P.A 26.

6 (SGD)

Define and describe the etiology , types, exposure ,

genetic environmentalinfluence , pathogenesis ,
stages , morphology, microscopic appearance
,metastases and complications of tumours of the lung.

Dr. Suchi Godhani

• Most common cause of cancer-related deaths
in industrialized countries
• 1/3 of cancer deaths in men

• Risk factors:
Cigarette smoking “contain 60 carcinogens”
Radon “formed by radioactive decay of
uranium”
Asbestos
Other etiological factors are –

• Tobacco smoking – has a carcinogens and

tumor promoter in it
• Atmospheric pollution – non smokers living in
industrialised area are affected
• Occupational causes - workers exposed to
asbestose , nickel , arsenic , metallic iron.
• Dietary factors – smokers with low vit. A has a
greater risk
Histological Types:

A) Small cell carcinoma (19%)

B) Non small cell carcinoma (85%)

• Squamous cell carcinoma 30%
• Adenocarcinoma 40%
• Large cell carcinoma 10%
• Carcinoid tumor 5%
Pathogenesis -

• Smoking is the leading cause; 85% of lung

cancer occurs in smokers in “ sp: Small cell
carcinoma & Squamous cell carcinoma”

• Step wise progression

metaplasia>dysplasia>carcinoma in situ >
carcinoma
Molecular pathogenesis –

1) activation of growth promoting oncogens –such as

mutation in K-RAS , EGFR, BRAF and MYK family

2) inactivation of tumor suppressor genes – mostly these

tumor suppressor genes are found on chromosome 3p
• And this includes inactivation of p53 and Rb gene

3) inherited predisposition –
• Not common but some patient of Li-fraumeni who inherit
p53 mutation can develop lung carcinoma
• Case of retinoblastoma having mutation in Rb gene can
develop lung cancer if they live upto adulthood.
• Mutation of cytochrome P450 ( metabolises chemican
carcinogen present in tobacco smoke )
Morphology -
• Based on location – lung cancer may be hilar (
Central ) or peripheral

1) Hilar type – hilar location is the most common site

, particularly squamous cell carcinoma arises in
central region ( in main bronchus or one of its
segmental branch in the hilum of lung .

2) Peripheral type – These tumors are in subpleural

location , mostly adenocarcinomas , originates from
a small peripheral bronchioles
Histologically –

Most common types malignant epithelial lung

tumors are
i. Adenocarcinoma
ii. Squamous cell carcinoma
iii. Small cell carcinoma
iv. Large cell carcinoma
The incidence of adenocarcinoma of lung has risen
and is the most frequent subtype if lung cancer
almost accounting for half of all the lung
tumors.
1) Adenocarcinoma

• Most common lung cancer in nonsmokers and females

• Activating mutation of K-Ras
• Associated with hypertrophic osteoarthropathy “clubbing”
• Located peripherally with central scar
• Glandular differentation with tubules or papillae and mucin
secretion

• Invasive adenocarcinomas further subclassified in :

i. Acinar (gland forming)
ii. Papillary
iii. lepidic
iv. Solid
v. micropapillary
Gross:
• poorly
circumscribed
• Gray-yellow lesion,
single/ multiple
• Mucoid, glairy
appearance
• Cavitations are rare
• More peripherally
located
• Small in size
• Grow slowly
• Metastasize widely
& earlier
• K-RAS mutation
seen
Histological features
Shows predominant
glandular pattern or
duct like
appearance
Often occur in the
large bronchi.
• 25-40% of
2) Squamous cell
brochogenic Ca carcinoma
• Male predominate
• Most of cases
presented with
hilar/perihilar mass
• Correlated with
smoking
• Central necrosis
with cavitations
seen
• Calcification is rare
Histological features:
Presence of keratin
pearls
Stratification of tumor
cells
Oncocytoid
appearance of tumor
cells
Higher mitotic activity
Highest frequency
with p53 mutations
 3) Small cell carcinoma
• Male predominance,
median age – 60 yrs.
• Strong relationship to
cigarette smoking
• Occur both in major
bronchi & in the periphery
of lung.
• Tumor is white - tan, soft,
friable, extensively necrotic.
• Most aggressive & widely
metastasize tumors
• P53 & RB tumor
suppressor genes are
frequently mutated
Histological features -

•Highly malignant tumor

• Epithelial cells are small, scant

cytoplasm, ill defined cell
borders, finely granular nuclear
chromatin (salt & pepper
pattern), inconspicuous nucleoli.

• Mitotic count is high

• Cells grow in clusters

• Necrosis is common & often

extensive
Small cell carcinoma
 4) Large cell carcinoma -

•Undiffrentiated malignant
epithelial tumor

•Cell typically have large

nuclei, prominent nucleoli,
moderate cytoplasm

•Patterns seen are:

organoid nesting,
trabecullar, rosette-like,
palisading patterns
Metastasis lung tumor –

• The lung is the most common site of metastatic

neoplasms. Both Ca & sarcomas arising anywhere in
the body may spread to the lungs via the blood /
lymphatics/ direct continuity.
• Growth of contagious tumors into the lungs occur
most often with esophageal Ca & mediastinal
lymphomas.
• Most metastases are multiple, bilateral, sharpely
outlined and rapidly growing.
• Multiple discrete nodules range from miliary to
cannon ball lesions more common in lower lobes.
Metastatic Tumors in The Lungs -

• Prostate
• Colon
• Cervix
• Breast
• Bone
• Bladder
 Clinical features -
• Cough
• Weight loss
• Pain
•  es sputum production
• Hemoptysis
• Malaise
• Fever
• Solitary mass
• lymphadenopathy
Complications

“SPHERE”
• S: superior vena cava syndrome
• P: pancoast tumor
• H: horner syndrome
• E: pleural effusion
• R: recurrent laryngeal symptoms (hoarseness) “left”
• E: endocrine
ADH > hyponatremia
ACTH> Cushing’s syndrome
PTH> hypocalcemia
HCG> gynaecomastia