morphological variants of lung cancer

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    Morphological variants of Lung Cancer- Squamous cell carcinoma- Adenocarcinoma- Small Lung Cell Carcinoma (SLCC)- Carcinoid airway cancer

    Stats- Leading cause of death- Men > women- Trend is increasing in women now- Peak incidence in 50s and 60s

    Eitiology

    - Tobacco smoke mutations- Proportional to duration, amount &

    quality of smoking & deep inhaling.- 90% are smokers and 10% are non

    smokers- 20 fold risk if >40cigarettes per day

    - >100 fold combined with Asbestos,coal, radon, etc.

    Smoke carcinogens.- Initiators Benzo-pyrenes- Promoters Phenol derivatives- Radioactive substances Polonium,

    C14, K40- Overall: damage p53 and KRAS etc.

    Overall causes:- Smoking*

    - Occupational exposure:- Asbestosis, Nickel, chromates, mustardgas, arsenic coal-tar distillation.

    - Fibrosis/scaring- TB, Pneumoconiosis, honeycomb lung

    Ad.ca.- Radioactive gases

    - Radon, Atomic bomb survivors.

    Clinical Features:- Weight loss Cytokines.. IL6, IL8, PIF.- Cough Bronchus, obstruction,

    necrosis.

    - Haemoptysis Invasion, less stroma,necrosis.

    ComplicationsLocal:

    - Obstruction- Effusion- Pneumonia* lipid, other.- Bronchiectasis- Atelectasis lung collapse- Haemoptysis- COPD (risk)

    Systemic: (paraneo symptoms)- Cachexia- Paraneoplastic syndrome- Clubbing- Pulm. Osteoarthropathy.- Bone pain

    - CNS dysfunction

    Bronchogenic Ca (95%)

    Small cell ca. SCC 15-20%(oat cell ca)

    Non Small cell NSCC 80%

    Squamous cell carcinoma 20-30%

    Adeno carcinoma(+Broncho-alveolar)30-40%

    Large cell anaplasticcarcinoma (rare)

    BronchialCarcinoidTumor (5%)

    MiscellaneousTumors

    (angio(sarco)ma,fibro(sarco)ma, etc) (

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    SCC NSCC- early spread- NO surgery- Responds to

    chemo

    - Late spread localized- Staging & Surgery - OK- Does not respond to

    chemo.

    Pathogenesis

    Cdewqd

    Investigations- Imaging X-Ray, US, MRI, CT, PET- Cytology sputum, Bronchial lavage- Bronchoscopy- Biopsy Needle, excision- Tumor markers.

    - Staging investigations: History, exam & CT scan chest &

    abdomen

    Complete blood count &differential

    Serum chemistry Liver, Kidney,

    Electro. & Ca+

    Pulm.FT & Mediastinoscopy for

    surgery.

    PET Scan.

    Multiple Mutations..oncogene activationcancer.

    KK--RasRasCC--mycmyc

    p53p53

    Irritation Carcinogens Initiation Promotion Ca.

    KK--RasRas

    MetaplasiaDysplasia Neoplasia

    Normal Hyperplasia Metaplasia

    Dysplasia Mild Severe Dysplasia Malignancy

    Cilia

    Goblet cell

    Nucleus

    Loss of Cilia

    & Columnar cells

    Cell death.

    Stratified Squamous

    Epithelium (metaplasia)

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    Lung cancer AP view

    Lung cancer Lateral view

    CT squamous cell carcinoma (NSCC

    bronchogenic) central location

    Adenocarcinoma peripheral (unlike squamous)

    Squamous Cell Carcinoma (NSCC)- M>W

    - Highly associated with smoking- Most arise near the hilum, and big bronchi

    (CENTRAL) LARGE AIRWAYSMicro- Dysplasia and carcinoma in situ- Thickening and irregularity of the

    bronchial mucosa may be seen with abronchoscope

    - Prominent keratin production andintercellularbridges

    Macro- Often have prominent necrosis and may

    cavitate- Tend to spread locally and metastasize

    later than other patterns

    Central near hilum + cavitate

    Origin in main bronchus

    Spread

    ClearMargin

    Smoke

    rslung

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    Cavitation in squamous cell carcinoma

    Microscopy

    IF PINK SQUAMOUS CELL KERATIN!!!

    CYTOLOGY (above) rest = microscopy

    Keratin pearls large nests of Keratin

    Note: pink (keratinized) cancer cells (dysplastic)

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    Adenocarcinoma- Less associated with smoking than

    squamous or small cell carcinomas, butmost

    - 75% patients have a history of smoking

    - Most common type of lung cancer inwomen and nonsmokers!

    Gross- Peripherally located; may be associated

    with a scarMicro

    - Gland formation mucus- more well differentiated- Columnar or cuboidal cells with

    pleomorphic nuclei, often large nucleoli- 80% contain mucin (MUCUS)Cytology- Round/ oval/cuboidal cells

    - Blue!- Prominent nucleiExamin with needle biopsy as in periphery oflung! SMALL AIRWAYS

    Peripheral adenocarcinoma

    Peripheral Adeno

    Peripheral adeno a non-smoker woman!

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    Cytology

    - Cuboidal cells

    - Glandular shapes/ formation- BLUE! colour

    - Glands- Lumen filled with mucin- Vacuolated

    Glandular, cuboildal, mucus

    Bronchoalveolar- A subtype of adenocarcinoma- peripherally located - arise in terminal

    bronchioles or alveoli- Show appearance on CXR like

    pneumonia extensive invasion of lung- Any age, both sexes equally.

    Morphology:- Multiple diffuse nodules more like

    pneumonia- Columnar-to-cuboidal epithelial cells that

    line up along alveolar septa withoutdestruction.

    - tall columnar to cuboidal epithelial cells(differentiation along linesof mucin-secreting bronchiolar cells, Clara cells,and/or type II pneumocytes)

    - Malignant cells grow along septal wall ofalveoli without invading them

    Clinical- Cough, hemoptysis, and pain, but

    atelectasis and emphysema areinfrequent.

    - Metastases are not widely disseminatedand do not occur early;

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    - Overall survival rate is approximately25%.

    Note:- Adenocarcinoma can progress to this- Cancer cells IN the alveoli (the cells that line

    up along alveolar)- Show bronchopneumonia like diffuse

    consolidation (NOT the tumour but theinflammatory response causes this)

    -

    The tumor cells diffusely infiltrate the alveolar

    spaces mimicking a pneumonic process

    Malignant cells grow along alveolar septumwithout disturbing it

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    Atypical adenomatous hyperplasia(AAH):

    o A form of Adenocarcinomao Cytologic atypia is less marked

    o Typically

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    Bronchogenic Mesothelioma (pleural)

    Small Cell Lung Carcinoma (SCLC)- >95% smokers- centrally located masses near hilum

    - invade/extension into the lung

    parenchyma early spread to hilar

    and medistinal lymph nodes- Aggressive and invasive metastatis

    widespread

    Paraneoplastic syndrome- These tumors are derived from

    neuroendocrine cells of the lung =they express a variety ofneuroendocrine markers

    - SLCC secrete neuroendocrinal paraneoplastic syndromes

    Macroscopic- LARGE central airways- 70% of cases present as perihilar

    mass- Extensive lymph node metastases are

    common- Typically peribronchial; endobronchial

    lesions are uncommon

    - neuroendocrine differentiation

    Microscopic

    - SMALL cells- Round to fusiform shape (look like

    lymphocytes) reduced cytoplasm +large relative hyperchromatic neuclei(nuclei>cytoplasm)

    - Salt/ pepper granulated chromatin- nuclear molding; faint or absent

    nucleoli; scant cytoplasm- Extensive necrosis

    Three histologic categories:o Small cell

    o Mixed small cell/large cell

    o Combined small cell/adeno- or

    squamous cell Carcinoma

    SCLC affecting the hilar lymph nodes +bronchus

    Infiltration pattern around major bronchus - Irregular border

    - Spread along bronchus lymph nodes

    Infiltration pattern around bronchusNote: black spots in lung = smokers lung

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    SCC some bronchiactiac changes

    Large nuclei compared to cytoplasmRound small cells

    Cytology

    Oat cells SCC- BAL bronchio-alveolar lavage fluid.- Gets sample of cells with brush during

    bronchoscopy and stained for visualization

    - Small Cell Barely any cytoplasm andmostly purple nucleus (cells are bigger thanlymphocytes)

    Large nuclei

    Looks like inflammatory cells

    Carcinoid Tumours

    Overview

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    Bronchial Carcinoid Tumour:

    Note: Benign gross appearance. Round cell clusters.

    (Neuroendocrine cells)

    - Slow growing, malignant tumour offrom cells of the neuroendocrinesystem.

    - 1% to 5% of all lung tumors- Mainly occur in individuals