Thymic Follicular Hyperplasia Research Articles

Comparison of juvenile and adult myasthenia gravis in a French cohort with focus on thymic histology

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile MG (JMG), we analyzed 85 pre- and 132 post-pubescent JMG (with a cutoff age of 13) compared to 721 adult MG patients under 40 years old using a French database. Clinical data, anti-AChR antibody titers, thymectomy, and thymic histology were analyzed. The proportion of females was higher in each subgroup. No significant difference in the anti-AChR titers was observed. Interestingly, the proportion of AChR+ MG patients was notably lower among adult MG patients aged between 30 and 40 years, at 69.7%, compared to over 82.4% in the other subgroups. Thymic histological data were examined in patients who underwent thymectomy during the year of MG onset. Notably, in pre-JMG, the percentage of thymectomized patients was significantly lower (32.9% compared to more than 42.5% in other subgroups), and the delay to thymectomy was twice as long. We found a positive correlation between anti-AChR antibodies and germinal center grade across patient categories. Additionally, only females, particularly post-JMG patients, exhibited the highest rates of lymphofollicular hyperplasia (95% of cases) and germinal center grade. These findings reveal distinct patterns in JMG patients, particularly regarding thymic follicular hyperplasia, which appears to be exacerbated in females after puberty.

Sporadic late onset nemaline myopathy with concurrent dermatological symptoms responding to immunosuppressive treatment

BackgroundSporadic late onset nemaline myopathy is a rare, progressive muscle disease, presenting in adulthood, mainly affecting proximal limb and bulbar muscles. Muscle biopsies show characteristic nemaline rods. The putative mechanism is considered immune-related. Other manifestations aside from neuromuscular symptoms have not been described previously.Case presentationWe present a case with atypical sporadic late onset nemaline myopathy (SLONM) of a non-HIV, non-MGUS subtype, where skin manifestations preceded neuromuscular symptoms, and a residual thymus with the histology of thymic follicular hyperplasia was detected during the diagnostic workup. Thorough dermatological investigations could not explain the skin presentations. Muscle biopsy revealed variation in fiber diameter, ragged-red and COX-negative fibers associated with discrete fibrosis. Electron microscopy detected atrophic muscle fibres with disorganization of the myofibrils, nemaline rods and abnormal mitochondria. Single-fiber EMG suggested signs of a neuromuscular transmission defect, EMG showed signs of myopathy. Analyses of antibodies associated with myasthenia gravis were negative. The patient showed improvement after intravenous immunoglobulin treatment regarding both the skin and the muscle symptoms.ConclusionsOur case highlights the heterogeneity of SLONM with its varied spectrum of presentation. A unique combination of dermatological symptoms and SLONM could be seen with skin lesions as primary presenting symptoms. An association can be considered between the different manifestations, presumably based on immune etiology, where immunosuppressive therapy has been beneficial.

A MIDDLE-AGED PATIENT WITH BILATERAL VISION LOSS AND NYCTALOPIA.

Purpose: To report a case of nonparaneoplastic autoimmune retinopathy in a patient with diagnosis of Lambert Eaton Myasthenic Syndrome. Case report. Main outcome measures included findings on retinal examination and analysis of fundus autofluorescence, spectral domain optical coherence tomography, and full field electroretinogram. Vitamin A levels and results of antiretinal antibody testing and paraneoplastic work up are also presented. A 47-year-old male presented with a 1-year history of bilateral vision loss and nyctalopia. Past medical history was significant for Lambert-Eaton myasthenic syndrome (LEMS), confirmed by positive voltage-gated calcium channel (VGCC) antibodies, and thymectomy reported as thymic follicular hyperplasia. OCT showed bilateral diffuse outer retinal atrophy and ellipsoid zone loss. Fundus autofluorescence displayed a bull's pattern of hyperautofluorescence around each fovea. Full field ERG showed an extinguished rod response and a severely depressed cone response in each eye. We describe a case of nonparaneoplastic autoimmune retinopathy in a patient with Lambert Eaton Myasthenic Syndrome. Multimodal retinal imaging and ERG confirmed the presence of autoimmune retinopathy with severe rod-cone degeneration. The association of this myasthenic syndrome with AIR is novel.

Retrospective histopathology audit of thymectomy specimens: A clinicopathological study of 303 cases spanning the non-neoplastic, benign and malignant spectrum.

Thymectomy specimens are uncommon in routine histopathology practice. However, awareness of various pathologic entities and definite reporting of these specimens is paramount to optimal patient management. Our objective was to determine the histomorphologic spectrum of thymectomy specimens spanning the non-neoplastic, benign to malignant spectrum. Thymectomies received over an 8-year period were retrospectively analyzed by reviewing clinical details and histologic findings in detail, incorporating the latest World Health Organization (WHO) 2015 histologic classification. A total of 303 thymectomy specimens (179 males/124 females, mean age 45.3 years [3-84 years]) were included. Around 51.2% (n = 155) patients had associated myasthenia gravis (MG), while 17.5% (n = 53) had incidentally detected anterior mediastinal mass (AMM). Non-neoplastic and benign pathologies comprised 31% (n = 94) cases and showed stronger association with MG (P = 0.009). Thymic follicular hyperplasia (TFH) was the commonest non-neoplastic pathology (n = 32), while the benign tumor group included thymic hemangioma/lymphangioma, thymolipoma, and ectopic parathyroid adenoma. Thymic epithelial tumors (TETs) comprised 64.7% cases, with majority being thymomas (185/303; 61.1%). Thymoma type B2 was the commonest histologic subtype and Stage I/T1 was the most frequent stage. Type A and AB thymomas affected older patients (P = 0.005) and were in lower stage (both Masaoka and American Joint Committee on Cancer [AJCC]) than type B thymomas (P = 0.007). No significant association between MG and thymoma subtype, patient sex or Masaoka stage was seen (P > 0.05). Thymic carcinomas comprised 11 cases and showed no association with MG (0/11, P < 0.001); squamous cell carcinoma was the commonest histologic type (8/11; 72.7%). TETs are the commonest thymic lesions; however, a diverse spectrum of pathologic processes can affect the thymus.

Thymoma pathology and myasthenia gravis outcomes.

There is limited evidence regarding the impact of World Health Organization (WHO) subtype of thymoma on post-thymectomy outcome of thymoma-associated myasthenia gravis (TAMG). The objective was to determine if the pathological subtypes of thymoma were associated with post-thymectomy outcomes of myasthenia gravis (MG), in patients with TAMG. We performed a retrospective study of consecutive patients with TAMG who attended the neuromuscular clinic between January 2018 and December 2019 with a minimum follow-up of 1 y after thymectomy. Outcome measures were MG Impairment Index (MGII), single-simple question (SSQ), Myasthenia Gravis Foundation of America post-intervention status (MGFA PIS) and non-responder MG status at last assessment. Ninety-five patients were included; mean age at onset was 48.1 ± 12.1 y; 54(56.8%) were females. Thirteen patients developed MG post-thymectomy. The most common thymoma was WHO type B2 in 39 (41.1%). Most patients (40, 42.1%) had Masaoka stage II thymoma. There was no association of thymoma subtypes or Masaoka stage of disease with age, gender, MG phenotype, serology, post-thymectomy onset, interval from onset to thymectomy, MGII, SSQ, MGFA PIS, or non-responder status. Associations were found between positive serology and lower MGII (11.1 ± 14.2 vs 23 ± 12.9, P=.050), thymic follicular hyperplasia (TFH) and higher SSQ (89.3 ± 11.7 vs 80.1 ± 20.2, P-.043), and lack of recurrence and higher SSQ (84.1 ± 18 vs 72.5 ± 20, P=.037). The WHO pathological subtype of thymoma did not correlate with MG outcomes. However, positive acetylcholine antibody serology, presence of TFH, and non-recurrence of thymoma predict a favorable outcome.

Magnetic resonance imaging characteristics of thymoma in Vietnamese patients with myasthenia gravis in relation to histopathological type and disease staging.

IntroductionMyasthenia gravis (MG) is a relatively uncommon neuromuscular disease. The thymus plays an important role in the pathogenesis of MG, with 70% of patients presenting with thymic follicular hyperplasia and 20% presenting with thymoma. This study aimed to characterize magnetic resonance (MR) images of thymomas in patients with MG, associated with various stages and types.Material and methodsA prospective study was performed in 46 MG patients with thymoma, who underwent surgery between August 2014 and September 2018, in Vietnam. Differences in MR imaging (MRI) images, according to type and stage, were assessed by the χ2 test or Fisher’s exact test and Student’s t-test. A p-value < 0.05 was considered significant.ResultsThe proportions of each type of thymomas found to be invasive were 28.6%, 61.1%, 66.7%, 90.9%, and 100%, for type A, AB, B1, B2, and B3 thymomas, respectively. Heterogeneous signal intensities on T1- and T2-weighted images, necrosis, and cysts were more commonly observed in high-risk thymomas than in low-risk thymomas. Non-invasive thymomas were more likely to display smooth margins than invasive thymomas (p < 0.05). Only 16.7% of invasive thymomas were detected in MR findings.ConclusionsOnly a few characteristic MRI features could be used to differentiate thymomas by stage or type.

Histopathological study of mediastinal lesion in a medical college-3 years study

Background: It is very important to know about Histological pattern, incidence in relation to age, sex and location of mediastinal lesions for better outcome of patients. This will help the clinicians in both treating the patient and determining the outcome of the disease process. Material and method: The material for the study was collected from the in patients being admitted in N.H.L. Medical College, V.S. Hospital Ahmedabad affiliated with Gujarat University. Data was collected in pretested proforma. Results: Total 35 cases of mediastinal lesions were studied. The data according to age incidence, sex incidence, location, nature of the lesion and clinical symptoms was prepared and analyzed. Most common lesion was thymic follicular hyperplasia (26%) followed by Mailgant thymoma (23%). Maximum number of cases were found in 1st & 5th decade (23% in each decade) which were followed by fourth decade. Anterior mediastinum was the commonest to be involved in present study (comprising of 66% of lesions). Conclusion: Most common lesions are thymic lesion (including benign/malignant thymoma, thymic hyperplasia, Cystic lesion, and neurogenic lesion and Germ cell tumor. Benign lesions were more common (74%) than malignant lesion and have better prognosis.

The pathology of the thymus in myasthenia gravis

Myasthenia gravis (MG) is an autoantibody mediated autoimmune disease characterized by skeletal muscle fatigability and weakness through different types of immune attacks against various proteins of the postsynaptic membrane or in the neuromuscular cleft of the neuromuscular junction. In a subset of patients with autoantibodies against the muscle type acetylcholine receptors (AChRs) there is strong evidence that the thymus is involved in the pathogenesis of MG, while its role is questionable or unknown in MG due to autoantibodies against muscle specific kinase (MuSK), lipoprotein receptor like protein 4 and agrin. Here we describe the thymic alterations that have repeatedly been encountered in MG, i.e., thymic follicular hyperplasia (TFH) (thymitis), ‘thymic atrophy’, thymoma and thymolipoma. The potential link of non-thymic tumors [e.g., follicular dendritic cell (FDC) sarcoma] with MG will be discussed.

Effect of thymectomy for thymic atrophy in myasthenia gravis: A retrospective study on 93 patients

To clarify the efficacy of thymectomy among myasthenia gravis (MG) patients with and without thymoma. We classified MG patients who underwent thymectomy into 3 groups, such as thymic atrophy group, thymic follicular hyperplasia (TFH) group and thymoma group. We compared the data of clinical features and postoperative prognosis at very short-term, short-term, and medium-term. The clinical course of MG patients with atrophic thymus after thymectomy was even better than those of TFH or thymoma, in this retrospective study. However, we found no significant differences in the comparison of mean dose of prednisolone between the 3 groups at each time point.

Role of the thymus in autoimmune myasthenia gravis

AbstractThymic pathologies are frequently associated with myasthenia gravis. Although thymoma is found in both men and women mostly after the age of 40 years, thymic follicular hyperplasia is very common in young women. Thymomas are associated with high autoreactivity and reduced efficiency of tolerance mechanisms, at least partially due to the absence of functional medullary epithelial cells. In follicular hyperplasia, the presence of ectopic germinal centers is evocative of what is described in other autoimmune disorders, where germinal centers are found in the inflamed tissues. The grade of follicular hyperplasia is correlated with the serum level of anti‐acetylcholine receptor (AChR) antibody, suggesting that the thymic hyperplasia contributes to the production of anti‐AChR antibodies. Cellular and molecular analysis of thymic follicular hyperplasia shows changes in the Th1/Th17/regulatory T cell balance, with increased expression of Th1 and Th17 cytokines, and defective function of regulatory T cells. Follicular hyperplasia is also characterized by active neo‐angiogenesis, and increased chemokine synthesis, namely CXCL13 and CCL21, which play a major role in the generation of germinal centers. This inflammatory environment recruits peripheral B cells, and together with the overexpression of the autoantigen could specifically lead to the anti‐AChR autoimmune response. The individual predisposing background includes gene polymorphism, but also hormones, vitamin D level and other environmental components. Overall, the functional and morphological changes observed in the thymus, the improvement of patients after thymectomy, and the correlation between the degree of follicular hyperplasia and the level of anti‐AChR antibodies suggest a causal relationship between thymic pathology and MG.

Thymic Germinal Centers and Corticosteroids in Myasthenia Gravis: an Immunopathological Study in 1035 Cases and a Critical Review.

The most common form of Myasthenia gravis (MG) is due to anti-acetylcholine receptor (AChR) antibodies and is frequently associated with thymic pathology. In this review, we discuss the immunopathological characteristics and molecular mechanisms of thymic follicular hyperplasia, the effects of corticosteroids on this thymic pathology, and the role of thymic epithelial cells (TEC), a key player in the inflammatory thymic mechanisms. This review is based not only on the literature data but also on thymic transcriptome results and analyses of pathological and immunological correlations in a vast cohort of 1035 MG patients without thymoma. We show that among patients presenting a thymic hyperplasia with germinal centers (GC), 80% are females, indicating that thymic follicular hyperplasia is mainly a disease of women. The presence of anti-AChR antibodies is correlated with the degree of follicular hyperplasia, suggesting that the thymus is a source of anti-AChR antibodies. The degree of hyperplasia is not dependent upon the time from the onset, implying that either the antigen is chronically expressed and/or that the mechanisms of the resolution of the GC are not efficiently controlled. Glucocorticoids, a conventional therapy in MG, induce a significant reduction in the GC number, together with changes in the expression of chemokines and angiogenesis. These changes are likely related to the acetylation molecular process, overrepresented in corticosteroid-treated patients, and essential for gene regulation. Altogether, based on the pathological and molecular thymic abnormalities found in MG patients, this review provides some explanations for the benefit of thymectomy in early-onset MG patients.

Resection of Intrapericardial Schwannoma Co-Existing with Thymic Follicular Hyperplasia through Sternotomy without Cardiopulmonary Bypass

A 35-year-old man was admitted to Korea University Anam Hospital for evaluation of intermittent chest pain. Computed tomography of the chest showed enlargement of a previously identified anterior mediastinal mass and also a well-defined, circumscribed mass in the subcarinal area, surrounded by the roof of the left atrium, right pulmonary artery, and the carina. Complete resection of the intrapericardial tumor was performed through median sternotomy without cardiopulmonary bypass. Pathologic examination identified the tumor as schwannoma, of an ancient type, diffusely positive for the S-100 antigen. Unlike other reported cases, grossly, the tumor did not seem to be involved with any nerve.

A Case Report of T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Arising in the Background of Thymic Follicular Lymphoid Hyperplasia

A Case Report of T-Cell/Histiocyte-Rich Large B-Cell Lymphoma Arising in the Background of Thymic Follicular Lymphoid Hyperplasia

Carcinoid tumor arising in a thymic bronchogenic cyst associated with thymic follicular hyperplasia

Bronchogenic cysts are congenital malformations of the embryonic tracheobronchial tree and are the most common cause of mediastinal cysts, encountered mainly in pediatric patients and young adults. Conservative treatment has been proposed for asymptomatic patients. However, malignant transformation occurs occasionally and the clinicopathological features of secondary malignancy are not well characterized. In this report, we present a carcinoid tumor found in the thymic bronchogenic cyst of a 41-year-old female complaining of mild chest pain. The thymic tissue also shows follicular lymphoid hyperplasia. Atypical imaging features were found in her chest computed tomography. Additional 22 cases of bronchogenic cysts with malignant transformation were also reviewed from the literature. The clinicopathological data were summarized. The tumorigenesis of these tumors is unclear, but bronchogenic cysts of the lung may undergo malignant changes at a younger patient age and more frequently than mediastinal ones. Carcinoid tumors were also seemingly overrepresented in mediastinal cases. Some atypical imaging features may serve as clues for early detection and guide clinical management.

Thymic Follicular Hyperplasia Presenting as a Large Mediastinal Mass in a 42-Year-Old Woman

In Brief Lesions originating within the anterior mediastinum are not uncommon, and among such lesions, thymic abnormalities are quite prevalent. A wide variety of conditions may affect the thymus, ranging from biologically indolent to overtly aggressive. Several thymic lesions are frequently associated with systemic manifestations of disease. An understanding of the cross-sectional imaging appearances of thymic lesions, in combination with an appreciation of the clinical context in which these lesions are often encountered, may facilitate accurate diagnosis. A 42-year-old woman presented to a multidisciplinary health institution with the chief complaint of back pain. The focus of this case study is to describe the radiographic and clinical evaluation of a patient with an unsuspected anterior mediastinal mass. Imaging characteristics and the common differential diagnostic considerations of a rare case of thymic follicular hyperplasia manifesting as an asymptomatic anterior mediastinal mass are presented. A rare cause of mediastinal widening in a 42-year-old woman is presented. Conventional radiography and contrast-enhanced computed tomography of the chest demonstrated a large anterior mediastinal mass in the region of the thymus gland. The histopathological diagnosis was thymus tissue with follicular lymphoid hyperplasia.

MYASTHENIA GRAVIS IN IRANIAN CHILDREN

Objective This study was undertaken to evaluate the clinical spectrum of myasthenia gravis in children and determine factors that help the clinician in his/her diagnosis and management. Materials & Methods A retrospective review was performed on all pediatric patients suffering from myasthenia gravis (M.G) admitted in the department of pediatric neurology of the Mofid Hospital of the Shaheed Beheshti University, between 1994 and 2002. Results Of the thirty-two children with M.G. enrolled in our study, seven were suffering from the congenital type while the remaining (25 cases) had the juvenile M.G. Initial symptoms of congenital M.G were ptosis (7/7), limitation of eye movement (2/7) and mild generalized weakness (6/7). Although the Tensilon test was positive in 85% of congenital M.G cases, no myasthenia crisis or spontaneous remission was observed in any of them. In children with juvenile M.G, the age of presentation was 1.2 to 12.5 years, mean age 5.7+4.2 years (15 girls and 10 boys). The most common presenting symptoms in juvenile group were ptosis in 96% and generalized weakness in 76%. Eight of them (32%) had had at least one myasthenia crisis. EMG was diagnostic in 83% and one case the tensilon test was positive in 84%. One patient had hyperthyroidism and had already been diagnosed with hypothyroidism; two of them were epileptics. Eight patients underwent thymectomy microscopically; in specimens examined, five (62%) showed thymic follicular hyperplasia while in remaining three results were normal. One patient (12.5%) recovered completely after thymectomy with no need for medication during the follow up. Four patients (50%) showed relative improvement and in three cases (37%) improvement was negligible. Conclusion The results showed a female to male ratio of 1.5/1 which was correlated to adult M.G. The most common presenting symptoms consisted of ophtalmoplegia, with bilateral ptosis being the most significant. Although this study revealed that thymectomy lacks any remarkable prognostic influence, all patients had thymectomy after two years of disease onset. Some reports have indicated positive results if surgery was performed within two years of onset of disease. Key words: Myasthenia gravis, Children, Thymectomy, Congenital

Thymic Hyperplasia in a Patient with Graves’ Disease

A 23-yr-old man who was previously healthy was evaluated after a fall. Computed tomography of the chest showed an anterior mediastinal mass. Percutaneous biopsy showed benign thymic tissue. Three months later the patient developed ophthalmopathy and signs and symptoms of hyperthyroidism. Serum-TSH level measured less than 0.004 IU/ml (0.35–5.50 IU/ml), serum-free T4 4.93 ng/dl (0.61– 1.76 ng/dl), and serum-thyroid peroxidase antibody more than 70 IU/ml ( 2 IU/ml). Radioiodine uptake was increased in a diffusely enlarged gland. Based on these findings, the patient was diagnosed with Graves’ disease. The patient was treated with radioactive iodine. His thyroid decreased substantially in size, but a repeat chest computed tomography 1 month later demonstrated persistence of the mediastinal mass (Fig. 1). The patient complained of pain and a sensation of fullness and obstruction in his chest; thus, radical thymectomy was performed. The thymus was enlarged and measured 11.5 7.5 3 cm. Pathology revealed thymic follicular hyperplasia with focal germinal center formation. There is a rare but well-documented association between Graves’ disease and thymic hyperplasia (1). In most cases thymic enlargement is minimal; however, it may occasionally present as an appreciable anterior mediastinal mass (2). Whereas surgical resection has been a common treatment of such a mass, the literature supports following up the mass closely (3). A decrease in size after treatment of the hyperthyroidism supports the diagnosis of thymic hyperplasia, and thymectomy can be avoided (3). Clinicians should be aware of the usually benign clinical course of thymic hyperplasia associated with Graves’ disease.

Micronodular thymoma: an epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development

The aetiology of primary B-cell lymphomas of the thymus is enigmatic. Although thymic follicular lymphoid hyperplasia (TFH) is commonly associated with myasthenia gravis (MG), lymphoma is not a complication of this condition. The present paper reports a high frequency of monoclonal B-cell populations (6 of 18 cases; 33%) in micronodular thymoma (MNT), a peculiar thymic epithelial neoplasm with a B-cell-rich stroma, while B cells were consistently polyclonal in TFH (25 cases) and other types of thymomas (15 cases) (p < 0.001). An intratumoural lymphoma could be identified in three of the six monoclonal MNTs. Sequencing of the monoclonal IgH chain revealed partially overlapping VDJ gene usage in MNT and thymic mucosa-associated lymphoid tissue (MALT) lymphomas. The neoplastic epithelium of MNTs, but not of TFH and other types of thymoma, expressed high levels of dendritic cell, T-cell, and B-cell chemoattractants, such as CCL18, CCR6, and CCL20. It is concluded that abnormal chemokine expression in an epithelial tumour, MNT, can promote the recruitment of MALT, the emergence of monoclonal B cells, and, eventually, the subsequent development of mediastinal lymphomas. More generally, the concept that expression of a 'high-risk' spectrum of chemokines due to local or genetic factors may interfere with B-cell homeostasis and may contribute to MALT lymphoma development in chronic inflammatory states is proposed.

Mucosa-associated lymphoid tissue of the thymus hyperplasia vs lymphoma.

In the thymus, the relationship between lymphofollicular hyperplasia and mucosa-associated lymphoid tissue (MALT)-type lymphoma is uncertain. We analyzed 14 cases with a diagnosis of thymic follicular hyperplasia in patients with connective tissue disease (n = 2), myasthenia gravis (n = 11), or both (n = 1). In 11 cases, well-defined reactive lymphoid follicles were surrounded by a continuous layer of medullary epithelial cells. A polyclonal rearrangement of the immunoglobulin heavy chain gene (IgH) was observed. In 3 cases, ill-defined lymphoid follicles with sheets of centrocytic-like B cells disrupting the medullary cytokeratin epithelial network were observed on certain sections. These cells expressed the phenotypic features of memory B cells with CD20, CD79a, and bcl-2 positivity and CD5, CD10, CD23, and bcl-6 negativity, and a monoclonal rearrangement of the IgH gene was detected. Appropriate sampling, cytokeratin staining, and molecular analyses may help to identify early MALT-type lymphoma developing in the setting of thymic lymphofollicular hyperplasia.

Neurofilament is an autoantigenic determinant in myasthenia gravis

Intratumorous expression of a 153-kd protein (p153), which contains an acetylcholine receptor-like epitope, is the only tumor marker described to date that significantly associates with thymoma in paraneoplastic myasthenia gravis (MG). Here, we report that p153 is identical to the midsize neurofilament, as verified by immunohistochemistry, immunofluorescence, and western blot analysis. Furthermore, the acetylcholine receptor-like epitope of the midsize neurofilament (NF-M) was identified by peptide epitope mapping. We also show, using T-cell proliferation assays, a significantly increased response of intratumorous T cells to a recombinant midsize neurofilament fragment in thymoma patients with MG compared with MG patients with thymic follicular hyperplasia or thymoma patients without MG. The T cells of thymic follicular hyperplasia and thymoma patients without MG seem to be unresponsive to NF-M. In contrast, we found increased T-cell responses to recombinant acetylcholine receptor fragments in MG patients in general compared with non-MG patients. Increased T-cell responses to NF-M in patients with paraneoplastic MG might be the result of an abnormal positive selection of immature T cells within thymomas, caused by the expression of NF-M in neoplastic thymic epithelial cells. Our results offer further evidence that NF-M expression in thymomas is an autoantigenic determinant in MG.