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The incidence of myasthenia gravis which is characterized by progressive muscular weakness on the background of structural disorders of the thymus, has increased. Myasthenia gravis is a multifactorial autoimmune disease, it has a pronounced clinical heterogeneity, and therefore the standard diagnostic and treatment protocol is not always effective. To substantiate an individual approach to the treatment of various clinical forms of myasthenia, we conducted a study of mechanisms and markers of loss of central and peripheral self-tolerance in thymus-independent myasthenia (M) and thymus-dependent myasthenia gravis with thymus hyperplasia (MH) and thymoma (MT), involving a total of 427 patients examined. In patients with different phenotypes of myasthenia, we used the methods of spectrophotometry, flow cytometry, enzyme immunoassay. In patients with MH on the background of lymphofollicular thymus hyperplasia we revealed a pronounced humoral sensitization in comparison with the reference values: the concentration of C4 complement, C-reactive protein, circulating immune complexes and the initiation of an indirect autoimmune reaction a reliable increase in autoantibodies (AAbs) to the α1 and α7 subunit of subunit of nicotinic receptors (nAChR). In M and MT groups a high similar titer of AAbs to other epitopes was revealed: DNA, β2-glycoprotein I, membranes of intestinal and stomach cells, lung, liver, kidney cells. A pronounced blast-transforming response to the presence of the mitogen PHA was revealed in the MT group. In the MT group, a decrease in the content of CD4+ CD28+ co-stimulatory molecules and in the MH group, a decrease in СD4+ CD25+ Treg lymphocytes was revealed. Individual methods for correcting the loss of self-tolerance in patients with different clinical phenotypes of myasthenia were justified taking into account the use of immunosuppression, specific viral-neutralizing immunoglobulins and massive IgG immunoglobulin therapy, and the application of anti-inflammatory recombinant interleukins.

Introduction The ability to distinguish between normal thymus, thymic hyperplasia, and thymoma should aid clinical management and decision making in patients with myasthenia gravis (MG). We sought to determine the accuracy of routine imaging in predicting thymic pathology. Methods We retrospectively analyzed records of patients with MG from the Oxford Myasthenia Centre registry who had undergone thymectomy. Each patient received 1 radiological diagnosis and 1 histological diagnosis. Results We included 106 patients. Radiological and histological diagnoses agreed in 73 (68.9%) patients. Sensitivity and specificity, respectively, were calculated for each radiological diagnosis as follows: thymoma 90% and 95.5%, hyperplasia 17.6% and 98.6%, and normal 96.9% and 60.8%. Discussion Routine chest computed tomography and MRI can effectively identify thymoma. However, they are not reliable tools to differentiate between thymic hyperplasia and normal thymus in patients with MG. Muscle Nerve, 2018.

The MGTX trial provided evidence that, in general, thymectomy is beneficial in adult patients up to 60 years of age with anti-acetylcholine receptor-positive, nonthymomatous myasthenia gravis (MG). This finding supports the long-held view that the pathogenesis of this type of MG (early-onset MG (EOMG)) starts inside the thymus, results in the long-term intrathymic recruitment of autoantibody-producing B cells and plasma cells, and eventually spreads to the peripheral immune system. However, observed clinical responses to treatment in the MGTX trial were diverse. This might be due to heterogeneous epidemiological and genetic features of EOMG patients and variable durations of corticosteroid treatment before surgery, including a paucity of patients that were corticosteroid naive. Furthermore, the observed histological heterogeneity suggests that a single pathogenetic model may not fully reflect the spectrum of events that modify the course of EOMG. Here, we describe the morphology of the normal and MG-associated thymus, how to evaluate morphological changes, and the current pathogenetic model of EOMG and discuss how it could be refined by integrating MGTX-derived histological findings in thymectomy specimens and associated clinical observations.

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.

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.

Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against proteins at the neuromuscular junction. Juvenile-onset MG (JMG) has been reported to have special characteristics. It is still unclear whether there are any pathogenic and genetic differences between juvenile and adult MG. In this study, we evaluated the clinical characteristics, autoantibody status (antibodies against AChR, MuSK, LRP4, titin and RyR) and genetic susceptibility (CHRNA1, CTLA4 and AIRE) in 114 Chinese JMG patients, and compared with 207 young adult MG patients (onset age 18–40 years). JMG patients were classified into two subgroups: the very early onset group (

The checkpoint protein programmed cell death ligand-1 protein (PD-L1) binds to its receptor (PD-1) activating the PD-L1/PD-1 pathway, an important therapeutic target. There is limited information regarding PD-L1 and PD-1 expression in thymic lesions. Sections from nonneoplastic thymi (n = 20), thymomas World Health Organization types A, AB, B1, B2, and B3 (n = 38) and thymic squamous cell carcinoma (n = 8) were stained for PD-L1 (clone SP142; Spring BioScience), PD-1 (MRQ22; Cell Marque), CD4 (clone SPO32; Cell Marque), and CD8 (JCB117; Ventana). Immunoreactivity for each antibody was classified as focal or diffuse and scored as follows: 0, negative; 1%-5%, 1+; 6%-20%, 2+; and >20%, 3+. The proportions of cases expressing PD-L1, PD-1, CD4, and C8 at score ≥1+ were compared by diagnosis, using χ2 statistics. PD-L1 was expressed in 90% of nonneoplastic thymi, 92% of thymomas, and 50% of carcinomas, with significantly higher scores (P < .01) in B2 and B3 thymomas and carcinomas than in AB and B1 thymomas; PD-L1 was diffuse in most B2 and B3 thymomas and focal in carcinomas. PD-1 was focally expressed, and mostly with scores 1+, in 55% of nonneoplastic thymi, 63% of thymomas, and 37.5% of carcinomas. CD4+ and CD8+ cells were diffusely distributed with scores 3+ in all lesions other than B3 thymomas and carcinomas. The latter showed CD4+ cells mostly at the interface between neoplastic cells and stroma. PD-L1 and PD-1 are not expressed in similar locations and cellular proportions in thymic lesions, raising a question as to whether the PD-L1/PD-1 pathway is an actionable therapeutic target in these lesions.

Myasthenia Gravis is an autoantibody-mediated, neuromuscular junction disease, and is usually associated with thymic abnormalities presented as thymic tumors (~10%) or hyperplastic thymus (~65%). The exact role of thymus in Myasthenia Gravis development is not clear, yet many patients benefit from thymectomy. The apoptotic ligand TNF-Related Apoptosis-Inducing Ligand is thought to be involved in the regulation of thymocyte counts, although conflicting results are reported. We investigated differential expression profiles of TNF-Related Apoptosis-Inducing Ligand and its transmembrane receptors, Nuclear Factor-kB activation status, and apoptotic cell counts in healthy thymic tissue and pathological thymus from Myasthenia Gravis patients. All tissues expressed TNF-Related Apoptosis-Inducing Ligand and its receptors, with hyperplastic tissue having the highest expression levels of death receptors DR4 and DR5. No detectable Nuclear Factor-kB activation, at least via the canonical Protein Kinase A-mediated p65 Ser276 phosphorylation, was evident in any of the tissues studied. Apoptotic cell counts were higher in MG-associated tissue compared to the normal thymus. Possible use of the TNF-Related Apoptosis-Inducing Ligand within the concept of an apoptotic ligand-mediated medical thymectomy in thymoma- or thymic hyperplasia-associated Myasthenia Gravis is also discussed.

A 23-year-old woman was referred to our center with hirsutism, acne, weight gain, weakness, and irregular menses. Laboratory tests revealed increased levels of cortisol and sex hormones, and reduced adrenocorticotropic hormone levels. The patient underwent a right adrenalectomy. Pathology of the resected right adrenal gland showed an adrenal carcinoma. Computed tomography 8 months after the surgery revealed a thymic mass that was not detected preoperatively. The frequency of rebound thymic hyperplasia after normalization of hypercortisolism is not known, but possibly as high as 40%. Physicians must be aware of this phenomenon to avoid unnecessary thoracic surgery.

Introduction: Some myasthenia gravis (MG) patients are refractory to conventional treatments. Methods: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. Results: Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10-6 ). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003). Discussion: HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188-191, 2019. info:eu-repo/semantics/publishedVersion

BACKGROUND True thymic hyperplasia (TTH) is characterized as a distinct increase in both size and weight of thymus, which retains normal microscopic and immunohistochemical appearances. Massive true thymic hyperplasia (MTTH) is an extremely rare but significant subtype of TTH in pediatric ages due to its potentially serious consequences. It was reported that the age of cases with MTTH was predominantly between 1 and 15 years, while those before 1 year rarely occurred. By presenting the diagnosis and treatment process of our case as well as reviewing the related literature, we aimed to analyze the clinical characteristics of MTTH for patients younger than 1 year. CASE A 3-month-old male infant was admitted to our department with a chief complaint of gradually increasing polypnea over 9 days, whose preoperative imaging examination showed a large intrathoracic soft tissue shadow predominantly on the right side. The percutaneous fine-needle biopsy guided by ultrasonography was performed to identify its diagnosis. However, proliferating lymphocytes and Hassall`s corpuscles were seen microscopically in the biopsy tissues, which were immunohistochemically positive for CD3, CD19, CD20, CD99, TdT, PCK and Ki67 ( > 90%). Due to the aggravating symptoms, a second operation with total thymectomy was carried out successfully for this infant, which confirmed the diagnosis of TTH again by both morphological study and immunohistochemical staining from the surgical specimen. CONCLUSIONS By reviewing the literature, there were only 10 cases with MTTH reported between 1975 and 2020 for children aged < 1 year of life, together with our present one. In MTTH patient`s sex had an obviously male predominance (70%). Nine out of 10 presented initial symptoms or signs related to respiratory system and 6 patients showed respiratory distress. All patients were successfully treated by surgical thymectomy without any postoperative complications. The prognosis of MTTH was very successful.

Thymomas are a heterogeneous group of tumors arising from the epithelium of the thymus. They are categorized by the proportion of neoplastic epithelia to lymphocytes and by the degree of cytologic atypia. Thymomas constitute 0.2-1.5% of all malignancies and nearly all occur in patients over 20 years. We reviewed the available literature and found less than 50 cases of thymoma reported in children (

Ocular myasthenia gravis (OMG) is sometimes difficult to diagnose and is probably both under-diagnosed and misdiagnosed. We studied the epidemiological parameters, relevant serology, electromyographic (EMG) findings, and the relationship between OMG and thymoma, thymus hyperplasia and other autoimmune disorders compared to generalized MG (GMG) in a case control study of 133 patients with MG (32 patients with OMG and 101 patients with GMG). The proportion of OMG among all MG patients was relatively high (24.1%). It affected more males than females and its onset was at an older age. Although anti-AChR Ab was detected in fewer OMG patients compared to GMG patients, the rate of positive serology in OMG patients was higher than previously reported. Male OMG patients had a higher positive serology rate than female OMG patients. OMG patients tended to have less supportive EMG evidence of neuromuscular disorder. Female OMG patients had higher rates of thymus hyperplasia and higher rates of other autoimmune disorders than males. Diagnosing MG in patients with solitary ocular manifestation may be difficult due to lower rates of paraclinic supportive tests. Awareness of the characteristics of OMG is important in order to avoid delayed or misdiagnosis of MG and to prevent avoidable iatrogenic complications., Highlights • A relatively high prevalence of ocular myasthenia gravis • Ocular myasthenia gravis affected more male than females. • Anti-AChR Ab detected fewer ocular MG patients than generalized MG patients. • Female with ocular MG had more thymus hyperplasia and other autoimmune disorders than male.

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.

A tri-modal distribution of age-at-onset emerged among females patients with myasthenia gravis (MG) in our database. This finding may be indicative of different gender-based disease mechanisms.We retrospectively reviewed the files of 127 MG patients for the clinical, serology and thymus pathology according to their age at disease onset: ≤40 years (early-onset, EOMG), 40-70 years (intermediate-onset, IOMG) and70 years (late-onset, LOMG).EOMG was more common among females, and IOMG was more common among males. Ocular MG was more common among the male MG patients with an IOMG. Patients with EOMG had lower rates of positive anti-acetylcholine receptor (anti-AChR). IOMG females, but not IOMG males, had lower rates of positive anti-AChR. IOMG and EOMG females had high rates of thymic hyperplasia, while EOMG males had high rates of thymoma. Comorbidity with autoimmune diseases was common among females with IOMG and LOMG.The prevalence of IOMG was the reason for the trend reversal of MG prevalence between genders. The clinical features of patients with IOMG differed between genders in the rates of positive anti-AChR, follicular hyperplasia of the thymus and comorbidity with autoimmune diseases. This may suggest a different gender-based mechanism of immune intolerance towards AChR and other antigens.

Thyrotoxicosis and orbitopathy are the best-known expressions of Graves' disease. There are also rarer and less-known phenomena, such as thymic hyperplasia. Identification of these is important in order to avoid potentially unnecessary invasive interventions.In the case of two young women with lung embolisms, CT pulmonary angiography also revealed an enlarged thymus. This turned out to be caused by as of yet unknown Graves' disease. Since pathological examination of a thymus-biopsy sample was unable to rule out thymoma, thymectomy was performed on the first patient. Pathological examination of the entire thymus revealed hyperplasia. Additional FDG-PET/CT scan of the second patient revealed diffuse hyperactivity in the diffusely enlarged thymus. In this case, we opted for expectant treatment. A follow-up FDG-PET/CT scan 1 year later, revealed a non-abnormal thymus.An enlarged thymus caused by thymic hyperplasia is a less well-known manifestation of Graves' disease. In case additional abnormalities develop in patients with Graves' disease, it is important to consider that these might be related to the disease before diagnosing an additional new condition.

Rationale: Myasthenia gravis (MG) is the most common cause of acquired neuromuscular junction disorder. Thymectomy has been established as an effective therapy for MG, as it attenuates the natural course of the disease and may result in complete remission. Patient concerns: We report the case of a 22-year-old female with a 6-year history of MG presented with bilateral ptosis, diplopia, and intermittent dysphagia. She denied shortness of breath, dysarthria, and fatigue. Diagnoses: She had been diagnosed with MG 6 years previously at the Neurology Department of our hospital. A computed tomography (CT) scan revealed thymic hyperplasia Interventions: She was treated with modified unilateral VATET that minimized incision size. Outcomes: Unilateral VATET was performed using two 5-mm incisions to minimize pressure on intercostal soft tissues/nerves and reduce postoperative pain. Lessons: The lesson learnt from this case report is that this modified VATET method could be a useful approach to the management of non-thymomatous MG. The ability to achieve complete dissection with good cosmetic results may lead to wider acceptance of this technique by patients with MG and their neurologists for earlier thymectomy and improved outcomes. Additional studies are needed to determine the superiority of this approach to established methods.

Background: To report the first and largest series of robotic-assisted mediastinal surgeries performed in a single center by the same surgical team in mainland China. Methods: From May 2009 to June 2017, 167 patients (100 males, 67 females), with a mean age of 50.2 years (range, 12–78 years), underwent robotic surgery for the treatment of a mediastinal mass. Data regarding the operation time, docking time, blood loss, conversion rate, morbidity, mortality and survival follow-up were collected and analyzed. Results: The mean operation time and docking time were 70.01±29.49 and 10.12±2.77 min. There were 56 thymomas, 52 cysts, 17 schwannomas, 9 bronchogenic cysts, 6 thymic hyperplasias, 6 foregut cysts, 4 squamous carcinomas and 17 others. The mean drainage on the first day after operation was 122.83±107.58 mL, and the mean post-operative drainage duration and post-operative hospital stay were 2.95 days, ranging from 1–7 days, and 4.09 days, ranging from 2–10 days, respectively. The post-operative complication rate was 3%, and the conversion rate was 1.8%. No perioperative mortality occurred. One patient died due to tumor recurrence. Conclusions: Our experience indicates that this robotic surgical system is a safe and established technique for mediastinal mass resection.

Rationale: The development of rebound thymic hyperplasia (RTH) has been reported in patients who have recovered from stressful conditions such as surgery and steroid therapy. We report a case of RTH following the resolution of hypercortisolism after adrenalectomy for the treatment of adrenocortical adenoma in a patient with Cushing syndrome. Patient concerns: A 5-month-old female infant with a history of overeating, hirsutism, and excessive weight gain for the previous 2 months was referred to the hospital. The laboratory results revealed elevated 24-hour urinary free cortisol levels. An overnight dexamethasone suppression test showed no response. Abdominal imaging revealed a right-sided suprarenal mass measuring 4_3cm. Histology showed an adrenocortical adenoma. Thus, she underwent a right adrenalectomy. Diagnoses: The patient showed clinical improvement with weight loss and normal cortisol levels over the next 4 months. Six months after the operation, a chest computed tomography showed enlargement of the left thymic lobe, which was previously nonexistent. Interventions: A fine needle aspiration biopsy was performed, and histological examination revealed diffuse thymic hyperplasia. Outcomes: At the 1-year follow-up, the chest imaging studies showed resolution of the RTH. Lessions: An understanding of RTH after adrenalectomy as a treatment for cortisol-producing adrenocortical tumors is important for the prevention of unnecessary surgical intervention and therapy.

Background: Thymectomy improves clinical outcomes and decreases the need for medical treatment in patients with myasthenia gravis (MG). Aim: To describe the immediate and long-term results of extended transsternal thymectomy (ETT) in patients with MG. Material and Methods: A review of databases, surgical protocols, clinical records and interviews of patients subjected to extended transsternal thymectomy for MG between 1990 and 2016. Perioperative clinical characteristics, anticholinesterase treatment, immediate and remote surgical results were analyzed and patients were followed from one to 10years. Results: We studied 58 patients aged 35 ± 14years (72%) women. In the preoperative period, according to Osserman classification, nine patients (15,5%) were in grade I, eight (13,8%) in grade IIA 8 and 40 (69%) in grade IIB. The pathological study of the surgical piece showed thymic hyperplasia in 39 cases (67,2%). Four patients had postoperative complications but none died. In the Follow-up at 1, 3, 5, 8 and 10years the Masaoka palliation rate was 71.7, 77.5, 67.7, 70.0 and 70,6% respectively. The figures for remission rate were 13.0, 15.0,19.4, 35.0 and 35,3% respectively. The figures for Zielinski positive results were 79.6, 87.5, 87.1, 90.0 and 82,4% respectively. The DeFilippi score improved by 80.4, 87.5, 87.1, 90.0 and 82.4% respectively. The Myasthenia Gravis Foundation of America Post-Intervention State improved by 67.4, 77.5, 77.5, 75.0 and 70,6% respectively. Mean Myasthenia Gravis Activities of daily living (MGADL) and Myasthenia Gravis Quality of life scale 15 (MGQOL 15) were 1.65 and 6.31 respectively. Conclusions: In selected patients with MG, extended transsternal thymectomy in MG has good immediate and long-term results.

Background: Thymectomy improves clinical outcomes and decreases the need for medical treatment in patients with myasthenia gravis (MG). Aim: To describe the immediate and long-term results of extended transsternal thymectomy (ETT) in patients with MG. Material and Methods: A review of databases, surgical protocols, clinical records and interviews of patients subjected to extended transsternal thymectomy for MG between 1990 and 2016. Perioperative clinical characteristics, anticholinesterase treatment, immediate and remote surgical results were analyzed and patients were followed from one to 10years. Results: We studied 58 patients aged 35 ± 14years (72%) women. In the preoperative period, according to Osserman classification, nine patients (15,5%) were in grade I, eight (13,8%) in grade IIA 8 and 40 (69%) in grade IIB. The pathological study of the surgical piece showed thymic hyperplasia in 39 cases (67,2%). Four patients had postoperative complications but none died. In the Follow-up at 1, 3, 5, 8 and 10years the Masaoka palliation rate was 71.7, 77.5, 67.7, 70.0 and 70,6% respectively. The figures for remission rate were 13.0, 15.0,19.4, 35.0 and 35,3% respectively. The figures for Zielinski positive results were 79.6, 87.5, 87.1, 90.0 and 82,4% respectively. The DeFilippi score improved by 80.4, 87.5, 87.1, 90.0 and 82.4% respectively. The Myasthenia Gravis Foundation of America Post-Intervention State improved by 67.4, 77.5, 77.5, 75.0 and 70,6% respectively. Mean Myasthenia Gravis Activities of daily living (MGADL) and Myasthenia Gravis Quality of life scale 15 (MGQOL 15) were 1.65 and 6.31 respectively. Conclusions: In selected patients with MG, extended transsternal thymectomy in MG has good immediate and long-term results.

The familial occurrence of thymic pathology, even though rare, is widely reported in the literature and mainly concerns cases of familial autoimmune myasthenia gravis. Other less frequent cases of familial occurrence of thymoma, thymic carcinoid and thymic hyperplasia have been described. It seems that the familial occurrence is poorly recorded and thus its prevalence is underestimated. We report two families whose members presented different forms of thymic pathology and discuss the necessity of screening programs in family members of patients presenting a thymic lesion.

The mediastinum can present a surgical challenge for patients and their surgeons. In some situations, to obtain sufficient diagnostic tissue or to completely resect relatively small lesions requires sizeable incisions that can result in unnecessary pain and debility. Minimally invasive techniques have not consistently provided the needed angles of approach, dexterity within the confined space of the mediastinum, and the surgeon-directed visibility necessary to perform a thorough and safe procedure. The robotic surgery platform meets those demands. The special considerations for an efficient procedure are reviewed.

Background Myasthenia Gravis (MG) is caused, in approximately 80% of the patients, by autoantibodies against the nicotinic acetylcholine receptor (AChR). The disease is often associated with pathological changes of the thymus: thymic epithelial tumours are present in about 10–20% of the patients, while up to 80% of the patients with early disease onset have thymic hyperplasia. Folate metabolism is required for the production of DNA precursors and for proper DNA methylation reactions, and impaired folate metabolism has been often associated with cellular growth and cancer. Methods We investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C > T, MTR c.2756A > G, MTRR c.66A > G and TYMS TSER (a 28-bp tandem repeat in the 5′ promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR + MG patients. A total of 526 AChR + MG patients, including 132 patients with normal (involuted) thymus, 146 patients with thymic hyperplasia, and 248 patients with a thymoma were included in the study. Allele and genotype comparisons were performed among the three study groups, after correcting for multiple testing. Results The frequency of the TYMS TSER 3R allele was significantly higher in MG patients with thymic hyperplasia (P = 0.004), and the TYMS TSER 3R3R genotype was significantly associated with increased risk of thymic hyperplasia [OR 2.71 (95% CI: 1.34–5.47)]. Conclusions The 3R allele in the thymidylate synthase promoter enhancer region results in increased protein production, required for the synthesis of DNA precursors. The present study suggests that the TYMS TSER 3R allele increases the risk of thymic lymphoid hyperplasia in AChR + MG patients.