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Carcinoma - Lung


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Target: UG medical students.

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Carcinoma - Lung

  1. 1. Carcinoma of the Lungs Dr.CSBR.Prasad, M.D.
  2. 2. CLASSIFICATIONI. Non small cell lung Ca (70 - 75 %)II. Small cell lung carcinoma (20 – 25%)III. Combined patterns (5 - 10 %)
  3. 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. 4. EPIDEMIOLOGY• Cigarette smoking• Asbestos• Industrial chemicals • PETROCHEMICAL • METAL REFINING • ARSENIC• Diet - Deficiency of • Vit-E • ß-Carotene
  5. 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. 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. 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. 8. Tobacco smoking1. Statistical evidence2. Clinical evidence3. Experimental evidence
  9. 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. 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. 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. 12. Sir Richard Doll, the scientist who first confirmed the link between smoking and lung cance
  13. 13. Air pollution• Indoor air pollution - Radon• Ubiquitous radioactive gas• Inhalation - bronchial deposition of radioactive decay products and attachment to environment aerosols
  14. 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. 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. 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. 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. 18. Precursor lesions of squamous cell carcinomas
  19. 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. 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. 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. 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. 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. 24. Centrally located gray white tumorwith cavitation
  25. 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. 26. Peripherally located gray white tumor - typical ofadenocarcinoma
  27. 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. 28. Radiologically they mimic Pneumonia
  29. 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. 30. Gray white tumor spreading along thebronchial tree
  31. 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. 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. 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. 34. Paraneoplastic syndromesHormone Clinical manifestationADH HyponatremiaACTH Cushing’s syndromePTH, PRP, PG HypercalcemiaCalcitonin HypocalcemiaGonadotropins GynecomastiaSerotonin , Bradykinin Carcinoid syndrome
  35. 35. Paraneoplastic syndrome• Lambert-Eaton syndrome• Peripheral neuropathy• Acanthosis nigricans• Leukemoid reaction• Hypertrophic pulmonary osteoarthropathy• Horner syndrome• Pancoast tumor
  36. 36. Horner’s syndrome• Enophthalmos• Ptosis• Miosis• Anhidrosison the same side of the lesion
  37. 37. Horner’s syndrome
  38. 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. 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. 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. 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. 42. Clinical Features• Cough, weight loss, chest pain, dyspnoea• Increased sputum• Tumor cells in sputum on cytology• FNAC / BAL
  43. 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. 44. Prognosis• Outlook POOR in most patients• 5 year survival -- 9%
  46. 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. 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. 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. 49. Active peptides • Serotonin • NSE • Bombesin • Calcitonin • Other peptides ex: VIP
  50. 50. Clinical features: • Intraluminal growth can cause obstructive symptoms: Collapse, Chronic Pneumonia • Carcinoid syndrome Intermitant attacks of - Flushing - Cyanosis - Anxiety - Diarrhea
  51. 51. Prognosis:• GOOD• Amenable to surgeryHistological type 5yr survival 10yr survivalTypical carcinoid 87% 87%Atypical carcinoid 56% 35%
  52. 52. E N Dgoto Pleura