Target: UG medical students.

1. Carcinoma of the Lungs
Dr.CSBR.Prasad, M.D.

2. CLASSIFICATION
I. Non small cell lung Ca (70 - 75 %)
II. Small cell lung carcinoma (20 – 25%)
III. Combined patterns (5 - 10 %)

3. CLASSIFICATION
I. Non small cell lung Ca (70 - 75 %)
a. Squamous cell carcinoma (3 to 50%)
b. Adenocarcinoma (30-35 %)
c. Large cell carcinoma (10 -15 %)
II. Small cell lung carcinoma (20 – 25%)
III. Combined patterns (5 - 10 %)
a. Mixed SCC & Adeno Ca
b. Mixed SCC & SCLC

4. EPIDEMIOLOGY
• Cigarette smoking
• Asbestos
• Industrial chemicals
• PETROCHEMICAL
• METAL REFINING
• ARSENIC
• Diet - Deficiency of
• Vit-E
• ß-Carotene

5. 5 main histologic types of lung cancer
1. Squamous cell ca (3 to 50%)
2. Small cell ca (20 to 25 %)
3. Adenocarcinoma (15 to 35 %)
4. Large cell ca (10 to 15 %)
5. Adenosquamous ca (1 to 3 %)

6. Ca lung – 3 therapeutic groups.
1. Small cell carcinoma (20 to 25 %)
2. Non – small cell ca (70 to 75 %)
(squamous, adeno ca, large cell ca)
3. Combined / Mixed patterns (5 to 10 %)

7. Etiology of Bronchogenic carcinoma
• 40 - 70 yrs [peak 50 - 60 yrs]
• Tobacco smoking
• Industrial hazards
• Air pollution
• Dietary factors
• Genetic factors
• Scarring of lung tissue

8. Tobacco smoking
1. Statistical evidence
2. Clinical evidence
3. Experimental evidence

9. Tobacco smoking - Statistical evidence
• Amount of daily smoking
• Tendency to inhale
• Duration of smoking habit
average smoker – 10x risk
40 cigarettes/day/yrs – 20x risk
8% lung cancer in smokers, Lip, tongue, floor of
mouth, pharynx, larynx, esophagus, urinary
bladder, pancreas, kidney

10. Tobacco smoking – clinical evidence
• Histologic evidence –
Atypical hyperplastic changes
10 % smokers
1 to 2 % of filter tipped cigarettes
96 % who died of ca lung

11. Tobacco smoking - Experimental evidence
• 1200 substances, initiators / promoters
• Initiators:
• Polycyclic hydrocarbons
• Benzo(a)pyrene
• Promoters - Phenol derivatives
• Radioactive elemets - Polonium 210
Carbon 14
Potassium 40
• Contaminants - Arsenic, Nickle, Moulds
• Bronchioalveolar carcinoma NOT strongly
associated with smoking

12. Sir Richard Doll, the scientist who first confirmed
the link between smoking and lung cance

13. Air pollution
• Indoor air pollution - Radon
• Ubiquitous radioactive gas
• Inhalation - bronchial deposition of
radioactive decay products and attachment
to environment aerosols

14. Molecular studies
• 10 to 20 genetic mutations
• Dominant oncogenes (activated)
c-myc in small cell carcinoma
k-ras in adenocarcinoma
• Deleted recessive genes (inactive)
p53, RB-gene
Unknown gene in short arm of chromosome #5
• Role of polymorphisms in cytochrome P 450 gene
CYPIA 1

15. Industrial hazards
• All radiations are carcinogenic
• Hiroshima, Nagasaki uranium is weakly
radioactive
• Smoking in miners - 10x higher incidence
• Asbestos latent period 10 to 30 yrs
• Nickel, chromates, coal, mustard gas, arsenic,
beryllium, iron, news papers workers, African
gold miners, halothane workers

16. Scarring
• Scar cancer – Adenocarcinoma
• Old infarct, metallic foreign body, wounds,
granulomatous infections ex - TB
Name the other scar cancers?
Marjolin’s ulcer – SCC arising in an old skin scar

17. Precursor lesions
1. Squamous dysplasia and Ca in situ
2. Atypical adenomatous hyperplasia
3. Diffuse idiopathic pulmonary
neuroendocrine cell hyperplasia
Sq cell ca: Smoking > Sq Metaplasia
> Dysplasia > Ca in situ

18. Precursor lesions of squamous cell carcinomas

19. Main differences between Small Cell &
Non-small cell carcinomas
Feature Small cell Ca Non small cell Ca
Immunophenotyping Mutation p53 / RB Inactivation of p16
gene / CDK / N2A gene
Response to Rx Chemotherapy Surgery

20. Morphology - General Considerations:
• Except Adeno ca, lung cancers arise centrally
Right lung > Left lung
Upper lobes > Lower lobes
• Ulceration Hemoptysis
• Airway obstruction
a ) Absorption collapse
b ) Impaired drainage

21. Morphology - Bronchogenic carcinoma
• ¾ ths – I, II, III order bronchi
• Periphery - terminal bronchiole / alveolar
septa
• Area of atypia, 1cm, Irrregular warty
excrescence
• Intramural growth - parenchymatous growth
• Cavity, spread to pleura
• Distant - adrenals, liver, brain, bone

22. Morphology cont.….
• Adenocarcinoma – bronchial derived
bronchioalveolar derived
Mucin producing, slow growth
• Small cell ca – 2x times size of small Lymphocyte
E/M- dense core granules
• Large cell Ca: intracellular mucin, giant cell, spindle

23. Morphology - Squamous cell carcinoma
• More in men than women
• Arise centrally local hilar LN
• Disseminate later than other histologic types
• Histologically : WD to PD carcinomas

26. Centrally
located gray
white tumor
with cavitation

31. Morphology - Adenocarcinoma
• Patients < 40, women, non smokers
• More peripherally located
• Related to lung scars
• Form smaller masses but metastasizes early
• DD from metastatic Adeno Ca is difficult

33. Peripherally
located gray
white tumor -
typical of
adenocarcinoma

35. Morphology –
Bronchioloalveolar carcinoma
• Not related to: Gender, occupation, social
class, cigarette smoking
• Highly diff Ca, grows upon the walls of pre-
existing alveoli – lepidic spread
• Histologically cells have peg like luminal
aspects with no stromal reaction

36. Radiologically they mimic Pneumonia

39. Morphology - Small cell carcinoma
• Early dissemination
• Associated with paraneoplastic syndrome
• Varieties - a) Oat cell Ca
b) Polygonal SCLC
c) Spindle cell SCLC
• EM - dense core cytoplasmic granules
• IHC - NSE

43. Gray white
tumor
spreading
along the
bronchial tree

47. Morphology - LARGE CELL CARCINOMA
• Def: Non small cell carcinoma in which
there is neither SQUAMOUS nor
ADENOCARCINOMA differentiation
• Cells – large, polygonal, vesicular nuclei

49. Local effects of lung tumor spread
Pneumonia, abscess, Tumor obstruction
collapse
Lipid pneumonia Foamy macrophage with
cellular lipid
Hoarseness Recurrent laryngeal nerve
invasion
Dysphagia Esophageal invasion
Diaphragm paralysis Phrenic nerve invasion

50. Local effects of lung tumor spread cont….
Rib destruction Chest wall invasion
SVC syndrome SVC compression by tumor
Horner syndrome Sympathetic ganglia
invasion
Pericarditis, tamponade Pericardial involvement

51. Paraneoplastic syndromes
Hormone Clinical manifestation
ADH Hyponatremia
ACTH Cushing’s syndrome
PTH, PRP, PG Hypercalcemia
Calcitonin Hypocalcemia
Gonadotropins Gynecomastia
Serotonin , Bradykinin Carcinoid syndrome

52. Paraneoplastic syndrome
• Lambert-Eaton syndrome
• Peripheral neuropathy
• Acanthosis nigricans
• Leukemoid reaction
• Hypertrophic pulmonary osteoarthropathy
• Horner syndrome
• Pancoast tumor

55. Horner’s syndrome
• Enophthalmos
• Ptosis
• Miosis
• Anhidrosis
on the same side of the lesion

56. Horner’s syndrome

57. Pancoast tumor
• Apical lung cancers in superior pulmonary
sulcus
• Invasion of neural structures around
trachea + cervical sympathetic plexus
• Severe pain along distribution of ulnar
nerve
• Horner’s syndrome

60. Staging of LUNG CANCER
• T1 - Tumor < 3 cm without pleural / main stem bronchus
involvement
• T2 - Tumor 3 cm / involvement of main stem bronchus 2
cm from carina, visceral, pleural, lobar atelectasis
• T3 - Tumor with involvement of chest wall, diaphragm,
mediastinum pleura, pericardium, main stem bronchus 2 cm
from carina, entire lung atelectasis
• T4 - Tumor with invasion of mediastinum, heart, great
vessels, trachea, oesophagus, vertebral body, carina, pleural
effusion

61. • N0 - No demonstrable metastasis to regional LNs
• N1 - Ipsilateral hilar / peribronchial LNs
• N2 - Ipsilateal mediastinal / subcarinal LNs
• N3 - Contralateral mediastinal / hilar, ipsilateral /
contralateral scalene or supraclavicular LN
• M0 - No distant metastasis
• M1 - Distant metastasis present

62. STAGE GROUPING
• Stage Ia T1 N0 M0
• Stage Ib T2 N0 M0
• Stage IIa T1 N1 M0
• Stage IIb T2 N1 M0
• Stage IIIa T1-3 N2 M0
T3 N1 M0
• Stage IIIB AnyT N3 M0
T3 N3 M0
T4 Any N M0
• Stage IV Any T Any N M1

63. Clinical Features
• Cough, weight loss, chest pain, dyspnoea
• Increased sputum
• Tumor cells in sputum on cytology
• FNAC / BAL

64. Figure 15-43 Cytologic diagnosis of lung cancer is often possible.
A, A sputum specimen shows an orange-staining, keratinized
squamous carcinoma cell with a prominent hyperchromatic nucleus
(arrow). B, A fine-needle aspirate of an enlarged lymph node shows
clusters of tumor cells from a small cell carcinoma, with molding
and nuclear atypia characteristic of this tumor. [Note the size of the
tumor cells compared with normal polymorphonuclear leukocytes in
the left lower corner].

65. Prognosis
• Outlook POOR in most patients
• 5 year survival -- 9%

66. CARCINOID TUMOR

67. CARCINOID TUMOR
• Low grade malignant epithelial neoplasm
• Show neuroendocrine differentiation
• 1- 5 % of primary lung tumors
• M=F
• Neither smoking nor environmental pollution is a
risk factor
• Peak incidence at a younger age < 40yrs

68. Gross:
• Finger like / polypoid masses
projecting into lumen of bronchus
• Collar button lesion
• Covered by intact epithelium
• Rarely exceed 3 - 4 cms
• Site: Main stem bronchus

69. Microscopy
• Nests / cords / masses separated by delicate
fibrovascular stroma
• Individual cells - uniform round nuclei
• Salt & Pepper chromatin
• Infrequent mitosis
• Cytoplasm is moderately eosinophilic
• EM - Dense core granules
• IHC – Chromogranin, Synaptophysin

72. Active peptides
• Serotonin
• NSE
• Bombesin
• Calcitonin
• Other peptides ex: VIP

73. Clinical features:
• Intraluminal growth can cause obstructive
symptoms: Collapse, Chronic Pneumonia
• Carcinoid syndrome
Intermitant attacks of
- Flushing
- Cyanosis
- Anxiety
- Diarrhea

74. Prognosis:
• GOOD
• Amenable to surgery
Histological type 5yr survival 10yr survival
Typical carcinoid 87% 87%
Atypical carcinoid 56% 35%

75. E N D
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