Pathology of Lung Cancer

Question 1

describe lung neoplasms

Answer 1

primary;
benign (rare)
malignant (common)

metastatic;
very common

Question 2

describe the effect of tobacco smoke in lung cancer

Answer 2

tobacco smoke contains;
polycyclic hydrocarbons 
aromatic amines 
phenols
nickel
cyanates

20% of smokers die of lung cancer (also suffer laryngeal, cervical, bladder, mouth, oesophageal, colon cancer)

Question 3

describe risk factors of lung cancer

Answer 3

tobacco smoke 
asbestos
nickel
chromates 
radiation 
atmospheric pollution 
genetics

Question 4

describe respiratory acinus

Answer 4

functional unit of the lung

extends through respiratory bronchioles, alveolar ducts and alveoli

Question 5

describe the classification of lung tumours

Answer 5

very heterogenous 
4 common smoking associated types;
adenocarcinoma (35%)
squamous carcinoma (30%)
small cell carcinoma (25%) 
large cell carcinoma (10%)
neuroendocrine tumours 
bronchial gland tumours

Question 6

describe prognosis

Answer 6

indicate survival time;
small cell is worst (almost all dead in one year)
large cell worse than squamous or adenocarcinoma

Question 7

describe treatment and histology of lung cancers

Answer 7

small cell known to be chemosensitive but with rapidly emerging resistance
surgery the treatment of choice in other types
no small cell regimens have also been developed in chemotherapy/radiotherapy
new targeted treatments based on pathologically identified abnormal DNA or other markers in tumour

Question 8

describe new developments in chemotherapy

Answer 8

differing NSCLC regimens for squamous cell and adenocarcinoma (e.g. pemetrexed contraindicated in squamous carcinoma)
there is often real difficulty in sub typing tumours on small biopsies
immunohistochemistry can help - adenocarcinoma expresses TTF (thyroid transcription factor) 1. Squamous carcinoma expresses nuclear antigen p63 and high molecular wt. cytokeratins

Question 9

describe molecular genetic abnormalities (Potential therapeutic targets)

Answer 9

refer to PP

Question 10

describe molecular pathology and targeted treatment

Answer 10

specific point mutations render the EGFR gene active in absence of ligand (epidermal growth factor) binding
these mutations can be identified in DNA extracted from biopsy or cytology samples
mutation seen almost exclusively in adenocarcinoma (especially in non-smokers and asian populations)
these tumours respond to tyrosine kinase inhibitors (erlotinib)
EML4-ALK fusion oncogene also identifies a target for specific drug treament (crizotinib)

Question 11

describe targeting the immune response in lung cancer(NSCLC)

Answer 11

PD-L1 binds to PD (programmed death) receptor on T lymphocytes inactivating the cytotoxic immune response
targeted therapy can inhibit this effect and enhance immune killing of tumour

Question 12

describe the importance of tissue resource

Answer 12

has to be balanced between diagnosis and identifying therapeutic targets

Question 13

describe pathogenesis of lung cancer

Answer 13

pulmonary epithelium;
bronchial - ciliated, mucous, neuroendocrine, reserve
bronchioles/alveoli - clara cells, types 1 and 2 alveolar lining cells

Question 14

describe bronchial (large airway) tumours

Answer 14

squamous metaplasia
dysplasia
carcinoma in situ
invasive malignancy

Question 15

describe peripheral adenocarcinomas

Answer 15

atypical adenomatous hyperplasia
spread of neoplastic cells along alveolar walls (bronchiolalveolar carcinoma)
true invasive adenocarcinoma

Question 16

describe prognostic indicators in lung cancer

Answer 16

tumour stage

tumour histological subtype

Question 17

describe other lung neoplasms

Answer 17

carcinoid - neuroendocrine neoplasms of low grade malignancy
bronchial gland neoplasms (tumours more often seen in salivary glands) - adenoid cystic carcinoma, mucoepidermoid carcinoma

Question 18

describe pleural neoplasia

Answer 18

benign tumours rare
primary malignant neoplasm - mesothelioma
very common site of invasion by lung carcinomas and metastatic cancers