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Carcinoma - Lung
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Carcinoma - Lung

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  • 1. Carcinoma of the Lungs Dr.CSBR.Prasad, M.D.
  • 2. CLASSIFICATIONI. 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 cancer1. 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 smoking1. Statistical evidence2. Clinical evidence3. 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 - TBName 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 hyperplasiaSq 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 carcinomasFeature Small cell Ca Non small cell CaImmunophenotyping Mutation p53 / RB Inactivation of p16 gene / CDK / N2A geneResponse 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
  • 24. Centrally located gray white tumorwith cavitation
  • 25. 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
  • 26. Peripherally located gray white tumor - typical ofadenocarcinoma
  • 27. 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
  • 28. Radiologically they mimic Pneumonia
  • 29. 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
  • 30. Gray white tumor spreading along thebronchial tree
  • 31. Morphology - LARGE CELL CARCINOMA• Def: Non small cell carcinoma in which there is neither SQUAMOUS nor ADENOCARCINOMA differentiation• Cells – large, polygonal, vesicular nuclei
  • 32. Local effects of lung tumor spreadPneumonia, abscess, Tumor obstructioncollapseLipid pneumonia Foamy macrophage with cellular lipidHoarseness Recurrent laryngeal nerve invasionDysphagia Esophageal invasionDiaphragm paralysis Phrenic nerve invasion
  • 33. Local effects of lung tumor spread cont….Rib destruction Chest wall invasionSVC syndrome SVC compression by tumorHorner syndrome Sympathetic ganglia invasionPericarditis, tamponade Pericardial involvement
  • 34. Paraneoplastic syndromesHormone Clinical manifestationADH HyponatremiaACTH Cushing’s syndromePTH, PRP, PG HypercalcemiaCalcitonin HypocalcemiaGonadotropins GynecomastiaSerotonin , Bradykinin Carcinoid syndrome
  • 35. Paraneoplastic syndrome• Lambert-Eaton syndrome• Peripheral neuropathy• Acanthosis nigricans• Leukemoid reaction• Hypertrophic pulmonary osteoarthropathy• Horner syndrome• Pancoast tumor
  • 36. Horner’s syndrome• Enophthalmos• Ptosis• Miosis• Anhidrosison the same side of the lesion
  • 37. Horner’s syndrome
  • 38. 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
  • 39. 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
  • 40. • 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
  • 41. 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
  • 42. Clinical Features• Cough, weight loss, chest pain, dyspnoea• Increased sputum• Tumor cells in sputum on cytology• FNAC / BAL
  • 43. Figure 15-43 Cytologic diagnosis of lung cancer is often possible.A, A sputum specimen shows an orange-staining, keratinizedsquamous carcinoma cell with a prominent hyperchromatic nucleus(arrow). B, A fine-needle aspirate of an enlarged lymph node showsclusters of tumor cells from a small cell carcinoma, with moldingand nuclear atypia characteristic of this tumor. [Note the size of thetumor cells compared with normal polymorphonuclear leukocytes inthe left lower corner].
  • 44. Prognosis• Outlook POOR in most patients• 5 year survival -- 9%
  • 45. CARCINOID TUMOR
  • 46. 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
  • 47. 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
  • 48. 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
  • 49. Active peptides • Serotonin • NSE • Bombesin • Calcitonin • Other peptides ex: VIP
  • 50. Clinical features: • Intraluminal growth can cause obstructive symptoms: Collapse, Chronic Pneumonia • Carcinoid syndrome Intermitant attacks of - Flushing - Cyanosis - Anxiety - Diarrhea
  • 51. Prognosis:• GOOD• Amenable to surgeryHistological type 5yr survival 10yr survivalTypical carcinoid 87% 87%Atypical carcinoid 56% 35%
  • 52. E N Dgoto Pleura