3- pathology of lung cancer Flashcards
what are risk factors for lung cancer?
- smoking
- asbestos →mostly associated with mesothelioma + lung cancer
- nickel and chromates
- radiation
- atmospheric pollution
- genetics
what are some examples of local effects of lung cancer?
- obstruction of airway (might lead to pneumonia)
- invasion of chest wall (pain)
- ulceration (tumour that causes epithelial surface of bronchus to become ulcerated so tumour exposed which are vascular so mean cough up blood - haemoptysis)
what are some systemic effects of lung cancer? (just a couple - more in other lecture)
- weight loss
- ectopic hormone production (hormones that are normally produced in body but they are produced in wrong place and often abnormal numbers)
where does gas exchange occur?
respiratory bronchioles, alveolar ducts, alveoli
why is classification of tumours important?
- treatment (personalised medicine)
- prognosis - helps know how tumour formed
- pathogenesis/biology
- epidemiology
what changes occur in response to risk factors in cells in large airways cancers?
Squamous metaplasia (change from 1 cell type to another) - reversible change, in response to stimuli so if take away stimuli, reverts back. when different form more likely to progress to dysplasia which isn’t reversible = Carcinoma in situ – dysplasia of entire epithelium, precursor lesion, may progress and lead to Invasive squamous cell carcinoma
what changes occur in response to risk factors in cells in peripheral lung cancers?
Atypical adenomatous hyperplasia – precursor lesion (not tumour in itself yet but first step), may progress if epithelium more fragile and prone to mutations to Adenocarcinoma in situ (pure lepidic pattern) – still a precursor, may progress to Invasive adenocarcinoma
what are the 4 most common types of lung tumours?
- Adenocarcinoma
- Squamous cell carcinoma
- Small cell carcinoma
- Large cell neuroendocrine carcinoma
*can occur in non-smokers (mostly adenoma) but mostly in smokers
what are neuroendocrine
a) high grade tumours
b) low grade tumours?
a) Small cell carcinoma, large cell neuroendocrine carcinoma
b) Typical carcinoid, atypical carcinoid
what can be used to get pathological tissue samples? and why want?
- bronchoscopy
- CT guided lung biopsy
= want to make sufficient diagnosis, to identify the tumour and make more targeted treatment
what are some characteristics of adenocarcinoma?
- gland forming tumour(can show other patterns but should have gland somewhere)
- mucin
- hyperchromatic nuclei (darkly staining)
- pleomorphism (different sizes + shapes of nuclei)
- prominent nucleoli
- cytoplasmic mucin vacuoles
what are some characteristics of squamous cell carcinoma?
- sheets of cells
- dense eosinophilic cytoplasm
- pleomorphic nuclei
- intercellular bridges (desmosomes) →seen normally in squamous cells but if see in tumour you know it’s squamous tumour
- keratinisation (the tumours can produce keratin)
= bottom 2 are main distinguishing features
what are some characteristics of small cell carcinoma?
- Hyperchromatic nuclei
- Stippled chromatin
- Nuclear moulding
- Minimal cytoplasm
- Streaking/smudging artefact = very little cytoplasm so easily squished
- Mitotic figures = very rapidly dividing (aggressive)
- Single cell necrosis = spotty necrosis, little distinct spots
- No prominent nucleoli
what are some characteristics of large cell neuroendocrine carcinoma?
- Organoid/neuroendocrine architecture – nests, trabeculae (long), rosettes, palisading (lines around groups)
- Large cells with abundant cytoplasm
- Prominent nucleoli
- Extensive necrosis
what is significance between non-small cell lung cancer and small cell lung cancer?
2 general classifications
- non-small cell lung cancer = not specific type just general idea
- small cell lung cancer = generally more aggressive but susceptible to chemo
what is immunohistochemistry?
test that uses antibodies to detect specific antigens within tissue
An enzymatic colour-producing reaction allows the presence of the antibody-bound antigens to be visualised = makes colour so can see
*different tumours express particular antigens which can help identify - needs to be interpreted along with histological features
what are some specific genetic alterations found in some lung cancers?
- specific point mutation on EGFR gene
- specific mutation on EML4-ALK
what is the EGFR mutation?
the normal gene is active in absence of ligand binding. in tumour cell, this gene switches on all the time so if tumours have this mutation then it’s bypassing normal checkpoint so can just keep growing
- the mutation responds to tyrosine kinase inhibitors like erlotinib
what is EML4-ALK mutation?
it’s a fusion oncogene, it inactivates the cytotoxic immune response (T cell response that usually attacks tumour)
- can be treated with crizotinib
what is assessed on pathological staging on resection specimens?
= system used to classify the extent and spread of lung cancer within the body
assess:
- Size of tumour
- Site of tumour(s)
- Nodal metastasis
