Clinical Impression:BRONCHOGENIC CARCINOMA

Types of Bronchogenic Carcinoma

Squamous Cell CA

Adenocarcinoma

Small Cell/ Oat cell

Large Cell/ Undif-ferentiated

Small cell lung carcinoma

•20 % of lung cancer•Anaplastic and highly malignant•Displays neuroendocrine properties•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• Includes adenocarcinoma,

squamous, large cell carcinoma, bronchioloalveolar carcinoma, and mixed version.

• 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, men>women

Major bronchi & periphery of the lung

Oat-cell CA, highly malignant tumor; grading inappropriate; classified as ‘limited’ or ‘extensive’

Non-small cell lung carcinoma

Adenocarcinoma Nonsmokers, women>men

Periphery of the lung (single nodule that appear consolidated or multiple diffuse nodules that coalesce)

Malignant epithelial tumor;Bronchioalveolar pattern of spread

Squamous cell carcinoma

Smoking, men>>women

Central (from segmental or subsegmental bronchi); periphery

Squamous pearls (keratinization)

Large cell carcinomaSmoking, exposure to asbestos

Can occur in any part of the lung & spread rapidly

Undifferentiated malignant epithelial tumor

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

Small Cell Lung CA

• changes in all myc family members

Non-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

Adenocarcinoma

• Point mutation in the coding region of RAS family of oncogene (KRAS)• Mutation of tyrosine kinase domain of the EGFR

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.