Is myasthenia gravis (MG) associated with cancer?

Myasthenia Gravis and Cancer Association

Yes, myasthenia gravis is significantly associated with cancer, particularly thymoma, which occurs in approximately 10-15% of myasthenia gravis patients. 1

Thymic Malignancies and Myasthenia Gravis

Thymoma Association

• One-third of patients with thymoma present with autoimmune disorders, with myasthenia gravis being particularly common in type AB, B1, and B2 thymomas 2
• Myasthenia gravis is present in:
  • 15% of type A thymomas
  • 20% of type AB thymomas
  • 40% of type B1 thymomas
  • 50% of type B2 and B3 thymomas
  • <5% of thymic carcinomas 2

Clinical Implications

• Approximately 30-50% of patients with thymomas have myasthenia gravis 2
• Before any surgical procedure, all patients suspected of having thymomas should have serum anti-acetylcholine receptor antibody levels measured to determine whether they have myasthenia gravis, even if asymptomatic 2
• In patients with myasthenia gravis, the disease should be medically controlled before surgical resection is performed 2

Extrathymic Malignancies

Prevalence and Risk

• Extrathymic malignancies are common in myasthenia gravis patients, with studies showing:
  • 15.4% of myasthenia gravis patients had extrathymic malignant tumors of various origins 3
  • 22.4% of myasthenia gravis patients developed extrathymic cancers in a nationwide Swedish register study 4

Types of Extrathymic Cancers

• Most common extrathymic cancers in myasthenia gravis patients include:
  • Skin cancer
  • Cancers of the male genital organs
  • Cancers of the female genital organs
  • Digestive organ cancers
  • Breast cancer 4

Risk Factors for Cancer in Myasthenia Gravis

• Older age at myasthenia gravis onset 3, 5
• Presence of thymoma 5, 4
• Immunosuppressive treatment, particularly with two or more corticosteroid-sparing immunosuppressants 4

Clinical Management Considerations

Diagnostic Approach

• The National Comprehensive Cancer Network recommends testing for anti-striated muscle antibodies alongside anti-acetylcholine receptor antibodies, particularly for detecting thymoma association 1
• Chest imaging (CT/MRI) is recommended to evaluate for thymoma, especially in acetylcholine receptor antibody-positive patients 1

Treatment Implications

• For patients with thymoma and myasthenia gravis:
  • Total thymectomy and complete surgical excision of the tumor are the gold standard of treatment 2
  • Myasthenia gravis should be medically controlled before surgery to avoid respiratory failure 2

Monitoring

• Patients with myasthenia gravis, especially those with thymoma or late-onset disease, should be monitored for the development of extrathymic malignancies 4
• Patients on immunosuppressive therapy may have an increased risk of certain cancers and require appropriate surveillance 4

Controversies and Conflicting Evidence

Interestingly, some studies suggest a potentially protective effect of myasthenia gravis against certain cancers:

• One study reported a significantly lower rate of extrathymic malignancies in patients with myasthenia gravis than in controls, particularly for colorectal cancer, breast cancer, and cancer in the upper digestive tract 6
• Another study showed that myasthenia gravis had a slight protective effect on overall survival in thymoma patients in univariate analysis, though this was not confirmed in multivariate analysis 7

These conflicting findings highlight the complex relationship between autoimmunity and cancer, suggesting that while certain cancers (particularly thymoma) are clearly associated with myasthenia gravis, the immune dysregulation in myasthenia gravis might potentially protect against other malignancies.