Carcinoma of lung

Lung cancer is most frequent by a major cause

with high mortality worldwide.
In 2008, in USA, the estimated No of cancer were
215,020, out of which 15% were diagnosed and
29% cancer related deaths
In 2008, the estimated death from the lung cancer
in USA were161,840
Since 1990, the death rate is decreasing in men
most likely due to the decreased smoking rate
over the past 30yrs
Since 1987,more women have died each year of
lung cancer than breast cancer
Lung cancer more often occur b/w the age
of 40-70 yrs with peak incidence in the
50s or 60s. Only 2% of all the cases
appear before 40
1yr survival rate has increased from 34%
(1975) to 41% (2007), largely b/c of
improvement is surgical technique
5yr survival rate for all stage is only 16%
Etiology and pathogenesis

The well known carcinogens are
Tobacco smoking :
87% of the lung cancer occur in active
smoker or who stopped smoking recently
There is statistical association b/w the
frequency of lung cancer and the
1) The amount of daily smoking
2) The tendency to inhale
3) Duration of smoking habit
The heavy smoker (40 cigarette/ day for
several years) has 60 fold greater risk .
There are often genetic factors involved
There is an association b/w cigarette
smoking and cancer of mouth, pharynx,
larynx, esophagus, pancreas, uterus,
cervix, kidney and urinary bladder
Second hand smokers or enviremental
smoker accounts about 3000 non smoking
adults die of lung cancer
Smokeless tobacco is not a safe choice
Industrial hazards
Uranium is weakly radioactive, but incidence
of lung cancer is high 4times among
miners than those in general population
The incidence of lung cancer is in
asbestose exposure specially when
coupled with smoking
Air pollution
Radon is a ubiquitous radio active gas, and
incidence is high among those who are
relatively more exposed, (mine worker)
Molecular Genetic : The exposure to the
carcinogen act by genetic alteration in the
lung cells and lead to neoplastic
phenotype
10-20 genetic mutation occur by the time
cancer is actively appear
Histological classification of
bronchogenic carcinoma
I. Non small cell carcinoma 70-75%
a) Squamous cell carcinoma 25-35%
b) Adeno carcinoma including
bronchioalveolar carcinoma 30-35%
ii Small cell lung carcinoma 20-25%
iii Combine pattern 5-10%
a) Mixed squamous cell carcinoma and
adenocarcinoma
b) Mixed squamous cell carcinoma +SCLC
Morphology
Squamous cell carcinoma are often
preceded by squamous metaplasia or
dysplasia in the bronchial epithelium which
then transform to carcinoma in situ.
(a phase that may last for yrs .
At this stage
a) Atypical cells may be: Identified to
cytoplasmic smear of sputum
Or in bronchial levage fluid or brushing. At
this time the lesion is undetectable on x-ray
and remain asymptomatic
Eventually the growing neoplasm
reaches to detectable size and obstruct the
lumen of major bronchus, often producing
distal atelectasis and infection
This tumor may adopt a variety of paths.
It can penetrate rapidly to .
a) Wall of the bronchus to infiltrates peri
bronchial tissue
b) Into the adjacent region of mediastinum
c) It can also grow along a broad form to
produce cauliflower like intraparenchymal
mass
In almost all pattern, the neoplastic tissue is
gray white and firm to hard specially
when tumor are bulky

Yellow white motling and softening are
seen in focal areas of hemorrhage or
necrosis
Some time these foci cavitate
Often these tumor erode the bronchial
epith
Extension may occur to the pleural
surface, pleural cavity or into the
pericardium and to the tracheal, bronchial
and mediastinal nodes
Distal spread occur through both lymphatic
and hemorrhagic pathway
No organ or tissue is spared in the spread
of the lesion. Liver 30-50%, brain 20%,
bone 20% .
It is most common type of lung cancer in
man, strongly associated with smoking
Squamous cell carcinoma show the highest
frequency of P53 mutation of all histologic
type of lung carcinoma
Adenocarcinoma
This is a malignant epith, tumor with glandular
differentiation or mucin production by the
tumor cells .
Adenocarcinoma grow in various pattern
including
a) Acinus
b) papillary
c) bronchioalveolar
d) solid with mixed tumor
It is common type lung cancer in women and
non-smokers
As compared with squamous cell carcinoma,
the lesions are on periphery and smaller
A majority are positive for thyroid transcription
factor TTF-1 and about 80% contain mucin
At periphery, there is often
bronchioalveolar pattern of spread and
tend to metastasize widely and earlier
KRAS mutation occur in adenocarcinoma.
In smoker the frequency is 30% and in non
smoker 5%
P53,RB1,P16 mutation and inactivation
have the same frequency in
adenocarcinoma as in squamous cell
carcinoma
Bronchioalveolar carcinoma
Occur in the pulmonary parenchyma in the
terminal bronchioalveolar region
Macroscopically, the tumor always almost occur
in the periphery of lung, either single nodule or
multiple nodule, which some time coalesce to
produce pneumonia like consolidation
Parenchyma nodule have mucinous gray
translucent when secretion is present, but other
wise appear as solid gray white areas
Histologically
The tumor is characterized by a pure
bronchioalveolar growth pattern with no
evidence of stromal, vascular or pleural
invasion
The growth pattern has been termed as
lepidic
(an allusion to the neoplastic cells
resembling butterfly sitting on fence)
It has 2 subtypes
1)Mucinous 2) non Mucinous
Non mucinous has columnar, peg shaped or
cuboidal cell. While the mucinous has
distinctive tall columnar cell with
cytoplasmic and intracellular mucin,
growing along the alveolar septa.
Non mucinous bronchioalveolar carcinoma
often consists of a peripheral lung nodule.
With surgical resection, it has 5yrs survival
Mucinus BAC form satellite tumor often
present as single or multiple nodule, or an
entire lobe may be consolidating by tumor
resembling lobar pneumonia. therefore less
likely to be cured by surgery
Atypical adenomatous hyperplasia
progressing to bronchio alveolar carcinoma
transform into invasive adenocarcinoma
which is monoclonal and share many
molecular aberration such as FGFR mutation
Small cell carcinoma
Is highly malignant and has a distinctive cell type
The epithelial cells are relatively small, with scanty
cytoplasm.
Cell borders are ill-defined, finally granular pattern
of nuclear chromatin and absent or inconspicuous
nucleoli
Cells are round, oval or spindle shaped. Nuclear
molding is prominent
Mitotic count is high, the cell grow in cluster
(neither glandular nor squamous) necrosis is
common often extensive
Azzopardi effect is present (due to encrustation
DNA from necrotic tumor cell, vascular wall stain
basophilic
All small cell carcinoma are high grade
Small cell carcinoma are often combined with
large cell neuroendocrine carcinoma and
sarcoma
Small cell carcinoma have a strong relationship
to cigarette smoking . Only 1% occur in non
smoker
They may arise in major bronchi or in the
periphery
P53,RB1 tumor supper genes are frequently
mutating
Large cell carcinoma
It lacks the cytoplasmic feature of small
cell carcinoma and glandular or squamous
differentiation
The cell typically has large nuclei,
prominent nucleoli and moderate amount
of cytoplasm
Large cell carcinoma (L.C.C) represent
squamous cell carcinoma and
adenocarcinoma, that can not be
diffentiated by light microscope
Large variant is neuroendocrine carcinoma
which can be confirmed by immunocyto
chemistry and electron microscope
The tumor has same molecular change as
SCC
Combined carcinoma : App 10% of all
lung carcinoma have a combined
histology, including two or more of above
type
Clinical features
Lung cancer is one of the most insidious and
aggressive neoplasm. 50% are diagnosed after
several months duration
The major presenting complains are coughs (75%)
Wt loss 40% chest pain 40% and dyspnea 20%
Squamous cell and adenocarcinoma tend to
remain localized longer and have slightly better
prognosis
Untreated LSC, survival time is 6-17 wks
Pts with metastasis, even with treatment, survival
is only about 1yr
Staging table 15-11 page 728 chapter 15, 8
th

edition

pathologic basis of disease robbin and
contran
Malignant mesothelioma
Arises from either the visceral or parietal pleura
Increase incidences have been observed
among people with heavy exposure to
asbestose
In mining areas USA, UK, Canada, Australia,
SA, 90% of reported mesothelioma are
asbestose related
Latest period for the development of malignant
mesothelioma is 25-45yr
Asbestose bodies are found in the lung of pts
with mesothelioma.
Another marker of asbestose exposure is
asbestose plaque
Morphology
It is a diffuse lesion that spread out in the pleural
space with extensive pleural effusion and direct
invasion of thoracic structure
The affected lung will cover by thick layer of soft,
gelatinous, grayish pink tumor tissue
Microscopically M.M may be epitheloid 60%,
sarcomatoid 20% or mixed 20%
The epitheloid type of mesothelioma consists of
cuboidal, columnar or flattened cell forming
tubular or papillary structure resembling
adenocarcinoma
Features that favor masothelioma include
1) Positive staining for acid mucopoly
saccharide
2)Lack of staining for carcinoembryonic
antigen and epitheliod glycoprotein
antigens
3)Strong staining for keratin protein


Mesenchymal type of mesothelioma
appear as a spindle cell sarcoma
resembling fibro sarcoma (sarcomatoid
type)
A mixed type of mesothelioma contains
both epitheloid or sarcomatous pattern
Pleural Effusion
It is defined as presence of fluid in the
pleura. It can be transudate or an
exudates
Hydrothorax : The pleural effusion that is
transudate is called hydrothorax e.g.
C.H.D
Pleuritis : it is characterized by a sp.gr
.L1.020 plus inflammatory cells
principal causes of pleural exudate are
1) Microbial infection either direct extension
of pulmonary infection or blood borne
2) Cancer e.g. bronchiogenic carcinoma,
metastatic neoplasm to the lungs or
pleural surface with mesothelioma
3) Pulmonary infarction
4) Viral pleuritis
Less common are : SLE, Rh.arthritis, uremia
following surgery and any Pt above 40, has
pleural exudates, who is afebrile has no pain
and has MT-ve, should be suspected cancer
Cytology may reveal malignant and
inflammatory cells
what ever the cause, transudate and exudates
reabsorbed without residual effect if the inciting
cause is controlled or removed
But the fibrinous, hemorrhagic suppurative
exudates may lead to fibrosis, yeilding
Adhesion or fibrin pleural thicking
Some time minimal to massive calcification
Pneumothorax
It refers to air or other gas in the pleural
sac
It may occur in young, apparently healthy
adult usually male
There is no known pulmonary disease
(simple or spontaneus pneumothorax)
It can occur as a result of some thoracic
or lung disorder (secondary
pneumothorax)
Secondary pneumothorax
Occur with rupture of any pulmonary lesion,
situated close to the pleural surface that
allow inspired air to gain excess to the
pleural cavity.
The lesion include,
1) Emphysema 2)Lung abcess 3) TB
4) CA and mechanical ventilatory support
with high pressure may also trigger
secondary pneumothorax
Complication of pneumothorax
A ball value leak may create a tension pneumothorax
that shift the mediastinum
Compromise of the pulmonary circulation may follow or
may even be fatal
If the leak seals and the lung is not
reexpanded with is a few weeks (either spontaneous or
surgical) medical intervention, scarring will be so much
that it never fully expanded
The serious fluid collects in the plural cavity and creates
the hydropneumothorax
With prolonged collapse, pneumothorax is vulnerable to
infection e.g. empyema
Secondary pneumothorax tend to reoccur
Hemothorax
The collection of whole blood in the pleural
cavity (in contrast with blood effusion), the
blood clots with in the pleural cavity can be
identified along with the fluid compartment
It is often a complication of a rapture
intrathoracic aneurysm. It is a fatal
complication

Chylothorax
Accumulation of milky fluid, usually of lymphatic
origin, in the plural cavity. Chyle is milky white
finally emulsified fats .
It is caused by thoracic duct trauma or obstruction
that secondarily causes rupture of the major
lymphatic duct
This disorder is encountered in the malignant
condition which arises in the thoracic cavity and
obstruct the major lymphatic ducts
Cancer may metastasize the lymphatic and
grow in right lymphatic or thoraces duct to
produce obstruction

Malignant Mesothelioma
Clinical Course
chest pain is presenting complain
Dysnea
Recurrent pulmonary effusion
Concurrent asbastosis is present is 20%
of individual with pleural (fibrosis)
masothelioma
Lung is directly invaded, often metastatic
spread to the hilar lymph
Fifty percent die in 12month of diagnosis
few survive longs than 2yr
In epitheloid mesothelioma, poor
prognosis is improved by pleural
pneumonectomy, chemotherapy, radiation
Mesothelioma arise is peritonium,
pericardium, tunica vulgaris, genital track