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Lung cancer and diseases > Pathology of lung cancer > Flashcards

Pathology of lung cancer Flashcards

1
Q

State the risk factors of lung cancer

A
  • 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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2
Q

Describe the effect of smoking and lung cancer

A
  • multi hit theory of carcinogenesis
  • host activation of pro-carcinogens
  • SCLC mostly associated
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3
Q

State the 2 main pathways of carcinogenesis in the lung

A

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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4
Q

Describe the formation of an adenocarcinoma in smokers

A

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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5
Q

Describe the formation of an invasive bronchogenic carcinoma in smokers

A

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

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6
Q

What mutations/rearrangements can therapies target (ADENOCARCINOMAS)

A
  • BRAF, HER2 EGFR mutations

- ALK, ROS1 rearrangements

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7
Q

What is targeted in squamous cell carcinomas?

A

-inactivating mutations in tumour suppressor genes

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8
Q

Types of tumours of the lung

A
  • 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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9
Q

State the cell types of lung carcinomas

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

(all organised according to most common)

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10
Q

What is non-small cell carcinoma (NSCLC)?

A
  • common

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

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11
Q

State features of primary lung cancer

A
  • presents late in its natural history
  • asymptomatic until disease is advanced
  • incidentally found during investigation of something unrelated
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12
Q

Local effects of lung cancer

A
  • bronchial obstruction:
  • collapse
  • endogenous lipid pneumonia
  • bronchiectasis
  • infection/abscess formation
  • pleural(inflammation/malignancy)
  • direct invasion(chest wall)
  • lymph node metastases
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13
Q

Lung cancer - direct invasion of chest wall

A

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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14
Q

Lung cancer - Lymph node metastases + symptom

A
  • lymphangitis carcinomatosa

- presented as dull ache on chest

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15
Q

Lung cancer - distant effects

A
  • Distant metastases: Liver, adrenals, bone, brain, skin (LABBS)
  • Secondary to local effects: neural, vascular
  • non metastic effects
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16
Q

State the non-metastic paraneoplastic effects of lung cancer

A
  • Skeletal
  • Endocrine
  • Neurological
  • Cutaenous
  • haematologic
  • Cardiovascular
  • Renal
17
Q

Non-metastic paraneoplastic effects of lung cancer - Skeletal

A

-clubbing, HPOA

18
Q

Non-metastic paraneoplastic effects of lung cancer - Endocrine

A
  • ACTH, SIADH, PTH
  • Carcinoid syndrome
  • gynecomastia
19
Q

Non-metastic paraneoplastic effects of lung cancer - Neurological

A
  • polyneuropathy
  • encephalopathy
  • cerebellar degeneration
  • myasthenia ( eaton-lambert)
20
Q

Non-metastic paraneoplastic effects of lung cancer - Cutaneous

A
  • Acanthosis nigricans

- dermatomyositis

21
Q

Non-metastic paraneoplastic effects of lung cancer - Haematologic

A
  • Granulocytosis
  • Eosinophillia
  • DIC
22
Q

Non-metastic paraneoplastic effects of lung cancer - Cardiovascular

A

-Thromboplebitis migrans

23
Q

Non-metastic paraneoplastic effects of lung cancer - Renal

A

-Nephrotic syndrome

24
Q

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

A

ACTH + SIADH (small cell)

PTH (squamous)

25
Q

State the non-metastatic effects of lung cancer

A
  • Finger clubbing

- Hypertrophic pulmonary osteoarthropathy (HPOA)

26
Q

Lung cancer - investigations

A

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

27
Q

Prognostic factors in lung cancer

A 
STAGE of disease
CLASSIFICATION:  Type of disease
Markers / Oncogenes / Gene expression profiles
Growth  Rate
Cell  Proliferation
DNA  Aneuploidy
Immune  Cell  Infiltration
28
Q

Lung cancer 5 year survival by histiological cell type

A

Non-cell carcinomas ( 10-25%)

Small cell carcinoma ( 4%) ; median survival is 9 months

29
Q

Predicitive biomarkers used to select patients for therapy - Adenocarcinoma

A

EGFR, KRAS, HER2, BRAF mutations,

ALK translocations, ROS1 translocations

30
Q

Predicitive biomarkers used to select patients for therapy - Squamous cell

A

-little/no effective molecular targeted therapy

31
Q

Predicitive biomarkers used to select patients for therapy - NSCLC

A

-immunotherapy

32
Q

The PD1/PD-L1 axis immune checkpoint in NSCLC

A

-therapeutic target + imp biomarker

33
Q

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

A
  • 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
34
Q

What checkpoints are targeted by drugs?

A

-PD-1, PD-L1, CTLA4

35
Q

What is small cell carcinomas associated with?

A
  • Polycyclic aromatic hydrocarbons
  • siADH ( syndrome of inappopriate ADH prod)
  • ACTH ( adrenocortitropic hormone
  • Lambert - Eaton Syndrome ( muscle weakness)
36
Q

What are adenocarcinomas associated with?

A
  • 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)
37
Q

What is paraneoplastic effect of squamous cell carcinomas

A

-Hypercalcaemia - PTH

Lung cancer and diseases (13 decks)

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