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.