DIAGNOSIS IN LUNG CANCERDIAGNOSIS IN LUNG CANCER

Dr. Hülya Bayız

Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital

Conflict of interestConflict of interest

NONE

ReferencesReferencesWahidi MM, et al. Evaluation for the treatment of patients with pulmonary noduls: When is it Lung Cancer. Chest 2007; 132: 94-107.

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Up to date.– Thomas KW, Gould KM. Diagnosis of staging of non small cell lung cancer. – Stark P. Role of imaging in the staging of non small cell lung cancer. – Sheski FD. Indications for diagnostic thoracoscopy.– Yasufuku K,Fujisawa T.Endobronchial ultrasound. Indications,advantages,and complications.– LeBlanc J.K.Endoscopic ultrasound-guided fine-needle aspiration in the mediastnum.

PlanPlan

Symptoms and clinical findings

Imaging methods

Tissue sampling methods

Malign epithelial tumorsMalign epithelial tumorsSquamous sell carcinoma

Papilarryclear cellSmall cellBasaloid

Small cell carcinomaCombined small cell carcinoma

Adenocarsinomamixed typeAsinaryPapillaryBronchioloalveolar Nonmucinous Mucinous Mixed mucinous and nonmucinous Solid adenocarcinoma with mucin secreting Fetal adenocarsinoma Mucinous (kolloid) carsinoma Mucinous cystadenocarsinoma Signet cell adenocarsinoma Clear cell adenocarsinom

Large cell carcinomaLarge cell neuroendocrine carcinomaCombined large cell neuroendocrine carcinoma

Basaloid carsinomaLymphoepithelioma like carcinomaClear cell carsinomaLage cell carcinoma with rhabdoid phenotype

Adenosquamous carsinoma

Sarcomatoid carsinomaPleomorfic carsinomaSpindle cell carsinomaGiant cell carsinomaCarsinosarkomPulmonary blastom

Carsinoid tumorsTypical carsinoidAtypical carsinoid

Salvary gland type carsinomasMucoepidermoid carsinomaAdenoid cystic carsinomaEpithelial-myoepithelial carsinoma

Frequency of initial symptoms and clinical findings in lung cancerFrequency of initial symptoms and clinical findings in lung cancerSymptoms and clinical findings

Frequency (%)

Coughing 75

Weight loss 68

Dyspnea 58-60

Chest pain 45-49

Hemoptysis 29-35

Bone pain 25

clubbing 20

Fever 15-20

weakness 10

Superior vena cava obstruction 4

Dysphagia 2

Wheezing, stridor 2

Symptoms and signs of intrathoracic spread

Symptoms and signs of intrathoracic spread

INVOLVEMENT OF NERVES

– Recurrent nerve

– Phrenic nerve

– Brachial plexus

– Sympathetic ganglion

Hoarseness

BreathlessnessMuscle wasting,

Pain and cutaneous temperature changeHorner syndrome

VASCULAR INVASION

– Vena cava superior obstruction

Swelling of face neck and eyelids

PERICARDIUM HEART

Supraventricular arrhythmias and effusion

ESOPHAGUS Dysphagia

PLEURA AND CHEST WALL

Localised persistant chest pain

Distant metastasis due to lung cancerDistant metastasis due to lung cancer

Metastatic site Frequency (%)

Central nervous system 0-20

Bone 25

Heart pericardium 20

Kidneys 10-15

Gastrointestinal system 12

Pleura 8-15

Adrenal glands 2-22

Liver 1-35

Skin and soft tissue 1-3

Clinical findings representing distant metastasis

Clinical findings representing distant metastasis

SYMPTOM SIGNS LAB. FINDIGS

Weight loss >5 kg

Focal skeletal pain

Headache seizure syncope

Recent change in mental status

Lymphadenopathy>1 cm

Hoarseness

VCS obstruction

Hepatomegaly

Papilledema

Soft tissue mass

Htc <%40 M

Htc <%35 F

ALP

GGT

SGOT

Paraneoplastic syndromes associated with lung cancer

Paraneoplastic syndromes associated with lung cancer

Endocrine Cushing syndrome, nonmetastatic hypercalsemia, SIADH production, gynecomastia, hypercalcitonemia, elevated levels of FSH, LH *, hypoglicemia*, hyperthyroidism*, carsinoid syndrome*

Neurologic Subacute sensory neuropathy, mononeuritis multiplex, intestinal pseudo-obstruction*, Lambert-Eaton syndrome*, cancer associated retinopathy, encephalomyelitis* (limbic, subacute cortical cerebellar), nekrotizing miyelopathy*

Metabolic Lactic asidosis*, hipouricemia*, hyperamilasemi*

Skeleton Clubbing, hypertrophic osteoartropathy

Renal Glomerülonephritis*, nephrotic syndrome*

Skin Hypertricosis lanuginosa, eritema gyratum repens, paraneoplastic acroketatozis, erythroderma (eksfoliative dermatitis), acanthosis nigricans*, ictiosis*, palmoplantar ceratodermia**, Sweet syndrome*, pruritus*, urticeria*

Hematologic Anemia, leucocytosis*, eosinophilia*, leucomoid reaction*, trombocytosis, trombocytopenic purpura*

Koagulopathies Disseminated intravascular coagulation*, trombophlebitis, trombotic nonbakteriyel endokardit*

Systemic Fever,anorexia cachexia ortostatic hypotension*, hypertension*

Collagen-vascular Dermatomyositis*, polymyositis*, systemic lupus erythematosus*, vasculitis**

Chest RadiographyChest Radiography

– Ill defined and anatomically superimposed nodules

– Apical and posterior segments of upper lobes

– Periphery of lungs– Retracardiac,subdiafragmatic and

retroclavicular

Bli

nd

reg

ion

s

Mass,nodule,infiltration

Atelectasis,pneumonia,pleural effusion,air trapping,diaphragma paralysis

Hilar and mediastinal enlargement

CT SCAN OF THE CHESTCT SCAN OF THE CHEST

1. A CT scan of the chest should be performed all cases of lung cancer.

2. Administration of IV contrast is prefered.

3. Upper abdomen is included.

4. The best anatomic study for thorax.

5. Evaluation of primary tumour, mediastinal involvement and upper abdominal metastasis

6. Road map for biopsy procuders.

LimitationsLimitationsLimited information for T and N staging.

The sensitivity (%55) and spesifity (%89) of identifying chest wall and mediastinal invasion is low (multiplanar MDCT solves the problem).

Involvement of lymph nodes (diameter of short-axis > 1 cm) – Sensitivity and spesifity of lymph nodes involvement is

low.

– >1 cm LN %40 benign

– BT (-) LN %20 metastatic

Evaluating superior sulcus tumours is limited because of axial status and shoulder artefact.

Lung CancerIntrathoracic radiographic characteristicsLung CancerIntrathoracic radiographic characteristics

A. Tumour with mediastinal infitration

Vessels and airways are encircled, no discrete lymph nodes

B. Mediastinal discrete lymph node enlargement

≥1 cm LN

C. Centra tumour or suspected N1

Normal mediastinal nodes.

D. Peripheral clinical stage 1 tumor

Normal mediastenN1 < 1 cm

Thorax CTThorax CT≤ 1 cm nodule %15-20 Malign

2 cm nodule %40-45 Malign≥ 3 cm nodule %80-95 Malign

Spiculated marginsVascular convergenceDilated bronchus leading into nodulePseudocavitation>15 mm Cavitation with thick and irreguler wallDynamic CT BT >15 HU

Magnetic Resonance ImagingMagnetic Resonance Imaging

MRI of chest should not be routinely performed for lung cancer.(low proton density,inhomogenous magnetic field,respiratory and cardiac artefacts).

MRI detects better intensity differences between tumor and normal tissues (bone,soft tisues,fat and vascular stractures,mediastinal,chest wall,vertebral body and diaphragm invasion).

MRI is recomended in evaluation of superior sulcus tumors.

PETPETPET scanning is a imaging modality based on the biological activity of neoplastic cells. 18 Fluoro 2 deoxi D glucose metabolite is most common used.Can be used in diagnosis, staging and treatment response evaluation.Differentiation of benign and malignaat pulmonary nodules (sensitivite %87 – spesifite %83)

– < 7 mm nodule– Bronchioloalveoler Ca– Carsinoid tumor– Mucinous adenocarsinom– Uncontrolled hyperglicemi ??

Infections and inflamatory conditions (tuberculous, romatoid nodule, sarcoidosis, endemic micosis) False positive

False negative

PETPETEvaluation of mediastinal lymph nodes

– sensitivity %74, specifity %85• >1 cm LAP: sensitivity > specifity• Normal size LAP: sensitivity < specifity

Better than CT and bone scintigraphy for detecting distant metastasis.Suggests unexpected distant metastasis in %20 patients .

Influence treatment decisions in %25 patients.

Avoids unnecessary thoracotomies.

– Stage 1 %1-8– Stage 2 %7-18– Positive results should be confirmed by bx.

LimitationsLimitations

Limited role in asessing tumor size and invasion (PET CT improves staging).

Insufficient brain metastasis evaluation.

Modarete PPV in evaluating mediastinal LN and histopathologic confirmation is needed.

Low NPV in;

– >1,5 cm LN,

– patients with central tumors,

– BAC

Diagnostic approach in patients with lung cancer

Diagnostic approach in patients with lung cancer

The main issue is to determine cell type.

The diagnostic method is selected according to presumed stage of disease.

Bx of lession with highest stage.

Diagnosis and staging is carried out simultaneously.

Tissue sampling technique– Tumor location– Ease,diagnostic accuracy,safety,local expertise

Primary tumor samplingPrimary tumor sampling

Central tumor location – Flexible bronchoscopy bx and cytologic

techniques– Sputum cytology

Peripheral tumor location – TTİBx – FOB bx CT or fluoroscopic guiedence– EBUS– EMN – EMN + EBUS

Lymph nodes sampling

Non surgical approaches– Need aspiration and bx of

peripheral ymph nodes – TBIA– EBUS– EUS– Combined modalities

Surgical approaches– Cervical mediastinoscopy– Anterior mediastinotomy– Thoracoscopy

Sputum cytologySputum cytology

Least invasive technique.

Preferred in patients whom invasive tests are avoided and with centrally located tumor.

Diagnostic accuracy is dependent on specimen numbers.1 specimen sensitivity 0.68, 2 specimens sensitivity 0.78, 3 specimens sensitivity 0.86

Patients with bloody sputum, >2.4 cm tumor, squamous cell cancers have positive cytology.

Assesment of pleural effusionAssesment of pleural effusionThoracentesis – Diagnosis in %50-60– Seperate fluid specimens increases diagnosis

(%30-80)

Closed pleural bx:– Limited increase in diagnosis (<%10)

Thoracoscopy:– Visualization and direct bx of pleura .– Evaluation of mediastinum and chest wall.

• Aorticopulmonary window, paraaortic LN• Paraeusophagial region and pulmonary LN

– Nodule bx

BronchoscopeBronchoscope19.th century rigid bronchoscopes were used for trakeabronchial assesment

1897 – removal of foreign bodies

1917 – resection of endobronchial tumor

1968 – flexible bronchoscope was developed

Rijid bronchoscope– Airway obstruction is less

– Superior suction

– Debulking of large tumors

– Fascilitate endobronchial laser therapy and stent placement

Inspects up to 4th order.

Diagnostic yield from FOB depends on the location of the lesion.

%70 of lung carcinomas can be reached with FOB.

Exophytic endobronchial lesion– >%90 diagnosis– 3-5 bx– From the viable areas bx +bronchial washings + brushings

>%90 diag.

Submucosal lesion

Peribronchial tumor compression+ TBIA tanı olasılığı artar.

Fiberoptic bronchoscopyFiberoptic bronchoscopy

TBIATBIAProvides better diagnosis than forceps biopsy in submucosal and peribrochial tumors (%71 vs potential%55) Safe in EBL include necrosis or high bleeding risk .Diagnostic yield is better than conventional methods in peripheral tumors.– The airway externally compressed to

such a degree that is not possible to negotiate biopsy forceps

– Complication from TBIA is lower than TBBx

TBIATBIA

Blind procedure.

Sampling lymph nodes adjacent to the tracea and major bronchusand hilar LN.

Diagnostic yield %14-91

– experience, LN size, aspiration number

LN TBIA should be performed before other sampling procedures.

Fiberoptic bronchoscopyFiberoptic bronchoscopyPeripheral lesion

Tumor sizeDistance from the hilumBronchus sign on CTBx number

Metastatic adeno CaBronchoalveoler Ca

Transbronchial Bx<3 cm %4-50>3 cm %46-80

BAL

Transthorasic Needle Aspiration Transthorasic Needle Aspiration Performed under fluoroscopic, US or CT guidance.

– sensitivity %96-100, specifity %89-92

– <3 cm diagnostic yield %80-95

Bx of solitary or multiple pulmonary nodules, consolidation,cavitary lesion and abscess

– Mediastinal lesion (>1,5 cm )

– Staging of hilar,mediastinum,chest wall and pleural malign infiltration

• Pneumothorax %15-42, chest tube drain % 3.3-15 ,intrapulmonary hemorage % 5-

16.9

• Number of puncture, size of tumour, distnace between skin and the lesion is related

to the complicaiton.

Diagnosis in malignancy with cytology or bx

Shold not be performed in patients with severe pulmonary hypertension, pneumonectomy,severe emphysema.

EBUSEBUS

Diagnostic evaluation of endobronchial lesions,peripheral pulmonary nodles and mediastinal abnormalities

Staging of non-small cell lung cancer

Guidance of endobronchial therapy

Diagnostic yield is higher<3 cm than TBBx (%80).

Diagnosis in<2 cm lesion %70

A study including 100 patients;avoids 29 mediastinoscopy, 21 thoracoscopy,8 thoracotomy, 9 TTBx with CT guidance.

EBUSEBUS

Visualize mediastinal structures adjacent to large airways.Anterior superior mediastinum can be reached.

>5 mm diameter LN can be sampled.

2, 4, 7, 10, 11 LN can be sampled.

Real time bx of LN is the main indication for convex probe EBUS

Insufficient aspiration, contamination results %15-20 FN.

Carcinoma insitu and bronchial displasia results FP.

Expert cytopathologists improve the results.

Radial probe EBUS achieves 360° and

advanced brochial wall layers imaging.

conveks probe EBUS achieves 60°

wedge shape imaging and real time bx.

sensitivity reached >90 %, specifity 100%.

Electromagnetic NavigationElectromagnetic NavigationA system uses low-frequency electro magnetic waves and asisting endobronchial accessories for bx .

1. Electro magnetic location board2. A locatable sensor probe (single use) and EWC3. A sofware converts CT scans to virtual

bronchoscopy and enables navigation.

AFTRE < 5mm < 2 cm peripheral lesion diagnostic yield approximate %80For middle lobe >%88 Transbronşial bx improves efficiency.

EUSEUSThe upper retroperitoneum – left adrenal gland,left lobe of the liver,lymph nodes

Posterior inferior mediastinum (heart,pleura,vessels,spine)

2L/4L, 7, 8 can be sampled.– 5 posible,6 large enough

The anterior trachea can not be examined.– 1, 2, 3 and 4R LN can not be detected.

Lymph nodes with hypoechoic core, sharp edges,round shape,diameter exceeding 1 cm inicates malignancy .

[ROSE] increases diagnostic yield.

Cervical MediastinoscopyCervical MediastinoscopyPerformed direct or with video by an incision just above the suprasternal notch.

2R, 4R, 2L, 4L anterior and pretracheal LN are assessed.

Complications are few.

FN rate is %10.

Aorticopulmonary window and para aortic lymph nodes can be assessed by extended medistinoscopy.

Anterir mediastinotomy assess the anterior superior mediastinum in patients with cancers in the left upper lobe.

Mediastinal Lymph Nodes Sampling TechniquesMediastinal Lymph Nodes Sampling Techniques

LN samplig method

Mediastinoscopy

TBIA

EUS

EBUS

VATS left

Thoracotomy

LN station

•2R/2L 4R/4Lanterior subcarinal

•2L/4L, 5, 7, 8

•2, 4, 7, 10, 11, 12

•5, 6

•All

Comparison mediastinal lymph nodes samplig methods

Comparison mediastinal lymph nodes samplig methods

Method Case no

Sensitivity Specifity Prevalanc

CT 5111 0,51 (0,47-0,54) 0,80 (0,84-0,88) 0,28

PET 2865 0,74 (0,69-0,79) 0,85 (0,82-0,88) 0,29

TBIA 1329 0,78 0,99 0,7

TTIA 215 0,89 1 0,81

EUS 1201 0,83 (0,78-0,87) 0,97 0,61

EBUS 1339 0,78 0,89 0,75

Mediastinoscop 6505 0,78 1 0,39

SCLCSCLC

The diagnosis should be acchieved easiest way

(sputum cytology, thoracentesis, supraclavicular LN Bx, bronchoscopy)

Limited? Extensive?(thorax CT, cranial MR or CT,

bone scan)

NSCLCNSCLC

Diagnostic method according to presumed stage<3 cm

nodule

Surgery

Pleural effusion Acchieve diagnosis

Metastatic lesion

Bx (technically possible)or

Primary tumor bx (easiest,reliable method)

Thank you…Thank you…