Histopath - Respiratory disease Flashcards
3 types of cancer in order from most to least common
Squamous cell
Adenocarcinoma
Small cell carcinoma
How common is lung cancer in women? most common cancers in women?
Breast,
Bowel
Lung
Smoking has the strongest association with which types of lung cancer?
Squamous cell carcinoma
Small cell carcinoma
Smoke contains..??
. Tumor initiators - polycyclic aromatic hydrocarbons
. Tumour promoters - Phenols, nicotine
. Carcinogens - Nickel, Arsenic
Risk factors for smoking
Smoking Asbestos exposure Radiation Head metals - arsenic, nickel Genetics
Susceptibility genes for lung cancer
- Nicotine addiction
- Polymorphisms of cyp450 enzymes which metabolise carcinogens
- Susceptibility to chromosomal breaks + DNA damage.
How can a pathologist look at cytology to determine type of lung cancer
- Sputum
- Bronchial washings
- Pleural fluid
- Endoscopic FNA of tumour/lymph nodes
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
Describe the general changes in cells during development of SCC
Normal epithelium –> hyperplasia –> squamous metaplasia –> dysplasia –> carcinoma in situ –> invasive carcinoma
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
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
Preceding histology to adenocarcinoma? describe it?
Atypical adenomatous hyperplasia
= proliferation of atypical larger cells lining the alveolar walls.
Progression of AAh
Atypical adenomatous hyperplasia –> non-mucionous –> mixed pattern adenocarcinoma
Risk factors for adenocarcionma
Far east, female, non-smoker
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
2 main molecular pathways in adenocarcinoma?
. Smokers - K-ras + p53 mutation, DNA methylation
. Non-smokers - EGFR mutation/amplification
Large cell carcinomas - what are they?
Large cells which are poorly differentiated
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.
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
NSCLC - general management?
20-30% suitable for surgery
LESS chemosensitive than SCLC
What drug do some adenocarcinomas respond well to?
anti-EGFR = tarceva
Which stains are useful for sub typing NSCLCs?
- TTF1 = adenocarcinoma
- CK5/6 + P63 = SqCC
3 key molecular markers in lung cancer?
- ERCC1
- EGFR
- EML4-ALK1
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
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