Neuromuscular

Home, Search, Index, Links, Pathology, Molecules, Syndromes,
Muscle, NMJ, Nerve, Spinal, Ataxia, Antibody & Biopsy, Patient Info

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

Thymus: Size & Other 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 27

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
1. J Neuroimmunol 1996;65:125-131, Biomed Res Int 2013;2013:404053
2. J Autoimmunity 1997;10:407-413
3. Neurology 1999;52:447-452, Neuromuscular Disorders 2017; Online Feb, Eur J Neurol 2023 Oct 16
4. Neurology 2001;57:1579-1582, Neurology 2002;59:92–98, J Neuroimmunol 2016;292:108-115
5. Neurology 2001;57:1555-1560
6. Eur J Haematol 2002;69:318–320
7. J Autoimmunity 2003;21:105–110
8. Neurology 2004;62:1894–1896, Arch Neurol 2000;57:527-531, Eur J Neurol 2007;14:617-620
9. Clin Cancer Res 2004;10:7270–7275
10. Rheumatology (Oxford) 2005; Sep 27
11. Proc Natl Acad Sci U S A. 2004;101:15464-15469
12. Genes Immun 2009 Aug 20
13. Journal of Neuroimmunology 2009; Online November
14. Ann Neurol 2010;67:726-738
15. J Neurol Sci 2011 Jan 12
16. Autoimmune Dis 2011;2011:740583
17. European Journal of Neurology 2012; Online Jan
18. Mult Scler 2011 Dec 19
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
27. Ann Neurol 2021 Jul 19
28. J Med Genet 2021 Aug 16
29. Mod Pathol 2022 Mar 25
30. J Neurol 2022 Nov 16

11/18/2022