Thymoma, Myasthenia Gravis, and Other Paraneoplastic Syndromes
Section snippets
Myasthenia Gravis
Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission involving the production of autoantibodies directed against the nicotinic acetylcholine receptor. Acetylcholine receptor antibodies are detectable in the serum of 80% to 90% of patients with MG [5]. The prevalence of MG is about 1 in 10 to 20,000. Women are affected about twice as often as men. Symptoms may begin at virtually any age, with a peak in women in the second and third decades, while the peak in men occurs
Clinical Features
The hallmark of MG is fluctuating or fatigable weakness. The presenting symptoms are ocular in half of all patients (25% of patients initially present with diplopia, 25% with ptosis) and by 1 month into the course of illness, 80% of patients have some degree of ocular involvement [6]. Presenting symptoms are bulbar (dysarthria or dysphagia) in 10%, leg weakness (impaired walking) in 10%, and generalized weakness in 10%. Respiratory failure is the presenting symptom in 1% of cases. Patients
Diagnosis
The diagnosis is based on a history of fluctuating weakness with corroborating findings on examination. There are several different ways to validate or confirm the clinical diagnosis.
Prognosis: The Natural Course of the Disease
Appropriate management of the patient with autoimmune MG requires understanding of the natural course of the disease. The long-term natural course of MG is not clearly established other than this it is highly variable. Several generalizations can be made. About half of MG patients present with ocular symptoms, and by 1 month, 80% have eye findings. The presenting weakness is bulbar in 10%, limb in 10%, generalized in 10%, and respiratory in 1%. By 1 month, symptoms remain purely ocular in 40%,
First Line Therapy
Cholinesterase inhibitors (CEI) are safe, effective, and first line therapy in all patients [12]. Inhibition of acetylcholinesterase (AChE) reduces the hydrolysis of acetylcholine (ACh), increasing the accumulation of ACh at the nicotinic post-synaptic membrane. The CEIs used in MG bind reversibly (as opposed to organophosphate CEIs, which bind irreversibly) to AChE. These drugs cross the blood-brain barrier poorly and tend not to cause central nervous system side effects. Absorption from the
History
In 1899, Oppenheim [15] reported a patient with MG and a coexisting tumor of the mediastinum found at autopsy to be a lymphosarcoma. At the time, the significance of the association was unclear. In 1901, Leopold Lacquer [16] presented the clinical case of a 30-year-old man with MG who died after a 1-year illness. Pathologist Carl Weigert reported the autopsy findings and noted the presence of aspiration pneumonia and a normal central nervous system. A thymoma made up of epithelioid and lymphoid
Thymectomy
Ferdinand Sauerbruch [20] performed the first thymectomy in a patient with MG in 1911 in Zurich. The patient was a 2l-year-old woman with hyperthyroidism and MG, and the surgery was performed in an attempt to treat her thyroid condition. The thymus was found to be hyperplastic. Following surgery, the thyroid and the myasthenic symptoms both temporarily improved. Eventually, a thyroidectomy was performed, and again both conditions were said to improve. About the same time, Haberer [21] was
Corticosteroids
There are no controlled trials documenting the benefit of corticosteroids in MG. However, nearly all authorities have personal experience attesting to the virtues (and complications) of corticosteroid use in MG patients. In general, corticosteroids are used in patients with moderate to severe disabling symptoms, which are refractory to CEI. Patients are commonly hospitalized to initiate therapy because of the risk of early exacerbation. Opinions differ regarding the best method of
Alternative Immunosuppressive Drug Therapy
Mycophenolate mofetil (CellCept) is a purine inhibitor widely used in recent years for the treatment of MG. Anecdotal uncontrolled experience would suggest that about 75% of MG patients benefit from the drug, with the typical onset of improvement within 2 to 3 months [31], [32], [33]. In general, the drug is well tolerated and the typical dose in treating adults with MG is 1,000 mg by mouth twice a day. Two recently completed prospective controlled double blind trials [34], [35] failed to
Other Neurologic Paraneoplastic Syndromes
Patients with one autoimmune disease frequently have additional immune-mediated conditions. In patients with thymoma, 40% have one or more paraneoplastic autoimmune conditions [1]. About 10% to 15% of patients with thymoma have paraneoplastic conditions other than myasthenia gravis [2], [3]. Four to seven percent of myasthenic patients with thymoma have more than one paraneoplastic syndrome [2], [4]. The following is a discussion of thymoma-associated conditions that occur with and without
Myocarditis
Thymoma and myocarditis are most frequently reported in patients with polymyositis [74], [79] and myasthenia gravis [74], but this association has also been reported in isolation [80]. Autopsy examination of two patients with thymoma and myocarditis revealed diffuse degeneration of the myocardium, with infiltration of inflammatory giant cells [74], [81]. Activated T-cells appear to be important in the pathogenesis of myocarditis associated with thymoma [81].
Graft-Versus-Host Disease
GVHD is an autoimmune phenomenon
Acknowledgments
The authors would like to thank Phyllis Cowherd for her assistance in preparation of the manuscript.
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Poor responses and adverse outcomes of myasthenia gravis after thymectomy: Predicting factors and immunological implications
2022, Journal of AutoimmunityCitation Excerpt :Thymoma occurs more frequently in the elderly males but thymus hyperplasia in the young females, which may be corresponding to the two peaks of MG onset [2–4]. Among MG patients, about 10%–15% of them present with thymoma, while approximately 50%–70% are possessed of thymic hyperplasia containing proliferative germinal centers (GCs) [5]. Almost 80% of the individuals exhibiting thymic hyperplasia with GCs are female, and the extent of thymic follicular hyperplasia has a correlation with the titer of anti-AChR antibody (AChR-Ab) [6].
Recent thymic emigrants as the bridge between thymoma and autoimmune diseases
2022, Biochimica et Biophysica Acta - Reviews on CancerAn updated review on phenocopies of primary immunodeficiency diseases
2020, Genes and DiseasesIncreased Galectin-1 Expression in Thymic Epithelial Tumors
2019, Clinical Lung CancerCitation Excerpt :Galectin-1 has been shown to induce apoptosis in human thymocytes.19 Galectin-1 inhibitors are currently in development, and targeting thymic cancers by galectin-1 inhibition may be a promising therapeutic strategy in thymic malignancies.18,20 After obtaining approval from the institutional review board of Stanford University School of Medicine and the Scientific Research Committee at Stanford Cancer Institute, 68 patients with a pathologic diagnosis of thymic carcinoma or thymoma and 8 benign thymus controls with pathology were identified.