Carcinoma of Lung Lecture

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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