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1. Tumours of Lung and Pleura
David Gibbons
St. Vincent’s University Hospital

2. Learning Objectives:
Be able to
•Classify the main lung tumours and
distinguish between them
•Discuss the clinical presentation of lung
carcinoma
•Classify and discuss the pathological
features of lung carcinoma
•Discuss mesothelioma

3. Classification
•General
–Benign
–Malignant
•Primary
–Bronchogenic
–Other
»Mesenchymal
»Lymphoma
»Miscellaneous
•Secondary

4. Background
•Commonest cause of Cancer Death
•Second in incidence after Prostate and
Breast but more often fatal
•Huge increase in incidence in men and
Women between 1950 and 2000 in
developed World

5. Aetiology
Smoking
Industrial Hazards
Air Pollution
Molecular Genetics
Scarring

6. Tobacco Smoking
•80% of Lung Cancers occur in Smokers
•Association between
–Amount of daily smoking
–Tendency to inhale
–Duration of smoking habit
•Cessation of smoking for 10 yrs reduces
risk to control levels
•Cigar and Pipe not excluded

7. Evidence of smoking as an
aetiological factor
Histologic Evidence
Experimental Evidence
Epidimeologic Evidence

8. Industrial Hazards
•Radiation
–Hiroshima & Nagasaki
–Uranium miners x 4
–Radon Gas
•Asbestos x5
– +smoking x50-90
•Nickel, Chromates, Arsenic, Beryllium,
Coal, Mustard Gas and Iron

9. Molecular Genetics
•Small cell Carcinoma c-myc
•Non-small cell K-ras
p53
•Adenoca EGFR
ALK
•10-20 Genetic Hits before clinically apparent

10. Clinical Presentation
•Cough
•Sputum
•Haemoptysis
•Breathlessness
•Incidental
•Paraneoplastic syndrome
•Metastatic
•Weight loss
•Clubbing

11. Diagnostic Modalities
Cytology Diagnosis
•Sputum
•Brushings
•Washings
•BAL
•Endoscopic FNA
•Percutaneous FNA
Surgical Pathology Dx
•Endoscopic Biopsy
•Percutaneous CT
guided biopsy
•Open Biopsy +/-
frozen section
•Surgical resection

12. Classification of Brochogenic
Carcinoma
Squamous(25-40%)
Adenocarcinoma(25-40%)
Small Cell(20-25%)
Large Cell undifferentiated(10-15%)
Combined

13. Clinical Classification
Small Cell
v’s
Non-small cell

14. Squamous Cell Carcinoma
•M>F
•Strongly associated with smoking
•Central
•Grows rapidly, spreads late
•Keratin and Intercellular bridges
•Adjacent epithelial atypia
•Paraneoplastic hypercalcaemia
•Positive for CK5/6 and p63 by immunohistochem

15. Squamous Cell Carcinoma

16. Squamous Cell Carcinoma

17. Adenocarcinoma
•Adenocarcinoma
–Bronchial
•Acinar, Papillary, Solid, micropapillary
–Bronchioloalveolar
•F>M
•Less strong association with smoking
•Peripheral (scarring)

18. Adenocarcinoma

19. Adenocarcinoma of Lung

20. Endocrine Tumours
•WHO Classification
–Carcinoid
–Atypical carcinoid
–Small cell
–Large cell neuroendcrine

21. Bronchial Carcinoid
•Kulchitsky Cell
•Tumourlets---Carcinoid—Small cell
•5% of Lung Tumours (Bronchial
Adenoma)
•Not associated with smoking
•Good prognosis

22. Carcinoid Pathology
•Mainstem Bronchi
•Collar-Button Lesion
•Nests and ribbons of small uniform blue
cells with scant cytoplasm and salt and
pepper chromatin
•EM—Neuroendocrine granules
•Immunohistochemistry—Chromogranin,
NSE, Synaptophysin, CD56

23. Slide 16.53

24. Atypical Carcinoid
•Intermediate in biology between classic
carcinoid and small cell carcinoma
Atypia
Necrosis
Mitoses

25. Small Cell Carcinoma
•Aggressive
•Smoking
•Hilar
•Neuroendocrine EM
–Kulchitsky cell
•Small round hyperchromatic cells, scant
cytoplasm, salt and pepper chromatin
•Immunoprofile: Pos for Cytokeratins,
Chromogranin, Synaptophysin, CD56

26. Small Cell Carcinoma

27. Large Cell Neuroendocrine
•Larger cells than Small Cell.
•More Cytoplasm
•Often Prominent nucleoli
•Endocrine architecture
•Pos for endocrine markers
–Chromogranin, Synaptophysin, CD56
•Often treated similarly to Small Cell

28. Large Cell Undifferentiated
•Undifferentiated
•Poorly differentiated Squamous or
Adenocarcinoma
•Sub-types
–Giant cell
–Spindle cell
–Clear cell

29. Slide 16.50

30. Bronchioloalveolar Carcinoma
(Subtype of Adenocarcinoma)
•1- 9% of lung cancers, M=F
•Subtype of Adenocarcinoma
•Jagziekte
•Periphery
–Single nodule
–Or diffuse pneumonic type consolidation
•25% 5 year survival
•Often Non-smokers

31. Mutation of EGFR Tyrosine
Kinase domain
Bronchioloalveolar derived adenocarcinoma
•Female
•Asian
•Nonsmokers

32. EGFR mutations
•Nonmucinous BAC derived adenocarcinoma
responds to EGFR (Epidermal Growth Factor
Receptor) Tyrosine Kinase inhibition and are
usually TTF1 Pos
•10-20% 0f nonSmall cell Ca’s respond
•Molecular test for EGFR mutation
•Protein expression of EGFR by Immunos not
helpful

33. Bronchioloalveolar Carcinoma

34. Slide 16.52

35. TTF1 (primary vs secondary)
•Thyroid Transcription Factor 1
•Immunohistochemical stain
•Present in primary lung adenocarcinomas.
•Present in Thyroid carcinomas.
•Present in Small Cell Carcinomas (Lung
and non-Lung)
•NOT seen in metastatic adenoca to lung

36. Spread
•Local
•MetastasesAny Organ
–Adrenals
–Liver
–Bone
–Brain

37. Secondary Pathology
•Obstructive
–Emphysema, Atelectasis, Bronchiectasis
–Pneumonia
•Local Invasion
–Superior Vena Cava Syndrome
–Pericarditis
–Pleuritis
–Pancoasts Syndrome
•Paraneoplastic Syndromes

38. Paraneoplastic Syndromes
•Cinically sig. Syndromes 1- 10%
•Any tumour—Any Hormone
•ACTH—Cushings—Small Cell
•ADH—Hyponatraemia—Small cell
•Parathormone—Hypercalcemia—Squamous
•Serotonin—Carcinoid Syndrome—Carcinoid
•Calcitonin—Hypocalcemia—Squamous
•Gonadtrophins—Gynaecomastia—Any Hormone

39. Paraneoplastic Syndromes
•Lambert-Eaton myasthenic syndrome
•Sensory peripheral neuropathy
•Acanthosis Nigricans
•Hypertrophic pulmonary
osteoarthropathy
•Leukaemoid reaction

40. Metastatic Tumours of Lung
•Frequent
•Carcinomas, Sarcomas and direct
spread
•Peripheral multiple discrete lesions
•Lymphangitis carcinomatosis
•Cannon ball

41. Metastatic Carcinoma

42. Lung Cancer
Common malignancy
Rapidly Fatal
Environmental in aetiology
Almost entirely preventable

43. Mesothelioma
•Arise in visceral or parietal pleura
•Uncommon
•Asbestos
•10% lifetime risk with heavy exposure
•Long latent period--------- 25-- 40 yrs
•Very high risk of Bronchogenic Ca in smokers
exposed to asbestos
•Positive for Calretinin immunostain

44. Mesothelioma

45. Slide 16.56

46. Slide 16.57

47. Prognosis
•Surrounds and encases lung
•50% dead at 12 months
•100% dead at 2 years
•Invades lung--------Direct extension
•Metastasizes to hilar nodes, liver and
elsewhere

48. Asbestos (Ferruginous) Bodies
•Golden Brown
•Dumb-bell or beaded rod
•Asbestos core surrounded by Iron
•Arise when macrophages phagocytose
asbestos fibre
•Seen in normal people exposed but much
more prevalent in asbestosis and
mesothelioma

49. Asbestos body

50. The End