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Carcinoma of lung
Lung cancer is most frequent by a major causewith high mortality worldwide.
In 2008, in USA, the estimated No of cancer were215,020, out of which 15% were diagnosed and
29% cancer related deathsIn 2008, the estimated death from the lung cancerin USA were161,840
Since 1990, the death rate is decreasing in men
most likely due to the decreased smoking rateover the past 30yrs
Since 1987,more women have died each year oflung cancer than breast cancer
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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 casesappear before 40
1yr survival rate has increased from 34%
(1975) to 41% (2007), largely b/c ofimprovement is surgical technique
5yr survival rate for all stage is only 16%
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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 thefrequency of lung cancer and the
1) The amount of daily smoking
2) The tendency to inhale3) Duration of smoking habit
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The heavy smoker (40 cigarette/ day forseveral 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 envirementalsmoker accounts about 3000 non smoking
adults die of lung cancer Smokeless tobacco is not a safe choice
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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
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Air pollution
Radon is a ubiquitous radio active gas, andincidence is high among those who are
relatively more exposed, (mine worker)
Molecular Genetic :The exposure to thecarcinogen act by genetic alteration in the
lung cells and lead to neoplastic
phenotype10-20 genetic mutation occur by the time
cancer is actively appear
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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 andadenocarcinoma
b) Mixed squamous cell carcinoma +SCLC
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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
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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 producingdistal atelectasis and infection
This tumor may adopt a variety of paths.
It can penetrate rapidly to .
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a) Wall of the bronchus to infiltrates peribronchial tissue
b) Into the adjacent region of mediastinumc) It can also grow along a broad form to
produce cauliflower like intraparenchymal
massIn almost all pattern, the neoplastic tissue is
gray white and firm to hard speciallywhen tumor are bulky
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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, bronchialand mediastinal nodes
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Distal spread occur through both lymphaticand hemorrhagic pathway
No organ or tissue is spared in the spreadof the lesion. Liver 30-50%, brain 20%,bone 20% .
It is most common type of lung cancer inman, strongly associated with smoking
Squamous cell carcinoma show the highest
frequency of P53 mutation of all histologictype of lung carcinoma
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AdenocarcinomaThis is a malignant epith, tumor with glandular
differentiation or mucin production by thetumor cells .
Adenocarcinoma grow in various patternincluding
a) Acinus
b) papillary
c) bronchioalveolar
d) solid with mixed tumor
It is common type lung cancer in women andnon-smokers
As compared with squamous cell carcinoma,
the lesions are on periphery and smaller
A majority are positive for thyroid transcriptionfactor TTF-1 and about 80% containmucin
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At periphery, there is often
bronchioalveolar pattern of spread andtend to metastasize widely and earlier
KRAS mutation occur in adenocarcinoma.
In smoker the frequency is 30% and in nonsmoker 5%
P53,RB1,P16 mutation and inactivation
have the same frequency in
adenocarcinoma as in squamous cell
carcinoma
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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 ormultiple 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
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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
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(an allusion to the neoplastic cellsresembling 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 hasdistinctive tall columnar cell withcytoplasmic and intracellular mucin,
growing along the alveolar septa.
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Non mucinous bronchioalveolar carcinomaoften 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 anentire lobe may be consolidating by tumor
resembling lobar pneumonia. therefore lesslikely to be cured by surgery
Atypical adenomatous hyperplasia
progressing to bronchio alveolar carcinomatransform into invasive adenocarcinomawhich is monoclonal and share manymolecular aberration such as FGFR mutation
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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 inconspicuousnucleoli
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
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Azzopardi effect is present (due to encrustationDNA from necrotic tumor cell, vascular wall stain
basophilic All small cell carcinoma are high grade
Small cell carcinoma are often combined withlarge cell neuroendocrine carcinoma and
sarcoma Small cell carcinoma have a strong relationship
to cigarette smoking . Only 1% occur in nonsmoker
They may arise in major bronchi or in theperiphery
P53,RB1 tumor supper genes are frequentlymutating
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Large cell carcinoma
It lacks the cytoplasmic feature of smallcell 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) representsquamous cell carcinoma and
adenocarcinoma, that can not be
diffentiated by light microscope
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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 alllung carcinoma have a combined
histology, including two or more of above
type
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Malignant mesotheliomaArises from either the visceral or parietal pleura
Increase incidences have been observedamong people with heavy exposure toasbestose
In mining areas USA, UK, Canada, Australia,SA, 90% of reported mesothelioma areasbestose related
Latest period for the development of malignant
mesothelioma is 25-45yrAsbestose bodies are found in the lung of pts
with mesothelioma.
Another marker of asbestose exposure is
asbestose plaque
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Morphology
It is a diffuse lesion that spread out in the pleuralspace with extensive pleural effusion and direct
invasion of thoracic structure
The affected lung will cover by thick layer of soft,
gelatinous, grayish pink tumor tissueMicroscopically M.M may be epitheloid 60%,
sarcomatoid 20% or mixed 20%
The epitheloid type of mesothelioma consists ofcuboidal, columnar or flattened cell forming
tubular or papillary structure resembling
adenocarcinoma
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Features that favor masothelioma include
1) Positive staining for acid mucopolysaccharide
2)Lack of staining for carcinoembryonic
antigen and epitheliod glycoproteinantigens
3)Strong staining for keratin protein
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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
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Pleural Effusion
It is defined as presence of fluid in thepleura. It can be transudate or an
exudates
Hydrothorax :The pleural effusion that istransudate 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
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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
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Less common are :SLE, Rh.arthritis, uremiafollowing surgery and any Pt above 40, has
pleural exudates, who is afebrile has no pain
and has MT-ve, should be suspected cancer
Cytologymay reveal malignant and
inflammatory cellswhat 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
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Pneumothorax
It refers to air or other gas in the pleuralsac
It may occur in young, apparently healthy
adult usually maleThere is no known pulmonary disease
(simple or spontaneus pneumothorax)
It can occur as a result of some thoracicor lung disorder (secondarypneumothorax)
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Secondary pneumothorax
Occur with rupture of any pulmonary lesion,situated close to the pleural surface thatallow inspired air to gain excess to the
pleural cavity.The lesion include,
1) Emphysema 2)Lung abcess 3) TB
4) CA and mechanical ventilatory supportwith high pressure may also triggersecondary pneumothorax
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Complication of pneumothorax
A ball value leak may create a tension pneumothoraxthat shift the mediastinum
Compromise of the pulmonary circulation may follow ormay even be fatal
If the leak seals and the lung is notreexpanded with is a few weeks (either spontaneous orsurgical) medical intervention, scarring will be so muchthat it never fully expanded
The serious fluid collects in the plural cavity and createsthe hydropneumothorax
With prolonged collapse, pneumothorax is vulnerable toinfection e.g. empyema
Secondary pneumothorax tend to reoccur
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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
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Chylothorax
Accumulation of milky fluid, usually of lymphaticorigin, in the plural cavity. Chyle is milky whitefinally emulsified fats .
It is caused by thoracic duct trauma or obstruction
that secondarily causes rupture of the majorlymphatic duct
This disorder is encountered in the malignantcondition which arises in the thoracic cavity and
obstruct the major lymphatic ductsCancer may metastasize the lymphatic andgrow in right lymphatic or thoraces duct toproduce obstruction
M li t M th li
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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
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Fifty percent die in 12month of diagnosis
few survive longs than 2yr
In epitheloid mesothelioma, poorprognosis is improved by pleural
pneumonectomy, chemotherapy, radiation
Mesothelioma arise is peritonium,pericardium, tunica vulgaris, genital track