A 42-year-old female farmer presented with chest pain, breathlessness, hoarseness of voice, and double vision over the past 1 month. Imaging revealed a large cystic lesion in the left thymus. The thymus was surgically excised and found to have a multilocular thymic cyst with thymic hyperplasia. Laboratory tests confirmed myasthenia gravis. The patient was started on treatment for myasthenia gravis and the thymic cyst.
3. HOPI• c/o chest pain- 6 months
- intermittent
- left sided
- pricking
- not radiating
- not ass.with sweating/palpitation
- no aggravating/relieving factors
• c/o breathlessness- 1 month
- insidious
- gradually progressing
-not ass.with orthopnoea/PND
• c/o double vision - 1 month
- intermittent
- appears as the day advances
• h/o drooping of eyelids- past 1 month
- occasionally; after severe exertion or prolonged
exposure to sun light
• h/o LOA &LOW- lost 3 kgs over 2 months
4. No h/o
• Cough/hemoptysis
• Syncope
• Leg swelling
• Abdomial distension
• ↓ed urine output
• Dysphagia
• Headache/vomiting
• Difficulty in appreciating colours
• No other h/s/o cranial N abnormalities
• No h/s/o weakness/sensory abnormalities/cerebellar
involvement
5. Past history
• Not a k/c of HTN/DM/BA/PT/CAD
• No h/o sugeries/RT
• No h/o chronic drug intake
6. Personal history
• Married
• 2 children
• Normal regular menstrual cycles
• Taking mixed diet
• Non-smoker
• Non-alcoholic
7. General examination
• Conscious, dyspnoeic, oriented, afebrile
• No pallor/cyanosis/clubbing/icterus/pedal edema/SLA
• VITALS:
• BP- 130/90 mmHg
• PR- 90/min, regular, normal volume, no spl.characters
• RR- 22/min
• JVP- not raised
• Temp- 99F
8. Systemic examination- RS
• INSPECTION:
• Trachea app.to be in midline
• Apical impulse –not visible
• Chest movements- bilaterally equal
• No chest wall deformity
• No scars/sinuses
• No distended veins
9. • PALPATION:
• Trachea- midline
• Apical impulse- left 5th
ICS at MCL
• Chest movements –bilaterally equal
• Chest measurements- WNL
• No TF
• VF- ↓ed in left infraclavicular & mammary
regions
• No Intercostal tenderness
10. • PERCUSSION:
• Dullnote + in left infraclavicular & mammary
regions
• No percussion tenderness
• Traube’s space- normal tympanitic note +
11. • AUSCULTATION:
• Breath sounds ↓ed in left infraclavicular &
mammary regions
• VR ↓ed in the same regions
• Rhonchi + in the same regions
• No BBS
12. Other systems
• CVS- S1,S2 +, no murmurs
• P/A- soft, no organomegaly, no FF clinically
13. • CNS-
• HMFs- normal; MMSE- 26/30
• Cranial nerves- clinically normal
• Spinomotor system: Bulk- normal
Tone- normal
DTRs- brisk
Power- 4/5 in shoulder,
elbow, hip, knee
5/5 in wrist, ankle
sup reflexes- normal
plantar - ↓ ↓
• Sensory, cerebellar, autonomic- normal
• Spinum & cranium- normal
19. CXR PA
• A homogenous semi-rounded opacity of 8×3.5
cm, with well-defined border, in left midzone
• Silhoutted with most of the left cardiac border
• Trachea in midline
• Mediastinal widening
20. Chest Physician’s opinion
• CXR- left hilar mass lesion-
• ? Mediastinal mass- Anteriorly located
• Adv:
• CECT Chest
35. Contents of mediastina
Anterior mediastinum Middle mediastinum Posterior mediastinum
Thymus
Anterior group of
mediastinal lymph nodes
Internal mammary vessels
Heart
Ascending & transverse
aortic arches
Vena cavae
Brachio-cephalic vessels
Pulmonary vessels
Phrenic nerve
Trachea & main bronchus
Descending aorta
Esophagus
Thoracic duct
Azygous & hemi azygous
veins
Posterior group of
mediastinal lymph nodes
36. TUMORS IN MEDIASTINA
DIVISION OF MEDIASTINUM TUMORS
Anterior mediastinum Thymoma, lymphoma, teratoma &
thyroid masses
Middle mediastinum Vascular masses, lymph node
enlargements from metastases and
granulomatous diseases &
pleuropericardial and bronchogenic cysts
Posterior mediastinum Neurogenic tumors, meningoceles,
meningomyeloceles, gastro-enteric cysts
& esophageal diverticula
37. THYMOMA
Thymoma is a neoplasm of thymic epithelial
cells & excludes other tumors affecting the
thymus such as lymphoma & GCTs.
Most common tumor of anterior superior
mediastinum
43. Thymoma –Physician’s role
commonly encountered paraneoplastic syndromes
Myasthenia gravis
Pure red cell aplasia
Immunodeficiency
Lamber-Eaton myasthenic syndrome
44. Mechanism of paraneoplastic syndromes
in thymoma
Epithelial cells & other stromal tissues of thymus influence the
selection & maturation of T lymphocytes
dysregulation of this system
in thymoma
Dysregulation of the lymphocytes’ positive & negative selection
Abnormal proliferation, autoimmunity & immunodeficiency
Paraneoplastic syndromes
46. Lab studies
• CBC- anemia, thrombocytopenia,
granulocytopenia (in pure red cell aplasia)
• Peripheral smear study
• Quantitative immunoglobulin assay to r/o
immunodeficiency
• Anti ACh receptor antibodies/repititive nerve
stimulation tests/Edraphonium ameliorative
tests to r/o myasthenia gravis
• Bone marrow aspiration to r/o pure red cell
aplasia
47. Imaging studies
• CXR- mediastinal widening in PA views,
retrosternal opacification in lateral view
• CT Chest- to exclude or to characterize
thymoma; to detect morphology of the mass,
fat invasion, cysts, necrosis
• Oncotropic tracers- thallium, Tc99m
49. Pure red cell aplasia
• Occurrence in thymoma -5%
• Thrombocytopenia, granulocytopenia,
autoantibody formation
• 30% of patients resume normal hematopoiesis
after thymectomy
53. Myasthenia gravis
• Neuromuscular disorder characterized by
weakness & fatigability of skeletal muscles
• Underlying defect- ↓ in the no. of ACh
receptors at neuromuscular junction
54. Normal physiology at NMJ
ACh synthesized & stored in presynaptic vesicles
Released into synaptic cleft
(in calcium dependent manner)
Combines with binding sites on the AChR
In the post synaptic membrane
55. Channel in the AChR opens
Rapid entry of cation, chiefly Na+
Depolarization at the end-plate
Initiation of APs that is propagated along the
Muscle fiber
Muscle contraction
62. Clinical features
• Cardinal features are weakness & fatigability of
muscles
• Cranial muscles- lid & extra ocular muscles- involved
early
• Diplopia & ptosis – common initial symptoms
• Difficulty in chewing
• Slurred sppech
• Difficulty in swallowing with nasal regurgitation &
aspiration
• Proximal & asymmetric weakness
• Preserved DTRs
65. Anti AChR & MuSK antibodies
• Anti AChR Ab- Detected in 85% of generalized
MG patients & 50% of ocular MG patients
• Levels don’t correlate with severity
• Anti MuSK Ab -40% of Anti AChR Ab negative
patients with generalized MG patients
• Anti MuSK Ab – rarely present in AChR Ab +ve
patients & in ocular MG patients
66. Electrodiagnostic testing
• Anti AChE medication –stopped 24 hour
before
• Electric shocks delivered at a rate of 2-3/sec
to the appropriate nerves
• APs recorded from the muscles
• Decremental response- Rapid reduction of
>10% in the amplitude of evoked responses
67. Edraphonium (Tensilon) test
inj.atropine 0.6 mg iv
(sos) to treat
cholinergic crisis
2 mg
iv
Improvement in
strength of muscle
Test is positive
(test terminated)
8 mg
iv
If no change in
strength of muscle
Test is terminated
(independent of the result)
69. Myasthenia gravis LEMS
Postsynaptic disorder Presynaptic disorder
Auto antibodies directed against
AChR in post synaptic membrane
Auto antibodies directed against P/Q
calcium channels in presynaptic
membrane
Normal release of ACh from presynaptic
nerve terminals
Impaired release of ACh from presynaptic
terminals
Preserved DTRs Depressed or absent reflexes
No autonomic changes Autonomic changes +
Decremental response in repetitive nerve
stimulation test
Incremental response
Most commonly associated with
thymoma
Most commonly associated with Small
cell lung cancer
71. Anti cholineEsterase
• Pyridostigmine is most widely used drug
• Starting dose: 30-60 mg TID/QID
• Maximal dose: 120 mg QID
• Over doasage may cause increased weakness
or muscarinic effects
• Atropine
72. Glucocorticoides
• Starting dose: 15-25 mg/day
• Stepwise increase in dose: 5mg/day by 2-3
days interval
• Maximal dose: 60 mg/day
• Improvement within few weeks
• Maximal dose maintained for 3 months
• Changed to alternate day regimen for next 3
months
• Gradually tapered over months
73. Immunosuppressives
• Azathioprine is most widely used drug
• Dose range: 2-3 mg/kg
• Given in divided doses
• Synergistic therapeutic effect with
glucocorticoides & may decrease the need of
high dose of glucocorticoides
• Beneficial effects in 3-6 months
• Adverse effects:flu-like symptoms, BM
depression & Liver function abnormalities
74. Plasmapheresis
• 5 exchanges over a period of 2 weeks
• 3-4 L/exchange
• myasthenic crisis
• improving patients condition prior to surgery
(thymectomy)
Indications
75. IVIGs
• 2 gm/kg administered over 5 days
• 400 mg/kg/day
• myasthenic crisis
• improving patients condition prior to surgery
(thymectomy)
Indications
76. Thymectomy
• Surgical removal of thymoma- to prevent local
tumor spread
• Even in the absence of tumor, 85% of patients
with MG, improves after thymectomy;
• Of these, 35% achieve drug-free remission
• MG patients with Anti-MuSK antibody, may
not respond to thymectomy
77. Carry home messages…
• Abnormal thymus in MG may be thymoma or thymic
hyperplasia
• Medical disorders associated with abnormal thymus may
precede/with/succeed the onset of thymoma- follow up must
after thymectomy; immunodeficiency may occur many years
after thymus resection
• Even MG patients with normal thymus, 85% of patients
improve after thymectomy, of that 35% will achieve
drug-free remission
• Lone ocular myasthenia also associated with thymic
abnormality
• Anti MuSK Ab positive in 40% of Anti-AChR Ab negative MG
patients.