VIP Call Girls Pune Vrinda 9907093804 Short 1500 Night 6000 Best call girls S...
Bronchogenic Carcinoma ppt.pptx
1. LUNG CANCER
DR O.O ODUJOKO
DEPT. OF MORBID ANATOMY AND
FORENSIC MEDICINE, OBAFEMI
AWOLOWO UNIVERSITY, ILE-IFE.
2. • A variety of benign and malignant tumours
may arise from the lungs, but 90-95% of them
are carcinomas.
• About 5% are bronchial carcinoids and 2-5%
are mesenchymal and other miscellanous
neoplasms.
3. Epidemiology
• Lung cancer is currently the most frequently
diagnosed major cancer in the world with an
estimated 1.6million new cases in 2008.
• It is also the most common cause of cancer
mortality worldwide.
• The number of new cases of lung cancer that
occurred in the US in 2012 was estimated to be
226,160 accounting for about 14% of cancer
diagnosis and there were 160,340 deaths which
was roughly 28% of all cancer deaths.
4. • The yearly mortality almost matches the yearly
incidence.
• The overall outlook for affected patients remain
bleak.
• Since the early 1990s, lung cancer incidence and
mortality rates have been decreasing in men due
to the decreasing smoking rates
• Women however have a slower decline in lung
cancer incidence and more women die of lung
cancer than breast cancer now in US.
5. • Cancer of the lungs occur most often between
the ages of 40-70 years with a peak incidence
in the 50s and 60s.
• Only 2% of all cases occur in individuals that
are less than 40 years.
6. Etiology and Pathogenesis
• Environmental and genetic factors predispose
to the development of bronchogenic
carcinomas.
7. Environmental factors
• Tobacco smoking
• About 80% of lung cancers occur in smokers or in
those that recently stopped.
• The increased risk becomes 60 times greater
among habitual heavy smokers (two packs a day
for 20 years) compared with non-smokers.
• Lung cancer develops in only 11% of smokers and
many people who have never smoked cigarette
have also developed lung cancer
8. • Women seem to have a higher susceptibility
to carcinogens than men
• Although, cessation of smoking decreases the
risk of lung cancer overtime, it may never
return to baseline levels
• Passive smoking increases the risk for lung
cancer development to approximately twice
that of non-smokers.
9. • Not all individuals exposed to tobacco smoke will
develop lung cancer.
• It is likely that the mutagenic effects of
carcinogens in smoke is modified by genetic
variants.
• Specific P-450 polymorphisms have an increased
capacity to activate procarcinogens in cigarette
smoke and smokers with these genetic variants
appear to incur a greater risk of lung cancer.
10. • Also, individuals whose peripheral blood
lymphocytes show more numerous
chromosomal breakages after exposure to
tobacco related carcinogens have a greater
than 10-fold increase of developing lung
cancer.
• This is presumably due to genetic variations in
genes involved in DNA repair.
11. • The carcinogenic effects of tobacco smoke extend
to those who live and work with smokers
• These second-hand ‘smokers’ are also exposed to
numerous human carcinogens
• It is estimated that about 3000 non-smoking
adults die of lung cancer each year as a result of
breathing of second hand smoke.
• Smokeless tobacco may predispose to oral
cancers
12. Industrial hazards
• Some industrial materials like asbestos, arsenic,
chromium, uranium, nickel, vinyl chloride and
mustard gas increase the risk of developing lung
cancer.
• High exposures to ionizing radiations also
predispose to lung cancers as seen in increased
incidence in survivors of Hiroshima and Nagasaki.
• Asbestos exposure also increases the risk of lung
cancer and has a latent period of 10-30 years.
13. Air pollution
• Air pollution is thought to increase the risk of
lung cancer especially in those who smoke
cigarette.
• It is thought to do this as a result of the
chronic irritation that occurs in those who are
exposed to irritants within the atmosphere.
• Radon gas is also thought to increase the risk
of lung cancer. It is more commonly seen in
uranium miners.
14. Genetic factors
• Different genetic factors also increase the risk
of lung cancer.
• These include mutations in different genes
including P53, Kras, Met, EGFR, Rb, RET
amongst others
• Some syndrommes like Li-Fraumenni and
Peutz-Jeghers syndrome also predispose to
lung cancer.
16. • Carcinomas with pleomorphic, sarcomatoid or
sarcomatous elements
• Carcinoid tumour
Typical and atypical
17. Molecular Genetics
• Smoking related carcinomas of the lungs arise
by a stepwise accumulation of oncogenic
mutations
• Each of the histologic subtypes have their
distinctive molecular features.
18. Squamous cell carcinoma
• Many of the mutations are chromosome
deletions involving tumour suppressor loci
• These loci includes deletions on chromosome
3p, 9p (the CDKN2A locus) and 17p(P53 locus)
• All these are seen in normal epithelial lining of
the lungs in smokers
• They are thus thought to be early events in
oncogenesis.
19. • Squamous cell carcinomas show the highest
frequency of p53 mutation of all the histologic
types.
• Other genes that are less commonly mutated
are the Rb gene, CDKN2A, and FGFR1
• Small cell carcinomas also share many genetic
mutations with squamous cell carcinomas
including mutation in the p53, Rb and
amplifications of genes in the MYC family.
20. Adenocarcinomas
• Genetic mutations in adenocarcinomas
include gain of function mutation in multiple
genes encoding tyrosine kinases like EGFR,
ALK, ROS, MET and RET.
• The tumours without tyrosine kinase
mutations often have mutations in kras
oncogene.
21. Lung cancer in never-smokers
• WHO estimates states that 25% of lung
cancers occur in never smokers.
• These cancers occur more commonly in
females and are usually adenocarcinomas.
• These cancers are more likely to have EGFR
mutations and never kras mutations
24. Frequencies of the different histologic
patterns
• Adenocarcinoma (38%)
• Squamous cell carcinoma (20%)
• Small cell carcinoma (14%)
• Large cell carcinoma (3%)
• Others (25%)
Mixture of histologic subtypes may occur.
Adenocarcinomas have risen in frequency lately.
25. MORPHOLOGY
• Squamous carcinoma occurs most commonly
in men and strongly associated with smoking
• They occur most often on the central parts of
the lungs
• They are usually larger than adenocarcinomas
• They may grow into the lumen of the
bronchus causing obstructive symptoms and
atelectasis
26. • They usually grow for a long time before they
metastasize.
• They are preceeded by carcinoma in-situ which
may last for years. The abnormal cells here may
be identified on sputum cytology or bronchial
lavage fluids.
• Squamous cell carcinoma is usually firm and
greyish-white in colour with areas of
haemorrhage and necrosis.
• The necrotic areas may cavitate.
30. • Histologically, squamous cell carcinoma is
characterised by proliferating malignant
squamous cells with or without keratinization.
31. • Adenocarcinomas tend to arise from the
peripheral parts of the lungs.
• They vary histologically from well
differentiated tumours with obvious glandular
elements to papillary lesions and solid masses.
• There is often a lepidic growth at the
periphery of the tumour in which the tumour
cells crawl along normal appearing alveolar
septa.
32. • Mucinous adenocarcinomas tend to spread
aerogenously forming satellite tumours.
• They may present as solitary or multiple
nodules leading to consolidation of an entire
lobe.
• It may thus mimic a pneumonia.
33. • Small cell carcinoma is strongly associated
with smoking with only 1% occuring in non
smokers.
• They are thought to arise from
neuroendocrine cells lining the walls of the
bronchi
• They are the most aggressive histological type
of all lung cancers
34. • They usually grow as small cells with scant
cytoplasm, ill-defined cell borders with a finely
granular chromatin pattern
• The cells grow in clusters that usually do not
show glandular or squamous pattern
• There are usually areas of necrosis
• They often exhibit high levels of BCL-2
35. • Large cell carcinoma is an undifferentiated
epithelial tumour that lacks the cytologic
features of other forms of lung cancer.
• One histologic variant is large cell
neuroendocrine carcinoma.It has molecular
features similar to that of small cell carcinoma
but the cells are larger
36. Pulmonary carcinoids
• They can be divided into typical and atypical
carcinoids
• Most patients are younger than 40 years.
• They may arise centrally or from the
peripheral aspects
• They are low grade malignant epithelial
neoplasms.
• They may cause the carcinoid syndrome.
40. Metastasis
• Metastasis usually occurs late in the course of
squamous cell carcinoma but earlier in
adenocarcinomas.
• Metastasis may go to the hilar, mediastinal,
and paratracheal lymph nodes.
• Other sites of metastasis are liver, kidneys,
brain, adrenals. Virtually any organ may be
involved by metastatic disease.
41. Secondary pathology
• Focal emphysema
• Atelectasis
• Severe suppurative or ulcerative bronchitis
• Bronchiectasis
• Lung abscess
• Superior vena cava syndrome
• Horner’s syndrome
42. Clinical symptoms
• Cough
• Weight loss
• Chest pain
• Dyspnea
• Migratory thrombophlebitis
• Symptoms may result from metastasis.
43. • The overall 5-year survival rate is 16% even
with treatment.
46. Metastasis to the lungs
• Metastatic lung disease is far more common
than primary lung tumours.
• Both carcinomas from different organs as well
as sarcomas can metastasize to the lungs.
