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Myasthenia Gravis: Other associations

Genetic
  AChR
  HLA
  PTPN22
  TNF
Inflammatory myopathy
  BCIM
  Myositis
Other antibodies
Pregnancy
Striational antibodies
Systemic disorders
Thymus
  Size changes
  Thymoma
 
Thymoma in patient with Myasthenia Gravis
Chest X-ray: Right anterior mediastinal mass


Thymoma

  • Thymoma: General
    • Definition: Neoplasm of epithelial cells of thymus
    • Location
      • Anterior mediastinum: 90%
      • Most common anterior mediastinal mass in adults (20% to 50%)
    • Age
      • Most common in 4th to 6th decades
      • Uncommon in children
    • Male = Female
    • Prognostic features
      • Invasive (35%): Poorer prognosis
      • Non-Invasive (Encapsulated; 65%): Better prognosis
      • Thymic carcinoma: Poor prognosis
    • Treatments
      • Stage 1 (Encapsulated)
        • Tumor resection
      • Stage 2 (Macroscopic invasion into capsule, fat or pleura)
        • Tumor resection
        • Then Irradiation
      • Stage 3 (Macroscopic invasion into neighboring organs)
        • Neoadjuvant Chemotherapy
        • Tumor resection
        • Irradiation
        • Consolidation Chemotherapy
  • Thymoma: Associated Paraneoplastic syndromes (PNS) 23
  • Thymoma: Associated autoantibodies 9
    • Anti-AChR antibody (Binding) association
      • Patients with MG and thymoma: Frequency = 95% to 100%
      • Thymoma without clinical MG
        • Other associated neurological disorders: 50%
        • No associated neurologic disorders: 30%
    • Striational: Titin
    • Ryanodine receptor
    • KCNA4
    • Glutamic acid decarboxylase
      • Frequency: 22%
      • Higher with associated neurological syndromes
    • Hu (Antineuronal nuclear antibody-type 1 (ANNA-1))
    • CASPR2
    • DCC
    • Lgi1
  • Thymoma types: Lymphoepithelial
    • Noninvasive thymoma
      • Almost all are > 25 years old
      • Most common: 5th to 6th decade
      • Calcification in 5-20%
    • Invasive thymoma
      • Metastasis to pleura and lungs (6%); rarely extrathoracic
  • Thymic tumors & Myasthenia gravis
    • Frequency
      • Most common thymoma paraneoplastic syndrome
      • 25% to 40% of Thymomas
      • Serum: Nicotinic AChR antibodies (99%) 15
      • Thymoma in MG
        • 7% to 15% of MG patients
        • Mostly in MG patients > 30 years
      • MG: Frequency varies with thymoma type
        • Thymomas + MG: Usually composed of cortical cells
        • Other thymomas
          • Mixed pattern
          • More undifferentiated malignancy
      • Tumor type relations
        Tumor Spread MG
        frequency
        Cortical ++ +++
        Well differentiated +++ +++
        Medullary - +
        Mixed - ++
        Undifferentiated +++ -
    • Myasthenia gravis + Thymoma: Clinical 25
      • Similar to other AChR-Ab+ MG
      • May be: More Severe; Difficult to treat; Worse prognosis
      • May be associated with: Other paraneoplastic disorders
      • Thymoma recurrence: May be related to transient MG worsening
      • Non-resectable thymoma: MG may be more severe
      • No HLA association identified
      • MG Prognosis better 24
        • AChR antibody: Positive
        • Thymic follicular hyperplasia
        • Non-recurent neoplasm
        • No relation to tymoma tissue subtype
    • Muscle pathology: Increased frequency of lymphorrhages
  • Clinical work-up
    • Computed tomography scan of the thorax
      • Performed to look for thymoma in MG patients aged ≥ 20 years
    • MRI examinations of the chest
      • More expensive
      • Not clearly superior
  • Therapeutic implications
    • Removal of thymoma: Trans-sternal approach
    • MG: ? More difficult to manage after thymoma removed


Thymoma (Anterior mediastinal mass)
in patient with Myasthenia Gravis
  

Bell 1917

Thymic size changes


Anti-striational antibodies 16


Myasthenia Gravis: Other antibodies


Myasthenia Gravis & Systemic disorders


Acquired MG: Genetic Associations 1, 2

AChR
HLA
Other
PTPN22
TNF


    Familial recurrence risk

    Acetylcholine receptor

    HLA: Myasthenia Gravis associations 7


Acquired MG: Other genes



HLA molecules

HLA disease associations
HLA-B27 Reiter's
Ankylosing spondylitis
HLA-DR4 Rheumatoid arthritis
Sjögren's syndrome
Giant Cell Arteritis
Lyme arthritis
HLA-DR3 SLE
Dermatomyositis
CREST
HLA-B8 Myasthenia Gravis
Grave's disease
Chronic active hepatitis
HLA-A3 Multiple sclerosis
Hemochromatosis


Return to Myasthenia

References
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19. Acta Neurol Scand 2012 Jun 23
20. J Neurol 2012;259:1290-1297
21. Hum Immunol 2013 Aug 7
22. J Clin Neurosci 2017 Mar 2
23. J Thorac Cardiovasc Surg 2019 Dec 2
24. Muscle Nerve 2021 Mar 6
25. Eur J Neurol 2021 Mar
26. J Cachexia Sarcopenia Muscle 2021 Mar 26

3/28/2021