• Epidemiology

• Etiology and Pathogenesis

Tumours
• Classification
of
• Gross appearance
Lung
• Microscopic appearance

• Clinical course
 Epidemiology
• In India, in the year 2018, 22.5 million people were inflicted with
cancer. 11.5 million new cases and 7.8 million cancer deaths
were reported in the same year.
• Top five cancers affecting Indians are - cancer of breast, oral
cavity, cervix, stomach and lung.
• In India, around 50,000 people were newly diagnosed with lung
cancer (LC) in the year 2018
• Lung cancer is ~ 4.5 times commoner in males and mean age at
diagnosis is 54.6 years.
• LC are generally divided into two main categories: small cell
lung cancer (SCLC) and non-small cell lung cancer (NSCLC).
• NSCLC accounts for approximately 85% of all lung cancers.
• Histologically, NSCLC is further sub-divided as adenocarcinoma,
squamous cell carcinoma (SCC) and large cell carcinoma
 Etiology and Pathogenesis
• Three important factors are implicated in pathogenesis of LC:
– Cigarette smoke
– Environmental factors
– Genetic factors
1. Cigarette Smoke
• About 80 - 90% cases of LC can be attributed to tobacco smoke
(TS).
• TS has more than 300 harmful substances of which 40 are known
to be potent carcinogens. For e.g.
– Polyaromatic hydrocarbons and nicotine-derived nitrosamine
ketone (NNK) found in TS causes DNA damage by forming
adducts.
– Benzo-A-pyrine induces AKT molecular signaling pathway. It
also produces mutations in p53 and other tumor suppressor
genes.
• However, not all persons exposed to tobacco smoke go on to
develop LC.
• Genetic variation in mitochondrial P- 450 monooxygenase system
(converts procarcinogens to carcinogens) is possibly responsible
for this variation.
• Heavy smokers have 60 times greater risk of developing LC as
compared to non-smokers.
• Increased risk decreases but does not fade away with cessation of
smoking.
2. Environmental Factors
– Industrial factors - e.g. asbestos, arsenic, chromium, nickel,
mustard gas and vinyl chloride. In non-smokers asbestos
increases risk 5 times
– Air Pollution - adds to the risk in persons already exposed to
carcinogens. Perhaps 1-2% cases of LC can be attributed to air
pollution
3. Genetic factors
– Squamous cell carcinoma - shows mutations in TP53, RB
tumor suppressor gene, CDKN2A and FGFR1 gene.
– Adenocarcinoma - gain of function mutations in EGFR, ALK,
MET, RET and KRAS genes
– Small cell carcinoma - loss of function mutations in TP53 and
RB genes. Amplification of MYC family genes.
4. Others
– COPD, TB, Interstitial fibrosis, Ionizing radiation exposure

Clinical Significance:
Some persons who have never smoked develop LC. These
patients are genetically distinct from smoking- related NSCLC.
There is lower frequency of K -ras and higher incidence of EGFR
mutations. EGF receptor inhibitors are more efficacious in such
patients.
 Classification
• Lung cancers are generally divided into 2 main categories:
1. Small cell lung cancer (SCLC) and
2. Non -small cell lung cancer (NSCLC).
• NSCLC accounts for approximately 85% of all lung cancers.
• NSCLC is divided further into:
– Adenocarcinoma,
– Squamous cell carcinoma (SCC) and
– Large cell carcinoma.
• Other rare forms of LC are:
– Adeno-squamous cell carcinoma
– Carcinoma with sarcomatous elements
– Carcinoid tumour
– Carcinoma of salivary gland type.
Gross Appearance
 Squamous cell carcinoma
• Found more often in central or
hilar region of the lung.
• More common in men.
• H/O smoking is often present.
• The tumour may grow
– Into the bronchial lumen -
produces obstruction and
atelectasis.
– Into the surrounding lung
parenchyma having a broad
front.
– Neoplastic tissue is gray
white in color with areas of
hemorrhage and necrosis
– The tumour may undergo
cavitation.
Bronchoscopic appearance of SCC
Squamous cell carcinoma
Squamous cell carcinoma
Adenocarcinoma Lung
• Tends to occur in peripheral Adenocarcinoma
regions of lung.
• In some cases it occurs at the
site of pre-existing scars,
wounds, or inflammation (scar
carcinoma).
• Occurs more often in non -
smokers.
• Its incidence is increasing and
in some regions it is more
common than squamous cell
carcinoma.
• A distinct sub-type is broncho-
alveolar carcinoma - cells grow
along alveolar septae.
• This form may appear as a
nodule, multi-focal disease of in
a pneumonic form.
 Adeno-
carcinoma
with
metastasis
• Occurs mostly in smokers. Small cell cancer
• Only 1% cases are seen in non-
smokers.
• Most malignant form of LC.
• Can occur in large bronchi or
at the periphery.
• A neuroendocrine cancer that
spreads early to distant sites
• Very responsive to chemo and
radiotherapy.
• Frequently associated with
paraneoplastic syndromes like
hypercalcemia, Eaton-Lambert
syndrome, syndrome of
inappropriate antidiuretic
hormone secretion (SIADH)
 Small cell
cancer with
lung collapse
 Large cell carcinoma
• It is an undifferentiated malignant epithelial tumour.
• Constitutes ~ 10 -15% of LCs
• It is usually seen in peripheral part of the lung.
• It lacks cytological features of other types of lung
cancer.
• Many large cell LC when investigated with makers
are found to be poorly differentiated SCC or
adenocarcinoma.
• Hence to classify a tumour as large cell LC, markers
of any other form of LC should be absent.
• Prognosis is similar to adenocarcinoma.
Microscopic Appearance
 Squamous cell carcinoma
• Tumour cells show
keratinization and/or
intercellular bridges.
• Tumour grade may range from
well to poorly differentiated.
• Adjacent to tumour mass,
squamous metaplasia,
dysplasia of carcinoma in situ
may be seen.
• As tumour cells exfoliate
readily, sputum cytology is
often positive.
• Hypercalcemia is seen most
commonly with this form of
LC.
Squamous cell carcinoma
Poorly differentiated SCC
• Histology may range in Adenocarcinoma
appearance from well -
differentiated glands to a more
solid appearance with presence
of few mucinous cells.
• If the cells grow along the
alveolar septae, the pattern is
called lepidic (broncho-
alveolar). Such tumours have
better prognosis than pure
adenocarcinoma..
• Mucinous adenocarcinoma
spreads through airways to
other parts of the lung, even
resembling pneumonic
consolidation.
• Majority of AC express thyroid
transcription factor 1 (TTF-1)
Lepidic adenocarcinoma
• It is formed of small cells with Small Cell Carcinoma
scant cytoplasm and finely
granular chromatin (salt and
pepper appearance).
• Nuclear molding is seen.
• Mitotic count is high.
• Often extensive necrosis is
seen.
• They are high grade tumour
derived from progenitor
neuro-endocrine cells
• Often exhibit para-neoplastic
manifestations especially
hypercalcemia.
• BCL2 is expressed in > 90%
cases.
Small cell carcinoma
Small cell carcinoma
 Large cell
carcinoma
• Tumour cells have
large nuclei with
prominent nucleoli
and moderate
amount of
cytoplasm.
• Do not express
markers associated
with SCC or AC.
• It is a diagnosis of
exclusion.
• Local effects
Complications
– Focal emphysema
– Atelectasis
– Suppurative bronchitis
– Lipoid pneumonia
– Pulmonary abscesses.
– Destruction of ribs.
– Diaphragm paralysis
– Superior vena cava syndrome
– Horner syndrome
– Pleural and pericardial effusion
• Distant effects:
– Depends on site of metastasis.
– Para-neoplastic syndromes.
 Clinical Course
• Overall 5-year relative survival rate of LC
– 55.6% for localized disease

– 28.9% for regional disease

– 4.5% for distant-metastasis disease

• Survival rate of small cell lung cancer (SCLC)

– Approximately 60-70% of patients have clinically
disseminated disease at presentation which is incurable.

– With combination chemotherapy, patients having

disseminated disease - Mean survival is one year. Only 2%
are alive at 5 years.

– ~ 20% cure possible if disease is localized.