Respiratory System Neoplasia Flashcards
What is the estimated number of deaths from lung cancer every year?
9198 (5229 males and 3969 females)
What percentage of deaths are caused by lung cancer?
18.9%
What is the rank of lung cancer as a cause of death in people?
It is the number 1 cause of death by cancer for both men and women
What are the causes of lung cancer?
80% of lung cancers occur in smokers or recently stopped smokers.
Industrial exposure (asbestos, arsenic, chromium, uranium)
Radiation
Air pollution risk is unclear
How much does asbestos increase risk of lung cancer?
5x
How much does the combination of smoking and asbestos increase the risk of lung cancer?
55x
How much does the risk of lung cancer increase for people that smoke 2 packs of cigarrettes a day?
60x
What percentage of people that smoke develop cancer?
10 - 15% of smokers
What does the knudson hypothesis state?
Cancer is a multi-step process of mutations that influence growth, cell division, apoptosis progression, treatment and resistance.
What do cells/tissues have to block/slow cancer development?
intrinsic barriers to cancer development
What are the sequential histological abnormalitiws involved in pathogenesis of squamous cell carcinoma?
Hyperplasia -> Squamous metaplasia -> Squamous dysplasia -> Carcinoma in situ -> Invasive squamous cell carcinoma
What are glandular lesions?
Discrete parenchymal lesion arising in alveoli close to terminal and respiratory bronchioles.
What is atypical adenomatous hyperplasia?
The first stage of a simple adenocarcinoma. (Commonly seen in cancers with extensive lepidic pattern)
However the pattern is more complex in other instances
Why do squamous cells form?
They are protective of lining of respiratory epithelium.
What are the underlying effects that lead to lung cancer?
Many different genetic mutations identified for both squamous cell and adenocarcinomas.
What are the genetic mutations that cause squamous cell carcinoma?
chromosomal losses (3p, 9p (CDKN2), 17p (TP53) losses)
p53 overexpression (TP53)
What percentage of squamous cell carcinomas of the lung are caused by CDKN2/p16 loss?
65%
What mutations cause adenocarcinoma?
Many mutations of receptor tyrosine kinases: EGFR, ALK, ROS, MET, and RET
ALK and KRAS mutations have a bad prognosis
What are the pathological findings in lung cancer?
Mass in the lung which can be central or peripheral
Pleural effusion
Paraneoplastic syndromes
What tissue can be affected by a mass in the lung?
Pleura
Bronchi
Lymph nodes (direct or lymphatic spread)
Chest wall
Nerve involvement
Diaphragm
What are the symptoms of a lung cancer?
Lethargy
Tiredness
Weight loss
Breathlessness
Cachexia
Haemoptysis
Hoarse voice
Recurrent chest infections
Liver/brain/bone pain symptoms are in the late stages
How is a lung cancer diagnosed?
Sputum cytology (low sensitivity)
Pleural fluid cytology (moderate to high sensitivity and specificity)
Fine needle aspirate under CT guidance
Bronchoscopy
Biopsies of tumout
Resection
What percentage of lung cancer patients develop paraneoplastic syndromes?
1 - 10%
What are the paraneoplastic syndromes that can be caused by lung cancer?
May include hormone-like factors mimicking effects of:
ADH (hyponatremia)
ACTH (cushing syndrome)
Parathormone
Calcitonin
Gonadotropins
Serotonin
What other conditions can be caused by paraneoplastic syndromes of the lung?
Lambert-Eaton myasthenic syndrome
Peripheral neuropathy
Dermatological manifestations
Hypertrophic pulmonary osteoarthropathy
Why can lambert-Eaton myasthenic syndrome be caused by lung cancer?
Paraneoplastic syndrome can result in auto-antibodies to neuronal calcium channels
How are respiratory neoplasms classified?
Lower vs upper tract
Benign vs malignant
Primary vs secondary
Tissue of origin
What kind of tissues can be an origin for a tumour of the respiratory tract?
Epithelium (99% of tumours in the lung are epithelial)
Cartilage
Smooth muscle
Blood vessels
Fibrous tissue
Lymphoid tissue
What type of tumours commonly are primary tumours?
Solitary tumours
They can be either benign or malignant
What type of metastases spread to the lungs?
Commonly carcinomas, melanomas, and sarcomas.
Any tumour that spreads via haematogenous route can end up in the lungs
What morphology do secondary malignant tumours commonly take in the lungs?
Multiple and bilateral
What are the common epithelial lung tumours?
Squamous cell carcinoma
Adenocarcinoma
Neuroendocrine: Small cell carcinoma, large cell neuroendocrine carcinoma, and carcinoid tumours
Large cell (undifferentiated) carcinoma
Why is it important to make the distinction between small cell and non small cellcarcinomas?
Small cell carcinoma can’t be operated on whereas all the others can
Why is it important to distinguish between squamous cell carcinoma and adenocarcinoma in the non-small cell carcinoma group?
Treatments for adenocarcinoma can cause problems in people with squamous cell carcinoma thus shortening their lives
What are characteristic features of adenocarcinomas?
They are peripherally located
More common in women than men
Most common epithelial carcinoma in non-smokers
Forms glands
What are the different patterns of adenocarcinomas of the lung?
Lepidic
Acinar
Papillary
Micropapillary
Solid
Mucinous
Others
Why are adenocarcinomas so important to detect early?
They grow slowly but metastasize early and widely.
What mutations can trigger adenocarcinomas of the lung?
EGFR mutations (survival can be prolonged with EGFR inhibitors)
KRAS or ALK mutations (Have bad prognoses)
What shape do squamous cell carcinomas often take?
Enlarged cells with atypical nuclei and prominent dense eosinophilic cytoplasm with intracellular bridges and dyskeratosis (whorls)
Where are squamous cell carcinomas of the lung typically found?
Central location (bronchocentric)
What kind of spread is common for squamous cell carcinomas of the lung?
Lymphatic spread more common than haematogenous spread
What kind of damage do squamous cell carcinomas cause?
They are locally aggressive and often necrotic tumours
What do large cell undifferentiated carcinomas look like?
No differentiating features by light microscopy
Marked atypia
Multinucleation, giant cells and frequent mitoses.
What percentage of lung cancers are small cell carcinomas?
20%
Where in the lung do small cell carcinomas typically occur?
Nearly always central
How do small cell carcinomas spread?
Lymphatic spread and metastasize early
Do small cell carcinomas cause ectopic hormone production?
Yes, they are neuroendocrine carcinomas
How are small cell carcinomas treated?
Chemoradiotherapy
Who most often gets small cell carcinomas?
99% of cases are in smokers
What do the cells in small cell carcinomas look like?
Large nuclei but not much cytoplasm and fine chromatin
What is a carcinoid?
Low grade neuroendocrine tumours. They are malignant but grow slowly.
Who most often gets carcinoid tumours?
Young (<40yo) males and females equally get it
Where are carcinoid tumours located?
Can be central or peripheral and can be typical and atypical (mitotic count and necrosis)
What is the survival rate for carcinoid tumours?
80% 10 year survival rate for resected typical carcinoids and 50% 5 year survival for atypical carcinoid tumours
What is grading of tumours?
The extent to which neoplastic parenchymal
cells resemble the corresponding normal parenchymal cells, both morphologically and functionally (worse = higher grade)
What determines prognosis in adenocarcinomas besides grading?
In adenocarcinoma, prognosis is also determined by architectural pattern (lepidic, acinar, papillary, solid)
How are tumours staged? Why is this useful?
How far has the tumour spread?
Enables comparison of cases for research and risk stratification
What systems are used for staging of lung cancers?
AJCC system
TNM system
How is lung cancer approached prior to treatment?
Prevention (Stop people smoking, help people stop smoking, help people addicted to smoking quit and prevent complications)
Early detection: Difficult
How is lung cancer treated?
Surgery
Radiotherapy (Slow down growth of tumour but not curative)
Chemotherapy (slow down growth of tumour but is not curative)
Immunotherapy
What targets are there for immunotherapy?
EGFR-specific antibodies
EGFR -TKIs
mTOR inhibitors
What is the prognosis like for immunotherapy treatment?
Depends on type and stage
Only 15 - 30% are diagnosed at early stage
75% of NSCLC are inoperable and survival is only 12 - 18 months
SCLC: median survival is 11 months
What are some issues with managing lung cancer?
Appropriate early referral to accessible high quality diagnosis and treatment (variability with access to PET scan, thoracic surgery units,
CT guided core biopsy, pathology, molecular testing)
– Multidisciplinary collaboration in the consideration of
treatment options
• Safe delivery of effective care
• Different regimens of chemotherapy and radiotherapy
for different tumours
• Laser therapy
• Improved palliative options
• National guidelines for the management of lung cancer
How does asbestos increase chances of lung disease?
Causes localised pleural plaques
Pleural effusions
Asbestos-interstitial fibrosis
Bronchiogenic carcinoma
Mesothelioma
Laryngeal and colonic carcinoma
What is the main cancer that affects pleura?
Pleural tissue is lined by mesothelium. The cancer is called mesothelioma
What other cancers affect the pleura?
Lymphomas, mesenchymal tumours and metastases
What aetiological factors increase chance of mesothelioma?
Asbestos
Chronic inflammation, smoking, and other inhaled lung disease
How long is the latency period of mesothelioma?
20 - 30 years
Pathology of mesothelioma:
Infiltrative tumour, tracks along pleural surfaces o Often florid ‘desmoplastic’ response (dense fibrosis) o Epithelioid, sarcomatoid and biphasic types o Often presents with chest pain, pleural effusion o Poor prognosis (12-18 month survival) o Limited treatment efficacy
