Lung cancer is characterized by uncontrolled cell growth in lung tissues. Worldwide, it is the leading cause of cancer death in men and women, responsible for 1.3 million deaths annually. The main causes are smoking and exposure to radon, asbestos, viruses and other particulates. Symptoms include coughing, shortness of breath, and weight loss. Diagnosis involves imaging tests and biopsies. Treatment depends on cancer type and stage but may include surgery, chemotherapy, and radiation therapy.

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LUNG CARCINOMA

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DEFINITION
• Lung cancer is a disease characterized by
uncontrolled cell growth in tissues of the lung.
• If left untreated, this growth can spread
beyond the lung in a process
called metastasis into nearby tissue and,
eventually, into other parts of the body.

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Epidemiology:
Worldwide, lung cancer is the most common
cause of cancer-related death in men and
women, and is responsible for 1.3 million
deaths annually, as of 2004.
Ref: WHO (February 2006). "Cancer". World
Health Organization. Retrieved 2007-06-25.

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Signs and symptoms:
• dyspnea (shortness of breath)
• hemoptysis (coughing up blood)
• chronic coughing or change in regular coughing
pattern
• wheezing
• chest pain or pain in the abdomen
• cachexia (weight loss), fatigue, and loss
of appetite
• dysphonia (hoarse voice)
• clubbing of the fingernails (uncommon)
• dysphagia (difficulty swallowing)

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Causes:
Smoking
• Smoking, particularly of cigarettes, is by far
the main contributor to lung cancer. Cigarette
smoke contains over 60 known carcinogens.
• Additionally, nicotine appears to depress the
immune response to malignant growths in
exposed tissue.

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• Passive smoking—the inhalation of smoke
from another's smoking—is a cause of lung
cancer in nonsmokers.
• Studies from the U.S., Europe, the UK, and
Australia have consistently shown a significant
increase in relative risk among those exposed
to passive smoke.
• 10–15% of lung cancer patients have never
smoked.

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Radon gas
• Radon is a colorless and
odorless gas generated by the breakdown of
radioactive radium, found in the Earth's crust.
• The radiation decay products ionize genetic
material, causing mutations that sometimes
turn cancerous. Radon exposure is the second
major cause of lung cancer in the general
population, after smoking.

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Asbestos
• Asbestos can cause a variety of lung diseases,
including lung cancer.
• Asbestos can also cause cancer of the pleura,
called mesothelioma(which is different from
lung cancer).

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Viruses
• Viruses are known to cause lung cancer in
animals, and recent evidence suggests similar
potential in humans.
• These viruses may affect the cell cycle and
inhibit apoptosis, allowing uncontrolled cell
division.
• Implicated viruses include:
– human papillomavirus,
– JC virus, simian virus 40 (SV40),
– BK virus, and
– cytomegalovirus.

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Particulate matter
• Studies of the American Cancer Society cohort
directly link the exposure to particulate
matter with lung cancer. For example, if the
concentration of particles in the air increases
by only 1%, the risk of developing a lung
cancer increases by 14%.
Krewski D, Burnett R, Jerrett M, Pope CA, Rainham D, Calle E,
Thurston G, Thun M (2005 Jul 9-23). "Mortality and long-term
exposure to ambient air pollution: ongoing analyses based on
the American Cancer Society cohort". J Toxicol Environ Health
A 68 (13–14): 1093–109.

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Pathogenesis:
• Oncogenes:
– activation of oncogenes or inactivation
of tumor suppressor genes.
– Proto-oncogenes are believed to turn into
oncogenes when exposed to particular
carcinogens.
– Mutations in the K-ras proto-oncogene are
responsible for 10–30% of lung
adenocarcinoma.

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• Epidermal Growth Factor Receptor (EGFR)
– EGFR regulates cell
proliferation, apoptosis, angiogenesis, and
tumor invasion
– Mutations and amplification of EGFR can lead
to cancerous growth, esp. non-small-cell lung
cancer (basis for the treatment with EGFR-
Inhibitors)

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• Chromosomal damage:
– Chromosomal damage can lead to loss of
heterozygosity
– This can cause inactivation of tumor suppressor
genes.
– Damage to chromosomes 3p, 5q, 13q, and 17p are
particularly common in small-cell lung carcinoma.
– The p53 tumor suppressor gene, located on
chromosome 17p, is affected in 60-75% of cases.

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• Genetic polymorphisms
– People with genetic polymorphisms are more likely
to develop lung cancer after exposure
to carcinogens.
– These include polymorphisms in genes coding for
» interleukin-1,
» cytochrome P450,
» apoptosis promoters such as caspase-8,and
» DNA repair molecules such as XRCC1

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Diagnosis:
• Chest Radiograph:
Look for-
o An obvious mass
o Widening of mediastinum
(suggestive of spread to lymph nodes there)
o atelectasis (collapse)
o consolidation (pneumonia), or
o pleural effusion.

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• Blood stained sputum present, but radiograph
normal, then:
– Bronchoscopy
– CT Scan
– CT Scan guided biopsy(to find the tumor type)
– Sputum Cytologic examination

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Differential Diagnosis:
• Abnormalities on chest radiograph:
– infectious causes such as tuberculosis or
pneumonia,
– inflammatory conditions such as sarcoidosis
– mediastinal lymphadenopathy or lung nodules,
sometimes mimic lung cancers

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Classification:
• Lung carcinomas classified according to
histological types:
– Non-small-cell Carcinoma
– Small-cell carcinoma

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• Non-small-cell carcinoma:
– squamous cell lung carcinoma
– adenocarcinoma, and
– large-cell lung carcinoma.

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Others
• Currently, the most widely recognized and utilized lung
cancer classification system is the 4th revision of the
Histological Typing of Lung and Pleural Tumours, published in
2004 as a cooperative effort by the World Health
Organization and the International Association for the Study
of Lung Cancer.
• It recognizes numerous other distinct histopathological
entities into several subtypes.

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Metastasis:
• The lung is a common place for metastasis of
tumors from other parts of the body.
• Secondary cancers are classified by the site of
origin; e.g., breast cancer that has spread to
the lung is called breast cancer.
• Metastases often have a characteristic round
appearance on chest radiograph.

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• Micrograph of a lung lymph node biopsy
showing metastatic colorectal
adenocarcinoma. (Field stain).

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Lung Cancer Staging:
• Staging is the process of determining how
much cancer there is in the body and where it
is located.
• Staging information which is obtained prior to
surgery, for example by x-rays and endoscopic
ultrasound, is called clinical staging and
staging by surgery is known as pathological
staging.

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TNM Classification of Malignant
Tumours (TNM):
• T describes the size of the tumor and whether
it has invaded nearby tissue,
• N describes regional lymph nodes that are
involved,
• M describes distant metastasis

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T: size or direct extent of the primary tumor
• T- CIS
• T0
• T 1-4

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N: degree of spread to regional lymph nodes
• N0: tumor cells absent from regional lymph nodes
• N1: regional lymph node metastasis present; (at
some sites: tumor spread to closest or small number
of regional lymph nodes)
• N2: tumor spread to an extent between N1 and N3
(N2 is not used at all sites)
• N3: tumor spread to more distant or numerous
regional lymph nodes (N3 is not used at all sites)

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M: presence of metastasis.
• M0: no distant metastasis
• M1: metastasis to distant organs (beyond
regional lymph nodes)

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Staging modalities:
• CT and PET scans
• PFTs
• Endoscopic ultrasound (EUS)
• Endobronchial ultrasound (EBUS)
• Mediastinal staging
– Nearly half of lung cancers
have mediastinal disease at diagnosis, involving
any of the mediastinal lymph nodes.
– on the same side lymph nodes - N2
– if they are on the other side - N3

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Management:
• Non-surgical
– Radiotherapy
– Chemotherapy
• Surgical

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Radiotherapy:
• Radiation therapy works by damaging the DNA of cancerous
cells.
• the older, most common form of radiation therapy, Intensity-
modulated radiation therapy (IMRT) or photon radiation
therapy.
• Direct damage to cancer cell DNA occurs through high-LET
(linear energy transfer) where charged particles such
as proton, boron, carbon or neon ions which have an
antitumor effect, are used to break DNA strands.
• Brachytherapy (localized radiotherapy) may be given directly
inside the airway when cancer affects a short section of
bronchus. It is used when inoperable lung cancer causes
blockage of a large airway.

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Chemotherapy:
• The chemotherapy regimen depends on the tumor type.
• Small-cell lung carcinoma
– Even if relatively early stage, small-cell lung carcinoma is
treated primarily with chemotherapy and radiation.
– Cisplatin and Etoposide are most commonly used.
• Non-small-cell lung carcinoma
– Advanced non-small-cell lung carcinoma is often treated
with Cisplatin or Carboplatin, in combination
with Gemcitabine.
– For adenocarcinoma and large-cell lung cancer, Cisplatin
with Pemetrexed-more beneficial than cisplatin and
gemcitabine.
– Bronchoalveolar carcinoma may respond to Gefitinib
and Erlotinib.

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Surgical Management
 Wedge resection: If the patient does not have
enough functional lung, this technique is
preferred.
 Segmentectomy
 Lobectomy: In patients with adequate respiratory
reserve this is preferred, as this minimizes the
chance of local recurrence.
 Pneumonectomy

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Pneumonectomy specimen containing a squamous
cell carcinoma, seen as a white area near the
bronchi.

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THANK YOU