were composed of epithelial tumor cells arranged in a micronodular growth pattern set in a stroma showing florid lymphoid hyperplasia. Contrary to micronodular thymoma, the epithelial cell component of the present cases showed unequivocal signs of malignancy characterized by cytological atypia and increased mitotic activity. Immunohistochemical studies showed the lymphoid component to be of mixed B- and T-cell lineage. None of the patients had a history of myasthenia gravis or other autoimmune disorder. Follow-up revealed that 4 patients were alive and well 3-26 months after diagnosis while 1 patient was dead of disease 21 months after diagnosis. The tumors in this series represent a distinct subtype of thymic carcinoma histologically strongly resembling micronodular thymoma with lymphoid hyperplasia. Awareness of this type of thymic carcinoma is important in order not to dismiss this tumor for a neoplasm of lower-grade malignancy.     

Clear cell thymoma in a dog

The light and electron microscopical structure of an invasive clear cell thymoma in a 10-year-old female German shepherd suffering from myasthenia gravis is described.     

Thymoma in childhood: a clinicopathological study of five cases

The histological and clinical findings in five cases of thymoma arising in paediatric patients have been studied. The age range was 11-15 years and no patient was affected by myasthenia gravis. All tumours were macroscopically encapsulated, but two of them displayed evidence of microscopic capsular invasion. Histologically, four cases were of the predominantly cortical type (organoid thymoma) with prominent areas of medullary differentiation and Hassall's bodies; one case was of the cortical type. All patients are alive and disease-free 3 months to 9 years after surgery. These findings suggest that thymoma in the paediatric age group may be characterized by fairly uniform clinicopathological features, with a low rate of association with myasthenia gravis and a favourable prognosis.     

IMMUNOPATHOLOGICAL STUDY RELATED TO MYOGLOBIN IN MYASTHENIC AND NON-MYASTHENIC THYMUSES

Twelve biopsied thymuses taken from 4 cases with myasthenia gravis (MG group) and 8 cases without myasthenia gravis (control group) including 2 thymoma cases in each group were immunopathologically investgated in relation to myoglobin (Mb). Mb positive cells of various degrees were detected in all thymuses of both groups, and immunoelectron microscopical examination disclosed that Mb positive cells corresponded to interdigitating reticulum cells and myoid cells in non-neoplastic thymuses, and neoplastic epithelial reticular cells in thymomas. Anti-Mb antibody staining by direct immunoperoxidase technique revealed positive localization to the lymphoid cells in the thymuses of 2 cases of MG group with thymoma. In addition, indirect immunofluorescent study with the serum of each case which was applied to the normal human skeletal muscle, showed positive staining of the sarcoplasm in 3 cases of MG group, including 2 thymoma cases, and using peroxidase labeled serum IgG F(ab')₂ of the same patients this anti-muscle antibodies were proved to be against both postsynaptic cytosol and sarcoplasm of the extraocular muscle of the guinea pig. From these results, it was suggested that Mb may conduct itself as a homologous antigen between the thymus and the skeletal muscle in the myasthenic patient with thymoma, and in the thymus the interdigitating reticulum cell, the myoid cell, or the neoplastic epithelial reticular cell may retain or produce Mb as an antigen-presenting cell.     

Immunopathological study related to myoglobin in myasthenic and non-myasthenic thymuses

Twelve biopsied thymuses taken from 4 cases with myasthenia gravis (MG group) and 8 cases without myasthenia gravis (control group) including 2 thymoma cases in each group were immunopathologically investigated in relation to myoglobin (Mb). Mb positive cells of various degrees were detected in all thymuses of both groups, and immunoelectron microscopical examination disclosed that Mb positive cells corresponded to interdigitating reticulum cells and myoid cells in non-neoplastic thymuses, and neoplastic epithelial reticular cells in thymomas. Anti-Mb antibody staining by direct immunoperoxidase technique revealed positive localization to the lymphoid cells in the thymuses of 2 cases of MG group with thymoma. In addition, indirect immunofluorescent study with the serum of each case which was applied to the normal human skeletal muscle, showed positive staining of the sarcoplasm in 3 cases of MG group, including 2 thymoma cases, and using peroxidase labeled serum IgG F (ab')2 of the same patients this anti-muscle antibodies were proved to be against both postsynaptic cytosol and sarcoplasm of the extraocular muscle of the guinea pig. From these results, it was suggested that Mb may conduct itself as a homologous antigen between the thymus and the skeletal muscle in the myasthenic patient with thymoma, and in the thymus the interdigitating reticulum cell, the myoid cell, or the neoplastic epithelial reticular cell may retain or produce Mb as an antigen-presenting cell.     

Myasthenia gravis with thymoma is not associated with an increased incidence of non-muscle autoimmune disorders.

Three groups of thymectomized patients with myasthenia gravis (MG) were selected for study, 16 with thymoma, 16 with thymic atrophy and 32 with follicular hyperplasia of the thymus. All 16 patients with thymoma, 15/16 with thymus atrophy and 30/32 with follicular hyperplasia had AChR antibodies. Non-receptor muscle (CA) antibodies were found in sera of 15/16 patients with thymoma, 3/16 with thymus atrophy and in none of the sera from patients with follicular hyperplasia. There were 2 patients with thymoma and polymyositis, but none of the thymoma patients had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or other autoimmune disorders. Among the 32 patients with follicular hyperplasia of the thymus were 2 with SLE, 2 with RA and 1 with juvenile diabetes mellitus. In this study, there was an increased incidence of non-muscle autoimmune disorders among MG patients with follicular hyperplasia of the thymus but not among MG patients with thymoma.     

胸腺瘤病例回顾分析

目的分析胸腺瘤临床表现及消化系统症状的发生率。方法回顾性分析173例胸腺瘤临床资料。结果胸腺瘤常见首发症状是肌无力(53.75%)和肿瘤所致胸部不适症状(22.54%),部分患者体检偶然发现(13.29%)。患者具有突出的自身免疫倾向,可检测到多种自身抗体并伴随多种与免疫异常有关的疾病(副肿瘤综合征):神经系统疾病58.95%(重症肌无力56.65%)、内分泌疾病5.78%、第二肿瘤4.62%、血液系统疾病6.37%、结缔组织病1.73%、消化系统疾病1.16%。消化系统症状总发生率9.83%(17/173),以慢性腹泻最多(5.78%),多数腹泻病因不明。结论胸腺瘤具有突出的自身免疫倾向,临床表现差异大,伴随多种与自身免疫相关的疾病。不明原因的慢性腹泻常见,似与自身免疫性肠病有关。     

Multimodal immunotherapy ameliorates myasthenia gravis preceded by thymoma-associated multiorgan autoimmunity

Thymoma-associated multiorgan autoimmunity (TAMA) is a rare autoimmune disorder associated with thymoma that causes a pathology similar to graft-versus-host disease (GVHD) targeting the skin, digestive organs, and liver. Herein, we report the case of a 38-year-old male with myasthenia gravis (MG) preceded by TAMA. The patient developed intractable diarrhea 2 years before admission. Subsequently, dysphagia, dysarthria, and left blepharoptosis were observed. The patient was admitted to the hospital because of fever and dyspnea, was positive for anti-AChR antibody, and chest-computed tomography revealed thymoma, which led to the diagnosis of thymoma-related MG. Biopsied specimens from the sigmoid colon revealed apoptotic colonopathy with lymphocyte-rich lamina propria. Immunohistochemical staining revealed that the infiltrating cells were predominantly labeled with anti-CD3-antibody. The patient did not show skin lesions or liver dysfunction. Therefore, TAMA limited to the gastrointestinal tract was diagnosed. Although TAMA typically has a poor prognosis, immediate multimodal immunotherapy for MG was successful, resulting in a good outcome for TAMA of this case. TAMA is caused by the inability of the thymoma to suppress self-reactive T lymphocytes, which subsequently leads to a disease that is clinically indistinguishable from GVHD. Based on the characteristics of this case, limited gastrointestinal tract involvement in TAMA without lesions in other organs may lead to a favorable prognosis. TAMA cases lacking skin lesions may present with nonspecific gastrointestinal or liver disease. If a patient with thymoma-associated MG has gastrointestinal symptoms such as diarrhea, TAMA should be considered, and the diagnosis should be made early by pathological evaluation of gastrointestinal tissues.

     

The immunopathology of myasthenia gravis.

Experimental autoimmune myasthenia gravis, induced by immunization with solubilized acetylcholine receptors, has proven an excellent animal model for the study of myasthenia gravis. The role of the thymus in myasthenia gravis is not yet known. Its content of skeletal muscle elements and acetylcholine receptors and the presence of germinal centers in myasthenia gravis suggest that the thymus could be a site of autoimmunization. An effector role has not been demonstrated for T cells in the pathogenesis of experimental autoimmune or clinical myasthenia gravis, but helper T cells participate in the rat's autoantibody response to acetylcholine receptors. Antibodies and lymphocytes reactive with acetylcholine receptors are demonstrable in the peripheral blood of patients with myasthenia gravis and appear to be specific for this disease. Parallel studies of both experimental autoimmune and clinical myasthenia gravis have provided evidence for an autoimmune basis for the pathophysiology in myasthenia gravis. Antiacetylcholine receptor antibodies appear to play a central role in impairing neuromuscular transmission. Numerous antibody specificities have been described, but none seems to be directed at the acetylcholine binding site of the receptor. Addition of antiacetylcholine receptor antibodies to cultured muscle cells, in the absence of complement, causes redistribution of the receptors on the membranes of myotubes, accelerated receptor degradation, apparent impairment of ionophore function, and loss of sensitivity to acetylcholine. In vivo complement appears to be an important mediator of antiacetylcholine receptor antibody pathogenicity. Its presence is essential for the passive transfer of experimental autoimmune myasthenia gravis with antibodies. In muscle biopsy specimens from patients with myasthenia gravis, IgG and C3 have been demonstrated on the postsynaptic membrane and on degenerated fragments of membrane in the synaptic cleft. This suggests that complement activation in vivo is associated with focal lysis of the postsynaptic membrane. A causal relationship appears to exist between the binding of antibody to acetylcholine receptors, the reduction in muscle acetylcholine receptors, and impairment of neuromuscular transmission.     

CD20在胸腺瘤中的表达及其临床病理意义

目的 探讨CD20在胸腺瘤中的表达及其临床和病理学意义.方法 对179例手术切除的胸腺肿瘤病例,按照2004年的WHO分类标准并结合临床病理资料,重新进行病理组织学分类,并选取其中资料完整的102例肿瘤组织,运用免疫组织化学EnVision法分别标记CD20、CKpan、末端脱氧核苷酸转移酶、CD3、CD5、CD43、CD99、S-100蛋白.其中重点观察肿瘤性上皮细胞及背景淋巴细胞的CD20表达特征,其他指标用以标记细胞.同时将所有病例按是否伴有重症肌无力分为两组,对结果进行统计学分析.结果 102例胸腺瘤中,A型7例、AB型32例、B1型17例、B2型15例、B3型17例,胸腺癌14例,CD20表达于肿瘤性上皮细胞,在A、AB、B1、B2、B3型胸腺瘤和胸腺癌中的阳性率分别为3/7、84.4%(27/32)、1/17、2/15、0/17、0/14.肿瘤的背景淋巴细胞的阳性率分别为3/7、18.8%(6/32)、14/17、11/15、11/17、6/14.伴重症肌无力组(40例)肿瘤内淋巴细胞的CD20阳性表达率为67.5%(22/40),不伴重症肌无力组(62例)阳性表达率为35.5%(22/62),CD20阳性的B淋巴细胞主要分布于伴重症肌无力组,两组间差异有统计学意义(P＜0.05).结论 A型、AB型和极少数的B1、B2型胸腺瘤的上皮细胞均具有表达CD20蛋白的特征,这类上皮细胞属于肿瘤性上皮;而B3型胸腺瘤及胸腺癌的肿瘤性上皮细胞缺乏表达CD20蛋白的特征.胸腺瘤伴重症肌无力者,肿瘤内B淋巴细胞增生,数量明显多于不伴重症肌无力者.AB型胸腺瘤并非A型与B型胸腺瘤的单纯混合,可能属于不同的细胞起源而表现出不同的组织形态和免疫表型.