SqCC - Site? - Behaviour? - Histology? - Subtypes?

- Tend to be central. Incidence of peripheral SCCs is rising - Local spread. late metastasis - Keratinisation and intracellular 'prickles' - Papillary, Basaloid

Adenocarcinomas - Site? - Behaviour - Histology

- peripheral and more often MULTIPLE sites - Extrathoracic mets are common and early - 80% present with mets - Glandular differentiation and mucin vacuoles

Small cell carcinomas - RF? - Site? - Behaviour? - Histology and mutations?

- Smoking is an RF - Central near bronchi - Presents with advanced disease + paraneoplastic syndromes - Small, poorly differentiated cells. p53 + RB1 mutations.

Histopath - Respiratory disease Flashcards by Lottie Barot

3 types of cancer in order from most to least common

Squamous cell
Adenocarcinoma
Small cell carcinoma

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How common is lung cancer in women? most common cancers in women?

Breast,
Bowel
Lung

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Smoking has the strongest association with which types of lung cancer?

Squamous cell carcinoma

Small cell carcinoma

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Smoke contains..??

. Tumor initiators - polycyclic aromatic hydrocarbons
. Tumour promoters - Phenols, nicotine
. Carcinogens - Nickel, Arsenic

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Risk factors for smoking

Smoking
Asbestos exposure
Radiation 
Head metals - arsenic, nickel
Genetics

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Susceptibility genes for lung cancer

Nicotine addiction
Polymorphisms of cyp450 enzymes which metabolise carcinogens
Susceptibility to chromosomal breaks + DNA damage.

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How can a pathologist look at cytology to determine type of lung cancer

Sputum
Bronchial washings
Pleural fluid
Endoscopic FNA of tumour/lymph nodes

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How can a pathologist look at histology to determine type of lung cancer

Biopsy at bronchoscopy
Percutaneous CT-guided biopsy
Mediastinoscopy
Frozen section from a biopsy at time of surgery
Resection specimen from final excision

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Describe the general changes in cells during development of SCC

Normal epithelium –> hyperplasia –> squamous metaplasia –> dysplasia –> carcinoma in situ –> invasive carcinoma

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Special type of dysplasia seen in smoker with or without SqCC? what is seen on histology??

Angiosquamous dysplasia

Intramucosal CAPILLARY LOOPS
BM thickening + vascular budding

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SqCC

Site?
Behaviour?
Histology?
Subtypes?

Tend to be central. Incidence of peripheral SCCs is rising
Local spread. late metastasis
Keratinisation and intracellular ‘prickles’
Papillary, Basaloid

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Preceding histology to adenocarcinoma? describe it?

Atypical adenomatous hyperplasia

= proliferation of atypical larger cells lining the alveolar walls.

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Progression of AAh

Atypical adenomatous hyperplasia –> non-mucionous –> mixed pattern adenocarcinoma

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Risk factors for adenocarcionma

Far east, female, non-smoker

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Adenocarcinomas

Site?
Behaviour
Histology

peripheral and more often MULTIPLE sites
Extrathoracic mets are common and early - 80% present with mets
Glandular differentiation and mucin vacuoles

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2 main molecular pathways in adenocarcinoma?

. Smokers - K-ras + p53 mutation, DNA methylation

. Non-smokers - EGFR mutation/amplification

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Large cell carcinomas - what are they?

Large cells which are poorly differentiated

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Small cell carcinomas

RF?
Site?
Behaviour?
Histology and mutations?

Smoking is an RF
Central near bronchi
Presents with advanced disease + paraneoplastic syndromes
Small, poorly differentiated cells. p53 + RB1 mutations.

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General prognosis and treatment of small cell lung carcinoma

2-4months if untreated. 10-20 months if treated.

- CHEMO + RADIO as most are too spread for surgery

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NSCLC - general management?

20-30% suitable for surgery

LESS chemosensitive than SCLC

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What drug do some adenocarcinomas respond well to?

anti-EGFR = tarceva

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Which stains are useful for sub typing NSCLCs?

TTF1 = adenocarcinoma

- CK5/6 + P63 = SqCC

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3 key molecular markers in lung cancer?

ERCC1
EGFR
EML4-ALK1

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ERCC1 - what is it? how is measuring its levels prove useful?

A protein which removes drug-DNA adducts.

High levels - cisplatin based chemo will be ineffective at treating the advanced NSCLC

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EGFR - what does it do? | In whom is it upregulated?

Promotes angiogenesis, proliferation, cell migration | - asians, non-smokers, females

Drugs used in NSCLC which is EGFR positive

Cetuximab

Indication for use of TKI

Young/female/nonsmoker Responder mutation!! EGFR amplification Recurrent adenocarcinoma

Contraindication for use of TKI

``` Kras mutation Resistance mutation(to TKI) = 790M ```

Significance of K-ras mutation

Predicts non-response to anti-EGFR therapy | Often seen in smokers

Translocation that is a useful molecular marker in lung cancer?

EML4-ALK

EML4-ALK lung cancers - what does this translocation result in? - who is affected? common histology?

- Translocation --> increased Alk function - Seen in young/nonsmokers/adenocarcinoma - signet ring pattern or solid pattern

Staging of lung cancer

TNM Tumour (T1-4) - the SIZE and invasion of pleura/pericardium Nodes (N0-2) - N1 vs 2 depends on extent of LN involvement Metastasis (M0-1)

Local effects of lung tumour - 3 main categories

1. Bronchial obstruction 2. Invasion of local structures 3. Invasion of pleura/pericardium

Effects of bronchial obstruction

1. collapse of distal lung - SOB | 2. impaired drainage of bronchus - cheese infection

5 effects of invasion of local structures

1. Oesophagus affected - dysphagia 2. Large vessels - SVC syndrome w dusky skin 3. Local airways and vessels - haemoptysis 4. Chest wall - pain 5. Nerves - Horners syndrome

Effects of invasion of pleura/pericardium

Pleuritis/pericarditis - Cardiac compromise, SOB

Physical effects of mets

Seizures Skin lumps Liver pain/deranged LFTs Bone pain/fractures

Paraneoplastic syndromes

- Cushing from ACTH secretion - SIADH - PTH related peptides causing hypercalcemia

Small cell carcinoma is associated with which paraneoplastic syndromes?

ACTH secretion --> Cushings | SIADH --> hyponatremia

3 rare lung tumours

Rare epithelial tumours Sarcomas MALT type lymphoma

Mesothelioma - what is it? - Epidem and time course? - Cause - Behaviour + prognosis - Sx?

- Tumour of the pleura - presents 4/50 years post-asbestos exposure. Peaking now. MALES. - Fatal diagnosis - SOB, chest pain

3 common congenital lung disorders

1. Lung genesis + hypoplasia 2. Tracheal/bronchial stenosis 3. Congenital cysts

3 main causes of pulmonary oedema

1. Alveolar injury 2. Left Heart Failure 3. Neurogenic

Cells seen on histology in pulmonary oedema?

Heart failure cells = iron laden macrophages

What is diffuse alveolar damage in adults called? what can cause it?

ARDS | Infection, aspiration, trauma, irritant gas inhalation, shock, DIC, drug OD,

Macroscopic appearance in diffuse alveolar damage?

Heavy, airless lung. | PLUM coloured

pathophysiology of diffuse alveolar damage

1. Diffuse alveolar damage leads to blood cells in alveoli 2. Protein rich fluid in alveoli 3. Hyaline membrane formation in alveoli 4. Organising phase

Complications of diffuse alveolar damage?

Superimposed infection | Fibrous scarring of lung --> bronchopulmonary dysplasia in RDS children

Associations with hyaline membrane disease

``` Prematurity GDM 2nd twin C-section Birth asphyxia ```

Complications of RDS

- Infection - Resp failure - Interstitial emphysema (from over ventilation) - Bronchopulmonary dysplasia

Causes and associations of asthma

allergens and atopy NSAIDS occupational physical exertion (cold)

macroscopic features in asthma

mucus plug | Overinflated lung

Microscopic features of asthma (2 v important ones)

SM cell hyperplasia, eosinophils, excess mucus - Curshmann spirals - Charcot-Leyden crystals

Definition of chronic bronchitis

Chronic productive cough | On most days for at least 3 months in 2 consecutive years

Histology of chronic bronchitis

Goblet cell hyperplasia and dilatation of airways

4 complications of chronic bronchitis

1. Recurrent infections 2. chronic hypoxia 3. Pulm HT (RHF) 4. Lung Ca

Causes of emphysema

Smoking a1 antitrypsin deficiency IVDU, Marfans

Pathogenesis of emphysema

Cigarette smoke --> neutrophil and macrophage activation --> elastase activity --> emphysema

Difference in location affected in smoking vs a1 antitrypsin deficiency associated emphysema

Smoking - alveolar loss is centred on the bronchioles (centrilobular) a1- diffuse loss of alveoli (panacinar)

3 Complications of emphysema

Large bullae Resp failure Pulmonary HT

Causes and associations of bronchiectasis

- Post-infectious - Post-inflammatory - Abnormal host defence(1 ciliary dyskinesia) - Obstruction from tumour/stenosis - Secondary to fibrotic lung disease

3 complications of bronchiectasis

recurrent infections Haemoptysis Amyloidosis

CF - manifestations?

``` Lung - infections, airway obstruction GIT - meconium ileus, malabsorption Liver - cirrhosis Pancreas - pancreatitis Infertility ```

Bronchopneumonia vs lobar pneumonia

Broncho: - patchy, peribronchial distribution - elderly its - low virulence organisms Lobar: - v acute presentation - Strep pneumonia Widespread fibrinosuppurative consolidation

Histopathology of lobar pneumonia

1. congestion 2. red hepatisation (neutrophils) 3. grey hepatisation (fibrosis) 4. Resolution

5 Complications of pneumonia

``` Abscess Pleuritis Empyema Fibrous scarring Septicaemia ```

Atypical pneumonia

interstitial inflammation without accumulation of inflamm cells in alveoli

What is a granuloma

Collection of histiocytes and macrophages +/- multinucleate giant cells

Causes of granulomatous infections

TB!!!! | FUNGAL - cryptococcus, coccidioides, aspergillus

Non-infectious granulomatous conditions

- Sarcoid - aspiration - IVDU - OCCUPATIONAL lung disease

Presumed pathogenesis of sarcoidosis

Abnormal host response to commonly encountered antigens

lung involvement in sarcoid? | Diagnosis?

epithelioid and giant cell granulomas - in upper zones - fibrotic and cystic changes -biopsy (non-caseating granulomas), elevated ACE