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Clinical Impression: BRONCHOGENIC CARCINOMA. Histopathologic image of small cell carcinoma of the lung. CT-guided core needle biopsy. H & E stain. Non-small cell lung carcinoma. 75% of lung cancer Grows and spreads more slowly than small cell Ca Types: Adenocarcinoma Squamous cell ca - PowerPoint PPT Presentation
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Clinical Impression:BRONCHOGENIC CARCINOMA
Types of Bronchogenic Carcinoma
Squamous Cell CA
Adenocarcinoma
Small Cell/ Oat cell
Large Cell/ Undif -ferentiated
Small cell lung carcinoma
• 25 % of lung cancer• Anaplastic and highly
malignant• Displays neuroendocrine
properties• strongly related to smoking• RB mutation in 90% and
p16 abnormalities in 10% but never have KRAS and EGFR mutation
Histopathologic image of small cell carcinoma of the lung. CT-guided core needle biopsy. H & E stain.
Non-small cell lung carcinoma
• 75% of lung cancer• Grows and spreads more
slowly than small cell Ca• Types:
• Adenocarcinoma• Squamous cell ca• Large cell ca
• RB mutation 20%, p16 changes 50%, KRAS mutation 30%, and EGFR 10%
Bronchiolo-alveolar carcinoma of the lung with mucin production. Hematoxylin and eosin stain
History Location
Small cell carcinomaSmoking, exposure to asbestos, more common in men
Major bronchi & periphery of the lung
very aggressive neoplasm, generally having metastasized at the time of diagnosis
Oat-cell CA, highly malignant tumor; grading inappropriate; classified as ‘limited’ or ‘extensive’
AdenocarcinomaNonsmokers, more common in women
Periphery of the lung (single nodule that appear consolidated or multiple diffuse nodules that coalesce)
Manifests as multifocal tumors in a bronchoalveolar form
Malignant epithelial tumor;Bronchioalveolar pattern of spread
Squamous cell carcinoma
Smoking, more common in men
Central (from segmental or subsegmental bronchi); periphery classic manifestation: cavitary lesion in a proximal bronchus.
A well differentiated squamous cell carcinoma may form keratin pearls and intercellular bridges.
Large cell carcinomaSmoking, exposure to asbestos
Can occur in any part of the lung & spread rapidly;manifests as a large peripheral mass on chest radiograph.
Undifferentiated malignant epithelial tumor
History Location
Pathogenesis of Bronchogenic Cancer
Cigarette smoking/ Tobacco exposure (~90%)Occupational associations: asbestos,
uranium( in miners), arsenical fumes, nickel,radon gas.
Genetic factorsChronic lung disease: TB & COPDOther factors include air pollutions , ionizing
radiation .
Etiology & Pathogenesis
Etiology & Pathogenesis Initiated by activation of dominant oncogenes and
inactivation of tumor-suppressor gene or recessive oncogenes
A small subpopulation of cells with a tumor are responsible for the full malignant behavior of the tumor which are called cancer stem cell this will be important to identify since successful treatment of the tumor will require the eradication of this stem cell component.
Activation of Dominant Oncogene
• changes in all myc family members
Small Cell Lung CA
•occasional mutations in BRAF and PIK3CA or activation of the PIK3CA/AKT/mTor pathway•amplification, rearrangement, and/or loss of transcriptional control of myc family oncogenes (c-, N-, and L-myc; changes in c-myc
Non-Small Cell Lung CA
• Point mutation in the coding region of RAS family of oncogene (KRAS)• Mutation of tyrosine kinase domain of the EGFR
Adenocarcinoma
Inactivation of tumor-Suppressor gene
• genes involved in lung cancer pathogenesis: p53, RB, RASSF1A, SEMA3B, SEMA3F, FUS1, p16, LKB1, RAR, and FHIT.
tumor-acquired inactivating mutation of one allele
tumor –acquired inactivation of expression by tumor-acquired
promoter DNA methylation
tumor cell with only the functionally inactive allele
loss of function of the growth-regulatory tumor-suppressor gene
Autocrine Growth Factors expresses nicotinic acetylcholine receptor nicotine
activates signaling pathway in tumor and normal cell that blocks apoptosis involvement of nicotine directly in lung cancer pathogenesis both as a mutagen and tumor promoter
Inherited Predisposition to Lung Cancer- People with inherited mutation on RB and p53 gene
may develop lung cancer.- First degree relative of lung cancer probands have a
two to threefold excess risk of lung cancer or other cancer, many of which are not smoking-related.