lung-tumors.ppt

lung tumor

1. LUNG TUMORS
Dr. V.Shanthi,
Associate Professor, Department of Pathology
Sri Venkateswara Institute Of Medical Sciences

2. LUNG TUMORS
Out of many benign and malignant tumors in the lung the vast
majority are –
90 –95% -Carcinomas
5% -Bronchial carcinoids
2 –5 % -Mesenchymal & other neoplasms

3. CARCINOMA-LUNG
•Most common cause of cancer mortality worldwide
•Age :40-70 yrs with peak incidence in 50s and 60s
•2% of cases appear before the age of 40 years
•Males > Females
•Since 1990 lung cancer mortality in men has reduced but in women it has
not changed because of lagging behind in changing patterns of smoking
•Due to which cancer mortality in women is more due to lung cancer than
breast cancer.

4. CARCINOMA LUNG -ETIOPATHOGENESIS
Tobacco smoking
•87 % of lung cancers occur in active smokers
•Linear correlation between -Amount of daily smoking
•Duration of the smoking habit
•Average smokers –10 foldrisk
•Heavy smokers (2 packs/ day)–60 fold risk
•Most common: Squamous & Small cell Ca >98%

5. CARCINOMA LUNG -ETIOPATHOGENESIS
Tobacco smoking
Cessation of smoking decreases the risk of cancer but never returns to
base line
Passive smoking increases the risk for lung cancer –twicethat of non-
cancer
Women have higher susceptibility to tobacco carcinogens than men
Smoking by cigars and pipes also increases the risk but less than that of
cigarette smoking
Smokeless tobacco is not safe substitute for cigarette smoking, as they
spare lungs but cause oral cancers and lead to nicotine addiction

6. CARCINOMA LUNG -ETIOPATHOGENESIS
Tobacco smoking
•More than 1200 substances are present in cigarette smoke, many of
which are potential carcinogens
•Initiators : Polycyclic aromatic hydrocarbons (Benzopyrene)
•Promotors : Phenol derivatives, Radio active elements (Carbon-14,
pot.40), Arsenic, nickel, molds etc

7. CARCINOMA LUNG -ETIOPATHOGENESIS
Industrial Hazards
Industrial exposures such as asbestos, arsenic, chromium, uranium, nickle,
vinyl chloride and mustard gas increases risk of lung cancer
High-dose ionizing radiation is carcinogenic
Uranium coupled with smoking –10 times
Asbestos coupled with smoking –50 times 
Asbestos workers with out smoking –5 folds increased risk

8. CARCINOMA LUNG -ETIOPATHOGENESIS
Air-Pollution
Adds to risk who smoke or non smokers exposed to second
hand smoke
Chronic exposure to air particulates in smog causes lung
irritation, chronic inflammation and repair which increases risk
for cancers
Radon-a ubiquitous radioactive gas attach to environmental
aerosols inhalation & Bronchial deposition

9. CARCINOMA LUNG -ETIOPATHOGENESIS
Dietary factors:
Vit-A deficiency if associated with smoking risk
Chronic scarring :
Adeno Carcinoma occurs in areas of chronic scarring
Eg: Old TB, Chronic interstitial fibrosis, Asbestosis, old infarcts,
Scleroderma

10. CARCINOMA LUNG -ETIOPATHOGENESIS
All the smokers do not develop lung cancer due to modified mutagenic
effect of carcinogens in smoke by genetic variants (11% of heavy
smokers develop lung cancers)
For example –many chemical carcinogens are converted to active
carcinogens via activation through highly polymorphic p-450
monooxygenase enzyme system.
Specific p-450 polymorphisms have an increased capacity to activate
procarcinogens in cigarette smoke, and smokers with this genetic
variant have increased risk

11. CARCINOMA LUNG –MOLECULAR GENETICS
10 to 20 genetic mutations occur by the time tumor is clinically
apparent
Dominant oncogenes : C-Myc, K-RAS
Commonly deleted / inactivated tumor suppressor genes : p53, RB,
p16 ch.3p
p53 mutations : Both small & non-small cell carcinomas

12. MOLECULAR PATHOGENESIS OF LUNG
CANCER
SQUAMOUS CELL CARCINOMA SMALL CELL CARCINOMA
ADENOCARCINOMA
LUNG CANCER IN NON-SMOKERS
•ASSOCIATED WITH SMOKING
•CHROMOSOMAL DELETION –3p, 9p (site of CDKN2A gene) and
17p (Site of TP53 gene)
•LOSS OF EXPRESSION of Rbtumor suppressor gene
•AMPLIFICATIONof FGFR1
•INACTIVATIONof cyclin dependent kinase inhibitor gene –p16
protein lost
•STRONGLY ASSOCIATED WITH SMOKING
•LOSS OF FUNCTION ABERRATIONS involving
TP53 and Rbgene
•Chromosome 3p deletions
•AMPLIFICATION of genes of Mycfamily
•GAIN OF FUNCTION MUTATIONS involving multiple
genes encoding tyrosine kinase receptors –EGFR,
ALK, ROS, MET and RET
•MUTATIONS in the KRAS gene in tumors without
tyrosine kinasegene
•More common in females and are
adenocarcinomas
•Common mutations –EGFR
•TP 53 mutations –not uncommon
INHERITED PREDISPOSITION
•Rare –found in Li-Fraumenisyndrome who inherit p53 mutations
•First degree relatives –2-3 folds increased risk

13. ETIOLOGICAL FACTORS
TOBACCO SMOKING
INDUSTRIAL HAZARDS
•ASBESTOS
•ARSENIC
•CHROMIUM
•URANIUM
•NICKLE
•VINYL CHLORIDE
•MUSTARD GAS
AIR POLLUTION
•AIR PARTICULATES
•RADON
DIETARY FACTORS
VIT A DEFICIENCY
CHRONIC SCARRING
•OLD TB, CHRONIC INTERSTITIAL
FIBROSIS, OLD INFARCT
•ADENOCARCINOMA
MOLECULAR GENETIC
ABERRATIONS

14. CARCINOMA LUNG
Etiopathogenesis
•Arises by stepwise accumulation of genetic abnormalities
•Bronchial epithelium Neoplastic tissue
•Normal mucosa Basal cell Hyperplasia squamous
Metaplasia Dysplasia Ca. insitu Invasive carcinoma

15. PULMONARY CARCINOGENESIS

16. CARCINOMA LUNG
HISTOLOGIC CLASSIFICATION
Adenocarcinoma (38%)
Minimally invasive adenocarcinoma (mucinous, non-mucinous)
Invasive adenocarcinoma -Lepidic, acinar, papillary , and solid
patterns
Mucinous adenocarcinoma
Squamous cell Carcinoma (20%)
Papillary, clear cell, small cell, basaloid
Small cell Carcinoma (14%) -combined small cell carcinoma
Large cell carcinoma (3%)–Large cell neuroendocrine carcinoma

17. CARCINOMA LUNG
HISTOLOGIC CLASSIFICATION
Others (25%)
Adenosquamouscarcinoma
Carcinoid tumors (Typical, Atypical)
Carcinomas with pleomorphic, sarcomatoidor sarcomatous
elements
Carcinomas of Salivary gland type
Unclassified carcinoma

18. CARCINOMA LUNG
Four types of precursor epithelial lesions are
Squamous dysplasia and carcinoma in-situ
Atypical adenomatous hyperplasia
Adenocarcinoma in-situ
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia

19. BRONCHOGENIC CARCINOMA
MORPHOLOGY
Arises most often in & about the hilus of lung
Adenocarcinoma –peripheral lung
Squamous cell carcinoma –central hilar region

20. SQUAMOUSCELLCARCINOMA
Most common in men
Strongest relationship with smoking
Initially starts as squamous metaplasia or dysplasia in bronchial
epithelium transforming into carcinoma in-situ
During this phase dysplastic epithelial cells are seen in sputum
or bronchial washings though not visible radiologically

21. SQUAMOUSCELLCARCINOMA
Squamous cell Ca. begins as thickening of bronchial mucosa warty
excrescenceFungate into bronchial lumen intra luminal mass
Penetrate the wall of bronchus infiltrate the peribronchial tissue
(Carina/ mediastinum) Cauliflower like intraparenchymal mass
Bronchial obstruction later leads to distal atelectasis and infection
Grossly –tumor is gray-white, firm to hard with areas of necrosis and
hemorrhage

22. SQUAMOUS CELLCARCINOMA

23. SQUAMOUS CELLCARCINOMA

24. SQUAMOUS CELLCARCINOMA
Microscopically:
Characterized by
Squamous pearls
Individual cell keratinization -cells with dense eosinophilic
cytoplasm
Intercellular bridges
Well differentiated –extensive keratinization with keratin pearls
Moderately differentiated–not extensive differentiation
Poorly differentiated–differentiation is focally seen

25. SQUAMOUS CELL CARCINOMA

26. SQUAMOUS CELL CARCINOMA

27. SQUAMOUS CELL CARCINOMA

28. ADENOCARCINOMA
Most common in women & non smokers (>75 % found in smokers)
More peripherally located & smaller lesions
Morphological types
Atypical adenomatous hyperplasia –precursor lesion
Adenocarcinoma in-situ –precursor lesion
Microinvasive adenocarcinoma
Adenocarcinoma

29. ATYPICAL ADENOMATOUS HYPERPLASIA
Small lesion –less than or equal to 5mm
Characterised by dysplastic pneumocytes lining alveolar walls
that are widely fibrotic
Can be single or multiple and can be in lung adjacent to invasive
tumor

30. ATYPICAL ADENOMATOUS HYPERPLASIA

31. ATYPICAL ADENOMATOUS HYPERPLASIA

32. ADENOCARCINOMA IN -SITU
Formerly called as Bronchioloalveolar carcinoma
Lesion less than 3cm
Composed of dysplastic cells growing along pre-existing alveolar
septae
Cells are more dysplastic than atypical adenomatous
hyperplasia and may or may not have intracellular mucin
(Mucinous or non-mucinous respectively)

33. ADENOCARCINOMA IN -SITU

34. ADENOCARCINOMA IN-SITU

35. MICROINVASIVE ADENOCARCINOMA
Tumors with less than 3cms with a small invasive component
(less than 5mm) and peripheral lepidic growth pattern i,e.
tumor cells crawl along the normal alveolar septae
This has far better prognosis when compared to invasive
carcinomas of size larger

36. ADENOCARCINOMA
Invasive malignant epithelial tumor with glandular differentiation or
mucin production by tumor cells
Lesions are peripherallylocated and are smaller
Present as solitary or multiple nodules
Various histological patterns include –acinar, lepidic, papillary,
micropapillary and solid with mucin formation
At the periphery of the lesion tumor shows lepidic pattern of spread

37. ADENOCARCINOMA
Non mucinous: cuboidal / low colummar
Mucinous: Tall, Columnar cells with cytoplasmic & intra-
alveolar mucin, growing along alveolar septa
Tumor cells express Thyroid transcription factor –1 (normally
identified in thyroid cells) and is required for normal lung
development

38. ADENOCARCINOMA

39. ADENOCARCINOMA

40. ADENOCARCINOMA

41. ADENOCARCINOMA

42. ADENOCARCINOMA

43. SMALLCELLCARCINOMA
Strongest association with smoking
Highly malignant tumor
Localization –either in central bronchi or in periphery
There is no preinvasive phase
More aggressive widely metastasize and always prove fatal

44. SMALLCELLCARCINOMA
Microscopy
Small cells with scant cytoplasm, finely granular nuclear chromatin (salt
& pepper pattern),ill defined cell borders and absent or inconspicuous
nucleoli
Cells are round to oval showing nuclear moulding
Size of the cell –smaller than 3 times the diameter of small lymphocytes
Cells grow in clusters without glandular and squamous differentiation
Azzopardi effect –basophilic staining of vessel wall due to encrustation
by DNA of necrotic tumor cells
Necrosis is common
Electron Microscopy: Dense-core neurosecretory granules

45. SCC -Arising centrally in this lung and spreading extensively

46. Small cell
Carcinoma
SMALLCELLCARCINOMA

47. Small cell
Carcinoma
SMALLCELLCARCINOMA
NUCLEARMOULDING

48. SMALLCELLCARCINOMA
AZZOPARDIEFFECT

49. LARGECELLCARCINOMA
Undifferentiated malignant epithelial tumor lacking cytologicfeatures
of both squamous or adenocarcinoma
Common in men / smokers
Large nuclei, prominent nucleoli
Variant –large cell neuroendocrine carcinoma
It is a diagnosis of exclusion as it neither expresses markers of
adenocarcinoma (TTF-1, napsinA) and squamous cell carcinoma (p63,
p40)

50. LARGECELLCARCINOMA

52. More important in the life is not your
standard of living but living a life with
correct standards
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