Week 3 Part 2 - Lung Cancers Flashcards
Two Main Types of Lung Cancer
Non-small cell lung cancer (NSCLC)
- adenocarcinoma: arise in glandular epithelial cells and make up approx. 40% of all lung cancers
- SCC: commonly develops in the medial larger respiratory tracts of the lung
- large cell undifferentiated carcinoma: can occur in any part of the lung
Small cell lung cancer
- must be differentiated because the treatment very different to NSCLC
- SCA (SCLC) usually commence in the medial aspect of lung, are usually more aggressive tumours and account for approx 15% of lung cancer
Risks of Lung Cancer
Lung cancer is more commonly diagnosed in those aged >60yrs
- rate of lung cancer deaths increases with age
Tobacco/smoking is the greatest risk factor
- current smokers have 9X higher risk of developing lung cancer than non smokers
- ex-smokers reduce this risk by more than half compared to smokers
Symptoms of Lung Cancer
The most commonly recognised symptom is shortness of breath, followed by:
- haemoptysis - coughing up blood
- changes to the voice such as hoarseness
- chest pain
- developing a new cough that does not go away
- chest infection that lasts more than 3 weeks
- loss of appetite
- unexplained weight lost
- tiredness
Pathogenesis of Lung Cancer
K-ras oncogene - mutations in this gene are found in ~25% of adeno ca, 20% of large cell tumours, only 5% in SCC
Myc oncogene - overexpression of this gene occurs in 10-40% of SCLC
BCL-2 - an antiapoptotic protooncogene, expressed in ~25% of SCC and 10% of adeno ca
RB and P53 - mutations in both of these tumour suppressor genes are found in 80% of SCLC
EGFR - Mutations of the tyrosine kinase domain of this gene seen in adeno ca
Squamous Cell Carcinoma
Presents with weight loss, haemoptysis, hoarseness, persistent cough and mucopurulent sputum due to frequent bronchial obstruction by an endobronchial lesion
Morphologically:
- usually found in the medial aspect of the respiratory tree
- regional LNds are often involved with invasion
- appear coarsely granular and this corresponds to sheets of keratinised malignant cells
- necrosis is common and usually widespread
- associated with inflammation
Histopathology of SCC
SCC is defined by sheets and nests of keratinisation of groups of tumour cells or single cells
- these cells show well defined cell borders with intercellular spaces or gaps/bridges suggesting desmosomes and hemidesmosomes
- Nuclei are usually positioned in the centre of the cells and prominent nucleoli are visible
- SCC can be keratinising or non-keratisining
- when well differentiated display keratinisation, keratin pearl formation (onion skin), nuclear characteristics of malignancy
Mitotic Tumour Grading
G1 - mitotic counts 0-3/HPF (x400) with only minor nuclear pleomorphism, small nucleoli
G2 - mitotic counts 4-8/HPF, nuclear polymorphism clearly visible, medium sized nucleoli
G3 - mitotic counts >8/HPFz, obvious nuclear polymorphism, multinucleated cells and macronucleoli and irregular shaped nuclei
IHC of SCC
The most common markers for SCC are;
- P63: a basal cell marker or/P40 - its splice variant, both are the same isoforms
- high MW cytokeratins: CK3, CK5, CK6 and basic CK13 and CK14 all stain SCC
Diff SCC lung from those of other locations;
- CK4 to diff SCC of oesophagus
- SCC from oral cavity can express CK1 and CK2 which is not expressed by lung SCC
Adenocarcinoma
Most commonest form of NSCLC, which arise from the mucus secreting cells in the deeper parts of lungs
Clinically features are similar to other malignancies
- usually seen in smokers,
- usually located in more peripheral locations in 75% of cases
- tumours may be asymptomatic until quite advanced due to the peripheral location
Age - mainly occur in the 50-80 yr age group
Adenocarcinoma - Macroscopic
Poorly circumscribed, grey/yellow lesions
If they are mucin secreting, they have a mucoid appearance
With 77% involving the visceral pleural at the time of excision, resulting in pleural puckering
Small peripheral tumours invade into the pleural space and coat both pleural layers
Patients may present with pneumonia like consolidation or diffuse bilateral lung disease
A high % will arise with a peripheral scar or honeycombing pattern
Adenocarcinoma - Histology
Mixed acinar and papillary
Lepidic - rare, characterised by tumour cells growing along alveolar septa
Acinar - tumour cells form well defined glandular like acinar arrangements, around a central stromal core
Papillary - true papillary projecting into lumens, these usually have a fibrovascular core
Micropapillary - the tumour cells form micropapillae, with no obvious stromal component but demonstrate epithelial proliferations
Solid - tumour cells how a solid growth pattern, with a small amount of mucin producing cells
IHC of Adenocarcinoma
Most common antigens used for adeno ca:
- CK7
- carcinoembryonic antigen BerEP4
- MOC31
About 1/3 of lung adenocarcinomas will express a single neuroendocrine markers such as CD56 or synaptophysin
Adeno Ca do not usually express cytokeratin 5 or 6, p63 or p40
Small Cell Carcinoma
Small cell lung cancer is the most important diagnosis in all tumour pathology associated with lung disease
SCLC is a high grade neuroendocrine carcinoma that arises in patient who have previously smoked or are currently smokers
Poor prognosis
Symptoms:
- cough
- dyspnoea
- haemoptysis
- rapid weight loss/Hormonal symptoms
- on imaging usually see a centrally located lesion/mass
Small Cell Carcinoma - Macroscopic
SCLC are usually lesions found centrally in the lung
Bronchoscopic biopsy is often positive
On gross appearance the tumour is white/tan, usually soft, friable and extensively necrotic
When centrally located in a large bronchus, it often involves the bronchus in a circumferential fashion and may spread widely beneath the mucosa
The bronchus may be totally occluded in the late diagnostic stages with predominant endobronchial involvement
Small Cell Carcinoma - Microscopic
Small cells nuclear between 16-23um
Nuclei are usually hyperchromatic
Inconspicuous nucleoli
Small cytoplasmic rim
