Thymomas in myasthenia gravis MG are neoplasms derived from thymic epithelial cells, and are usually of the cortical subtype WHO type B [ 1 ]. Cortical thymomas usually have some morphological similarities with thymic cortex; they share the capacity to propagate the maturation of immature naive CD4 T cells and export mature naive T cells into the periphery.
Thymomas lacking this ability do not induce MG [ 4 ]. Thymomas with histological similarities to medullary thymic tissue or thymomas lacking developing T cells are seldom associated with MG [ 4 ]. Histologically, thymomas are epithelial neoplastic cells surrounded by maturing T cells. The epithelial cells are capable of expressing epitopes cross-reactive with skeletal muscle proteins, such as acetylcholine receptor AChR , titin, and ryanodine receptor RyR [ 6 , 7 ].
The muscle-like epitopes are presented to T cells together with costimulatory molecules [ 7 ]. Thymoma epithelial cells present AChR peptides to T-cell lines in thymoma MG patients, facilitating intrathymic immunization [ 9 ]. The chance of having a thymoma increases with the number of thymoma-associated polymorphisms in an MG patient, indicating that thymoma MG is a polygenic disease and that thymoma patients with a particular genetic profile run higher risk of developing MG [ 11 ].
When MG occurs together with a thymoma, MG is a paraneoplastic disease caused by the presence of the thymoma. The immune response against an epitope expressed on thymoma cells spills over to neuromuscular junction components sharing the same epitope [ 14 ].
In thymoma MG, epitopes are shared between the thymoma and muscle proteins. AChR antibodies are the main cause of muscle weakness in thymoma MG [ 15 ]. These antibodies are usually associated with more severe MG [ 13 , 17 — 19 ]. Striational antibodies demonstrated in immunofluorescence are largely made up of titin antibodies [ 20 ].
Myositis and myopathy with muscle atrophy are seen in some thymoma MG patients [ 22 ]. Sera from MG patients also induce degenerative changes in muscle cell cultures where both apoptosis and necrosis are implicated [ 23 ]. The RyR is the calcium channel of the sarcoplasmic reticulum SR. There are also several reports of excitation-contraction coupling defects in thymoma MG [ 26 ]. MG patients with RyR antibodies are characterized by frequent involvement of bulbar, respiratory, and neck muscles at MG onset and a more severe disease.
Neck weakness at MG onset is a distinctive feature of patients with RyR antibodies, while respiratory symptoms are also found in patients with titin antibodies with and without RyR antibodies. Since many thymoma MG patients have RyR antibodies, neck weakness and nonlimb bulbar distribution of MG symptoms are initial characteristic features associated with thymoma MG. Such symptom distribution should always raise the suspicion about the presence of a thymoma in an MG patient. Thymoma MG is equally frequent in males and females and occurs at any age with a peak onset around 50 years [ 28 ].
Late MG onset age, similar serological profile, favorable pharmacological treatment response, severe MG, frequent use of immunosuppressive drugs, and the occurrence of MG related mortality are common features among thymoma MG and late-onset MG patients [ 29 ].
This profile differs from early-onset MG [ 30 ], that has higher AChR antibody concentrations, almost no titin or RyR antibodies, low need for immunosuppressive drugs, less severe MG, very low MG mortality rates, and a favorable thymectomy outcome [ 29 ].
Thymoma MG tends to be more severe than early-onset nonthymoma MG [ 29 ]. In one study, MG patients with thymoma or thymic atrophy i. The presence of a thymoma per se does not give a more severe MG. The presence of titin and RyR antibodies is associated with more severe disease in thymoma MG and in late-onset MG [ 29 ]. The diagnosis of MG is based on clinical disease history and typical clinical findings. These antibodies are present in virtually all patients with a thymoma [ 29 ]. In two thirds of MG patients, failure of neuromuscular transmission in leads to decremental response to repetitive nerve stimulation by electromyographical EMG examination [ 34 ].
Increased jitter on single-fiber EMG is even more sensitive than repetitive nerve stimulation when performed on affected muscles [ 34 ]. In addition to MG, a thymoma should be demonstrated in order to fulfill the criteria of thymoma MG diagnosis. The diagnosis of a thymoma in MG is finally established by histopathological examination postsurgery.
Titin and RyR antibodies and radiological examination of the anterior mediastinum share similar sensitivity for the presence of a thymoma in MG [ 29 , 35 , 36 ]. However, the presence of titin and RyR antibodies in a MG patient younger than 60 years strongly suggests a thymoma, while the absence of such antibodies at any age strongly excludes thymoma [ 13 , 37 ].
Retesting for these antibodies and a new radiological examination should always be considered whenever clinical deterioration is seen over time, to minimize the risk of a previously undetected thymoma in a MG patient. When the diagnosis of a thymoma in a MG patient is established, the neoplasm should be removed surgically, and it is crucial to ensure radical excision of the neoplasm.
Thymectomy can be performed transternally or through a video-assisted thoracoscopic approach, usually with similar outcome [ 38 ]. Radical excision of a thymoma does in most cases cure the thymic neoplasia, but patients will continue to suffer from MG after thymectomy, emphasizing the need of continuing followup and pharmacological treatment. When the thymoma invades the pleura or the pericardium, radical excision will not be possible and further oncological treatment is necessary. Presurgery plasmapheresis or intravenous infusion of immunoglobulin iv-IgG removes a great deal of circulating pathogenic antibodies [ 36 ].
In our department we give plasmapheresis or iv-IgG treatment to all patients with thymoma MG prior to thymectomy, to minimize the risk of postthymectomy MG exacerbation and myasthenic crisis. This practice varies however from department to another, and there is no consensus on this issue. Iv-IgG should be considered as first choice in patients at high risk of developing cardiopulmonary failure secondary to fluid overload caused by plasmapheresis [ 39 ].
The diagnosis of myasthenia gravis is made by learning the patient's symptoms and doing specialized blood tests. Also, several special electrical tests on muscles and nerves called electromyography EMG can be performed. At Penn, we have several clinical laboratories that do a super-specialized test called a single fiber electromyography SFEMG.
Thymic abnormalities are most frequently identified on a CT scan. This type of study can sometimes be helpful in distinguishing thymoma from lymphoma. We usually don't perform biopsies, in part because the scans and the clinical situation may be highly suggestive, and in part because thymomas reside in a location that's challenging to access. The sternum often blocks access for a needle biopsy, and with the proximity of the heart and great vessels, it can be difficult to safely obtain biopsy specimens.
If the mass or tumor is large, it may be easier to perform a biopsy. The Penn Myasthenia Gravis and Thymoma Program was developed to treat patients with myasthenia gravis MG and thymoma, which are often comorbid disorders. Because these diseases are related and can be complicated to treat, they require multiple specialists. We created the program to coordinate care across specialties in the management of these patients.
The team is comprised of neurologists, thoracic surgeons, radiologists, ophthalmologists and many others specialists, who together will develop a comprehensive treatment plan for your condition.
To improve the muscle weakness caused by myasthenia gravis, we provide medicines to suppress the immune system. In addition to pills, there are several kinds of emergency treatments that are available for people who are short of breath or are having trouble swallowing. These include intravenous gamma globulin IVIG and plasma pheresis.
At Penn, we also have clinical trials for patients with a severe disease who are not responding to conventional treatments.
Revision received:. Select Format Select format. Permissions Icon Permissions. Thymoma , Myasthenia gravis , Thymectomy , Remission rate , Survival. Open in new tab Download slide. Survival according to the WHO histological classification of thymomas. Survival according to the Masaoka staging of thymomas. Survival according to the neurological outcome. Cox-proportional regression of overall survival. Cox proportional regression of complete remission. Google Scholar Crossref.
Search ADS. Studies in myasthenia gravis: review of a twenty-year experience in over patients. Google Scholar PubMed. Thymoma and myasthenia gravis: a clinical study of patients from Japan. Thymectomy in myasthenia gravis: results of cases operated upon in 15 years. Myasthenia gravis: recommendations for clinical research standards. Extended thymectomy in myasthenia gravis: a team-work of neurologist, thoracic surgeon and anaesthesist may improve the outcome.
Histological typing of tumours of the thymus. International histological classification of tumours. Follow-up study of thymomas with special reference to their clinical stages.
Advanced stage thymomas and thymic carcinomas: results of multimodality treatments. Neurologic outcomes of thymectomy in myasthenia gravis: comparative analysis of the effect of thymoma. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of patients. Outcomes after extended transcervical thymectomies for myasthenia gravis.
Issue Section:. Download all slides. View Metrics. Email alerts Article activity alert. Advance article alerts. New issue alert. Subject alert. Receive exclusive offers and updates from Oxford Academic. More on this topic A microthymoma and no germinal centre in myasthenia gravis.
Impact of minimally invasive trans-cervical thymectomy on outcome in patients with myasthenia gravis. In the current paper, for the identification of thymoma malignancy, its invasiveness was adopted as the most significant factor From a histologic point of view criteria for the identification of thymoma malignancy are poor, the spreading of metastases is rare and in general takes place in the pleura and lungs 13,23, In most cases thymomas start in the thymic site and exceptionally develop in an ectopic site such as the lung Diagnosis of thymomas is reached at by clinical examination and ACT supported by immunologic tests 3,5,8,9, Using such procedures most thymomas are detected prior to surgery Immunologic assays may lead to suspect thymoma even prior to X-rays detection 3,4,8.
This is possible because of the high incidence of both antibodies anti-receptors such as anti-AChR and anti-ryanodine as well as antibodies against proteins antigens of skeletal muscle, in TMG ,8, This test is highly sensitive and specific for TMG diagnosis.
Most of the authors 2,4,5,7,15,34 agree that TMG prognosis is poorer than that for non thymomatous MG. However, early surgery with total excision of tumor and current MG management protocols have partially changed such prognosis, permitting SI and even CR of MG, especially in younger patients submitted to early surgery, as this series has proven.
Recurrence of thymoma is rare and does not alter prognosis 13, No recurrent tumors were recorded in the present series. Numerous efforts have been made to correlate prognosis to histopathology or with associated diseases that would be more frequent in TMG 35, In conclusion, TMG has a relatively favorable prognosis with regard to the survival rate. Such prognosis depends mainly on the thymoma characteristics; if invasive or not, on its total and early excision, on MG response to treatment and to an eventual associated pathology.
In the series under study the number of patients requiring long term management with steroid immunosuppressants was significantly high. Some authors 37 recommend RT in all patients with invasive thymomas and, also in those with a non excisable tumor. Others 15 use this therapeutic approach almost exclusively when the tumor has not been totally excised.
Bernatz et al. Such association is considered the best treatment strategy for invasive thymomas How we did not show any differences about morphologic and histologic changes in TMG and TWMG, is possible that the development of MG can depend on the presence of protein p Kd antigen in epithelial cells of cortical and well-differentiated thymomas associated myasthenia gravis Paulo E. Eneas C. Abrir menu Brasil. Arquivos de Neuro-Psiquiatria.
Abrir menu. Myasthenia gravis. Philadelphia: Saunders, Thymomas express epitopes shared by the ryanodine receptor. J Neuroimmunol ; Disorders of the neuromuscular junction. In Rowland LP. Merritt's textbook of neurology. Myasthenia gravis and thymoma. In Lisak RP. Handbook of myasthenia gravis and myasthenic syndromes. New York, Newsom-Davis J.
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