The Occult Thymoma

Thymomata which are too small to be detected by plain radiography, may be demonstrated by pneumomediastinography, thymic venography, and selenomethionine scanning of the mediastinum. These techniques were valuable in demonstrating a tumour in a woman with myasthenia gravis, leading to thymectomy.     

Thymic histology in myasthenia gravis.

Histological features of resected thymuses of 18 patients with myasthenia gravis were evaluated. Thymoma were seen in 16.6% of the patients. In the non-thymomatous group, thymic hyperplasia with follicle formation was seen in 33.3%, involuted thymus with occasional lymphoid follicle formation in 11.1%, thymitis with B cell infiltration in 16.6%, involuted thymus in 11.1% and normal thymus in 11.1% of patients. Immuno-histological staining for B and T lymphocytes delineated the group labelled as thymitis with B cell infiltration. Mast cell and eosinophils were frequently seen in thymuses with thymic hyperplasia with follicle formation and thymitis with B cell infiltration. Thymic hyperplasia with follicle formation was more frequent in young patients and these patients had better prognosis.     

THE THYMUS: EXPERIMENTAL PHYSIOLOGY,AND PATHOLOGY IN MAN

The thymus is an integral part of the immunological system. It is a site of intense lymphopoiesis, especially in early life. Neonatal thymectomy in mice causes runting and death due to gross immunological deficiencies. These deficiencies are determined by lymphopenia, and by lack of a lymphotrophic hormone secreted by the epithelial cells of the medulla; this hormone confers on lymphocytes the capacity to respond to antigenic stimulation. The thymus may be the main source of lymphoid cells carrying new or primary patterns of immune reactivity; it is thus “first-level” or “central” lymphoid tissue, which seeds cells to “second-level” or “peripheral” lymphoid tissues in the lymph nodes and spleen. Pathological lesions of the thymus in man include aplasia, hyperplasia, dysplasia and neoplasia. Gross aplasia characterizes the immunological deficiency diseases of infancy, including the lymphopenic type of congenital agammaglobulinæmia. Hyperplasia accompanies thyrotoxicosis. Dysplasia refers to the lymph follicle-germinal centre development in myasthenia gravis, probably an autoimmune disease, and to the proliferation in the medulla of spindle-epithelial cells in lupus erythematosus, an autoimmune disease. Neoplasia occurs as benign thymoma, which may be accompanied by extrathymic diseases which are possibly autoimmune in origin; these include myasthenia gravis, red cell aplasia, polymyositis, agammaglobulinæmia and lupus erythematosus. These diseases may in some way be caused by the thymoma; alternatively, the thymoma may represent the result of continuing hyperplasia of the thymus provoked by a primary autoimmune process. The place of thymectomy in the treatment of autoimmune disease is discussed. It is an established procedure in myasthenia gravis, and has been successful in two cases of autoimmune hæmolytic anæmia in infancy. We review our experience with thymectomy for three patients with systemic lupus erythematosus.     

Penicillamine-associated myasthenia gravis,antiacetylcholine receptor and antistriational antibodies

Myasthenia gravis with thymic hyperplasia developed in a patient with Wilson's disease after eight years of penicillamine treatment. Four months prior to the onset of myasthenia, penicillin hypersensitivity was observed. Immunofluorescence on the excised thymus revealed immunoglobulin and complement deposition, but the myasthenia persisted after thymectomy and continuation of penicillamine therapy. Increased antiacetylcholine receptor antibody was demonstrable throughout. This patient subsequently became pregnant, enabling studies to be performed on the transplacental transfer of the immunoglobulin G (IgG) class antiacetylcholine receptor antibody.     

Recurrence of thymic hyperplasia after thymectomy in myasthenia gravis: Its importance as a cause of failure of surgical treatment

Persistence of symptoms in patients with myasthenia gravis who have undergone previous thymectomy has been attributed to thymus remnants. Patients with partial or no recovery were studied 40 ± 31 months (mean ± SD) after surgery, which had been carried out by the transcervical approach in 20 and trans-sternal approach in four. Lateral x-ray tomography of the mediastinum after injection of air showed images compatible with residual thymus gland in 18 patients (75 percent). Thirteen of these underwent reoperation by the trans-sternal approach, and thymic tissue was found in 11 (85 percent). After repeated thymectomy, 67 percent of the patients improved clinically. Therefore, it is quite reasonable to infer that incomplete removal of the thymus was responsible, at least partly, for failure of the first procedure.     

Video-assisted thoracoscopic thymectomy for myasthenia gravis

Background: Thymectomy is an effective, but radical therapy for myasthenia. Video‐assisted thoracic surgery (VATS) may allow a minimally invasive altern­ative to the standard sternotomy approach. Aims: To audit prospectively the outcome of VATS thymectomy for myasthenia gravis in a unit specializing in advanced VATS techniques. Methods: Twenty‐six patients underwent VATS thymectomy between 1997 and 2001. Most underwent preoperative plasma exchange therapy. Seventeen women and nine men with a median age of 36 years (range 17?71 years) had a right‐sided VATS approach to remove all anterior mediastinal fat and thymic tissue. Results: There was no perioperative mortality and all procedures were concluded successfully, with one patient requiring sternotomy. Twenty‐five patients were extubated in theatre and one patient required 17 h of assisted ventilation . The other significant complication was a diathermy injury to the phrenic nerve, which recovered. Median postoperative stay was 4 days (range 2?6 days), with median postoper­ative chest drainage for 2 days (range 1?3 days). Three patients had progression of disease postoperatively. The remainder were asymptomatic (7), improved (14) or stable (2). Conclusion: In a dedicated unit with neurological and intensive care support, VATS thymectomy is a safe, effective method of obtaining remission or improvement in myasthenia gravis (MG). While achieving the same surgical goal, this approach offers advantages of improved cosmesis, shorter recovery time and minimal chest wall disruption over the gold standard of sternotomy. Better patient acceptance of this minimally invasive technique may result in wider application of the benefits of thymectomy in MG. (Intern Med J 2002; 32: 367?371)     

Predictors of outcome for myasthenia gravis after thymectomy

The aim of this study was to assess the clinical outcome of patients with myasthenia gravis treated with maximal thymectomy and to identify prognostic variables that predict the outcome. Over 15 years, from 1986 to 2001, we collected data on 100 patients with myasthenia gravis who underwent maximal thymectomy and retrospectively reviewed their outcome. Women comprised 63% and the median age was 25 years (range, 4 to 61). The median duration of the disease was 26 months (range, 1 to 240). According to the Osserman classification, there were seven patients in class I, 31 in class II, 47 in class III, and 15 in class IV. In non thymomatous patients (93 patients), complete remission rate progressively increased from 37.4% to 58.2% and 75% at 3, 10 and 15 years of follow-up respectively. These findings suggest that the complete remission rate is prone to increase with time after maximal thymectomy. The total benefit rate achieved was estimated to be 86% while 14% did not improve at a mean follow-up period of 7.6 years (range, 8 to 180 months). Univariate analysis (p < 0.05) showed that age, thymic histology and ectopic thymic tissue are significant prognostic factors for outcome.     

Video-assisted thoracic surgery thymectomy for nonthymomatous myasthenia gravis

STUDY OBJECTIVES: Minimal-access thymectomy has become increasingly popular as surgical treatment for patients with nonthymomatous myasthenia gravis (NTMG) because of its comparable efficacy, safety, and lesser degree of tissue trauma compared with conventional open surgery. We reviewed and analyzed our data on video-assisted thoracic surgery (VATS) thymectomy and present the clinical outcomes according to the Myasthenia Gravis Foundation of America classification. DESIGN: A retrospective review of VATS thymectomy for NTMG in a university hospital over a 12-year period. Data were collected from the medical records and supplemented with telephone surveys. The impact of surgery and other variables potentially affecting complete stable remission (CSR) were calculated using Kaplan-Meier survival curves; comparisons between survival curves was performed using the log-rank test. RESULTS: A total of 38 consecutive patients underwent VATS thymectomy for NTMG. Median postoperative stay was 3 days. Pathologic examination revealed thymic hyperplasia in 61.1% of cases, normal thymus in 22.2%, and thymic atrophy in 16.6%. There was no perioperative mortality; complications occurred in four patients. After a median follow-up of 69 months, 91.6% of patients experienced improvement, with crude CSR achieved in 22.2%. Kaplan-Meier survival curve demonstrated a 75% CSR rate at 10-year follow-up. On univariate analysis, only disease duration < or = 12 months (p = 0.03) was associated with a statistically significant improvement in CSR. CONCLUSIONS: VATS thymectomy for NTMG results in symptomatic improvement in the vast majority of patients, with a high rate of CSR. The procedure is associated with low morbidity and no perioperative mortality. Future studies on thymectomy for myasthenia gravis should be reported in a standardized manner to allow accurate comparisons between results in the absence of randomized prospective trials.     

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。     

A case of dermatomyositis associated with thymic abnormalities]

A case of dermatomyositis (DM) associated with thymic cyst with lymphoid follicle formations has been reported. A 57-year-old man developed polyarthralgia, muscle weakness, heliotrope rash and Gottron's sign. Laboratory findings showed elevated values of creatine-phosphokinase, aldolase and transaminase. He was diagnosed as DM and was treated with prednisolone 50 mg/day. Muscle weakness was improved immediately, although rash persisted unchangeably. He was examined for coexistence of malignant tumor which had been reported frequently as associated with DM. Enlargement of thymus was found by computer tomography and then thymectomy was performed. In his thymus, lymphoid follicle formations, which are as often encountered in other autoimmune diseases, were found. So far, the beneficial effect of thymectomy on the improvement of immunological abnormalities not only in patients with myasthenia gravis but also in patients with other autoimmune diseases has been recognized. In this case, intractable rash in DM improved after thymectomy. Further study needs to clarify the relationships between DM and thymic abnormalities.     

Studies in myasthenia gravis: Early thymectomy: Electrophysiologic and pathologic correlations

Indications for thymectomy in myasthenia gravis have been recently expanded to include all cases with extraocular symptoms as a result of the minimal morbidity and negligible mortality of the transcervical approach.As increasing numbers of patients with myasthenia gravis, covering the entire spectrum of generalized disease, have been added to the thymectomy population, a more accurate evaluation of the effects of the operation is possible.Our experience with 353 patients who have undergone thymectomy indicates that early thymectomy, particularly in patients who do not have thymic germinal centers, is followed by early remission of the disease. Delayed remission after thymectomy is related to the duration and severity of the disease, and to presence of thymic germinal centers. Germinal centers were found more frequently in patients with long duration of the disease and in patients in whom the disease had progressed to respiratory involvement. Marked improvement in electromyographic findings immediately after thymectomy was observed in the majority of patients who had had the disease for 1 year or less and where germinal centers were absent. The percentage of malignant thymomas was higher in patients who underwent thymectomy 1 year or more after the onset of symptoms of myasthenia gravis.These data indicate the importance of early thymectomy while the disease is still in the mild stages. Transcervical thymectomy is the treatment of choice as it is followed by a higher percentage of remissions and by less morbidity than other forms of treatment.     

Giant cell myositis associated with concurrent myasthenia gravis: a case-based review of the literature

The term “giant cell myositis” has been used to refer to muscle diseases characterized histologically by multinucleated giant cells. Myasthenia gravis is an autoimmune neuromuscular junction disorder. The rare concurrence of giant cell myositis with myasthenia gravis has been reported; however, the clinical and histological features have varied widely. Here, we present such a case and a review of the literature. An 82-year-old woman admitted for subacute, progressive, proximal muscle weakness developed acute-onset dysphagia, dysphonia, and respiratory distress 5 days after admission. Laboratory findings were positive for acetylcholine receptor binding antibodies and striational muscle antibodies against titin. Muscle biopsy demonstrated widespread muscle fiber necrosis with multinucleated giant cells, consistent with giant cell myositis. She died despite treatment with pulse methylprednisolone and plasma exchange. A literature review of the PubMed and Scopus databases from 1944 to 2020 identified 15 additional cases of these co-existing diagnoses. We found that giant cell myositis with myasthenia gravis primarily affects female patients, is typically diagnosed in the 6–7th decades, and is characterized by the presence of thymoma. Muscle histology predominantly shows giant cell infiltrate without granulomas. The onset of myasthenia gravis symptoms may precede, follow, or coincide with symptoms of myositis. Treatment with thymectomy, anticholinesterase inhibitors, or immunosuppressive therapy may lead to favorable clinical outcomes.

     

39例中老年重症肌无力患者淋巴样滤泡性胸腺增生的CT表现

目的探讨中老年重症肌无力患者淋巴样滤泡性胸腺增生的发生情况和CT表现. 方法对39例经手术病理确诊为淋巴样滤泡性胸腺增生的中老年重症肌无力患者作了影像学分析,并与健康中老年人、青年重症肌无力患者淋巴样滤泡性胸腺增生作对比分析.凡无胸腺区形态正常的软组织影、无胸腺区脂肪内边缘清楚的肿块（〉3 cm）或结节（〈3 cm）和边缘模糊的斑片影者视为不典型淋巴样滤泡性胸腺增生. 结果 31例（79.5%）呈不典型表现,全部表现为胸腺区脂肪内夹杂＜5 mm的斑点和细索条影;与健康中老年人和青年重症肌无力患者比较差异均有统计学意义（分别为χ^2=4.135,P＜0.05;χ^2=9.584,P＜0.01）.其中1级7例, 2级14例, 3级8例, 4级2例,1～3级与健康中老年人比较,差异有统计学意义（P＜0.01）.仅8例（20.5%）呈典型表现, 包括胸腺区结节2例、胸腺软组织影2例和胸腺区边缘模糊的斑片致密影4例. 结论大多数中老年重症肌无力患者淋巴样滤泡性胸腺增生的CT表现不典型,以男性多见,容易漏诊.     

胸腺基质淋巴细胞生成素对重症肌无力患者外周血中调节性T细胞的变化影响

目的：探讨胸腺基质淋巴细胞生成素对重症肌无力患者外周血中调节性T细胞的变化影响。方法：2008年9月到2013年12月选择在我院神经内科诊治的重症肌无力患者120例,都给予胸腺切除手术治疗,对预后情况进行观察与分析,对胸腺基质淋巴细胞生成素的表达与外周血中调节性T细胞的变化进行分析。结果：120例患者术后总有效率为91.7%,术后患者的CD4+CD25 Foxp3 /CD4 值明显高于对照组(P<0.05)。HE染色可见髓质部淋巴细胞增生与部分Hassall小体；免疫组化染色可见中髓质部Hassall小体数量明显减少,染色稍浅。相关性分析显示TSLP阳性表达的Hassall小体计数与CD4 CD25 Foxp3 Treg细胞表达水平之间存在呈线性相关(P<0.05)。Logistic回归模型分析结果表明CD4 CD25 Foxp3 /CD4 值和TSLP阳性表达是影响有效率的独立危险因素(P<0.05)。结论：胸腺切除手术是治疗重症肌无力疗效好,其机制在于能够有效维持免疫稳态功能,调节T细胞与胸腺基质淋巴细胞生成素的表达变化,保持患者健康。     

Myasthenia gravis, thymectomy and serum thymic hormone activity.

Serum thymic hormone activity was measured in 36 patients with myasthenia gravis and in 10 control subjects from each age decade. In all 25 patients under 50 years of age results were within, or close to, the normal range. Activity at levels considered normal for juveniles was detected in 10 of the 11 older patients whereas levels normally decline in older subjects. One week after thymectomy, 13 of 17 patients (76 per cent) had no demonstrable serum thymic hormone activity. However, 10 months or longer after thymectomy only five patients (30 per cent) lacked thymic hormone activity in the serum. There was a significant correlation between clinial improvement and sustained lowering of serum thymic hormone activity after thymectomy.     

Thymectomy versus tumor resection for early-stage thymic malignancies: a Chinese Alliance for Research in Thymomas retrospective database analysis

Background

To evaluate the surgical outcomes of tumor resection with or without total thymectomy for thymic epithelial tumors (TETs) using the Chinese Alliance for Research in Thymomas (ChART) retrospective database.

Methods

Patients without preoperative therapy, who underwent surgery for early-stage (Masaoka-Koga stage I and II) tumors, were enrolled for the study. They were divided into thymectomy and thymomectomy groups according to the resection extent of the thymus. Demographic and surgical outcomes were compared between the two patients groups.

Results

A total of 1,047 patients were enrolled, with 796 cases in the thymectomy group and 251 cases in the thymomectomy group. Improvement rate of myasthenia gravis (MG) was higher after thymectomy than after thymomectomy (91.6% vs. 50.0%, P<0.001). Ten-year overall survival was similar between the two groups (90.9% after thymectomy and 89.4% after thymomectomy, P=0.732). Overall, recurrence rate was 3.1% after thymectomy and 5.4% after thymomectomy, with no significant difference between the two groups (P=0.149). Stratified analysis revealed no significant difference in recurrence rates in Masaoka–Koga stage I tumors (3.2% vs. 1.4%, P=0.259). However in patients with Masaoka-Koga stage II tumors, recurrence was significantly less after thymectomy group than after thymomectomy (2.9% vs. 14.5%, P=0.001).

Conclusions

Thymectomy, instead of tumor resection alone, should still be recommended as the surgical standard for thymic malignancies, especially for stage II tumors and those with concomitant MG.     

Thymectomy for myasthenia gravis: 12-year experience

Thymectomy has been shown to be effective in the treatment of myasthenia gravis. The logical goal of operation is the complete removal of the thymus, but there is no consensus on the selection criteria of patients for surgery and the choice of surgical approach. We retrospectively reviewed 56 patients with myasthenia gravis who had been treated surgically by transsternal radical thymectomy between January 1990 and March 2002. The patients were symptomatically grouped according to the modified Osserman clinical classification. There was 1 hospital death, and 53 patients had been followed up for between 1 month and 12 years. Improvement after thymectomy was observed in 1 of 4 patients (25%) in Osserman group I, 25 of 34 patients (74%) in Osserman group IIA, and 16 of 18 patients (89%) in combined Osserman groups IIB and IIC. Transsternal radical thymectomy is an effective therapy for myasthenia gravis. Sustained improvement is achievable in female patients with moderate to severe symptoms and in patients with thymic hyperplasia.     

Development of systemic lupus erythematosus after thymectomy for myasthenia gravis. Studies of suppressor cell function

Systemic lupus erythematosus developed in an 18-year-old man three years after thymectomy for myasthenia gravis. The patient had considerable defects in suppressor cell function that seemed to be partially reversed in vitro by the addition of thymic hormone.     

Primary mucoepidermoid carcinoma of the thymus presenting with myasthenia gravis

Mucoepidermoid carcinoma (MEC) of the thymus is a rare malignant neoplasm of the anterior mediastinum. There are less than 30 cases described in the English literature. We report a case of a 47-year-old lady who presented with myasthenia gravis and was found to have a well-circumscribed anterior mediastinal mass in her medical work-up. This mass was surgically resected and subsequently found to be a primary MEC of the thymus. This is the first reported case of thymic MEC with concurrent myasthenia gravis. Her myasthenia symptoms have persisted following complete surgical resection of her tumour.     

Crohn's disease and myasthenia gravis: a possible role for thymectomy.

A female patient with a three year history of Crohn's disease of the colon developed myasthenia gravis. Despite diversion of the faecal stream by an ileostomy, and total colectomy, the patient had continuing problems with perineal and perianal abscesses and fistulas. Her myasthenia gravis became unresponsive to anti-cholinergics so a thymectomy was performed. The perineal and perianal disease improved subsequently. This case supports the theory that functional disturbances of the thymus may have a role in the pathogenesis of inflammatory bowel disease.