Lung cancer is a leading cause of cancer death worldwide, largely due to tobacco smoking. In the US in 2008, there were 215,020 new lung cancer cases and 161,840 deaths. The main types are non-small cell lung carcinoma (NSCLC), which makes up around 75% of cases, and small cell lung carcinoma (SCLC), which accounts for around 25% of cases. Tobacco smoking is associated with 87% of lung cancers, with risk increasing based on amount and duration of smoking. Other causes include exposure to radon, asbestos, and other industrial hazards. Surgery, chemotherapy, and radiation are used as treatment but survival rates remain low due to often advanced stage at diagnosis.
Lung cancer is a leading cause of cancer death worldwide, largely due to tobacco smoking. In the US in 2008, there were 215,020 new lung cancer cases and 161,840 deaths. The main types are non-small cell lung carcinoma (NSCLC), which makes up around 75% of cases, and small cell lung carcinoma (SCLC), which accounts for around 25% of cases. Tobacco smoking is associated with 87% of lung cancers, with risk increasing based on amount and duration of smoking. Other causes include exposure to radon, asbestos, and other industrial hazards. Surgery, chemotherapy, and radiation are used as treatment but survival rates remain low due to often advanced stage at diagnosis.
Lung cancer is a leading cause of cancer death worldwide, largely due to tobacco smoking. In the US in 2008, there were 215,020 new lung cancer cases and 161,840 deaths. The main types are non-small cell lung carcinoma (NSCLC), which makes up around 75% of cases, and small cell lung carcinoma (SCLC), which accounts for around 25% of cases. Tobacco smoking is associated with 87% of lung cancers, with risk increasing based on amount and duration of smoking. Other causes include exposure to radon, asbestos, and other industrial hazards. Surgery, chemotherapy, and radiation are used as treatment but survival rates remain low due to often advanced stage at diagnosis.
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
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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