a case of mediastinal mass
TRANSCRIPT
PHYSICIANS’ MEET
An interesting caseof Thoracic mass
Prof.S.SUNDAR’s unit,Dr.N. Arun Kumar, PG
Case scenario
Indra 42/F, farmer, thiruvallur,c/o chest pain- 6 monthsc/o breathlessness- 1 monthc/o hoarseness of voice- 1 monthc/o double vision - 1 month
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
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
Past history
• Not a k/c of HTN/DM/BA/PT/CAD• No h/o sugeries/RT• No h/o chronic drug intake
Personal history
• Married• 2 children• Normal regular menstrual cycles• Taking mixed diet• Non-smoker• Non-alcoholic
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
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
• 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
• PERCUSSION:• Dullnote + in left infraclavicular & mammary
regions• No percussion tenderness• Traube’s space- normal tympanitic note +
• AUSCULTATION:• Breath sounds ↓ed in left infraclavicular &
mammary regions• VR ↓ed in the same regions• Rhonchi + in the same regions• No BBS
Other systems
• CVS- S1,S2 +, no murmurs• P/A- soft, no organomegaly, no FF clinically
• 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
PROVISIONAL DIAGNOSIS
? Myasthenia gravis? Mediastinal mass
? Lung mass
Rx
• Nasal O2• Back rest• Antibiotics• Bronchodilators• Analgesics
InvestigationsCBC VALUES
Hb 11.6 gm%
TC 7,600 cells/cu.mm
DC P60, L37, E3
ESR 4/10
PLATELETS 1.6 lakhs
RBCs 4.1 million/cu.mm
PCV 34
MCV 86.2
MCH 30.1
MCHC 34.2
• RBS- 160 mg%• Blood urea- 20mg%• Serum creatinine- 0.8mg%• Peripheral smear study- normal
• ECG- NSR/WNL• Echo- normal study
CXR PA
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
Chest Physician’s opinion
• CXR- left hilar mass lesion-• ? Mediastinal mass- Anteriorly located• Adv:• CECT Chest
Scanogram
CT Chest
CT Chest
CT chest
Chest CT
• Thymic cyst • Suggested -HPE
Cardiothoracic surgeon’s opinion
• Mediastinal mass• ? Thymoma• ? Thymic cyst • Plan : excision & Bx
• Huge cyst noted in left lobe of thymus• Left lobe excised• Sent for Bx
Histopathological diagnosis
• Multilocular thymic cyst, with• Thymic hyperplasia
Anti AChR antibody
Repititive Nerve Stimulation test
• Nerve tested: Facial nerve• Result: Decremental response noted in
orbicularis oculi
Final diagnosis
Multilocular Thymic Cyst with Thymic HyperplasiaMyasthenia Gravis
Rx added
• Tab. Pyridostigmine 30 mg TID• Tab. Prednisolone 25 mg OD & stepping up
the dose• Tab. Azathioprine 50 mg BD
Indra 42/f
Approach to mediastinal masses
Contents of mediastinaAnterior 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
TUMORS IN MEDIASTINADIVISION 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
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
Sex distribution in thymoma
Age
• Most patients >40 years• Rare in children & adolescents; but aggressive
•Myasthenia gravis•Pure red cell aplasia• Neutrophil hypoplasia• Pancytopenia• Cushing’s syndrome• Carcinoid syndrome• DiGeorge syndrome• Lambert-EatonSyndrome• Nephrotic syndrome
•SIADH• Whipple’s disease• Lupus erythematosis• Pemphigus• Scleroderma• Polymyositis• Polyneuritis• Polyarthropathy• Addison’s disease• Hypogammaglobulinemia
Thymoma –Physician’s rolecommonly encountered paraneoplastic syndromes
Myasthenia gravisPure red cell aplasiaImmunodeficiencyLamber-Eaton myasthenic syndrome
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
Presentation in thymoma
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
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
Procedures
• Imaging guided FNAC/Biopsy of the mass lesion
Pure red cell aplasia
• Occurrence in thymoma -5%• Thrombocytopenia, granulocytopenia,
autoantibody formation• 30% of patients resume normal hematopoiesis
after thymectomy
Immunodeficiency
• Hypo/agammaglobulinemia • Thymoma – in 10% of hypo-
gammaglobulinemia cases• Combined humoral & cell-mediated
immunodeficiency• May occurs several years after thymoma
resection
Thymoma & Myasthenis Gravis
Myasthenia gravis
• Neuromuscular disorder characterized by weakness & fatigability of skeletal muscles
• Underlying defect- ↓ in the no. of ACh receptors at neuromuscular junction
Normal physiology at NMJACh 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
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
Pathophysiology
Anti- muscle specific kinase (Anti-MuSK) antibodies
Interfering with AChR clustering
Myasthenia Gravis
Prevalence of MG
• 1-7/10,000
Age
• Women – 20s & 30s• Men – 50s & 60s
Sex distribution(F:M=3:2)
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
Lab testing
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
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
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)
Differential Diagnoses of MG
• Congenital myasthenic syndromes (CMS)• Drug induced myasthenia• Lambert-Eaton myasthenic syndrome (LEMS)• Neurasthenia• Hyperthyroidism• Botulism• Intracranial mass lesion• Progressive external ophthalmoplegia
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
Treatment
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
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
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
Plasmapheresis
• 5 exchanges over a period of 2 weeks• 3-4 L/exchange
• myasthenic crisis• improving patients condition prior to surgery
(thymectomy)
Indications
IVIGs
• 2 gm/kg administered over 5 days• 400 mg/kg/day
• myasthenic crisis• improving patients condition prior to surgery
(thymectomy)
Indications
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
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.