Pathology of lung cancer Flashcards by Andile ngwenya

State the risk factors of lung cancer

tobacco
asbestos
enironmental radon
polycyclic aromatic hydrocarbons; found in tobacco smoke but also occupational risk of exposure ( road paving, aluminium production)
other occupational exposures chromatex, nickel
air pollution + urban environement
other radiation
pulmonary fibrosis
inherited polymorphism predispose ( certain inherited enzyme metabolise substances in tobacco smoke which makes them more carcinogenic + Nicotine addiction)

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Describe the effect of smoking and lung cancer

multi hit theory of carcinogenesis
host activation of pro-carcinogens
SCLC mostly associated

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State the 2 main pathways of carcinogenesis in the lung

NSCLC
Adenocarcinoma:
-located in lung periphery (brionchioles/alveolar wall)
-transformed from bronchioalveolar stem cells

Sqamous:

located in central airways
transformed from bronchial epithelial cells

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Describe the formation of an adenocarcinoma in smokers

Atypical adenomatous hyperplasia>Adenocarcinoma in situ > invasive adenocarcinoma

(Same sequence as non smokers so less assoc with smoking. Adenocarcinoma in situ is a subtype of adenocarcinoma)

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Describe the formation of an invasive bronchogenic carcinoma in smokers

Squamous dysplasia/Carcinoma in-situ(CIS)&raquo_space; Invasive bronchogenic carcinoma

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What mutations/rearrangements can therapies target (ADENOCARCINOMAS)

BRAF, HER2 EGFR mutations

- ALK, ROS1 rearrangements

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What is targeted in squamous cell carcinomas?

-inactivating mutations in tumour suppressor genes

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Types of tumours of the lung

benign causes of mass lesion
carcinoid tumour( lung neoplasms/low grade malignancy. NSCLC)
tumours of bronchial glands ( adenoid cystic carcionoma, mucoepidermoid carcinoma, benign adenomas)
lymphoma
sarcoma
metastases

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State the cell types of lung carcinomas

adenocarcinomas : 41%
squamous cell: 40%
small cell carcinoma: 15%
large cell carcinoma: 4%

(all organised according to most common)

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What is non-small cell carcinoma (NSCLC)?

common

- squamous, adenocarcinomas, large cell carcinomas + carcinoid tumour(others)

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State features of primary lung cancer

presents late in its natural history
asymptomatic until disease is advanced
incidentally found during investigation of something unrelated

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Local effects of lung cancer

bronchial obstruction:
collapse
endogenous lipid pneumonia
bronchiectasis
infection/abscess formation
pleural(inflammation/malignancy)
direct invasion(chest wall)
lymph node metastases

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Lung cancer - direct invasion of chest wall

Nerves:

Phrenic > diapgramatic paralysis
Left recurrent larngeal > hoarse, bovine cough
Brachial plexus(C5-T1) > pancoast T1 damage
cervical sympathetic > horner’s syndrome
mediastinum ( SVC, pericardium)
lymph node metastases

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Lung cancer - Lymph node metastases + symptom

lymphangitis carcinomatosa

- presented as dull ache on chest

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Lung cancer - distant effects

Distant metastases: Liver, adrenals, bone, brain, skin (LABBS)
Secondary to local effects: neural, vascular
non metastic effects

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State the non-metastic paraneoplastic effects of lung cancer

Skeletal
Endocrine
Neurological
Cutaenous
haematologic
Cardiovascular
Renal

Non-metastic paraneoplastic effects of lung cancer - Skeletal

-clubbing, HPOA

Non-metastic paraneoplastic effects of lung cancer - Endocrine

ACTH, SIADH, PTH
Carcinoid syndrome
gynecomastia

Non-metastic paraneoplastic effects of lung cancer - Neurological

polyneuropathy
encephalopathy
cerebellar degeneration
myasthenia ( eaton-lambert)

Non-metastic paraneoplastic effects of lung cancer - Cutaneous

Acanthosis nigricans

- dermatomyositis

Non-metastic paraneoplastic effects of lung cancer - Haematologic

Granulocytosis
Eosinophillia
DIC

Non-metastic paraneoplastic effects of lung cancer - Cardiovascular

-Thromboplebitis migrans

Non-metastic paraneoplastic effects of lung cancer - Renal

-Nephrotic syndrome

Non-metastic paraneoplastic effects of lung cancer - Endocrine ( lung cell types of cancer)

ACTH + SIADH (small cell)

PTH (squamous)

State the non-metastatic effects of lung cancer

- Finger clubbing | - Hypertrophic pulmonary osteoarthropathy (HPOA)

Lung cancer - investigations

Chest X-Ray ``` Sputum Cytology rarely used Bronchoscopy Bronchial biopsy Bronchial brushings and Washings Endobronchial US-guided aspiration (EBUS) Trans-thoracic Fine Needle Aspiration Trans-thoracic Core Biopsy Pleural effusion cytology and Biopsy ``` Advanced Imaging Techniques CT scanning MRI, PET scanning Other imaging

Prognostic factors in lung cancer

``` STAGE of disease CLASSIFICATION: Type of disease Markers / Oncogenes / Gene expression profiles Growth Rate Cell Proliferation DNA Aneuploidy Immune Cell Infiltration ```

Lung cancer 5 year survival by histiological cell type

Non-cell carcinomas ( 10-25%) | Small cell carcinoma ( 4%) ; median survival is 9 months

Predicitive biomarkers used to select patients for therapy - Adenocarcinoma

EGFR, KRAS, HER2, BRAF mutations, | ALK translocations, ROS1 translocations

Predicitive biomarkers used to select patients for therapy - Squamous cell

-little/no effective molecular targeted therapy

Predicitive biomarkers used to select patients for therapy - NSCLC

-immunotherapy

The PD1/PD-L1 axis immune checkpoint in NSCLC

-therapeutic target + imp biomarker

If there is an immune response, how does the tumour evade it?

- inhibitory immune checkpoints - most cancers are not immunogenic, hence will determine effectivenessof tumour directed immune - Immune checkpoints control immune reactions and are adopted by tumours to avoid immune destructionresponse

What checkpoints are targeted by drugs?

-PD-1, PD-L1, CTLA4

What is small cell carcinomas associated with?

- Polycyclic aromatic hydrocarbons - siADH ( syndrome of inappopriate ADH prod) - ACTH ( adrenocortitropic hormone - Lambert - Eaton Syndrome ( muscle weakness)

What are adenocarcinomas associated with?

- Nitrosamines - less associated with smoking - likely to occur in non-smokers than squamous cell carcinomas - mostly women - Oncogene addiction -KRAS(smoking induced), EGFR, BRAF, HER2 mutations ROS1+ ALK rearrangments ( not smoking induced)

What is paraneoplastic effect of squamous cell carcinomas

-Hypercalcaemia - PTH