1. DIAGNOSIS OF LUNG
CANCER
DR SHAHIR ASFAHAN
RESIDENT, DEPT OF PULMONARY MEDICINE
AJMER, INDIA
2. Lung cancer
The incidence of lung cancer is on the rise.
From being 1% of all cancers in 1958 in india to
nearly a millon new cases in india 2008, lung cancer
has come a long way.
Today it is the leading cause of cancer in men and a
dismal 5 year survival.
Pulmonologists are at the frontline this battle, hence
it is most essential to know the strategies to diagnose
it.
5. SCREENING
CONCEPT-IMPROVEMENT IN MORTALITY
RADIOLOGICAL- A STUDY INVOLVING 55000
SUBJECTS IN 1960s DIDNT DEMONSTRATE ANY
IMPACT ON MORTALITY
SUBSEQUENTLY IN 1970 FOUR RCTS
CONCLUDED THE SAME
6. LOW-DOSE CT SCREENING
IN 1990s A 3 YEAR POPULATION BASED STUDY
WITH MOBILE CT SCANNER WAS DONE IN RURAL
SETUP- IT DEMONSTRATED INCREASED
DETECTION OF RESECTABLE TUMORS AND
IMPROVED SURVIVAL.
EARLY LUNG CANCER ACTION PROJECT (ELCAP) IN
USA- 96% OF TUMORS DETECTED WERE
RESECTABLE. SAMPLE SIZE WAS DEEMED SMALL.
MAYO CT SCREENING STUDY DID FIND INCREASED
N0. OF RESECTABLE CANCERS BUT NO IMPACT ON
MORTALITY AND INCREASED DETECTION OF NON-CANCEROUS
NODULES LEADING TO HEALTH CARE
BURDEN.
7. The National Lung Screening Trial
TO SPECIFICALLY DETECT DECREASE IN
MORTALITY.
RCT INVOLVING 53524 PARTICIPANTS
TWO ARMS- 1) ANNUAL CHEST RADIOGRAPH
2) ANNUAL LOW DOSE CT.
24% OF CT SCREEN S/O LUNG CANCER OF WHICH
96% WERE FALSE POSITIVE.
CT GROUP HAD 63.2% RESECTABLE CANCERS
WHILE CXR GROUP HAD 48% RESECTABLE
CANCERS
CT GROUP HAD 20% DECREASE IN LUNG CANCER
SPECIFIC MORTALITY
8. GUIDELINES FOR SCREENING
ANNUAL DOW DOSE CT SCREENING
between 55 and 74 years of age, with a minimum of 30
pack-years of smoking. Former smokers meeting the
30 pack-year requirement could participate if they
had quit within the previous 15 years
ADULTS ABOVE 50YRS IF OTHER RISK FACTORS
ARE PRESENT
9. Sputum cytology
Also called “the poor
man’s bronchoscopy”.
In a meta-analysis by
Duke university centre, it
had a sensitivity of 66%
and specificity of 99%.
More useful in central
airways tumors.
Can also detect dysplastic
changes in pre-neoplastic
stages.
10. CXR
Due to the widespread availability of simple chest
radiography, the first suspicion of lung cancer is
raised most often by a CXR.
It can present as SPN(<3cm) or as a mass(>3m),
atelectasis of segment, lobe or lobes of lung,
airspace consolidation,pleural effusion, reticular
septal infiltration, chestwall/osseos/mediastinal
invasion or a combination of the above.
11. Solid pulmonary nodule
Favors benign Favors malignant
Location-no predilection
Size- no definite correlation
Margins-usually round in
shape with smooth margins
Presence of fat is highly s/o
of hamartomas
Calcification- central,
laminated, diffuse, popcorn
Cavity-wall thickness
<5mm
Contrast
enhancement<15HU
TDT- <30 days >2yrs
Located more in upper lobes
Size >3cm to be considered
malignant until proven
otherwise
Margins- spiculated margins
is highly s/o malignancy
Fat rarely present in
metastases from RCC or
liposarcoma
Calcification-amorphous or
eccentric
Cavity wall>15mm
Contrast enhancement>20HU
TDT- btw 30 days and 2 yrs.
13. ADENOCARCINOMA
CXR-ILL DEFINED
SPICULAR OR WELL
DEFINED LOBULER
WITH ASSO HILAR
LYMPHADENOPATHY
CT-PERIPHERAL MASS
WITH SPICULATED OR
LOBULER MARGINS.
CAVITATION IN UPTO
15%.
CALCIFICATION
USUALLY ECCENTRIC IN
UPTO 10% OF PATIENTS.
CONTRAST
ENHANCEMENT
14. BAC
CT-COMMONLY
GROUND GLASS
OPACITIES WITH AIR-BRONCHOGRAMS
AND
INTRATUMORAL CYSTIC
SPACES.
ALSO PRESENT AS
NODULE, MASS OR
CONSOLIDATION
the greater the degree of
ground-glass attenuation,
the better outcome, with 5-
year survival
15. SQUAMOUS CELL CARCINOMA
CXR-CENTRAL MASS FREQUENTLY
WITH SECONDARY ATELECTASIS
OR OBSTRUCTIVE PNEUMONIA
CAVITATION, LYMPHADENOPATHY
CT-CENTRAL MASS WITH ABRUPT
OBSTRUCTION OF BRONCHIAL
LUMEN
POST OBSTRUCTIVE
CONSOLIDATION ATELECTASIS
WITH CONRAST ENHANCEMENT OF
MASS MORE THAN LUNG IN CECT
CAVITATION - CENTRAL OR
ECCENTRIC WITH IRREGULAR
INNER SURFACE
MEDIATINAL OR SOFT TISSUE
INVASION WITH
LYMPHADENOPATHY MAY BE
PRESENT.
16. SMALL CELL LUNG CANCER
Central mass near major
bronchi; submucosal
tumor with rare mucosal
or endoluminal growth
Bronchial encasement
with extrinsic
stenosis/obstruction
Vascular
invasion/encasement
Peripheral nodule or mass
(approximately 5% of
cases)
Lymphadenopathy
17. LARGE CELL LUNG CANCER
Large. typically
peripheral tumors ;
often measure over 3
cm at presentation
Frequent necrosis
FREQUENT INVASION
HILAR
LYMPHADENOPATHY
18. POSITRON EMISSION TOMOGRAPHY
a standardized uptake
value (SUV) cutoff of 2.5
often was used to suggest
malignancy,
a sensitivity of about 90%
to 95% (range, 83% to
100%),
a specificity of about 80%
(range, 52% to 100%), and
an accuracy of about 90%
(range, 86% to 100%) were
reported
20. CT-PET
allow more precise evaluation of chest wall and mediastinal
infiltration or
correct differentiation between tumor and peritumoral
inflammation or atelectasis.
more accurate lymph node staging than CT alone, with an
overall sensitivity of 80% to 90% and a specificity of 85% to
95%
illustrates the location of suspect lymph nodes, thereby
helping to direct tissue sampling procedures
FOR DETECTION OF METASTASIS Uniformly superior to
CT alone, except in brain imaging, for which sensitivity is
unacceptably low owing to the high glucose uptake in
normal surrounding brain tissue. CT and, even better, MRI
remain the methods of choice for brain imaging.
21.
22. bronchoscopy
Bronchoscopy most commonly is performed in the
evaluation of patients with suspected lung cancer.
Central lesions can appear as exophytic growth,
extrinsic compression, submucosal infiltration or any
combination of these.
Central lesions usually are sampled with a combination
of bronchial washes, bronchial brushings, and
endobronchial biopsies.
The yield of endobronchial biopsy is highest for
exophytic lesions, with a diagnostic yield of
approximately 80%
Attempts should be made to obtain the biopsy
specimens from areas of the lesion that seem viable
EBNA should be obtained if lesion appears necrotic.
23. Peripheral lesions usually are sampled with a
combination of bronchial wash, brushes,
transbronchial biopsy, and TBNA.
The yield of bronchoscopy for lesions smaller than
3 cm varies, ranging from 14% to 50%,
diagnostic yield of 46% to 80% when the lesion is
larger than 3 cm.
24. Electro-magnetic navigation
Ct scan and virtual bronchoscopy is performed and
data stored in the console.
Electromagnetic field is generated and magnetic
probe attached to the tip of bronchscope advanced
under real time guidance.
EMN diagnostic sensitivity to range between 67%
and 74%, independent of lesion size.
25.
26.
27. Autoflourescence bronchoscopy
improved the detection of
dysplasia, carcinoma in situ, and
invasive carcinoma of the central
airways
AFB systems rely on the principle
that infiltrating tumors disturb the
fluorescence characteristics of
normal tissue..
Bronchial tree is illuminated with
blue light of wavelength 442nm.
Normal tissues emit light in the
green spectrum while neoplastic
tissues emit in the near-red
spectrum.
the sensitivity for detecting high-grade
dysplasia or carcinoma in
situ was increased two- to six-fold
on average
28. Narrow-band imaging
uses a unique filter to select light
wavelengths that preferentially are
absorbed by hemoglobin, thereby
permitting superior
microvasculature detection.
Because angiogenesis
preferentially occurs in dysplastic
and neoplastic lesions, NBI may
identify early dysplastic lesions
better than WLB or AFB.
Studies suggest similar sensitivity
between AFB and NBI, but
improved NBI specificity for
detecting abnormal lesions
29. OPTICAL COHERENCE TOMOGRAPHY
near-infrared light transit
time and reflection are
used and provides a
macroscopic optical cross-sectional
view of hollow
organs.
In the airway, dysplastic,
invasive cancer appear to
have unique OCT image
patterns.
Provides “optical biopsy”
and can be used for
longitudinal follow-up for
treatment response.
30. FIBERED CONFOCAL FLUORESCENCE
MICROSCOPY
based on cellular and
tissue autofluorescence
on laser excitation.
The predominant source
of airway wall
autofluorescence is the
subepithelial elastin
fibers, and alterations in
this elastin network can
be detected in
microinvasive and
invasive proximal airway
lesions.
31. transbronchial needle aspiration (TBNA)
Used for diagnosis and staging of bronchogenic carcinoma.
TBNA is highly specific for the identification of mediastinal
metastases, with sensitivity depending heavily on the study
population under investigation.
In studies that included patient populations with a
prevalence of mediastinal metastases of 34%, sensitivity
was only 39%,
whereas in a population with a prevalence of 81%,
sensitivity for detection of metastases was 78%.
lack of needle monitoring, difficulties in anticipation of
location of lymphnodes have limited its use.
32. ENDOBRONCHIAL ULTRASOUND
TECHNIQUE
a curved linear array ultrasound transducer sits on the distal end
and can be used either with direct contact to the mucosal surface
or with an inflatable balloon that can be attached at the tip.
Ultrasound scanning is performed at a frequency of 7.5 to 12
MHz, with tissue penetration of 20 to 50 mm. An ultrasound
processor generates the ultrasound image.
Lymph node stations that can be reached using EBUS are the
highest mediastinal (station 1), the upper paratracheal (2land
2R), the lower paratracheal (4R and 4L), the subcarinal (station
7), the hilar (station 10) nodes, as well as the interlobar(station
11) and lobar (station 12) nodes.
EBUS-TBNA has been shown to have a high pooled sensitivity of
93% and specificity of 100%
33.
34. EUS(endoesophageal ultrasound)
EUS-FNA has limited access, because only lymphnode
stations 2, 4, 7, 8, and 9 are accessible through a
transesophageal approach.
The left adrenal can be reached and identified in 97% of cases.
It has a characteristic “seagull” shape on ultrasound images
and is particularly well visualized in cases of metastatic
enlargement. Furthermore, the left lobe of the liver also can
be reached.
Even in cases in which mediastinal lymph node enlargement
is not seen on CT, EUS-FNA has been able to demonstrate
metastases in 25% of patients with lung cancer.
37. FNA and Core BIOPsy are analogous in sensitivity
but core needle biopsy offers more tissue material
for genetic studies
38. GENE MUTATIONS ASSOCIATED WITH LUNG
CANCER
MAJOR ROLES PLAYED BY
1) EGFR
2) K-RAS
3) EML-ALK4
4) P53
5) VEGF
6) Telomerase
7) BCL-2
39. EGFR
EPIDERMAL GROWTH FACTOR RECEPTOR ALSO KNOWN AS
HER1, MEDIATES EXTRACELLULAR SIGNALS INTRA-CELLULARLY
VIA TYROSINE KINASE PHOSPHORYLATION
AND INHIBITS APOPTOSIS.
EGFR-activating mutations tend to be present in a minority of lung
cancers (10% to 20%)
appear most commonly in nonmucinous adenocarcinomas
exhibiting a well-differentiated acinar or papillary growth pattern.
presenting demographically in younger Asian women who were
never-smokers or light smokers.
Targeted TKIs are effective for tumor regression when non–small
cell carcinomas have activating EGFR mutations.
40. K-RAS
KRAS is an oncogene found on the short arm of chromosome 12
(12p)
shows mutations in approximately 20% of non–small cell lung
cancers.
clinicopathologic correlations with older age combined with male
gender,history of heavy cigarette smoking, and advanced disease at
presentation, with relatively aggressive tumors and poor clinical
outcome.
These high-grade adenocarcinomas also show lymphovascular
invasion, mitotic activity, and tumor necrosis.
PRESENCE OF KRAS MUTATION IMPLIES RESISTANCE TO
TKIs EVEN IN PRESENCE OF EGFR MUTATION.
41. EML-ALK4
echinoderm microtubule-associated protein-like 4–
anaplastic lymphoma kinase.
occurring in less than 10% of non–small cell lung
cancers
present in younger persons without significant
smoking history
appears to be selective for adenocarcinomas.
IMPLIES RESISTANCE TO TYROSINE KINASE
INHIBITORS.
42. Pleural fluid examination
cytologic study of the pleural fluid establishes the
diagnosis of a malignant pleural effusion ranges
from 40% to 87%.
Predictors of malignancy in pleural fluid-a
symptomatic period of more than 1 month, the
absence of fever, the presence of serosanguineous
pleural fluid, and a chest CT scan suggestive of
pleural malignancy
43. Closed needle Pleural biopsy
Commonly used
needles are Abram’s
and Cope’s needle.
The percentage of
positive pleural needle
biopsies in patients
with malignant pleural
disease ranges from
39% to 75%.
44. thoracoscopy
It is considered the gold standard for diagnosis of
malignant pleural effusion.
The sensitivity of thoracoscopy ranges from 92 to 97
% ,
and its specificity is 99–100 % for patients with a
malignant pleural effusion
45. Tumor markers
Patz et al used 2D difference gel electrophoresis (DIGE)
and MALDI-TOF MS they found that 4 of these proteins
(CEA, RBP, α1-antitrypsin and SCC antigen) were able to
distinguish lung cancer cases from controls with 77.8%
sensitivity and 75.4% specificity.
indirect ELISA tests for known lung cancer TAAs (p53, NY-ESO-
1, cancer-associated antigen (CAGE), GBU4-5,
Annexin 1 and SOX2) . These efforts yielded an assay with
high reproducibility, precision, and linearity that was able
to identify nearly 40% of primary lung cancers via a
peripheral blood test
Future candidate markers- autoantibodies against the
protein gene product 9.5 (PGP 9.5)
