A long-term surviving patient with invasive thymoma who underwent radiotherapy and/or resection for chest wall, intrathoracic and intrapelvic recurrent tumors]

A 49-year-old woman with myasthenia gravis who underwent left panpleuropneumonectomy for an invasive thymoma that disseminated through the left thoracic cavity. After six year, radiotherapy was conducted on the recurrent tumor in the left anterior chest wall. Two years later, the recurrent tumors in the intrapelvic and intrathoracic cavities were resected. It was thought that long-term survival was obtained by combining radiotherapy and surgical treatment in view of the patient's general condition, and of the recurrent invasive thymoma present in this case.     

A patient with thymoma and four different organ-specific autoimmune diseases

This is the first report of a patient with four organ-specific autoimmune diseases; myasthenia gravis, type 1 diabetes mellitus, autoimmune hepatitis and Hashimoto's thyroiditis. The clinical history suggests a relationship with a non-removed thymoma. Not only the thymoma seems to have triggered these four diseases, the dramatic progressive course with an active autoimmune hepatitis and high concentrations of multiple autoantibodies was probably also associated with non-removal of the thymoma. Thymectomy should be performed in myasthenia gravis patients with thymoma and associated autoimmune diseases.     

Early and late results after thymectomy in myasthenia gravis: a retrospective study [correction of analysis]

BACKGROUND: This study aims to evaluate the early and late outcome of patients treated by surgery for myasthenia gravis and the diagnostic value of the Besinger Score, which is based on a correlation of severity of symptoms with specific antibodies to acetylcholine receptors, in the follow-up investigation after surgical therapy. METHODS: Between June 1984 and April 1992 thoracotomy was performed in 51 myasthenia gravis cases at our department. The retrospective analysis considered patients with (n = 13) or without thymoma (n = 38). The Besinger score was used to describe the severity of disease preoperatively and up to 5 years postoperatively. RESULTS: The Besinger score fell continually post surgery. Changes in relative serum concentrations of antibodies were similar to the Besinger score. Five years after thymectomy complete remission was diagnosed in 40% of the patients. The required dosage of pyridostigmine had fallen by two thirds after 5 years. Patients with follicular hyperplasia had significantly higher remission rates than those with thymoma. CONCLUSIONS: Surgery for myasthenia gravis is successful. The Besinger score well quantifies the severity of the disease.     

Case Report of Thymoma Tumor Reduction Following Plasmapheresis

For thymoma, multidisciplinary antitumor strategy is composed of surgery, chemotherapy, and radiotherapy. Meanwhile, ∼20% to 25% of patients with thymoma have myasthenia gravis and plasmapheresis is recommended for thymoma-associated myasthenia gravis.We report a case that a 40-year-old woman with thymoma experiencing tumor relapse after surgery showed significant response to plasmapheresis.This is the first case of thymoma responded to plasmapheresis, which may guide the study of the etiology and pathogenesis of thymoma.     

Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis

Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a glutenfree diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 （or, about 4.3%） was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.     

Pancreatic Cancer in a Patient with Myasthenia Gravis

Myasthenia gravis has been associated with several diseasessuch as hyperthyroidism and malignancy (thymoma,lung carcinoma) but so far no reports have demonstrated arelationship between this disease and pancreatic disease.We report a 66-year-old man with myasthenia gravis diagnosedon the basis of clinical symptoms (eyelid ptosis),typical abnormalities on repetitive nerve-stimulation tests,and the presence of Ach-R antibodies in the serum. The responseto anticholinesterasic agents (pyridostigmine) wasgood, but after 1 year, he developed pancreatic cancer andmyasthenia gravis symptoms recurred. After surgery andchemotherapy, myasthenia gravis symptoms disappeared.Some months later, the patient had a recurrence of pancreaticcancer after relapse of myasthenia gravis.     

Klinisch-pathologische Studie zur Klassifikation und Prognose von 57 Thymustumoren

Summary The most important prognostic determinants of the thymomas are the gross findings at operation (= the presence or absence of gross invasion of adjacent tissue) and the presence or absence of the thymoma-associated systemic disease, particulary myasthenia gravis. The histologic type of thymoma had no proof value in predicting prognosis with the exception of the so-called atypical thymomas.Thirty-four of 57 patients with thymomas were females and 23 males. The tumors in 40 cases were non-invasive thymomas, and in 17 cases the tumour were invasive of adjacent tissue. 35.1 percent of patients were asymptomatic, the tumours being discovered on roentgenograms done on a routine basis or for an unrelated porpose. 40.3 percent of patients have had a thymomaassociated systemic disease. The most common presenting symptoms were related to myasthenia gravis (26.3%). The 5-year survival rate was 90 percent for non-invasive thymomas without myastenia gravis and 50 percent for invasive thymomas. The 5-year survival rate for patients with myasthenia gravis and encapsulated (non-invasive) thymomas was approximately 60 percent, whereas that for invasive thymomas with myasthenia gravis was 40 percent. The primary form of therapy for all thymomas is the surgical excision. In cases with invasive and/or metastasizing thymomas, postoperative radiation and adjuvanted chemotherapy is indicated, but in most series, the longterm results of this form of therapy are discouraging.

     

A comparative clinical and pathological study on the classification and prognostic features of 57 thymomas. II. prognostic features (author's transl)]

The most important prognostic determinants of the thymomas are the gross findings at operation (equal to the presence or absence of gross invasion of adjacent tissue) and the presence or absence of the thymoma-associated systemic disease, particulary myasthenia gravis. The histologic type of thymoma had no proof value in predicting prognosis with the exception of the so-called atypical thymomas. Thirty-four of 57 patients with thymomas were females and 23 males. The tumors in 40 cases were non-invasive thymomas, and in 17 cases the tumour were invasive of adjacent tissue. 35.1 percent of patients were asymptomatic, the tumours being discovered on roentgenograms done on a routine basis or for an unrelated porpose. 40.3 percent of patients have had a thymoma-associated systemic disease. The most common presenting symptoms were related to myasthenia gravis (26.3%). The 5-year survival rate was 90 percent for non-invasive thymomas without myastenia gravis and 50 percent for invasive thymomas. The 5-year survival rate for patients with myasthenia gravis and encapsulated (non-invasive) thymomas was approximately 60 percent, whereas that for invasive thymomas with myasthenia gravis was 40 percent. The primary form of therapy for all thymomas is the surgical excision. In cases with invasive and/or metastasizing thymomas, postoperative radiation and adjuvanted chemotherapy is indicated, but in most series, the longterm results of this form of therapy are discouraging.     

Pleural dissemination of thymoma showing tumor regression after combined corticosteroid and tacrolimus therapy

We present the case of an elderly woman with myasthenia gravis who had pleural dissemination of thymoma reduced by treatments with a moderate dose of corticosteroids and a conventional dose of tacrolimus. A maintenance dose of prednisolone for myasthenia gravis could not shrink the size of the disseminated thymoma, but prednisolone (>30 mg daily) succeeded in reducing the size of the tumor. Moreover, a combination with tacrolimus enabled the daily dose of prednisolone to be tapered off without recurrence of myasthenia gravis, and the disseminated thymoma almost disappeared. A moderate or higher dosage of corticosteroids with tacrolimus may, in some cases, be an effective procedure for pleural dissemination of thymoma. Treatment should be undertaken on a trial basis for patients not indicated for surgery, radiotherapy, or chemotherapy.     

Myasthenia in elderly patients: a series of 23 cases

PURPOSE: There is evidence that myasthenia gravis is substantially underdiagnosed in older people, for which diagnosis and treatment may be difficult. METHOD: We report on a series of 23 cases of myasthenia gravis diagnosed after the age of 65. Diagnosis was ascertained by compatible symptoms, associated with electrophysiological evidence and/or presence of antibodies to the acetylcholine receptor (AchRAb) and/or positive prostigmine test. RESULTS: Twelve female and 11 male patients were identified, with a mean age of 77 (range: 66-89). Initial symptoms were ocular in 8 cases (35%), bulbar and ocular in 9 cases (39%), generalized in 6 cases (26%). Diagnosis was delayed in many patients (mean delay 31+/-47 months). Prostigmine test was positive in 16 cases (100%), AchRAb were positive in 19/23 cases (83%). Only one thymoma was found. Other diagnoses than myasthenia gravis, mainly stroke, were often considered. Treatment with anticholinesterase drugs, prescribed in all cases, has been able to control symptoms in only 3 cases. Corticosteroids were used in 10 cases, azathioprine or mycophenolate mofetil in 14 cases, intravenous immunoglobulins in 8 cases, and plasma exchanges in 2 cases. Thymectomy was performed on one patient with thymoma. Three patients were hospitalized in intensive care units for several weeks, and 3 patients died from their myasthenia. CONCLUSION: Diagnosis of myasthenia gravis is often missed or delayed in the elderly, because of a broad differential diagnosis in older people, and because the high incidence of the disease in middle and old age is often overlooked. The outcome of myasthenia gravis in older people is far from simple, and immunomodulation proves to be necessary in most cases. However, quality of life of surviving patients appears good.     

Current Trends in the Management of Myasthenia Gravis: Plasmapheresis and Immunosuppressive Therapy

Summary: Current trends in the management of myasthenia gravis: Plasmapheresis and immunosuppressive therapy. J. D. Pollard, A. Basten, J. E. Hassall, H. Kronenberg, R. Cobcroftand R. Dawkins, Aust. N.Z. J. Med ., 1980, 10, pp. 212–217.
In recent years a considerable body of evidence has accumulated to demonstrate autoimmune mechanisms in myasthenia gravis. This evidence has important implications for the aetiology, diagnosis and management of the disease
The primary abnormality in myasthenia gravis is related to the presence of antibody which reacts with the acetylcholine receptor. Measurement of this IgG antibody in the serum has become the most reliable diagnostic adjunct to the edrophonium test, and in an individual patient, the level of the serum antibody relates closely to the clinical indices. In cases of myasthenia where control with anticholinesterase drugs is unsatisfactory, methods to lower the antiacetylcholine receptor antibody are indicated: these may include thymectomy, immunosuppressive therapy or plasmapheresis
Two patients with very severe disease are described in whom all types of therapy were used and in whom survival depended ultimately on the use of plasmapheresis. These patients illustrate the importance of receptor antibody in the clinical manifestations of myasthenia gravis and in its management     

Thymomes et maladies auto-immunes

The association between thymoma and autoimmunity is well known. Besides myasthenia gravis, which is found in 15 to 20% of patients with thymoma, other autoimmune diseases have been reported: erythroblastopenia, systemic lupus erythematosus, inflammatory myopathies, thyroid disorders, Isaac's syndrome or Good's syndrome. More anecdotally, Morvan's syndrome, limbic encephalitis, other autoimmune cytopenias, autoimmune hepatitis, and bullous skin diseases (pemphigus, lichen) have been reported. Autoimmune diseases occur most often before thymectomy, but they can be discovered at the time of surgery or later. Two situations require the systematic investigation of a thymoma: the occurrence of myasthenia gravis or autoimmune erythroblastopenia. Nevertheless, the late onset of systemic lupus erythematosus or the association of several autoimmune manifestations should lead to look for a thymoma. Neither the characteristics of the patients nor the pathological data can predict the occurrence of an autoimmune disease after thymectomy. Thus, thymectomy usefulness in the course of the autoimmune disease, except myasthenia gravis, has not been demonstrated. This seems to indicate the preponderant role of self-reactive T lymphocytes distributed in the peripheral immune system prior to surgery. Given the high infectious morbidity in patients with thymoma, immunoglobulin replacement therapy should be considered in patients with hypogammaglobulinemia who receive immunosuppressive therapy, even in the absence of prior infection.     

Malignant thymoma complicated by amegakaryocytic thrombocytopenic purpura

We report the case of a 41-year-old man with malignant thymoma complicated by amegakaryocytic thrombocytopenia 10 years after diagnosis of myasthenia gravis. A bone marrow aspirate showed an absence of megakaryocytes with normal maturation and differentiation of myeloid precursors. Three months later, severe neutropenia occurred, and a bone marrow examination confirmed the diagnosis of severe aplastic anemia. Associations between thymoma and myasthenia gravis, between thymoma and pure red cell aplasia, and between thymoma and aplastic anemia are well documented. Amegakaryocytic thrombocytopenia is not a recognized paraneoplastic syndrome complicating thymoma. Amegakaryocytic thrombocytopenia complicating thymoma may be a very early presentation of impending aplastic anemia.     

Discordant thymectomy in identical twins concordant for myasthenia gravis

BACKGROUND: Thymectomy is standard therapy fornonthymomatousmyasthenia gravis despite the absence of randomized clinical trials (1). Myasthenia gravis is uncommonly reported in monozygous twins; disease concordance occurs in approximately one third of such identical twin pairs; and treatment for myasthenia gravis, when described,is usually concordant in identical twin pairs (2).OBJECTIVE: To report an 11-year clinical course of a pair of identical twins concordant for generalized acetylcholine receptor antibody–positive nonthymomatous myasthenia gravis in whom only 1 was treated with extended transsternal thymectomy. CASE REPORT: Twin A was a 19-year-old white woman who presented with an 8-week history of intermittent leg weakness, causing her to fall during activities, such as climbing stairs. On examination,she had moderately severe fatigable proximal muscle weakness and ptosis. Her weakness improved with intravenous edrophonium administration.Initial binding acetylcholine receptor antibody titer was 1.22 nmol/L (normal value, 0.03 nmol/L). Repetitive 2-Hz nerve(median, ulnar, and facial) stimulation studies demonstrated up to a 16% decremental response. Chest computed tomography showed residual thymic tissue without thymoma. An extended transsternal thymectomy was performed 11 weeks after the onset of symptoms.     

Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.

The binding of myasthenia gravis antibody acetylcholine receptor (AcChoR) as measured in vitro by Radioimmunoassay with 125I-labeled alpha-bungarotoxin (alpha-BuTx), can be blocked by amniotic fluid, maternal serum, and umbilical cord serum. This inhibitory effect is due to alpha-fetoprotein present in high concentrations in amniotic fluid and serum, as shown by: (i) selective removal of several components from amniotic fluid and serum; (ii) selective addition of different components present in amniotic fluid and serum, including alpha-fetoprotein, to be radioimmunoassay; (iii) correlation between the inhibitory effect of both amniotic fluid and serum and between the amounts of alpha-fetoprotein they contain; (iv) blocking of the alpha-fetoprotein in vitro suggests a similar effect in vivo in pregnant women with myasthenia gravis. This effect may explain in part the variability in the development of neonatal myasthenia gravis in the babies, due to transplacental transfer of maternal anti-AcChoR antibody, only after delivery and only in the minority of the cases. It also may explain the appearnace of remissions in females with myasthenia gravis during the second and third trimesters of pregnancy. Similar phenomena observed during pregnancy in other autoimmune and immunopathogenic diseases also might be attributed to activity of alpha-fetoprotein.     

Argyrophilic nucleolar organizer regions in cells of thymoma and thymic carcinoma: correlation with DNA ploidy and clinicopathologic characteristics

STUDY OBJECTIVES: To evaluate the usefulness of argyrophilic nucleolar organizer region (AgNOR) counting and flow cytometric DNA analysis in the differential diagnosis of thymoma and thymic carcinoma, as well as in the differences among various stages and histologic subtypes of these tumors. DESIGN AND INTERVENTIONS: Paraffin-embedded blocks of 64 thymic epithelial tumors (20 noninvasive thymomas, 34 invasive thymomas, and 10 thymic carcinomas) were studied by AgNOR counting and flow cytometric DNA analysis. The thymomas were histologically classified as medullary, cortical, or mixed subtype. MEASUREMENTS AND RESULTS: Invasive thymomas had more AgNORs (-/+ SD) than noninvasive thymomas (7.93+/-2.90 vs 5.97+/-1.77; p < 0.01). The number of AgNORs of thymoma increased progressively with advances in stage (p < 0.01). Cortical thymomas had the highest number of AgNORs among the three subtypes (p < 0.05). Patients with thymoma who presented with myasthenia gravis also had a higher number of AgNORs (8.30+/-3.12 vs 6.50+/-2.03; p < 0.01). The AgNOR number did not correlate with the DNA ploidy of all specimens. CONCLUSIONS: AgNOR counting is useful in differentiating between invasive and noninvasive thymomas, and in predicting the stage of thymomas. A greater number of AgNORs was observed in patients with cortical thymoma and in those who presented with myasthenia gravis.     

High-dose intravenous immunoglobulin in the management of myasthenia gravis

Intravenous immunoglobulin, 400 mg/kg, was administered daily for five days to 12 patients with exacerbation of generalized myasthenia gravis. Degree of weakness, duration of illness, use of prednisone, and history of thymectomy or thymoma did not affect the response to intravenous immunoglobulin. Eleven patients improved, beginning 3.6 +/- 2.7 (mean +/- SD) days after the start of treatment and becoming maximal in 8.6 +/- 4.6 days, with sustained improvement lasting 52 +/- 37 days. Vital capacity increased from 1748 +/- 510 to 2700 +/- 614 mL at peak effect. Decreases in strength occurred in four patients beginning on day 3.2 +/- 2.5, lasted 1.5 +/- 0.6 days, and were mild in three patients. Other effects were minimal. There was no significant change in acetylcholine receptor antibody titers, which were elevated in all patients. Immunoglobulin seemed to produce a more rapid improvement than corticosteroids and is recommended as an adjunct in the management of myasthenia gravis exacerbations.     

Thymoma with pemphigus foliaceus

A 75-year-old Japanese woman was referred to us because of an anterior mediastinal mass. Crusts and shallow erosions developed 10 months earlier on her upper chest, back, and scalp. Pemphigus foliaceus was diagnosed based on histological examination of skin biopsy specimens and positivity for serum anti-desmoglein 1 antibody by enzyme-linked immunosorbent assay. Neurological examination and electromyography ruled out myasthenia gravis. Total thymectomy was performed, and the postoperative pathology studies showed mixed lymphoepithelial thymoma. One year after the resection, the eruption and alopecia improved and the serum anti-desmoglein 1 antibody titer decreased, suggesting a beneficial effect of thymectomy on thymoma-related pemphigus.     

Giant cell myositis and myocarditis revisited

Giant cell myositis (GCMm) and giant cell myocarditis (GCMc) are two rare autoimmune conditions. Among these, GCMc is a life-threatening disease with a 1-year mortality rate of 70%. Lethal ventricular arrhythmias, rapid evolution to heart failure and sudden death risk makes GCMc an emergency condition. It is thought to be mediated by T-cells and characterized by the presence of myofiber necrosis and giant cells in biopsies. Most commonly co-manifesting conditions with GCMm and/or GCMc are thymoma, myasthenia gravis and orbital myositis, all of which are treatable. As suspicion is the key approach in diagnosis, the physician following patients with thymoma with or without myasthenia gravis and with orbital myositis should always be alert. The fatal nature of GCMc associated with these relatively benign diseases deserves a special emergency attention with prompt institution of combined immunosuppressive treatment and very early inclusion of heart failure teams.Key words: giant cell myositis, giant cell myocarditis, thymoma/myasthenia gravis, orbital myositis     

胸腺瘤伴重症肌无力患者瘤组织中Bcl-2和Fas的表达水平

目的 探讨凋亡相关基因bcl-2、Fas在胸腺瘤伴重症肌无力患者瘤组织中的表达状况及其临床意义。方法经手术治疗的25例胸腺瘤伴重症肌无力患者的肿瘤组织标本为病例组，25例先天性心脏病患者手术时切取的正常胸腺组织标本为对照组，通过免疫组化的方法检测两组标本中Bcl-2和Fas蛋白的表达水平。结果胸腺瘤中Bcl-2及Fas表达水平均显著高于对照组，经Ridit分析两者差异均有统计学意义（U值分别为2．645、3．200，P均〈0．05），但Bcl-2和Fas的表达水平与胸腺瘤患者的重症肌无力Ossermen分型、术前病程、年龄及性别等临床因素均无显著相关。结论 Bcl-2和Fas在胸腺瘤伴重症肌无力的发病中可能具有重要作用。