Search

Background: Graves' disease increases bone resorption in hyperthyroidism, leading to elevated serum calcium levels and a negative bone balance. Thymic hyperplasia is observed in some Graves' disease patients. What's more, there have been a few reports of increased serum calcium and severe osteoporosis induced by Graves' disease with thymic hyperplasia. It remains unclear whether Graves' disease with thymic hyperplasia is associated with higher serum calcium levels. Our study aimed to investigate the possibility of elevated serum calcium levels and aggravated bone mobilization in Graves' disease patients with thymic hyperplasia., Methods: Newly diagnosed and untreated patients with Graves' disease (n = 96) were enrolled. They were divided into two groups based on the incidental detection of thymic hyperplasia during imaging. Albumin, alkaline phosphatase, calcium, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, and thyrotrophin receptor antibody (TRAb) were measured, and a computerized tomography of the chest was obtained., Results: Patients with Graves' disease who had thymic hyperplasia were notably younger (P=0.018) and exhibited higher serum calcium levels (P=0.001) compared to those with Graves' disease without thymic hyperplasia. In the multiple regression analysis, thymic hyperplasia, TRAb, and female gender were significant variables associated with elevated serum calcium levels in patients with Graves' disease, collectively accounting for 31.7% of the variation in serum calcium., Conclusions: Graves' disease patients with thymic hyperplasia showed higher serum calcium levels. thymic hyperplasia, TRAb, and female gender were found to be correlated with increased serum calcium levels in Graves' disease, suggesting a potential association between thymic hyperplasia and bone mobilization in Graves' disease., (© 2024. The Author(s).)

Myasthenia gravis (MG) is an autoimmune disease (AD), and patients with MG often have other types of ADs. We analyzed the prognosis of patients with MG complicated by AD after thymectomy. A retrospective analysis was performed for patients with MG complicated by ADs treated surgically in our center over the past 22 years, and their general condition and follow-up data were collected and analyzed. 33 patients were included totally. 28 patients displayed improvement or even complete recovery of MG, and 23 of 36 ADs revealed improvement or even complete recovery. The prognosis of MG is significantly correlated with the duration of postoperative follow-up time (p = 0.028), and in patients with thymoma, the larger the tumor diameter, the better the prognosis of MG (p = 0.026). Thymic hyperplasia patients were predominantly female (p = 0.049) and young (p < 0.001). The most common concomitant AD in this study was a thyroid-associated AD, which was associated with thymic hyperplasia (p < 0.001), Osserman type I MG (p < 0.001), and young age (p < 0.001). Thymectomy had a good therapeutic effect on MG complicated by AD, and there was a close correlation between surgery, thymus, MG, and ADs., (© 2023. The Author(s).)

Thymic hyperplasia with lymphoepithelial sialadenitis-like features is characterized by thymic hyperplasia with lymphocytic infiltrates in the thymic epithelium. The lesion differs from other forms of thymic hyperplasia, including true and follicular thymic hyperplasia, in that it presents at an advanced age and has been reported to be unassociated with autoimmune diseases. We report a case of thymic hyperplasia with lymphoepithelial sialadenitis-like features in a 55-year-old male patient with a history of an immunoglobulin G4 (IgG4)-related disorder. Histologically, the resected mediastinal mass showed features consistent with those of thymic hyperplasia with lymphoepithelial sialadenitis-like features. In addition, the IgG4/IgG ratio was elevated in the polyclonal plasmacytoid infiltration. Thymic hyperplasia with lymphoepithelial sialadenitis-like features has not been reported to be associated with IgG4-related disorders; however, as shown in our report, it is crucial to include it in the differential diagnosis of a mediastinal mass in a patient with IgG4-related disorders.

Background: To describe the clinical features of patients with childhood-onset myasthenia gravis (MG) (CMG) and explore predictors affecting the treatment outcomes., Methods: A retrospective observational cohort analysis of 859 patients with CMG with disease onset before age 14 years was performed at Tongji Hospital., Results: Patients in the pubertal-onset group (n = 148) had a worse disease course than those in the prepubertal group (n = 711), including a higher incidence of generalized MG (GMG) at presentation, generalization of ocular MG (OMG), and more severe Myasthenia Gravis Foundation of America (MGFA) classification. All patients were initially treated with pyridostigmine, 657 with prednisone, and 196 with immunosuppressants (ISs). However, 226 patients were resistant to prednisone treatment. Multivariate analysis revealed that thymic hyperplasia, higher MGFA class, disease duration before prednisone administration, and thymectomy before prednisone administration were independent predictors of prednisone resistance. At the last visit, 121 of the 840 patients with OMG had developed GMG after a median of 10.0 years from symptom onset and 186 patients (21.7%) achieved complete stable remission (CSR). In multivariable analysis, age at onset, thymic hyperplasia, prednisone, and IS treatment were associated with generalization, whereas age at onset, disease duration, anti-acetylcholine receptor antibodies (AChR-ab), MGFA class II, short-term prednisone treatment, and IS treatment were associated with CSR., Conclusions: The majority of patients with CMG have mild clinical symptoms and favorable outcomes, especially those with earlier onset age, shorter disease duration, and negative AChR-ab. In addition, early prednisone and ISs are shown to be effective and safe for most patients with CMG., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Thymic hyperplasia is a rare condition generally caused by lymphoid follicular hyperplasia associated with autoimmune disorders. True thymic parenchymal hyperplasia unassociated with lymphoid follicular hyperplasia is extremely rare and may give rise to difficulties in diagnosis. We have studied 44 patients with true thymic hyperplasia (38 females and 6 males) aged 7 months to 64 years (mean, 36 years). Eighteen patients presented with symptoms of chest discomfort or shortness of breath; in 20 patients, the lesions were discovered incidentally. Imaging studies demonstrated enlargement of the mediastinum by a mass lesion suspicious for malignancy. All patients were treated with complete surgical excision. The tumors measured from 3.5 to 24 cm (median, 10 cm; mean, 10.46 cm). Histologic examination showed lobules of thymic tissue displaying well-developed corticomedullary architecture, with scattered Hassall corpuscles separated by mature adipose tissue and bounded by a thin fibrous capsule. No cases showed evidence of lymphoid follicular hyperplasia, cytologic atypia, or confluence of the lobules. Immunohistochemical studies showed a normal pattern of distribution for keratin-positive thymic epithelial cells against a background rich in CD3/TdT/CD1a + lymphocytes. Twenty-nine cases had an initial clinical or pathological diagnosis of thymoma or thymoma vs thymic hyperplasia. Clinical follow-up in 26 cases showed that all patients were alive and well between 5 and 15 years after diagnosis (mean, 9 years). Thymic parenchymal hyperplasia causing significant enlargement of the normal thymus that is sufficient to cause symptoms or worrisome imaging findings should be considered in the differential diagnosis of anterior mediastinal masses. The criteria for distinguishing such lesions from lymphocyte-rich thymoma are presented., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Rationale: Thymoma is a rare malignant tumor but it is the most common primary tumor of the anterior mediastinum. The current imaging methods for thymoma screening suffer from false positive rate problems, and thymoma pathogenesis remains elusive. Study of thymoma metabolic characteristics could provide clues for improving the diagnosis and understanding the pathogenesis of thymoma., Methods: Metabolic profiling of plasma from thymoma and thymic hyperplasia patients was performed using ultrahigh-performance liquid chromatography combined with high-resolution mass spectrometry in both positive and negative ionization modes. After pre- and post-processing, the dataset was divided into three age groups and statistical analysis was performed to select differential metabolites of thymoma. For feature identification, experimental tandem mass spectra were matched to those of databases and available chemical standards, and also manually annotated with plausible chemical structures to ensure high identification confidence., Results: A total of 47 differential metabolites were identified in thymoma. Significantly higher levels of histidine, sphinganine 1-phosphate, lactic acid dimer, phenylacetylglutamine, LPC (18:3) and LPC (16:1), and significantly lower levels of phenylalanine, indole-3-propionic acid (IPA), hippuric acid and mesobilirubinogen were associated with thymoma. Tryptophan level in thymoma-associated myasthenia gravis (TAMG) was significantly lower than that of the MG(-) group. IPA and hippuric acid abundances exhibited increasing trends from indolent to aggressive thymoma., Conclusions: Our study revealed aberrant aromatic amino acid metabolism and fatty acid oxidation might be associated with thymoma. The identified unique metabolic characteristics of thymoma may provide valuable information for study of the molecular mechanism of thymoma pathogenesis, and improvement of diagnosis and discovery of new therapeutic strategies for thymoma., (© 2023 John Wiley & Sons Ltd.)

Background: Several retrospective studies have identified risk factors associated with ocular myasthenia gravis (OMG) generalization in non-surgical patients. However, the outcomes of OMG after thymectomy have not been investigated fully. This study aimed to explore the clinical predictors of post-thymectomy OMG prognosis., Methods: We performed a retrospective review of OMG patients who underwent thymectomy at our institution from January 2012 to December 2021. Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate associations between clinical features and prognosis. The main outcome measures were OMG conversion, complete stable remission (CSR), and clinical improvement., Results: Fifty-eight patients were identified for conversion analysis. Thirteen (22.4%) developed generalized myasthenia gravis (GMG) at a median time of 12.7 (3-37.3) months from symptom onset. Repetitive nerve stimulation (RNS)-positivity was associated with increased risk of conversion to GMG (P = 0.002). Patients with histotype B2/B3 thymoma showed a higher risk of conversion (P = 0.002) than did patients with hyperplasia and AB/B1 thymoma. Fifty-two patients fulfilled the criteria for CSR and improvement. Sixteen (30.8%) achieved CSR at a median time of 28.7 (15-54) months after thymectomy. Fifteen (28.8%) showed clinical improvement at last follow up. Patients who achieved CSR showed a younger age of onset (P = 0.022), lower percentage of acetylcholine receptor antibody-seropositivity (P = 0.029). Histologically, patients with thymic hyperplasia and stage I thymoma showed a higher chance of CSR (P = 0.010) than did patients with stage II/III thymoma. Multivariate analysis revealed that RNS-positivity (hazard ratio [HR] 6.007, P = 0.021) and histotype B2/B3 thymoma (HR 4.611, P = 0.048) were associated with OMG conversion. Thymic hyperplasia and stage I thymoma (HR 0.300, P = 0.026) were associated with OMG CSR after thymectomy., Conclusion: For OMG patients after thymectomy, RNS-positivity and histotype B2/B3 thymoma are independent predictors of conversion to GMG. On the other hand, thymic hyperplasia and stage I thymoma independently predict CSR., (© 2022. The Author(s).)

Lymphoproliferative disorders may occur in patients with rheumatoid arthritis (RA) who are treated with methotrexate. However, follicular thymic hyperplasia (FTH) associated with RA (FTH-RA) is generally not considered a lymphoproliferative disorder. To investigate the pathogenesis of FTH-RA, we examined 12 cases of FTH involving thymic enlargement, four of FTH involving RA and eight of FTH involving myasthenia gravis (MG). Increased numbers and larger germinal center (GC) size were observed in FTH-RA group. The percentage of distorted GCs was 13.3% in FTH-RA group and 3.25% in FTH associated with MG (FTH-MG) group. A greater meshwork of follicular dendritic cells was observed in the GCs of FTH-RA group. Positive indices of CD27 + cells and PD-1 + cells per GC in FTH-RA group were significantly higher than those in FTH-MG group, though positive indices of CD68 + cells and CD163 + cells were similar. Myoid cell proliferation, as evaluated by α-SMA, tenascin-C, and l-caldesmon expression, was significantly increased in the FTH-RA group compared with the FTH-MG group. These results suggest that FTH should be considered in patients with RA treated with methotrexate. The pathogenesis of FTH-RA includes GC expansion and increased numbers of memory B cells, follicular helper T cells, and myoid cells, indicating humoral immunity activation., (© 2022 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Pure red cell aplasia caused by true thymic hyperplasia is extremely rare. We report the case of a 25-year-old female diagnosed with pure red cell aplasia. Following a thymectomy confirming true thymic hyperplasia and corticosteroid therapy, complete response was achieved. Patients diagnosed with pure red cell aplasia should be investigated with a computerized tomographic scan to assess for thymic pathology and if present, this should be resected. Follow-up is essential to monitor for recurrence., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background and Objectives: Thymic pathology is common in Myasthenia Gravis(MG) and plays a crucial role in its pathogenesis and clinical outcome. This study aims to discuss the clinicohistopathological spectrum of thymic lesions in MG., Methods: In this retrospective study, MG patients who underwent thymectomy from 2011 to 2020 were included. Clinical, radiological, serological, and histopathological details are described., Results: Of 83 patients(F = 45; M = 38), 7(8%) had ocular myasthenia, and the remaining 76(92%) had the generalized form. At onset, the median age was 36 years(M = 44; F = 31). AChR antibody was positive in 71/79 patients. RNST showed decrement response in 68/78 patients. The histopathological study demonstrated thymoma in 44(53%), thymic hyperplasias [32(38%)], involuted thymus [5(6%)], thymic cyst (1) and thymic lipoma (1). WHO grading of thymoma: B2- 48%, AB-18%, B-18%, B3-14%, A-2.3%. In these, capsular infiltration was noted in 11/44, 9 had focal and 2 had diffuse infiltration. Active germinal centers were present in 20/32 patients with thymic hyperplasia and 4/44 with thymoma. Thymomas were predominant in males and thymic hyperplasia in females. The age of onset and antibody positivity rate was higher in thymoma patients., Conclusion: In our cohort, there is a female preponderance. Thymoma was the commonest pathology followed by hyperplasia. We observed earlier onset of myasthenia in females. AChR antibody positivity rate was more frequent in thymomas. This study indicates that clinico-radiological evaluation adequately supported by serology and histopathology can effectively recognize the type of thymic pathology that can guide these patients' treatment planning, management, prognosis and follow-up.

Background: Idiopathic multicentric Castleman disease (iMCD) is an uncommon lymphoproliferative disorder and lacks treatment consensus. Herein, we report a case of iMCD complicated with Sjögren's syndrome (SS) and secondary membranous nephropathy (SMN)., Case Presentation: A 45-year-old female with dry mouth for 3 months and anasarca and proteinuria for 2 months was admitted. She also experienced chest tightness, wheezing, fever, weight loss, moderate proteinuria and hypoalbuminemia. A computed tomography (CT) scan revealed a tissue mass in the thymus area and enlarged multiple lymph nodes. Her symptoms did not improve after resection of the thymus mass. The pathological findings were "reactive hyperplasia of the mediastinal lymph nodes and thymic hyperplasia". Lymph node biopsy findings confirmed iMCD with human herpes virus-8 (HHV-8) negativity. Based on anti-nuclear antibody (ANA) 1:320, anti-SSA and anti-SSB antibody positivity, salivary flow less than 0.1 ml/min and lip biopsy with focal lymphocytic sialadenitis, SS was diagnosed. Kidney biopsy showed secondary membranous nephropathy with endocapillary cell proliferation and infiltration of plasma cells and lymphocytes in the tubulointerstitium. Serum interleukin-6 (IL-6) levels were significantly increased, and therapy with tocilizumab (anti-IL-6 receptor antibody) worked well. The combination of cyclophosphamide (CyS) with methylprednisolone (MP) maintained satisfactory remission., Conclusions: Our case of iMCD with SS and SMN is rare. There is a need for increased awareness of the disease to avoid unnecessary procedures and misdiagnoses. IL-6 was extremely high, and there was a rapid response to anti-IL-6 receptor agents. The combination of CyS with MP maintained complete remission.

Background: Hyperthyroidism-induced hypercalcemia has been reported previously, but hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement in patients with hyperthyroidism is quite rare. We report the coexistence of hypercalcemia, osteoporosis and thymic enlargement in a patient with Graves' disease., Case Presentation: A 22-year-old female was diagnosed as Graves' disease with obviously elevated serum calcium and reduced parathyroid hormone levels. Dual-energy x-ray absorptiometry and chest enhanced computer tomography (CT) revealed severe osteoporosis and a significant enlargement of thymus. After the successful control of hyperthyroidism with methimazole, hypercalcemia was corrected, bone mineral density was improved and thymus also shrank obviously., Conclusion: This is a very rare case of hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement induced by Graves' disease. In clinical practice, examination of thymus and bone density should be considered when a patient with Graves' disease was present with hypercalcemia.

Objective: To investigate the association between myasthenia gravis (MG) and human parvovirus B19 (B19V) infection in the thymus., Methods: The presence of human B19V DNA and protein was assessed in 138 samples-including 68 thymic hyperplasias (39 with MG), 58 thymomas (23 with MG), and 12 normal thymus tissues-using a nested polymerase chain reaction, immunohistochemistry, laser capture microdissection, and sequencing in a double-blinded manner., Results: B19V DNA was detected mainly in thymic hyperplasia, and the positivity rate (41.18%, 28/68) was significantly higher than that in thymoma (3.45%, 2/58) (p <0.001) but not that in normal thymic tissues. Correspondingly, the positivity rate in thymic hyperplasia with MG (30.77%, 12/39) was significantly higher than that in thymoma with MG (4.35%, 1/23) (p=0.021). However, it was higher in thymic hyperplasia without MG (55.17%, 16/29) than in thymic hyperplasia with MG (30.77%, 12/39) (p=0.043). Cells in thymic hyperplasia positive for B19V VP1/VP2 protein (63.24%, 43/68) were identified mainly in ectopic germinal centres and thymic corpuscle epithelial cells, but were rare in thymomas (1.72%, 1/58) (p <0.001). Moreover, the positivity rate was significantly higher in thymic hyperplasia with MG (74.36%, 29/39) than in thymic hyperplasia without MG (48.28%, 14/29) (p=0.027)., Conclusions: To our knowledge, the present study is the first to show that human B19V infection is closely associated with thymic hyperplasia and thymic-hyperplasia-associated MG, but is not related to thymoma or thymoma-associated MG. The findings reveal a previously unrecognized aetiopathogenic mechanism of thymic-hyperplasia-associated MG, evoking numerous questions that require further investigation., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

It has long been established that the thymus plays a central role in autoimmune myasthenia gravis (MG) because of either thymoma or thymic hyperplasia of lymphoproliferative origin. In this review, we discuss thymic changes associated with thymic hyperplasia and their implications in the development of an autoimmune response against the acetylcholine receptor (AChR).The hyperplastic MG thymus displays all the characteristics of tertiary lymphoid organs (TLOs): neoangiogenic processes with high endothelial venule and lymphatic vessel development, chemokine overexpression favoring peripheral cell recruitment, and ectopic germinal center development. As thymic epithelial cells or myoid cells express AChR, a specific antigen presentation can easily occur within the thymus in the presence of recruited peripheral cells, such as B cells and T follicular helper cells. How the thymus turns into a TLO is not known, but local inflammation seems mandatory. Interferon (IFN)-β is overexpressed in MG thymus and could orchestrate thymic changes associated with MG. Knowledge about how IFN-β is induced in MG thymus and why its expression is sustained even long after disease onset would be of interest in the future to better understand the etiological and physiopathological mechanisms involved in autoimmune MG., (© 2017 New York Academy of Sciences.)

This study aimed to reveal the clinical course and outcomes of myasthenia gravis (MG) in patients with thymic lymphoid hyperplasia and thymoma undergoing extended thymectomy and to identify the clinical prognostic factors of remission for MG. In total, 73 patients undergoing extended thymectomy were divided into two groups: group A with lymphoid hyperplasia (n=39) and group B with thymoma (n=34). According to the MG Foundation of America (MGFA) post-intervention status, the primary endpoint was a composite measure defined as achievement of complete stable remission (CSR), pharmacologic remission (PR), minimal manifestations (MM) or improvement (IM). The secondary endpoint was CSR. The cumulative probabilities of reaching the primary endpoint were 71.8% in group A and 85.3% in group B (p=0.164), respectively. Using Kaplan-Meier survival analysis, the probability of reaching the primary endpoint in group B was remarkably greater than group A (p=0.036). Cox multivariate analysis indicated that pre-operative MGFA class I (HR: 3.019, 95% CI: 1.084-8.410) and MGFA II (2.665, 95% CI: 1.033-6.873) compared to MGFA III and presence of thymoma (HR: 2.229, 95% CI: 1.079-4.606), showed the most consistent association with remission of MG after thymectomy. Finally, thymic lymphoid hyperplasia and severe symptoms may negatively affect prognosis of MG following thymectomy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To compare the post-thymectomy prognosis in different conditions of myasthenia gravis (MG) patients with thymus hyperplasia., Materials and Methods: Collecting medical record and carrying out the follow-up study of 123 myasthenia gravis patients with thymus hyperplasia who have underwent thymectomy during the period between 2003 and 2013. Dividing into different groups based on gender, age of onset, duration of disease and Myasthenia Gravis Association of America (MGFA) clinical classification to analyze different prognosis in different groups., Results: Complete stable remission (CSR) was achieved in 71 of 123 patients (59.5%). There is no gender-related difference in achieving CSR. Patients with early onset of MG (≤40 years old) or disease duration less than 12 months had significantly higher CSR rates than those with late onset of MG (>40 years old) or disease duration more than 12 months respectively, while no difference was found in remission rate between MGFA clinical classification I and MGFA II., Conclusion: Myasthenia gravis patients with thymus hyperplasia who had thymectomy are proved to possess greater chance of achieving CSR. The onset age of disease and duration are the prognostic factors.

Objective and Importance: Sarcoidosis is a multisystem inflammatory disorder of unknown etiology. It is characterized by the presence of noncaseating granulomas and an inflammatory process in which T lymphocytes, especially type-1 helper T (Th1) cells, macrophages and different cytokines are involved. Different studies have shown the importance of genetic background in addition to environmental exposure in explaining different clinical phenotypes and disease outcome. In addition, potential auto antigens that might lead to the disease have been identified., Clinical Presentation: Here, we present a 53-year-old female patient presenting with subcutaneous nodules and mediastinal hilar lymphadenopathies refractory for corticosteroid treatment. Computed tomography of the thorax revealed a soft-tissue lesion in the thymus location., Intervention: The lesions due to sarcoidosis resolved after thymectomy., Conclusion: The remission of skin and pulmonary sarcoidosis only after thymectomy does potentially indicate the critical role that the thymus might play in the pathogenesis of this disease in a certain group of patients.

To better define the role of IL-17A in myasthenia gravis (MG), we assessed plasma concentrations in 69 adult patients with MG prior to initiation of immunosuppression and monitored their clinical course for the subsequent 2years with quantitative MG scores (QMGS) and Osserman classification. IL-17A was higher among patients than healthy control subjects. Early-onset women without thymoma had greater elevations of IL-17A. Logistic regression analysis indicated that the absence of thymoma rather than women gender or early-onset was the significant determinant associated with IL-17A elevation. Elevated IL-17A levels were associated with more severe MG. In summary, IL-17A has role in the pathogenesis of a subgroup of patients with early-onset women with MG with greater disease severity who are most likely to have thymic hyperplasia. This subgroup may be a target for IL-17 treatments, which are under development., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We report a patient with congenital myasthenic syndrome (CMS) due to mutation in CHRNE with symptoms since the age of 4; mild to moderate fatigable weakness involved mainly ocular, bulbar and limb muscles; functional impact of the disease in their development and physical activity was modest. By the age of 34, the patient experienced gradual worsening of fatigue with dyspnoea and pronounced limb weakness, requiring significant increase of pyridostigmine. Further, a remarkable and sustained clinical improvement followed thymectomy with hyperplastic thymus. Despite of the absence of detectable antibodies to acetyl-choline receptor (AChR) (including clustered-AChR), muscle-specific kinase and low-density lipoprotein receptor-related protein-4 antibodies in the serum obtained nine years after thymectomy, the clinical, genetic and histological features are in keeping with the extremely rare association of two rare neuromuscular junction disorders - CMS and myasthenia gravis (MG). The inexistence of other conditions that could potentially associate with thymic hyperplasia also supports the diagnosis of MG., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Graves' disease (GD) is commonly associated with other autoimmune conditions, and there is also a rare but well documented association between GD and thymic hyperplasia (TH). It is hard to say the real frequency of this latter association because most cases remain asymptomatic and are consequently not thoroughly investigated., Materials and Methods: We reviewed the literature on GD-related thymus enlargement and found 107 cases published to date. Thymic cancer was only documented in four patients, while the majority of cases were diagnosed as TH. The causative mechanisms behind TH associated with GD have yet to be fully elucidated. Several studies support the hypothesis of a TSH receptor antibody (TRAb) mediating thymic enlargement., Results: We report on a female GD patient with an incidentally discovered anterior mediastinal mass. Our case is not consistent with the hypothesis of a TRAb-mediated mechanism because the thymus reached its largest volume at the onset of GD and shrank during remission of GD under medical treatment, despite persistently positive TRAb levels., Conclusion: We support the hypothesis that two different pathogenic mechanisms might be responsible for thymus enlargement: thymic cortical tissue expansion seems to be due to a hyperthyroid state, while lymphoid hyperplasia appears to correlate with immune abnormalities underlying GD.

Objective: Thymus alterations have been related to several autoimmune disorders. In particular, previous studies identified a significant frequency of gland abnormalities by chest high-resolution CT (HRCT) in SSc patients. In this study we aimed to investigate the prevalence of radiological thymic alterations and their correlation with clinical and serological features in a large SSc series., Methods: We retrospectively evaluated thymic shape on CT scans of 200 consecutive, unselected SSc patients aged over 30 years The presence of radiological abnormalities, i.e. enlarged gland >13 mm or nodular lesions >7 mm, was correlated with SSc clinico-serological features. Moreover, the patients were also classified using a second thickness cut-off of 7 mm in order to identify incomplete thymic involution., Results: Twenty-four of 200 (12%) SSc patients presented an abnormal thymus at HRCT, including hyperplasic (19/24) and nodular (5/24) glands. Otherwise, using the cut-off of 7 mm for gland thickness and excluding subjects with nodular thymus, 50/195 (25.6%) patients presented an incomplete thymic involution. Thymic radiological alterations are significantly correlated with younger age and diffuse cutaneous SSc. Moreover, an abnormally enlarged thymus tended to be more common in patients with shorter disease duration., Conclusion: The present report on a large series of SSc patients further reinforces previous data present in the literature that includes other cohort studies and a number of anecdotal observations. Even though the actual role of thymus radiological abnormalities remains unclear, possible involvement of the gland in the early phase of immune-mediated SSc pathogenesis might be supposed.

Importance: Hypokalemic periodic paralysis is a muscle channelopathy based on mutations or predisposing variants or secondary to potassium wasting. In contrast to myasthenia gravis, an association with thymic hyperplasia has not yet been reported, to our knowledge., Observations: We report a male patient in his mid-20s with progressive episodes of flaccid muscle weakness, associated low serum potassium levels, and a pathologic decrement in the long exercise test. Because the familial inheritance in the family was initially unknown, thorough diagnostic tests were performed including contrast-enhanced computed tomography scan, which displayed a mass in the anterior mediastinum. The test results for autoantibodies against myasthenia gravis (acetylcholine receptor, muscle-specific tyrosine kinase, and low-density lipoprotein receptor-related protein 4) and other end plate channelopathies were negative, and test results for hypokalemia-inducing hormones (thyroid, corticotropin, and cortisol) were negative. Surgery identified a thymus of 13 × 8 × 3 cm(3). Histologic analysis was consistent with thymic hyperplasia of the follicular subtype and immunohistologic analysis showed cytokeratin 5/6 in hyperplastic epithelial cells. A 2-year follow-up revealed the postoperative absence of weakness episodes. As in 30% of familial cases, molecular genetics testing failed to identify a mutation in periodic paralysis genes., Conclusions and Relevance: Thymic hyperplasia can clinically manifest susceptibility to hypokalemic periodic paralysis. For patients with late onset or increasing weakness episodes, we recommend imaging to assess for thymic enlargement and thymectomy at thymic hyperplasia.

Background and Purpose: The differences in the characteristics of thymus histology, coexisting autoimmune diseases and related autoantibodies between anti-muscle-specific receptor tyrosine kinase (MuSK)-antibody (Ab)-positive myasthenia gravis (MG) patients, and anti-acetylcholine receptor (AChR)-Ab-positive MG patients are not clearly defined., Methods: The types of thymus histology, coexisting autoimmune diseases and associated Abs in 83 MuSK-Ab-positive patients nationwide were investigated and were compared with those in AChR-Ab-positive patients followed at our institute (n = 83). As for the autoantibodies associated with thymoma, titin Abs were measured., Results: Thymoma was not present in any of the MuSK-Ab-positive patients but presented in 21 patients (25.3%) amongst the AChR-Ab-positive patients. Titin Abs were absent in MuSK-Ab-positive patients but positive in 25 (30.1%) of the AChR-Ab-positive patients. Concomitant autoimmune diseases were present in eight MuSK-Ab-positive patients (9.6%) amongst whom Hashimoto's thyroiditis and rheumatoid arthritis predominated, whereas 22 AChR-Ab-positive patients (26.5%) had one or more concomitant autoimmune diseases of which Graves' disease predominated., Conclusions: Differences in frequency of thymoma and thymic hyperplasia, coexisting autoimmune diseases and autoantibody positivity between MuSK-Ab-positive and AChR-Ab-positive MG were indicated, suggesting that, in contrast with AChR-Ab-positive MG, thymus does not seem to be involved in the pathogenic mechanisms of MuSK-Ab-positive MG., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Differential expressions of immune molecules have been shown in the thymi with pathological results, including myasthenia gravis (MG). CD25 is an activation marker expressed on T cells. CXCL13 mediates the homing and motility of B cells in secondary lymphoid tissues. Herein, we investigated the expressions of CD25 and CXCL13 in the thymi of thymic hyperplasia patients with MG or with non-MG. A total of 34 thymic hyperplasia patients with MG (20 generalized MG (GMG) and 14 ocular MG (OMG) and six thymic hyperplasia patients without MG were enrolled and analyzed using immunohistochemical staining and real-time polymerase chain reaction for CD25 and CXCL13. Our study demonstrated a higher expression of both CD25 and CXCL13 in hyperplastic thymi with OMG or GMG compared to those with non-MG. According to the immunohistochemical results, we observed that CD25 expression was significantly lower in atrophic thymi and non-MG hyperplastic thymi, compared with that in infant thymi (P = 0.002 and 0.005, respectively). In contrast to CD25 expression, we did not observe differential expression of CXCL13 among three control groups. And a similar CD25 mRNA expression was found in real-time polymerase chain reaction (PCR) results. We observed that both hyperplastic thymi with OMG or GMG expressed significantly higher levels of CD25 than those with non-MG (P = 0.007 and 0.001, respectively). And an increase of CD25 expression was observed in hyperplastic thymi with GMG compared to those with OMG (P = 0.030). Similarly, CXCL13 expression was significantly higher in hyperplastic thymi with GMG or with OMG than those with non-MG (P = 0.001 and 0.050, respectively). No significant CXCL13 expression difference was found between hyperplastic thymi with GMG and those with OMG (P > 0.05). The real-time PCR results showed a similar tendency of CD25 mRNA expression among the thymi of non-MG, OMG, and GMG patients, but the difference did not reach significance (P > 0.05). An obvious increased expression of CXCL13 was found in hyperplastic thymi with GMG patients, compared to those with non-MG and OMG patients (P = 0.003 and 0.071, respectively). There was no difference found between hyperplastic thymi with non-MG and with OMG. Regression analysis showed a positive correlation between thymic CD25 level and MG symptom severity (F = 28.240; P = 0.000, r = 0.523). Similarly, a positive correlation was found between thymic CXCL13 expression and MG disease severity (F = 36.093; P = 0.000, r = 0.671). Taken together, our findings suggest CD25 and CXCL13 participate in the pathogenesis of MG and may influence the clinical symptoms of MG.

Objectives: To analyze the predictive value of anti-acetylcholine receptor antibodies (anti-AChR Ab) and anti-muscle specific kinase antibodies (anti-MuSK Ab), as well as the thymus pathology to the clinical outcome in patients with generalized myasthenia gravis (MG)., Methods: We analyzed 138 patients with generalized MG, who were thymectomized and assayed for anti-AChR Ab and anti-MuSK Ab., Results: Anti-AChR Ab were detected in 84% of patients, while anti-MuSK Ab were present in 36% of the AChR Ab negative patients. Severe forms of the disease were more frequent in MuSK Ab positive, compared to the AChR Ab positive and complete seronegative patients. Thymic lymphoid follicular hyperplasia (LFH) was present in 60%, thymoma in 23%, atrophic thymus in 9% and the normal thymus in 8% of patients. LFH was more frequent among women, while thymoma and atrophic thymus were more frequent in men. The younger patients mainly had LFH and normal thymus, while thymoma and atrophic thymus were more frequent in older patients. The mildest clinical presentation was present in patients with normal thymus, while severe forms of the disease were registered in the patients with thymoma. The AChR Ab positive patients had more often LFH and thymoma, while within MuSK Ab positive patients atrophic thymus was most common., Conclusion: The best disease outcome was observed in patients with normal thymus or LFH with anti-AChR Ab or without both types of antibodies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Graves' disease (GD) and myasthenia gravis (MG) are common autoimmune diseases but their coexistence is very rare. They may possibly share the same pathogenetic mechanisms. Recent research has shown the involvement of autoantibodies, lymphocytes, cytokines and chemokines in the pathogenesis of MG and GD. It appears that Th17 cell lineage is involved in autoimmune thyroid disease (AITD) and seems to be key factor in the development of both MG and GD.A 34-year-old male with seronegative myasthenia gravis due to thymic hyperplasia was diagnosed with also GD and opthalmopathy. Several diagnostic and therapeutic issues regarding the relevant literature are discussed., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Thymus hyperplasia and Graves' disease association is not well known and is probably not incidental. We report the case of a young woman affected with Graves' disease in which a retrosternal mass was disclosed during a neck ultrasonographic-examination and confirmed by chest CT-examination. Follow-up ultrasound survey showed a decrease in the thymic mass size. Because of various antithyroid drugs allergy, a surgical procedure was performed, during which both her thyroid and thymic mass were removed. The histopathologic examination of this mass confirmed the hyperplasic nature of the thymic bulging. Ninety-one cases of thymus hyperplasia and Graves' disease association have been reported in literature, of which 20 were histologically confirmed. Among these cases 35 showed a thymic mass regression under medical treatment alone. Accordingly, surgical procedures are most frequently unnecessary in such associations because of the thymic mass decrease incurred by antithyroid drug treatment., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

We present the case of a 32-year-old-woman who was admitted to the hospital for evaluation of pericardial effusion. The subsequent diagnostic workup revealed the presence of a mediastinal mass along with systemic lupus erythematosus (SLE). The patient underwent thymectomy, and histological evaluation of the resected mass revealed thymic follicular hyperplasia without evidence of malignancy. SLE disease activity was promptly controlled by corticoids. Clinicians should be aware of the occasional association of autoimmune disorders with focal thymic hyperplasia, which might be confused with thymomas or thymocarcinomas.

Fatigue is a prominent feature of systemic lupus erythematosus (SLE), usually ascribed to various factors, such as muscle or joint involvement, anaemia or depression. The Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoantibody-mediated disorder of neuro-muscular transmission. We report on a well-defined LEMS associated with thymus hyperplasia in a SLE patient. An African 41 years-old SLE patient presented with persisting fatigue, myalgia and dyspnea, abolished reflexes and a bilateral ptosis. Neuromuscular electrodiagnostic study showed a clear-cut potentiation that was typical of a pre-synaptic neuromuscular junction disease. Anti-calcium gated channels antibodies were disclosed in serum and a diagnosis of LEMS was made. A total body CT-scan revealed an antero-superior mediastinal mass, compatible with thymoma. The tumour was surgically removed with a final diagnosis of follicular thymic hyperplasia. In conclusion, our observation provides a new example of entangled organ-specific and systemic autoimmunity in the context of thymus pathology. Potentiation study during electromyography should be performed systematically to rule out LEMS in patients with SLE and muscle weakness.

We report a case of thymic hyperplasia accompanied by pericardial lipomatosis and right facial hemihypertrophy in an 8-year-old boy. On imaging studies, the hyperplastic thymus had prominent curvilinear and nodular fatty areas simulating a fat-containing anterior mediastinal mass, which is an unusual finding in children. To our knowledge, this is the first report on a child with a combination of thymic hyperplasia, pericardial lipomatosis, and right facial hemihypertrophy. The radiologic findings are presented with a brief discussion.

The authors describe a rare case of thymolipoma in a 26-year-old, otherwise healthy woman presenting with general fatigue. Radiological examinations disclosed a large anterior mediastinal mass. Macroscopically, the resected tumor was approximately 5 × 10 cm², with nodular configuration, and microscopically, 3 components were identified: a normal thymic rim, hyperplastic thymic tissue, and a typical thymolipomatous component at the periphery of the hyperplastic area. The predominant component of the tumor was hyperplastic thymic tissue. The tumor was diagnosed as thymolipoma at the initial stage of development. This case suggests the histogenesis of thymolipoma-fatty regression or infiltration of fatty tissue into a previously hyperplastic thymus.

A case of true thymic hyperplasia (TTH) associated with thymic hemorrhage (TH) was observed in a 22-year-old male patient who presented with persistent cough and thoracic pain due to an anterior mediastinal mass. The diagnosis of TTH was supported by the observation that the mediastinal mass was essentially composed of histologically normal thymic lobules with preserved cortico-medullary differentiation. The TTH tissue presented multiple areas of hemorrhage associated with the presence of large, tortuous, abnormal vessels in the thymic stroma. Foci of spindle cell proliferations resembling an epitheliod hemangioma were also seen. This finding raises the possibility that vascular malformations, perhaps due to an abnormal growth of the thymus, may be responsible for some cases of TH associated with TTH., ((c) 2009 Elsevier GmbH. All rights reserved.)

Myasthenia gravis (MG) is an antibody and complement mediated autoimmune disease. Serum CXC chemokine ligand 13 (CXCL13) was found to be elevated in MG patients and high CXCL13 level was associated with severe clinical stages, especially in females with thymic lymphoid hyperplasia. Both protein and mRNA of CXCL13 and CXC chemokine receptor 5 (CXCR5) in the thymic tissues were significantly higher in MG patients with lymphoid hyperplasia than those with thymoma. Our data indicated that serum CXCL13 can be used as an index of disease severity and ectopic thymic expression of CXCL13 might be associated with aberrant cell trafficking to the thymus of MG., (Copyright 2010 Elsevier B.V. All rights reserved.)

An enlarged thymus adversely affected pulmonary artery development and perfusion in a 4-month-old boy with asplenia syndrome and a single ventricular circulation with aorto-pulmonary shunt. Steroid administration for 4 weeks successfully reduced thymus volume, concomitant with improvement of pulmonary vasculature and perfusion. Given the importance of pulmonary physiology in the Fontan circulation, the effects of thymic hyperplasia on pulmonary circulation should be taken into consideration in the overall management of candidates for Fontan surgery.

Introduction: Thymic enlargement is a rare phenomenon that can be challenging., Materials and Methods: We present a retrospective study over a 13-year period (from 1996 to 2008) of 13 cases of thymic hyperplasia that included 4 cases of true thymic hyperplasia (TTH) and 9 cases of follicular thymic hyperplasia (FTH)., Objectives: To describe the pathogenesis and different associations of these 2 entities; to emphasize the difficulties in accurate diagnosis without histological examination and to report an unusual association between TTH and cutaneous leishmaniasis., Results: There were 9 women and 4 men. All patients with FTH had a past medical history of myasthenia gravis (MG). In the group of TTH, 2 patients received chemotherapy and one patient had been administered amphotericin B for a cutaneous leishmaniasis. Radiologic findings showed a mediastinal mass in 7 cases. Thymectomy was performed in all patients with FTH and in one patient with TTH and suspect malignant disease. We observed no complications in any case., Conclusion: The two main types of thymic hyperplasia have different pathogenic characteristics and diverse treatment modalities.

Objective: To describe a case of an anterior mediastinal mass (AMM) in a patient with Graves disease., Methods: We report the clinical presentation, diagnosis, management, and outcome of a 34-year-old man with dyspnea on exertion., Results: Initial evaluation of the patient's complaints revealed a large AMM on chest radiography and then chest computed tomography. After occurrence of additional symptoms, the patient was diagnosed as having Graves disease and treated with antithyroid medications. Despite an appropriate biochemical response, he continued to experience severe dyspnea on exertion. A repeated computed tomographic scan 8 weeks after initiation of therapy showed no appreciable decrease in size of the AMM. He elected to undergo thymectomy. An intraoperative phrenic nerve injury resulted in a paralyzed left hemidiaphragm, leaving the patient with considerable difficulties in his career and profoundly decreased exercise tolerance., Conclusion: The differential diagnosis of an AMM includes several malignant lesions with a risk often warranting early surgical excision. In light of the association of benign thymic hyperplasia with Graves disease, thymectomy may be delayed in expectation of thymic regression with medical therapy. The timing of regression is variable, and very few reports exist in the literature. In our current case, the patient opted for thymectomy relatively early and had an unfortunate complication. The lack of clinical evidence regarding management of an enlarged thymus in patients with Graves disease, however, makes management decisions more difficult.

Purpose: Thymectomy has been widely employed in the treatment of myasthenia gravis (MG). However, little data exist in Iran demonstrating the efficacy and morbidity of thymectomy. The aim of this study was to determine the clinical features, diagnostic approach, and therapeutic outcome in patients with MG who underwent thymectomy., Methods: This historical cohort study was conducted in 3 university hospitals in Tehran. Preoperative and operative indices of 61 patients with MG who had been treated with thymectomy in these hospitals from September 2000 to July 2005 were reviewed. Among them, 20 patients were followed during one year after operation for determination of postoperative complications and one year mortality rate., Results: The most common manifestations of MG were ptosis (77.0%) and upper limbs weakness (70.4%). CT scans of the thymus showed thymus enlargement, thymoma and thymus hyperplasia in 51.5% (22/43), 11.6% (5/43) and 2.32% (1/43) of patients, respectively. The postoperative complications were found in 13.1% of patients and one year mortality rate of thymectomy was 6.6%., Conclusion: Regarding to high one year mortality rate of thymectomy in patients of MG in this study, the assessment of the factors related to the mortality and outcome of patients who underwent thymectomy in Iran are necessary.

We report a 40-year old woman with bilateral partial ptosis, complete external ophthalmoplegia, and weakness and fatiguability of upper limbs. She was on treatment for hypertension for 5 months at the time of admission. She was found to have generalised myasthenia gravis and membranous nephropathy with end-stage renal disease. Her symptoms and signs improved within 2 months on treatment with neostigmine and prednisolone. It is postulated that either thymic hyperplasia or the subclinical stage of a thymoma may be the underlying aetiological factor in this patient.

A 41-year-old man with progressive limb weakness manifested fluctuating muscle weakness as seen in myasthenia gravis (MG). Laboratory investigations revealed hyperthyroidism without the complication of MG. Electrophysiological studies demonstrated abnormal features of neuromuscular transmissions resembling those of the Lambert-Eaton myasthenic syndrome rather than those of MG. A CT scan showed a mediastinal mass that suggested thymic hyperplasia which often complicates MG or hyperthyroidism. Medical treatment of hyperthyroidism resulted in resolution of MG-like symptoms and regression of thymic hyperplasia on CT concomitant with normalization of thyroid function. This case highlights the fact that careful investigations are needed to differentiate MG-like symptoms from genuine MG in cases of hyperthyroidism with thymic lesions.

The thymus is frequently hyperplastic in young female myasthenia gravis (MG) patients presenting with anti-acetylcholine receptor (AChR) antibodies. This thymic pathology is characterized by the presence of ectopic germinal centers (GCs) containing B cells involved at least partially in the production of pathogenic anti-AChR antibodies. Our recent studies have furthered our understanding of the mechanisms leading to GC formation in the hyperplastic thymus. First, we showed that CXCL13 and CCL21, chemokines involved in GC formation, are overexpressed in MG thymus. Second, we demonstrated an increase in pro-inflammatory activity in the thymus from MG patients and its partial normalization by glucocorticoids, as evidenced by gene expression profile. Third, we found that pro-inflammatory cytokines are able to upregulate the expression of AChR subunits in thymic epithelial and myoid cells. Fourth, we showed that the function of T regulatory (Treg) cells, whose role is to downregulate the immune response, is severely impaired in the thymus of MG patients; such a defect could explain the chronic immune activation observed consistently in MG thymic hyperplasia. Altogether, these new data suggest that CXCL13 and CCL21, which are produced in excess in MG thymus, attract peripheral B cells and activated T cells, which are maintained chronically activated in the inflammatory thymic environment because of the defect in suppressive activity of Treg cells. Presence of AChR in the thymus and upregulation of its expression by the pro-inflammatory environment contribute to the triggering and maintenance of the anti-AChR autoimmune response.