ANATOMY,PATHOLOGY, INVESTIGATIVE WORK –UP AND STAGING OF LUNG CANCER

1. ANATOMY,PATHOLOGY,
INVESTIGATIVE WORK –UP
AND STAGING OF LUNG
CANCER
G.Lakshmi Deepthi

2. LUNG CANCERLUNG CANCER
•Accounts for more deaths than breast cancer, prostate
cancer, and colon cancer
•80-90% of patients who develop lung cancer will die of
the disease
•About 1 in 5 lung cancers are small cell, the rest are non-
small cell.
•An estimated 85% of lung cancers are related to tobacco
use
•Leading cause of cancer death in both men and women
(31%and 25%, respectively), and in all races

3. Anatomy of lungAnatomy of lung

4. AnatomyAnatomy
Pair of respiratory organs situated in the
thoracic cavity
Spongy in texture
Rt lung– 700g
50-100g heavier than left lung
Rt and left lungs are separated by mediastinum
• In the young lungs brown or grey colour
• Lungs are encased in membranes called visceral
pleura

5. SURFACE ANATOMY OFSURFACE ANATOMY OF
LUNGLUNG Apex
lies one inch above the medial 1/3
of the clavicle.
Anterior margin
Left lung -from
sternoclavicular joint to the level of
4th
costal cartilage, then deviates for
about 1 inch to left at 6th
costal
cartilage to form cardiac notch.
Right lung - vertically from
sternoclavicular joint to 6th
costal
cartilage.
Posterior margin : along the
vertebral column from the apex to
the inferior margin.

6. SURFACE ANATOMY OFSURFACE ANATOMY OF
LUNGLUNG
 Inferior margin: it passes round chest wall, on
the 8th
rib in midclavicular line, 10th
rib in mid-
axillary line but more horizontal and finally
reaching to the 10th
thoracic spine.
 Oblique fissure: represented by a line extending
from 3rd
thoracic spine, obliquely ending at 6th
costal
cartilage.
 Transverse fissure only in right lung:
represented by a line extending from 4th
right costal
cartilage to meet the oblique fissure.

7. Trachea
Bronchial tree
•Left and right
main bronchus
•Carina
•Lobar bronchus
•Segmental bronchus
•Bronchiole
•Alveoli

8. Conical in shape
It has an apex
base
3 borders
2 surfaces-costal
medial-mediastinal
vertebral

9. COSTAL SURFACE:
• Convex.
• Covered by costal pleura which separates lungs from ribs,
costal cartilages & intercostal muscles.
MEDIAL SURFACE :
• Anterior (mediastinal) part:
Contains a hilum in the
middle (it is a depression in
which bronchi, vessels, &
nerves forming the root of
lung).
• Posterior (vertebral) part:
bodies of thoracic
vertebrae, intervertebral discs,
posterior intercostal vessels &
sympathetic trunk.

10. ROOTS :
 Bronchus – principal – lt
eparterial and hyparterial – rt
 pulmonary artery
 2 pulmonary veins
 Bronchial arteries– rt – 1
 lt-2
 Bronchial veins
 Pulmonary plexus of nerves
 Lymphatics of lungs
 Bronchopulmonary lymph nodes
 Areolar tissue

11. Arterial supply of lungs
BRONCHIAL ARTERIES ::
supply nutrition to the bronchial tree and pulmonary
tissue.
Rt side – one –3rd
post intercostal or left bronchial artery
Lt side – 2 arteries arise from descending thoracic aorta
PULMONARY ARTERY : carries
non oxygenated blood
from rt ventricle to
lung alveoli.
2 PULMONARY VEINS :
return oxygenated
blood to
the heart.

12. Venous supply
Venous blood from first one or two divisions by
bronchial veins
Rt bronchial vein drains into azygous vein
Lt bronchial vein drains in to hemiazygous or lt
sup intercostal vein.
Greater part of venous blood drained by
pulmonary vein.

13. Lymphatic drainage
Drain peripheral lung
tissue lying beneath
pulmonary pleura
Vessels pass round
borders and margins of
lungs to reach hilum
Numerous valves
Drain bronchial tree,
pulmonary vessels, and
connective tissue septa
Run towards hilum and
drain into broncho-
pulmonary nodes
SUPERFICIAL DEEP

14. Lymph nodal stations can
be divided into :
supraclavicular
mediastinalmediastinal
bronchopulmonary(hilar)
intrapulmonary

15. Rt upper lobe –
tracheobronchial
lymphnodes
Lt upper lobe-
both sides venous
angle of superior
mediastinum
rt and lt lower
lobes-subcarinal
Rt sup mediastinum

16. Nerve supply
 Is by pulmonary plexus located at root of the lung
 Its formed by
parasympathetic– from vagus
motor to bronchial muscles– bronchospasm
secretomotor to mucous glands
sensory – stretch– cough reflex
sympathetic – 2nd
to 5th
spinal segments
inhibitory to smooth muscle and glands

17. BRONCHOPULMONARY
SEGMENTS
Well defined sectors of lung each one of which is
aerated by tertiary or segmental bronchus.
Each segmental is pyramidal in shape
Intersegmental planes : each segment is surrounded by
connective tissue which
is continuous on the
surface with pulmonary pleura.
Thus these are independent
Respiratory units..

19. APPLIED ANATOMYAPPLIED ANATOMY
lobectomy pneumonectomy segmentectomy
Sleeve lobectomy Wedge resection

20. Upper lobe primary
- Ipsilateral SC region
- Upper mediastinum
- Subcarinal area ( 5-6 cm / 2
vertebral bodies below carina)
Middle and lower lobes
-No gross mediastinal disease
Central mediastinal ( thoracic
inlet to 8-9 cm below carina)
No need to treat supraclavicular area
-Gross mediastinal disease
ipsilateral/bilateral SC region to be
included in the treatment volume
ROLE IN RT PLANNING

21. HISTOLOGY
Trachea and extrapulmonary bronchi – pseudostratified
ciliated columnar epithelium.
Terminal bronchiole – columnar epithelium with no
cilia or goblet cells
Respiratory bronchiole – cuboidal cells. Smooth muscle
and conn tissue around
Alveoli – squamous cells , no muscle,gland or cartilage
seen.

22. Pathology of lungPathology of lung
cancercancer

23. Lung cancer is used for tumors arising from
respiratory epithelium (bronchi, bronchioles,
alveoli)

26. Small cell carcinoma
Poorly diff neuroendocrine tumor
Presents as central mass with endobronchial growth.
Strongly ass with smoking
No known preinvasive phase
Produce neuroendocrine markers –cd56,
NCAM,synaptophysin,chromogranin
Produce peptide hormones such as ACTH , AVF, ANF,
GRP.
Ass with paraneoplastic syndromes.
IHC – high BCL2 and less BAX

27. histology
• scant cytoplasm
•small hyperchromatic nuclei with a fine(salt and pepper )
chromatin pattern
•Extensive necrosis
•Azzopardi effect

28. Squamous cell carcinoma
Similar to extrapulmonary squamous cell cancers.
Occur in central part of lung
Ass with smoking
Histologically char by keratin and intercellular bridges.
Keratin can be present as
Squamous pearls or individual
Cells with markedly eosinophi-
lic cytoplasm.
Highest frequency of p53
mutations

29. Adenocarcinoma
In periphery of lung
Presently the most common cause of cancer in both smokers
and non smokers.
Histology shows presence of glands,papillary structure,BA
pattern,mucin,or solid.
Variants ---mucinous
fetal
micropapillary
Clear cell and signet ring eliminated
Majority are positive – TTF 1

30. IASLC/ATS/ERSIASLC/ATS/ERS
multidisciplinary classification of lung adenocarcinoma.
Published in early 2011
Recommendations :
The terms BAC (bronchioloalveolar carcinoma) and mixed
subtype adenocarcinoma are no longer recommended
adenocarcinoma or NSCLC not otherwise specified (NSCLC-
NOS) should be tested for (EGFR) mutations.
adenocarcinoma histology or NSCLC-NOS are strong predictors
for improved outcome with pemetrexed therapy compared with
squamous cell carcinoma;

31. ContCont’d’d
KRAS mutations –
Occur primarily in adenocarcinoma
More in smokers
worse outcome and resistance to EGFR inhibitors
EGFR mutations –
mostly women , non smokers and asian origin
improved survival with upfront EGFR inhibitor
treatment

32. BAC
TERM BAC discontinued acc to
Latest classification.. IASLC/ATS/ERS
 Variant of adeno
 Grows along alveoli without invasion
 Radiologically as a single mass , as a diffuse multinodular lesion , fluffy
infiltrate
 Screening ct scan – ground glass opacity
Categorised into
adenocarcinoma in situ
minimally invasive adenocarcinoma
lepidic predominant adenocarcinoma
pred invasive adenoca
invasive mucinous adenoca

33. Large cell carcinoma
Occur peripherally
Poorly diff ca without any features
Sheets of large malignant cells ass with necrosis.
Variants –basaloid
lymphoepithelioma like carcinoma
Histology – large nuclei,prominent nucleoli and
moderate cytoplasm

34. IHC :IHC :
 markers such as neuron-specific enolase (NSE), CD56 or NCAM,
synaptophysin, chromogranin, and Leu7.
 differentiating primary from metastatic adenocarcinomas;
thyroid transcription factor-1 (TTF-1)—positive in tumors of
thyroid and pulmonary origin (70%),
 A negative TTF-1, however, does not exclude the possibility of a
lung primary. TTF-1 is also positive in neuroendocrine tumors of
pulmonary and extrapulmonary origin

35.  . Napsin-A (Nap-A) :
primary lung adenocarcinoma (Nap-A pos, TTF-1 pos)
primary lung squamous cell carcinoma (Nap-A ne, TTF-1 neg)
primary SCLC (Nap-A neg, TTF-1 pos).
 Cytokeratins 7 and 20
nonsquamous NSCLC, SCLC, and mesothelioma may stain pos for
CK7 and neg for CK20,
squamous cell lung cancer often will be both CK7 and CK20 neg.
 p63 is a useful marker for the detection of NSCLCs with squamous
differentiation when used in cytologic pulmonary samples.
 CK5/6, calretinin, and Wilms tumor gene-1 (WT-1), all of which show
positivity in mesothelioma.

36. Salivary gland tumors :Salivary gland tumors :
These carcinomas include mucoepidermoid carcinomas
(low and high grade), recognized by their characteristic
intermediate or transitional cells, adenoid-cystic
carcinoma, which shares the aggressiveness of its
salivary gland counterpart, and the low-grade, acinic
cell carcinoma
All are predominantly found in
large bronchi and thought to arise
from submucosal gland epithelium.

37. CarcinoidsCarcinoids
prominent neuroendocrine phenotype in morphology,
immunohistochemistry, and ultrastructural features.
 Histology is characterized by organoid, ribbon, or
festoon pseudorosette, and sometimes spindle patterns
of cuboidal cells with small and hyperchromatic nuclei.
found in large bronchi and feature an organoid pattern.
Carcinoids with necrosis,
mitotic figures and/or
progressive nuclear
Anaplasia –atypical type

38. Causes and Risk factors of Lung CancerCauses and Risk factors of Lung Cancer

39. pathogenesispathogenesis
Tobacco smoke -1920’s
Asbestos-1943
Viral causation –BAC
inherited genetic susceptibility to lung cancer
--early 1960s
1982-chromosome 3p deletion
Tumor supressor genes Rb and p53 inactivated
in SCLC and p53 is inactivated in NSCLC

40. Spread of diseaseSpread of disease
3 pathways --- local (intrathoracic)
regional(lymphatic)
systemic(hematogenous)
Undifferentiated small cell carcinoma (oat cell cancer)
has a higher incidence of distant metastasis than non–
small cell cancers.
 adenocarcinoma has shown higher potential for
distant metastasis.
lymph node metastases seem to occur earlier than
distant hematogenous spread.

41.  Mediastinal adenopathy occurs in 40% to 50% of operative
specimens .
 For right lung tumors, lower paratracheal nodes (station IV),
f/b subcarinal nodes (station VII).
 For left upper lobe lesions, the subaortic nodes (station V) f/b
subcarinal nodes.
 For lingular and left lower lobe lesions, the most frequently
involved nodes are subcarinal (10).
 Skip metastases are frequent in adenocarcinoma than in
squamous cell carcinoma
 The incidence of scalene (supraclavicular) nodal involvement
ranges from 2% to 37%. Metastases to these nodes are
predominantly from ipsilateral upper lobes or in patients with
superior mediastinal metastases.

42. Clinical presentation :Clinical presentation :
Most insidious and aggressive of all neoplasms
Only 15 % patients diagnosed at early stage
Major complaints are cough (75%),weight loss (40%) ,
dyspnea (20% )
Symptoms -3 categories
local growth and intrathoracic spread
Distant metastasis
Non specific systemic or paraneoplastic

43. Local growth—central –cough
airway obstruction
post obsrtuctive pneumonitis
peripheral –asymptomatic
pain
lung abscess
Intrathoracic extension –
direct --mediastinum
esophagus - dysphagia
phrenic nerve palsy – hemidiaphragm elevation
hoarseness- rec laryngeal n. palsy
horners syndrome

44. Vascular syndromesVascular syndromes
SVC syndrome
mediastinum mostly by
invasion of the vein
extrinsic compression by the tumor
Intaluminal thrombosis
Small cell ca > squamous cell ca
Right side – rt upper lobe
or rt mainstem bronchus

45. Pancoast syndromePancoast syndrome
Apical tumors
Invasion of lower brachial plexus –C8 and T1
stellate ganglion
chest wall
Shoulder pain radiating in
ulnar side often with
destruction of 1st
and 2nd
ribs
Radiographic –
asymmetric apical cap or mass’
Mostly squamous cell ca

46. Pleural inv – 15% at presentatiom
50% PE through course
Pericardial inv –through direct extension or lymphatics
accounts for 37 % of cases
tamponade,arrythmia or cardiac failure

47. Distant metastasisDistant metastasis
60% of SCLC and 30 – 40% of NSCLC present with
stage IV metastatic disease
At autopsy
> 50% - sq cell
80% adeno
>95% SCLC
Most common sites—
Adrenals mets are common
but rarely symptomatic

48. Nonspecific symptomsNonspecific symptoms
Anemia
Anorexia
Weight loss
Gen weakness
Night sweats

49. Paraneoplastic syndromesParaneoplastic syndromes
Common in SCLC
Types– endocrine
metabolic
neuromuscular
vascular
hematologic
inv skeletal system, muscular, skin.

51. SCREENINGSCREENING
Why don’t we screen for lung cancer?
"screening with annual CT has been shown to reduce
lung cancer deaths compared to chest Xray” …….
BUT
High false positives
best selection criteria for screening not yet known
cost effectiveness uncertain
risk of over diagnosis and invasive tests for benign
disease
need for lots of follow up CTs
Also smoking cessation and tobacco control are likely to
be much more (cost) effective

52. WORKUPWORKUP
Baseline investigations
Confirmation of diagnosis
sputum cytology
transthoracic FNAC
bronchoscopic biopsy
Extent of disease
imaging
bronchoscopy
mediastinoscopy
VATS

53. Chest-XRAYChest-XRAY
AP and lateral view
Visible when 7- 10 mm in diameter
Can localize site of disease
Can identify t4 disease when there is pleural effusion or
hemi diaphragm elevation
Advanced disease identified by rib destruction
Lymph nodes diff to identify

54. Small cell carcinoma adenocarcinomaSquamous cell Ca

55. Sputum cytologySputum cytology
Simple and non invasive
Less used now
three daily pooled specimens increase the diagnostic
yield.
Sensitivity – 65%
specificity –99.5%

56. CT scanCT scan
Most effective ,non invasive technique
In suspected cases and to see mediastinal inv
Disadv – sensitivity variable in identifying metastatic
disease in mediastinal lymph nodes 51% to 95%
 Neg predictive accuracy –85 to 92%
>1cm sized lymph node is significant
sensitivity of 60% & specificity of 80%

57. PET SCANPET SCAN
Detect lesions >5-8mm and has become standard work up for
NSCLC
PET is superior to CT in staging mediastinum
Sensitivity and specificity of PET-- 84% and 89% resp.
CT – 57% and 82% resp.
False neg – small tumors –limited spatial resolution
tumors with low glucose met- carcinoid and BAC
diabetes
lesions < 8 mm
False positive – benign inflammatory dis – abscess,active
granulomatous conditions,post rt
thus pet is never used alone to diagnose lung
cancer.

58. Pet/ctPet/ct
precise CT correlation with the extent of 18F-FDG
uptake, the location of the primary tumor can be
exactly defined
PET-CT can distinguish malignant lesions from benign
lesions with an accuracy of 82% with varying
sensitivity and specificity values (from 79% to 96% and
from 40% to 83%, respectively
mediastinal node stage, the benefit of PET-CT lies
especially in very high negative predictive value over
90%

59. MRIMRI
Equal to ct in identifying lymph nodes
Useful when tumors are adjacent to vertebral body or
spinal canal ----
as provides superior visualization of spinal
canal hence can detect invasion
Delineate superior sulcus tumors relation to major
vessels and brachial plexus at thoracic outlet
Brain metastasis

60. Bone scanBone scan
Once indicated in the presence of:
Bone or chest pain , Raised ALP , Elevated serum
calcium
Pet has replaced it

61. Fibreoptic bronchoscopyFibreoptic bronchoscopy
Essential and standard technique
Determining endobronchial extent of disease,measuring
tumor proximity to carina and various bronchi ,identifying
unsuspected occult lesions
Gives accurate histologic diagnosis 90% cases if lesion is
visible
Central lesions readily dia-
gnosed by this whereas peripher-
al lesions require transthoracic
biopsy

62. Percutaneous Fine-Needle AspirationPercutaneous Fine-Needle Aspiration
FNA is an excellent method for establishing tissue
diagnosis of pulmonary nodules. The positive yield
exceeds 95% even if lesions are less than 1 cm in
diameter.
Abnormalities involving bone, liver, and adrenal
glands, suggestive of metastatic disease on staging
studies, can be readily confirmed by FNA using
ultrasonographic or CT-guided techniques.

63. MEDIASTINOSCOPYMEDIASTINOSCOPY
Necessary for detection in mediastinal lymph nodes when
ct and pet report do corroborate each other
Evaluate upper ,middle peritracheal and subcarinal lymph
nodes
Subaortic and aortopulmonary window inaccesible by
standard cervical mediastinoscopy
Ant mediastinoscopy –Mcneil and Chamberlain
visual acces to ant mediastinum through 2,3,4 ant
interspace
used on left side to evaluate ds in subaortic,lateral
aortic and aortopulmonary window

65. Endoscopic USEndoscopic US --
 EUS-guided FNA is more accurate than CT in
identifying mediastinal nodal metastases
safe and minimally invasive method with high accuracy
Locations such as subcarinal,aortopulmonary window,
and paraesophageal area are especiallysuited for EUS-
guided FNA, as these locations are hard to access
during mediastinoscopy

66. ThoracentesisThoracentesis
Needle drainage of a pleural effusion associated with a
presumed lung cancer can identify inoperable, pleural
disease (T4).
In general, a diagnosis of cancer in can be established in
70% of malignant effusions by thoracentesis. If the
initial thoracentesis is negative, additional
percutaneous thoracenteses improve the diagnostic yield

67. VATSVATS
Principal use– excisional biopsy of peripheral lung nodules to
diagnose primary lung cancer or rule out synchronous or
metastatic disease
Less effective for lesions in post paravertebral space or in
deep lung parenchyma
Valuable adjunct to cervical mediastinoscopy and ant
mediastinoscopy for evaluating post mediastinum and
peritracheal,subazygous,hilar and aortopulmonary window

69. TNM STAGING – ajcc 7TNM STAGING – ajcc 7thth
edition.edition.
Determination of location of tumor and possible
metastatic sites (anatomic)
Assesment of patients ability to withstand antitumor
treatments (physiologic)
Major goal is to decide the further treatment plan
Surgical resection mainly NSCLC

70. Anatomic staging :Anatomic staging :

75. NODALNODAL

83. Lung Cancer Staging --SCLCLung Cancer Staging --SCLC
veterans administration lung study groupveterans administration lung study group
(VALG) staging system(VALG) staging system
Limited Disease
◦ No detectable disease outside of hemithorax
◦ With or without ipsilateral or contralateral, hilar,
mediastinal, or supraclavicular LN involvement
◦ Single radiation therapy port
Extensive Disease
◦ Any disease occurring beyond sites of limited disease

84. CONCLUSIONCONCLUSION
As only 15% of patients present at early stage there is a
need for effective screening procedures for lung cancer–
and still trials are on going for that , the best thing we
can do is prevent it by promoting smoking cessation.
 Accurate staging of the disease is an important part of
the management as it provides estimation of patient’s
prognosis and identifies treatment strategies.

85. referencesreferences
 Hochhegger B, Marchiori E, Sedlaczek O, et al. MRI in lung cancer: a
pictorial essay. The British Journal of Radiology. 2011;84(1003):661-668.
doi:10.1259/bjr/24661484.
 Halperin EC, Perez CA, Brady LW (eds). Principles and Practice of
Radiation Oncology, Fifth Ed. Philadelphia, Pa: Lippincott Williams &
Wilkins 2008.
 DeVita. Hellman And Rosenberg's Cancer Principles And Practise
Of Oncology-8th
edition
 Harrison's Principles of Internal Medicine, 18th Edition and 19th
edition
 Jeleric.et.al.Radiol Oncol. 2015 Mar .The role of PET-CT in radiotherapy
planning of solid tumours.