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Thymic tumour Highlights

SummaryOverview

Basics

Definition

Epidemiology

 Aetiology

PathophysiologyClassification

Diagnosis

History & examination

Tests

Differential

Step-by-stepCriteria

Guidelines

Case history

Treatment

Details

Step-by-stepGuidelines

Follow Up

Recommendations

Complications

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Prognosis

Resources

References

ImagesPatient leaflets

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History & exam

Key factors• myasthenia gravis• muscle weakness• facial and upper extremity oedema• facial plethora• distended veins in the neck, chest, and/or 

abdominal wall• left-arm swelling

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Other diagnostic factors• cough• dyspnoea• fever and/or weight loss

History & exam details

Diagnostic tests

1st tests to order •

chest x-ray• chest CT with intravenous contrast

Tests to consider • chest MRI• tissue biopsy• acetylcholine receptor antibodies• FBC

Emerging tests• PET/CT scan

Diagnostic tests details

Treatment details

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Acute

resectable tumour 

• surgery• postoperative radiotherapy• with myasthenia graviso medical optimisation pre-surgery

locally advanced tumour 

• preoperative chemotherapy ± radiotherapy• re-assessment followed by surgery or 

radiotherapy• postoperative radiotherapy or chemoradiotherapy• with myasthenia graviso medical optimisation pre-surgery

Ongoing

recurrent tumour 

• chemotherapy• surgery and/or radiotherapy• with myasthenia graviso medical optimisation pre-surgery

Treatment details

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Summary• The most common anterior mediastinal tumours

in adults.

•

Thymomas account for the vast majority of thymicneoplasms and are often associated with myastheniagravis.

•  About 50% of thymic tumours are diagnosed onincidental finding. A chest CT with intravenouscontrast is usually diagnostic.

•

Small encapsulated tumours are resected for both pathological diagnosis and treatment.Unresectable tumours are usually treated withinduction therapy (chemotherapy ± radiotherapy)followed by reassessment for surgery. Patients withmyasthenia gravis should have their myastheniaoptimised before surgery.

• Thymomas are relatively indolent tumours withhigh cure rates. Prognosis depends on Masaoka'sstage, WHO histology, and resection status.

DefinitionThymic tumours are rare, [1]  although they are the most common anterior mediastinal tumours in adults. Thymomas account for the majority of thymicneoplasms. Common presenting symptoms include chest discomfort, cough,

and muscle weakness involving ocular, facial, oropharyngeal and respiratory,and/or limb muscles due to associated myasthenia gravis. [2] However, about50% of thymic tumours are diagnosed as an incidental finding.

EpidemiologyThe relative prevalence of the WHO histological types of thymic tumour are:

 A: 8%; AB: 26%; B1: 6%; B2: 19%; B3: 10%; C: 13%. [5]  Most patients

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present with early stage tumours (Masaoka's stage I: 49%; stage II: 22%);about one third present with advanced thymomas (Masaoka's stage III: 19%;stage IVA: 7%; stage IVB: 3%). [5]  [2]  Collected case series from around theworld show that the WHO histological classification and Masaoka's stage aresimilar at time of presentation.

Thymomas are rare tumours, with an annual incidence of 0.15 cases per 100,000 person-years, based on data from the US National Cancer InstituteSurveillance, Epidemiology and End Results Program. [1]  Men and womenare affected equally. [2]  [7]  [8]  [9]  Thymomas have been reported in infantsand also in the very old. The mean age at diagnosis is about 50 years, with apeak broad range between 35 and 70 years. The prevalence of myastheniagravis in the thymoma population is about 30%; 10% to 15% of patients withmyasthenia gravis have an associated thymoma. [2]  These patients tend topresent at a slightly younger age.

Thymic carcinomas occur less frequently than thymomas but there are noreliable incidence data. [2]  [9]  The age distribution is broad, ranging fromearly childhood to adulthood, with a mean age of 46 years. These tumoursare slightly more common in men than in women (male-to-female ratio is1.5:1.0). Most patients present with advanced-stage thymic carcinoma.Myasthenia gravis and other parathymic syndromes are only rarelyassociated with thymic carcinoma.Thymic carcinoid (neuro-endocrine) tumours are an extremely rarehistological subtype, with only about 200 cases reported. [9]  [10]  Again, all

age groups may be affected. The male-to-female ratio is 3:1. About 30% of patients with thymic carcinoid tumours have associated Cushing's syndrome.Myasthenia gravis and other parathymic syndromes are not associated withcarcinoid tumours. The carcinoid syndrome has only rarely been reported inrelation to thymic carcinoid tumours.

AetiologyThe aetiology of thymic tumours is unknown. The only reliable risk factor ismyasthenia gravis.

PathophysiologyLarge or invasive thymomas may compress or invade mediastinal or chestwall structures, causing chest pain or cough. Invasive thymomas can involvethe phrenic nerve, causing marked dyspnoea, particularly when supine.

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Rarely, superior vena cava (SVC) syndrome occurs due to compression or invasion of the SVC by the tumour or as a result of a tumour thrombus.

Many immune-related disorders have been associated with thymomas: mostcommonly, myasthenia gravis. [6]  Patients with myasthenia gravis haveantibodies directed against the acetylcholine receptor of the neuromuscular 

 junction, resulting in muscle weakness. Other rare associations include red-cell aplasia, hypogammaglobulinaemia, polymyositis, systemic lupuserythematosus, rheumatoid arthritis, thyroiditis, and Sjögren's syndrome.

ClassificationWHO histological classification [3]  [4] [5]

Thymoma (the majority of thymic tumours)

• Type A: medullary, spindle cell

• Type AB: mixed

•

Type B1: predominately cortical, organoid

• Type B2: cortical

• Type B3: well-differentiated thymic carcinoma,squamoid.

Thymic carcinoma (also known as type C thymoma)

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• Tumours with low malignant potential includewell-differentiated squamous cell carcinoma, basaloidcarcinoma, and muco-epidermoid carcinoma.

• Tumours with more aggressive malignantpotential include high-grade lympho-epithelial-likecarcinoma, undifferentiated/anaplastic carcinoma,and small-cell, sarcomatoid, and clear-cellcarcinomas.

Neuro-endocrine carcinoma

• Carcinoid

•  Atypical carcinoid.

MonitoringPatients should be followed up regularly after treatment. Thymomas are lessaggressive and tend to recur later than other thymic tumours, sometimesmore than 10 years after treatment. Therefore, at least 10-year, if not lifetime,follow-up is required. [2]  [1]  [8]  [9]  [34]  Most clinicians use an annual chest CTto monitor low-risk thymoma patients. Locally advanced thymomas treatedwith multimodality therapy require more intensive follow-up and are generallyimaged at least every 6 months. Thymic carcinomas are more aggressive

and recur earlier than thymomas. Closer monitoring, with follow-up imagingevery 4 to 6 months, is therefore usually recommended.

Patient InstructionsPatients should be advised to report any likely symptoms of recurrencepromptly. Local recurrence symptoms can include chest pain, dyspnoea,

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cough, and oedema of the face and upper extremities (suggesting superior vena cava syndrome). Distant recurrence symptoms may include weight loss,fatigue, fever, bone pain, and headaches.

ComplicationsComplicationhide all

myasthenia gravis developing after thymoma resection

see our comprehensive coverage of Myasthenia gra Although rare, patients without a preoperative diagn

been known to develop the disease after thymoma rcounterintuitive, however, as thymectomy is an accegravis.

superior vena cava syndrome

see our comprehensive coverage of Superior vena c

 Although rare, can occur due to extrinsic tumour comintravascular tumour thrombus.

Clinical features include facial and upper-extremity odistended veins in the neck and chest wall, and occa

CT scan with intravenous contrast will confirm the di

Symptom resolution is achieved by treating the unde

true second cancer 

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Patients who have undergone resection of a thymomrisk of developing a second cancer, with colorectal ccommon. [1]  [45] 

PrognosisPrognosis depends on Masaoka's stage, WHO histology, and whether resection was complete. Additional prognostic factors include tumour sizeand invasion of great vessels. [2]  [8]  [9]  [34] 

Clinically encapsulated thymomaMost series of resected thymomas have a 10-year thymoma-related survivalrate of 70% to 90%. [2]  [8]  [9]  [34]  The Masaoka's stage is the most importantprognostic factor. In the largest surgical series, the 5-year survival rates were:100% for stage I, 98% for stage II, 88% for stage III, 70% for stage IVA, and52% for stage IVB. [9] 

Other thymic neoplasmsPoorly differentiated thymic carcinomas generally have a poor prognosis.Overall cure rates for neuro-endocrine tumours are low.

Differential diagnosis

Condition

Differentiating

signs/symptoms Differen

Lymphoma• History of 

persistently enlargedlymph nodes,constitutional or B

• ChePerilymp

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symptoms (fevers,night sweats, and/or weight loss).

Physical examinationrevealslymphadenopathy inone or more regions;hepatosplenomegalymay be present.

Mediastinal germ cell

tumour: seminoma• Occurs in people

aged 20 to 40 years,with malepredominance.

• Presentingsymptoms dependon tumour location,growth rate, andsize; they includechest pressure,

hoarseness, chestwall pain, dysphagia,and dyspnoea.

• Chemali

• Seru

of se

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90% of patients;substernal extensionis suggested if the

lower pole of thethyroid gland cannotbe identified. Airwaycompression maypresent with stridor and prolonged

inspiration/expiration. Signs of thyrotoxicosis,including weightloss, hypertension,and tachycardia,may be evident onphysicalexamination.Tracheal deviationcan occur if thegoitre isasymmetrical.

Pemberton's signs(neck vein distensionand facial flushingwhen arms are heldvertically above head

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[Pemberton'smanoeuvre]) may bepresent.

Thymic hyperplasia•  Always

asymptomatic. Canbe seen withmyasthenia gravis,

Graves' disease,burns; following viralillnesses; and as areboundphenomenon (e.g.,followingchemotherapy,especially for Hodgkin's disease).

• Chewith

• Chefrom

Case history A 55-year-old man presents to the emergency department with atypical chestpain. A PE-protocol chest CT is negative but demonstrates a 4 cm

homogeneous anterior mediastinal mass. The patient is otherwise healthy,with no significant past medical history. Physical examination and routineblood tests are all normal.

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Other presentationsPatients with large or invasive thymomas may present with cough or vaguechest pain. Dyspnoea is often a presenting sign and is due to a large, space-occupying tumour; consequent pleural effusion; or phrenic nerve paralysis.

Some 10% to 15% of patients with myasthenia gravis have an associatedthymoma. [6]  Therefore, muscle weakness involving ocular, facial,oropharyngeal and respiratory, and/or limb muscles may be evident atpresentation.

Rarely, patients may present with features suggestive of superior vena cavasyndrome (e.g., facial and upper extremity oedema) due to extrinsic tumour compression and invasion or intravascular tumour thrombus. Left-armswelling due to invasion and obstruction of the left innominate vein is a rarepresenting sign.

History & examinationKey diagnostic factorshide all

myasthenia gravis (common)

• 10% to 15% of patients with myasthenia gravis

have an associated thymoma. [2]  Considered theonly reliable risk factor.

muscle weakness (common)

• Suggests myasthenia gravis. Ocular weakness(double vision, drooping eyelids) may be the onlypresenting feature. Generalised weakness,

particularly facial and oropharyngeal weakness(suggested by difficulty in chewing andswallowing), as well as proximal limb weakness(suggested by difficulty with getting out of chairsor climbing stairs) may be present. In cases of 

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myasthenic crisis, respiratory muscle weaknessresults in severe respiratory involvement.

facial and upper extremity oedema (uncommon)

•

Suggests superior vena cava (SVC) syndrome.facial plethora (uncommon)

• Suggests SVC syndrome. Due to venousengorgement and oedema.

distended veins in the neck, chest, and/or abdominal wall(uncommon)

• Suggests SVC syndrome.

left-arm swelling (uncommon)

• Due to invasion and obstruction of the leftinnominate vein.

Other diagnostic factorshide all

cough (uncommon)

• Usually mild and non-productive withouthaemoptysis.

dyspnoea (uncommon)

• Non-specific symptom; usually mild. Markeddyspnoea, particularly when supine, is usuallydue to phrenic nerve invasion.

fever and/or weight loss (uncommon)

• Rare, non-specific systemic symptoms.Risk factorshide all

Strong

hx of myasthenia gravis

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• 10% to 15% of patients with myasthenia gravishave an associated thymoma. [2]  Considered theonly reliable risk factor.

Weak

age >45 years• The peak age of incidence of a thymoma is

between 45 and 65 years; the mean age for thymic carcinoma is 46 years. [2] 

Diagnostic tests1st tests to order hide all

Test

chest x-ray

Usually first test done but rarely diagnostic. A normatumour.

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chest CT with intravenous contrast

Most useful imaging test. [14]  [18]  Intravenous contrinvasion of blood vessels, which is crucial for preope

If thymoma, CT usually shows an enlarged thymus, image and preservation of fat planes; local invasion

If thymic carcinoma, CT shows an invasive, poorly dmediastinal fat plane. Vascular invasion, lymphadencommon. May also contain calcification and necrosis

Tests to consider hide all

Test

chest MRI

Mainly used to confirm suspected cardiac invasion (Chemical-shift MRI can be used to differentiate thym

tissue biopsy

Small non-invasive lesions are usually resected for bimage Large, invasive, or unusual lesions, or those w

approached with a CT-guided core-cutting needle biand video-assisted biopsy of pleural implants are alt

acetylcholine receptor antibodies

Present in 80% to 90% of patients with myasthenia g

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FBC Anaemia may be a result of paraneoplastic pure-red

Emerging testshide all

Test

PET/CT scan

Currently being investigated; it is unclear how usefuWHO histology becomes worse, the intensity of the increases.

Step-by-step diagnostic approachThe initial diagnosis of a thymic tumour is usually radiological. There are nospecific history or physical examination findings that allow an unequivocaldiagnosis of a thymic tumour. [11]  If a standard chest radiograph suggests ananterior mediastinal mass, the best imaging study is a chest CT withintravenous contrast. Most isolated anterior mediastinal masses in adultswithout lymphadenopathy will be due to a thymic tumour. Small encapsulatedlesions are usually resected for both pathological diagnosis and treatment.Large invasive lesions are usually sampled with a CT-guided core-cuttingneedle biopsy.

History About 50% of patients with an underlying thymic tumour are asymptomatic,and diagnosis is often incidental. However, the most important factor to elicitis a history of myasthenia gravis or muscle weakness consistent withmyasthenia gravis (about 30% of patients with a thymoma have associatedmyasthenia gravis). Patients with myasthenia gravis may have ocular 

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symptoms only (double vision, drooping eyelids) or generalised muscleweakness, especially facial and oropharyngeal weakness (suggested bydifficulty in chewing and swallowing) and/or proximal limb weakness(suggested by difficulty with getting out of chairs or climbing stairs).

 About one quarter of patients with a thymic tumour have non-specificsystemic symptoms such as fever and weight loss. About one third of patientspresent with local symptoms such as chest pain, cough, or dyspnoea, or symptoms consistent with superior vena cava (SVC) syndrome (e.g., facialand upper extremity oedema).

Physical examination

The physical examination is almost always normal. Muscle weakness may beevident if untreated myasthenia gravis is present. Fatiguable muscleweakness may be localised or generalised, involving the eyelids, extraocular eye muscles, face, oropharynx, neck, respiratory muscles, and/or limbs.Ptosis and diplopia occur early in the majority of patients. [12]  Ptosis time(normally >3 minutes) is checked by asking the patient to look up withoutptosis developing. When the facial and oropharyngeal muscles are affectedthere may be a characteristic flattened smile, nasal speech, or difficulty inchewing and swallowing. Examination of the limbs shows proximal muscleweakness with fatigue. Arm abduction time (normally >3 minutes) is checkedby asking the patient to hold the upper arms outstretched. There should beno evidence of muscle wasting, and reflexes are normal. Sensation is intactand there is no autonomic dysfunction. In cases of myasthenic crisis, there issevere respiratory involvement.If the SVC is obstructed, evidence of SVC syndrome may be present;examination reveals facial plethora, facial and upper-extremity oedema, anddistended veins in the neck and chest wall and, occasionally, the abdominalwall. [13] 

Rarely, patients are febrile or show signs of weight loss. Left-arm swelling,due to invasion and obstruction of the left innominate vein, is an uncommonfinding.

Imaging A chest radiograph is usually the first test to perform and may show ananterior mediastinal mass. A normal chest radiograph does not rule out a

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small tumour. The most important investigation is a chest CTscan. [14]  Intravenous contrast is essential in evaluating local tumour invasion of blood vessels, which is crucial for preoperative staging andtherapeutic planning. It will show the mass, its edge and internalcharacteristics, View image which structures it abuts or invades, View

imageView image lymphadenopathy (which increases the chance that thelesion is a lymphoma), and any associated chest pathology such as pleuralimplants, lung metastases, or evidence of SVC obstruction. View imageViewimageRoutine chest MRI is usually less useful than a CT scan because the tumour details are not as clearly defined. However, chemical-shift MRI may behelpful in differentiating thymic hyperplasia from a thymic tumour. [15]  Inaddition, cardiac-gated MRI may be useful if cardiac invasion is suspected.PET/CT scanning is being investigated; currently it is unclear how useful PET

scanning will be. [16]  In general, as the WHO histology becomes worse, theintensity of the PET uptake (standardised uptake value) increases.

Other investigationIt is important to obtain a tissue diagnosis when the radiological findings areatypical or show a locally advanced lesion that may be considered for induction therapy prior to resection, a metastatic lesion, or an otherwiseinoperable tumour. Small non-invasive lesions are usually resected for both

pathological diagnosis and treatment.

CT-guided core-cutting needle biopsy is almost always the best way to obtaina tissue diagnosis. Fine-needle aspiration is often non-diagnostic, as tissuearchitecture is usually required to make a diagnosis. An anterior mediastinotomy (Chamberlain's procedure) is usually done for large anterior tumours if a core needle biopsy is non-diagnostic. Mediastinoscopy is rarelyappropriate, as this approach usually samples only the middle mediastinumrather than the anterior mediastinum. Video-assisted thoracic surgery (VATS)is used if pleural implants are seen, View image as optimal pleural biopsyspecimens can be obtained using this technique. VATS is not appropriate for localised lesions, however, as any biopsy risks spilling tumour cells into thepleural space, possibly leading to metastatic pleural implants.FBC, although non-specific, may show anaemia due to paraneoplastic pure-red-cell aplasia. Elevated acetylcholine receptor antibody titre (range varies

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is

essentially treatment of theunderlying tumour.• Clinically encapsulated

thymomas are resected for both pathological diagnosisand treatment. [25]  Totalthymectomy (completeresection of the thymus gland)is necessary to reduce risk of recurrence. Macroscopicallytumour-free resection marginsshould be achieved.Operative morbidity and

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is

essentially treatment of theunderlying tumour.• Clinically encapsulated

thymomas are resected for both pathological diagnosisand treatment. [25]  Totalthymectomy (completeresection of the thymus gland)is necessary to reduce risk of recurrence. Macroscopicallytumour-free resection marginsshould be achieved.Operative morbidity and

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is

essentially treatment of theunderlying tumour .• Clinically encapsulated

thymomas are resected for both pathological diagnosisand treatment. [25]  Totalthymectomy (completeresection of the thymus gland)is necessary to reduce risk of recur rence. Macroscopicallytumour-free resection marginsshould be achieved.Oper ative morbidity and

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is 

essentially treatment of theunderlying tumour.• Clinically encapsulated

thymomas are resected for both pathological diagnosisand treatment. [25]  Total thymectomy (completeresection of the thymus gland)is necessary to reduce risk of recurrence. Macroscopicallytumour-free resection marginsshould be achieved.Operative morbidity and

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is

essentially treatment of theunderlying tumour.• Clinically encapsulated

thymomas ar e resected for both pathological diagnosisand treatment. [25]  Totalthymectomy (completeresection of the thymus gland)is necessary to reduce risk of recurrence. Macroscopicallytumour-f ree r esection marginsshould be achieved.Operative morbidity and

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is

essentially treatment of theunderlying tumour.• Clinically encapsulated

thymomas are resected for both pathological diagnosisand treatment. [25]  Totalthymectomy (completeresection of the thymus gland)is necessary to reduce risk of recurrence. Macroscopicallytumour-free resection marginsshould be achieved.Operative morbidity and

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is

essentially treatment of theunderlying tumour .• Clinically encapsulated

thymomas are resected for both pathological diagnosisand treatment. [25]  Totalthymectomy (completeresection of the thymus gland)is necessary to reduce risk of recur rence. Macroscopicallytumour-free resection marginsshould be achieved.Oper ative morbidity and

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is

essentially treatment of theunderlying tumour.• Clinically encapsulated

thymomas are resected for both pathological diagnosisand treatment. [25]  Totalthymectomy (completeresection of the thymus gland)is necessary to reduce risk of recurrence. Macroscopicallytumour-free resection marginsshould be achieved.Operative morbidity and

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is

essentially treatment of theunderlying tumour.• Clinically encapsulated

thymomas are resected for both pathological diagnosisand treatment. [25]  Totalthymectomy (completeresection of the thymus gland)is necessary to reduce risk of recurrence. Macroscopicallytumour-free resection marginsshould be achieved.Operative morbidity and

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Patient

group

Treatment line Treatmenthide all

resectabletumour 

1st surgery

• Resectability depends ontumour size, edgecharacteristics, apparentencapsulation, and symptoms

(absence of symptomsfavours an early stagetumour). For patientspresenting with symptoms of superior vena cava syndrome,first-line treatment is

essentially treatment of theunderlying tumour.• Clinically encapsulated

thymomas are resected for both pathological diagnosisand treatment. [25]  Totalthymectomy (completeresection of the thymus gland)is necessary to reduce risk of recurrence. Macroscopicallytumour-free resection marginsshould be achieved.Operative morbidity and

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Last updated: Jan 21,

Treatment approachThere are no randomised trials to compare treatment options; case seriesand expert opinion, therefore, provide the basis for 

treatment. [22]  [23]  [24]  Once a clinical diagnosis of a thymic tumour is madeon chest CT, most thoracic surgeons judge resectability on the basis of tumour size, edge characteristics, apparent encapsulation, and symptoms(absence of symptoms favours an early stage tumour). Small non-invasivetumours are resected for pathological diagnosis and treatment. Unresectabletumours are considered for induction treatment, usually chemotherapy alone,although radiotherapy may also be given. After induction therapy, operabilityof the tumour is reassessed from a repeat chest CT. Most are then eligible for resection. Patients with myasthenia gravis should have therapy of their 

myasthenia optimised before surgery. For those presenting with superior vena cava syndrome, first-line treatment is treatment of the underlyingtumour.

Resectable tumour Clinically encapsulated thymomas are resected for both pathologicaldiagnosis and treatment.[25]  Total thymectomy (resection of the thymusgland) is necessary to reduce risk of recurrence. Macroscopically tumour-free

resection margins should be achieved. Operative morbidity and mortality aregenerally very low.The pathology report, together with the surgeon's impression, determine theneed for adjuvant mediastinal radiotherapy. Masaoka's stage I tumours(encapsulated tumour with no evidence of invasion) are nearly alwayscompletely resected and do not require any adjuvant therapy. Masaoka'sstage II tumours (microscopic or macroscopic invasion, but not invadingthrough the mediastinal pleura) are almost always completely resected, butthere is controversy about whether they require adjuvant radiotherapy.

Several recent case series suggest that radiotherapy does not alwaysprevent relapses, that long-term freedom from relapse is possible withoutradiotherapy, and that the primary mode of failure is in the pleura, whichradiotherapy does not address. [26]  [27]  The complete resection status andthe impression of the operating surgeon probably remain the best factors toconsider when determining the need for adjuvant therapy. Masaoka's stage IIItumours (invasion into local structures) are more likely to be incompletely

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resected and generally have very tight resection margins. Most patients withstage III tumours are, therefore, referred for adjuvant radiation regardless of the complete resection status, as these tumours are biologically aggressiveand the resection margins are almost always, by necessity, minimal.However, there is no conclusive evidence that postoperative radiotherapy

reduces the risk of recurrence.

Locally advanced tumour Once a tissue diagnosis of a locally advanced thymoma or thymic carcinomais made, the patient usually receives inductionchemotherapy. [28]  [29]  [30]  [31]  Commonly utilised induction chemotherapyregimens include cisplatin-doxorubicin-cyclophosphamide, cisplatin-etoposide, and cisplatin-vincristine-doxorubicin-

cyclophosphamide. [31]  Response rates to induction chemotherapy rangefrom 40% to 100%, and pathological complete responses have beenobserved in 6% to 40%. Complete resection is achievable in 20% to 80% of patients who received induction chemotherapy.Occasionally, induction chemotherapy plus radiotherapy is performed largelyon the basis of institutional preference. [32]  Typically, patients receive 2 to 6cycles of induction therapy before surgery. Patients are then re-evaluated for resection following repeat chest CT. Most will be able to undergo resectionafter induction chemotherapy. The majority will then receive adjuvant

mediastinal radiotherapy or combination postoperative radiotherapy andchemotherapy, as some unresectable or partially resected tumours maybenefit from a combined approach.Some locally advanced thymic tumours remain unresectable followinginduction chemotherapy. In cases where the disease is confined within areasonable radiation portal, definitive thoracic radiotherapy can lead toprolonged progression-free survival. [33] 

Recurrent tumour In thymoma case series, the relapse rate is 10% to 20%, whereas in thosewith thymic carcinoma it is about 50%. [2]  [8]  [9]  [34]  The time to relapse alsodiffers: thymomas relapse at a median of 29 months after resection, whereasthymic carcinoma has a median relapse period of 19 months. [35]  The mostimportant factors associated with recurrence include Masaoka's stage, WHOhistology, and completeness of resection.

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Thymoma tends to relapse in the chest, usually in the pleura (locoregional87%; distant 13%), whereas thymic carcinoma tends to relapse at distantsites, particularly the lung, bone, brain, and liver (distant 60%; locoregional40%).

Distant recurrences are usually treated with chemotherapy. Activechemotherapy agents include cisplatin, paclitaxel, etoposide,cyclophosphamide, doxorubicin, vincristine, ifosfamide, pemetrexed, andoctreotide. [36]  Combination chemotherapy may also be utilised, and thismay result in higher response rates. Most locoregional recurrences aretreated in a multimodal fashion; resection, chemotherapy, and radiation areall important components of therapy. [29] [37]  [38]  [39] 

With myasthenia gravisPatients with thymoma and myasthenia gravis must be medically optimisedbefore undergoing surgery because the stress of surgery can precipitate amyasthenic crisis, leading to respiratory failure. [40]  Those with mild tomoderate symptoms should be treated with a cholinesterase inhibitor and/or immunosuppressant. Patients with severe myasthenia are typically preparedfor surgery with either plasmapheresis (to clear antibodies) or intravenousimmunoglobulin (IVIG). One study in patients with myasthenic exacerbationsfound no difference in outcome between plasmapheresis andIVIG, [41]  whereas others have reported plasmapheresis to be more effectivein patients with myasthenic crisis. [42]  As thymoma surgery is alwayselective, there is sufficient time to medically optimise patients.

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