Ppt lung carcinoma part1


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Ppt lung carcinoma part1

  1. 1. Dr.JUNED AHMAD
  2. 2. INTRODUCTION  Lung cancer is largely a disease of modern man.  Rare before 1900, with fewer than 400 cases described in the medical literature.  Raymond Pearl's landmark 1938 report conclusively established the devastating impact smoking has on longevity. : Abeloff's Clinical Oncology, 4th ed.
  3. 3.  Tobacco consumption is the primary cause of lung cancer.  More than 60% of new lung cancers occur in - Never smokers (smoked <100 cigarettes per lifetime) or - Former smoker (smoked 100 cigarettes per lifetime, quit 1 year)  1 in 5 women and 1 in 12 men diagnosed with lung cancer have never smoked. : Abeloff's Clinical Oncology, 4th ed
  4. 4. Epidemiology  Lung cancer is the most common cause of cancer death among American men and women.  More than 220,000 individuals will be diagnosed with lung cancer in the United States in 2010.  Lung cancer is rare below age 40, with rates increasing until age 80, after which the rate tapers off. Harrison's Principles of Internal Medicine, 18e
  5. 5. The projected lifetime probability of developing lung cancer is estimated to be approximately 8% among males and approximately 6% among females. The incidence of lung cancer varies by racial and ethnic group, with the highest ageadjusted incidence rates among African Americans. : Abeloff's Clinical Oncology, 4th ed
  6. 6. Demographic data of lung cancer from Indian studies. S. No Details 1958 – 1985 1986 - 2001 1. Total cases 1735 2973 2. M:F 6.67:1 5.76:1 3. Mean age (yrs) 52.16 54.6 4. Urban: Rural 19.6 - 81.6 18.4 - 80.4 5. Occupation Farmers Labourers Clerks/teachers Businessmen Housewives Others 13.9 - 48% 21.0 - 27.3% 16.7% 21.3% 8.0 - 14.7% 23% 6. Religion Hindus Muslims Christians 75.1% 18.9% 5.9% :IACM Journal April-June 2012
  7. 7. Lung cancer incidence in United States between 1975 and 2003. Age-adjusted to the 2000 U.S. standard population : Abeloff's Clinical Oncology, 4th ed
  8. 8. Tobacco use and lung cancer mortality in the United States 1900–2002. *Per 100,000, age-adjusted to the 2000 U.S. standard population : Abeloff's Clinical Oncology, 4th ed
  9. 9. Age-adjusted cancer death rates for selected sites in the United States, adjusted for the 2000 ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, 7/E
  10. 10. RISK FACTORS  Majority (80–90%) by cigarette smoking. -Cigarette smokers have a tenfold or greater increase in risk. -One genetic mutation is induced for every 15 cigarettes smoked. - Cigarette smoking increases the risk of all the major lung cancer cell types. - Environmental tobacco smoke (ETS) or secondhand smoke is also an established cause of lung cancer. Harrison's Principles of Internal Medicine, 18e
  11. 11.  In Indian patients with lung cancer, history of active tobacco smoking was found in 87% of males and 85% of females.  History of passive tobacco exposure is found in 3% in india. So 90% of all cases in india resulted from tobacco exposure.  The relative risk of developing lung cancer is 2.64 for beedi smokers 2.23 for cigarette smokers 2.45 as the overall relative risk (RR). IACM Journal April-June 2012
  12. 12. Occupational risk of lung cancer: S.No Occupational carcinogens Risk 1. Asbestos Insulation and shipyard workers,increase in risk of lung cancer after 10 years of exposure, with concurrent smoking increases risk 90 fold. 2. Arsenic Smelters and vineyard workers, Upper lobe predominance. 3. Nickel Squamous cell carcinoma-MC 4. Radiation Uranium mining, Oat cell carcinoma -MC 5. Haematite mining Due to radon exposure 6. Hard rock mining Chromium exposure,Squamous cell- MC 7. Chloromethyl Oat cell -MC 8. Ethers and mustard gas Squamous and undifferentiated -MC 9. Soots , Tars Coke oven workers 10 Oils and cokes Gas house workers, roofers :IACM Journal April-June 2012
  13. 13.  Low fruit and vegetable intake during adulthood. -This observation led to hypotheses that specific nutrients, in particular retinoids and carotenoids, might have chemopreventive effects for lung cancer.  Ionizing radiation -Increased rates of lung cancer among survivors of the atom bombs dropped on Hiroshima and Nagasaki  Prolonged exposure to low-level radon in homes Harrison's Principles of Internal Medicine, 18e
  14. 14.  Prior lung diseases such as -chronic bronchitis, -emphysema, and - tuberculosis  Air pollution:  Studies from china have shown : - Coal burning at home is a significant risk factor for development of lung cancer in non smoking females. - Coal smoke contains potential carcinogens: SO2 ,CO , TSP , B(a)P, radon , thoron. :IACM Journal April-June 2012
  15. 15. SMOKING CESSATION Physicians must promote tobacco abstinence. Stopping tobacco use before middle age avoids more than 90% of the lung cancer risk attributable to tobacco. Smoking cessation is beneficial in individuals even with an established diagnosis of lung cancer. Harrison's Principles of Internal Medicine, 18e
  16. 16.  Essential elements of smoking cessation therapy:  The individual must want to stop smoking. Must be willing to work hard to achieve the goal of smoking abstinence.  Therapy with : -an antidepressant (e.g., bupropion) or - nicotine replacement therapy (varenicline). - Clonidine and nortriptyline are recommended as secondline treatments Harrison's Principles of Internal Medicine, 18e
  17. 17. Inherited Predisposition to Lung Cancer  Environmental carcinogens can induce or facilitate the transformation from bronchoepithelial cells to the malignant phenotype.  Certain genetic polymorphisms of the P450 enzyme system, specifically CYP1A1, or chromosome fragility are associated with the development of lung cancer. Harrison's Principles of Internal Medicine, 18e
  18. 18.  First-degree relatives of lung cancer probands have a two- to threefold excess risk of lung cancer and other cancers, many of which are not smoking-related.  Individuals with inherited mutations in RB (retinoblastoma) and p53 (Li-Fraumeni syndrome) genes may develop lung cancer. Harrison's Principles of Internal Medicine, 18e
  19. 19.  Three genetic loci for lung cancer risk have been identified : -5p15 (TERT-CLPTM1L), -15q25(CHRNA5-CHRNA-3 nicotinic acetylcholine receptor subunits), and -6p21 (BAT3-MSH5).  A rare germline mutation (T790M) involving the epidermal growth factor receptor (EGFR) maybe be linked to lung cancer susceptibility in never smokers. Harrison's Principles of Internal Medicine, 18e
  20. 20. Pathology  The term lung cancer is used for tumors arising from the respiratory epithelium (bronchi, bronchioles, and alveoli). Harrison's Principles of Internal Medicine, 18e
  21. 21. 2004 World Health Organization Classification of Malignant Epithelial Tumors Squamous cell carcinoma Papillary Clear cell Small cell Basaloid Small cell carcinoma Combined small cell carcinoma Adenocarcinoma Mixed pattern Acinar Papillary Bronchioloalveolar Mucinous :Fishman’s Pulmonary Diseases and Disorders Nonmucinous
  22. 22. Mixed Solid with mucin production Fetal adenocarcinoma Mucinous (colloid) carcinoma Mucinous cystadenocarcinoma Signet ring Clear cell Large cell carcinoma Large cell neuroendocrine carcinoma Basaloid carcinoma Lymphoepithelioma-like carcinoma Clear cell carcinoma Large cell carcinoma, rhabdoid phenotype :Fishman’s Pulmonary Diseases and Disorders 4th Edition
  23. 23.  Adenosquamous carcinoma  Sarcomatoid carcinoma Pleomorphic carcinoma Spindle cell carcinoma Giant cell carcinoma Carcinosarcoma Pulmonary blastoma  Carcinoid tumor Typical carcinoid tumor Atypical carcinoid tumor  Salivary gland tumors Mucoepidermoid carcinoma :Fishman’s Pulmonary Diseases and Disorders 4th Edition Adenoid cystic carcinoma Epithelial-myoepithelial carcinoma
  24. 24. These four histologies account for approximately 90% of all epithelial lung cancers. 1.Small Cell Lung Cancer (SCLC) 2.Adenocarcinoma 3.Squamous Cell Carcinoma Non Small Cell Lung Cancer(NSCLC) 4.Large Cell Carcinoma :Harrison's Principles of Internal Medicine, 18e
  25. 25. Epithelial cell lung cancers WESTERN COUNTRIES Squamous Large INDIA-1986-2001 Others Adeno Small :Harrison's Principles of Internal Medicine, 18e Squamous Large Adeno :IACM Journal April-June 2012
  26. 26. Among women and young adults (<60 years), adenocarcinoma tends also to be the most common form of lung cancer. In lifetime never smokers, all histologic forms of lung cancer can be found, although adenocarcinoma tends to predominate. The incidence of small cell carcinoma is also on the decline. :Harrison's Principles of Internal Medicine, 18e
  27. 27. LUNG CANCER IN INDIA Non-small-cell lung cancer constitutes 75 - 80% of lung cancers. More than 70 % of them are in Stages III and IV, thus curative surgery can not be done in these cases. Small-cell lung carcinoma constitute 20% of all lung cancers . Extensive stage in 70% of patients at the time of diagnosis. While in many Western countries adenocarcinoma has become the commonest lung cancer. In India it is still squamous cell carcinoma in both males and females :IACM Journal April-June 2012
  28. 28. Small cell carcinoma  Poorly differentiated neuroendocrine tumor.  Highly prevalent in smokers.  Incidence rates are higher among men than women.  Central mass with endobronchial growth. :Abeloff's Clinical Oncology, 4th ed
  29. 29.  May produce specific peptide hormones such as - adrenocorticotrophic hormone (ACTH), - arginine vasopressin (AVP), -atrial natriuretic factor (ANF), and -gastrin-releasing peptide (GRP).  These hormones may be associated with distinctive paraneoplastic syndromes :Abeloff's Clinical Oncology, 4th ed
  30. 30.  Differential diagnosis : -poorly differentiated nonsmall cell carcinomas -neuroendocrine carcinomas, poorly differentiated squamous cell carcinoma -nonepithelial tumors lymphoma, small round blue cell tumors, sarcomas (e.g., synovial sarcoma). : Abeloff's Clinical Oncology, 4th ed
  31. 31. Small cell carcinoma with islands of small deeply basophilic cells and areas of necrosis :ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, 7/E
  32. 32. 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 :ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, 7/E
  33. 33.  Squamous cell carcinomas     Identical to extrapulmonary (i.e., head and neck) squamous cell carcinomas . Occur centrally . Classically associated with a history of smoking. Pattern is that of an infiltrating nest of tumor cells with central necrosis , resulting in cavitation. :Abeloff's Clinical Oncology, 4th ed
  34. 34.  Keratin can usually be seen when present.  Important variants-papillary pattern -basaloid variant  Differential diagnosis -reactive processes that may result in squamous metaplasia with reactive atypia such as that observed with infection or radiation-induced injury. :Abeloff's Clinical Oncology, 4th ed
  35. 35. Well-differentiated squamous cell carcinoma showing keratinization :ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, 7/E
  36. 36. Cavitation within a squamous cell carcinoma. :Fishman’s Pulmonary Diseases and Disorders 4th Edition
  37. 37. A sputum specimen shows an orange-staining, keratinized squamous carcinoma cell with a prominent hyperchromatic nucleus (arrow) :ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, 7/E
  38. 38.  Adenocarcinomas - Peripheral lung locations. - Associated with a history of smoking. - It is the most common type of lung cancer occurring never smokers. - Histologically, the tissue may contain : glands, papillary structure, bronchioloalveolar pattern, cellular mucin, or solid pattern if poorly differentiated. : Abeloff's Clinical Oncology, 4th ed
  39. 39. - Solid and micropapillary patterns in adenocarcinomas may predict a worse prognosis. - Variants of adenocarcinomas include -signet-ring, -clear cell, Primarily descriptive -mucinous, -fetal adenocarcinomas. Distinct Rare Young smokers Better Prognosis : Abeloff's Clinical Oncology, 4th ed
  40. 40. Gland-forming adenocarcinoma :ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, 7/E
  41. 41. Peripheral adenocarcinoma of the lung with pleural puckering. :Fishman’s Pulmonary Diseases and Disorders 4th Edition
  42. 42. Bronchioloalveolar carcinoma (BAC)  subtype of adenocarcinoma  grows along the alveoli without invasion.  present radiographically as a single mass, as a diffuse multinodular lesion, as a fluffy infiltrate. on CT scans as a "ground-glass" opacity (GGO). :Harrison's Principles of Internal Medicine, 18e
  43. 43. Bronchioloalveolar carcinoma, mucinous type. Tall columnar cells with abundant mucinous cytoplasm line the alveolar septa :Fishman’s Pulmonary Diseases and Disorders 4th Edition
  44. 44.  Large cell carcinomas -fewer than 10% of lung cancer. - occur peripherally. - poorly differentiated carcinomas - sheets of large malignant cells, often with associated necrosis. - Cytologically, the tumor is also arranged in syncytial groups and single cells. :Harrison's Principles of Internal Medicine, 18e
  45. 45. Variants of large cell carcinoma: - basaloid carcinoma- present as an endobronchial lesion and may resemble a high-grade neuroendocrine tumor, - lymphoepithelioma-like carcinoma- similar to the same-named tumor of other sites and is EpsteinBarr virus–related. :Harrison's Principles of Internal Medicine, 18e
  46. 46. Large cell carcinoma, featuring pleomorphic, anaplastic tumor cells and absence of squamous or glandular differentiation. :ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, 7/E
  47. 47. Immunohistochemistry  The diagnosis of lung cancer rests on the morphologic or cytologic features correlated with clinical and radiographic findings.  Immunohistochemistry may be used : 1. To verify neuroendocrine differentiation within a tumor, with markers such as neuron-specific enolase (NSE), CD56 or neural cell adhesion molecule (NCAM), synaptophysin, chromogranin, and Leu7. 2. Helpful in differentiating primary from metastatic adenocarcinomas. For example:Thyroid transcription factor 1 (TTF-1), is positive in more than 70% of pulmonary adenocarcinomas and is a reliable indicator of primary lung cancer, provided a thyroid primary has been excluded. 3. Cytokeratins 7 and 20 used in combination can help narrow the differential diagnosis. :Harrison's Principles of Internal Medicine, 18e
  48. 48.  Common Immunohistochemical Markers Used in the Diagnosis of Lung Tumors :Harrison's Principles of Internal Medicine, 18e Histology Positive Immunohistochemical Markers Squamous cell carcinoma Cytokeratin (CK) cocktail, e.g., AE1/AE3 CK5/6 , CK7 rare Adenocarcinoma Cytokeratin cocktail, e.g., AE1/AE3 CK7 , TTF-1 Neuroendocrine markers rare, e.g., CD56, NSE Large cell carcinoma Cytokeratin , TTF-1 rare Neuroendocrine markers rare (e.g., CD56, NSE) Large cell neuroendocrine carcinoma Cytokeratin cocktail, e.g., AE1/AE3 TTF-1 , CD56 , Chromogranin Synaptophysin Small cell carcinoma Cytokeratin cocktail (tends to be patchy) TTF-1 , CD56 , Chromogranin Synaptophysin
  49. 49. Molecular Pathogenesis  The exact cell of origin for lung cancers is not known.  In Lung adenocarcinoma , type II epithelial cells give rise to tumors.  In SCLC, cells of neuroendocrine origin have been implicated as precursors.  Lung cancer cells harbor multiple chromosomal abnormalities ,including mutations, amplifications, insertions, deletions, and translocations.  The earliest set of oncogenes found to be aberrant was the MYC family of transcription factors (MYC, MYCN, and MYCL). :Harrison's Principles of Internal Medicine, 18e
  50. 50. Genes Somatically Altered in Different Histologic Subtypes of Lung Cancer Histology Oncogene Tumor-Suppressor genes Adenocarcinoma EGFR KRAS ALK TP53 CDKN2A/B(p16, p14) LKB1 Squamous cell carcinoma EGFR PIK3CA IGF-1R TP53 TP63 Small cell carcinoma MYC BCL-2 TP53 RB1 FHIT Large cell carcinoma (not well studied) :Harrison's Principles of Internal Medicine, 18e
  51. 51. Early Detection and Screening  Low-dose, noncontrast, thin-slice helical or spiral chest CT has emerged as a possible new tool for lung cancer screening.  A major challenge confronting advocates of CT screening is the high false-positive rate.  It appears that nodules: <5 mm are unlikely to be cancerous and 5–10 mm in diameter are of uncertain significance. :Harrison's Principles of Internal Medicine, 18e
  52. 52. Two additional screening studies are ongoing: 1.The National Lung Cancer Screening Trial (NLST), a prospective comparison of spiral CT and standard chest x-ray in 50,000 current or ex-smokers 2.Study in Europe comparing CT scanning with standard of care in subjects with a history of heavy smoking. :Harrison's Principles of Internal Medicine, 18e
  53. 53. Clinical Manifestations Symptoms and Signs Range of Frequency Cough 8-75% Weight loss 0-68% Dyspnea 3-60% Chest pain 20-49% Hemoptysis 6-35% Bone pain 6-25% Clubbing 0-20% Fever 0-20% Weakness 0-10% SVCO 0-4% Dysphagia 0-2% Wheezing and stridor 0-2% :Harrison's Principles of Internal Medicine, 18e
  54. 54.  Clinical findings suggestive of metastatic disease: Symptoms elicited in history Constitutional : weight loss > 10 lb Musculoskeletal ; focal skeletal pain Neurologic: headache , syncope , seizures , extremity weakness Signs found on physical examination Lymphadenopathy(>1cm) Hoarsness , superior vena cava syndrome Bone tenderness Hepatomegaly (13> cm span) Focal neurologic signs , papilledems Soft – tissue mass Routine laboratory tests Hematocrit:<40% in men , <35% in women Elevated alkaline phosphatase , GGT ,SGOT and calcium levels :Harrison's Principles of Internal Medicine, 18e
  55. 55. Syndromes/Symptoms secondary to regional metastases:  Esophageal compression  dysphagia  Laryngeal nerve paralysis  hoarseness  Symptomatic nerve paralysis  Horner’s syndrome     (enophthalmos, ptosis, miosis, and anhidrosis) Cervical/thoracic nerve invasion  Pancoast syndrome. Lymphatic obstruction  pleural effusion Vascular obstruction  SVC syndrome Pericardial/cardiac extension  effusion, tamponade :Harrison's Principles of Internal Medicine, 18e
  56. 56. Paraneoplastic syndromes  SIADH – Small cell – Hyponatremia Resolves within 1–4 weeks of initiating chemotherapy. Demeclocycline can be a useful  ACTH-producing tumors – Small cell-Hypokalemia No changes in body habitus. Metyrapone and ketoconazole not effective. Treatment is effective management of underlying SLCS :Harrison's Principles of Internal Medicine, 18e
  57. 57.  PTH/PTH-rp – Squamous cell – Hypercalcemia Clinical symptoms include nausea, vomiting, abdominal pain, constipation, polyuria, thirst, and altered mental status.  Calcitonin  Gonadotropin  Serotonin
  58. 58. Skeletal–  Clubbing - 30% (usually NSCLCs)  Hypertrophic primary osteoarthropathy - 1–10% (usually adenocarcinomas).  Periostitis Cutaneous manifestations – 1% - Dermatomyositis and - Acanthosis nigricans :Harrison's Principles of Internal Medicine, 18e
  59. 59. Neurologic– Myopathic syndromes - 1% Myasthenic Eaton-Lambert syndrome and retinal blindness (SCLC).  Peripheral neuropathies, Subacute cerebellar degeneration, Cortical degeneration, and Polymyositis All lung cancer types
  60. 60. Hematologic manifestations – 1-8% -Migratory venous thrombophlebiti (Trousseau'ssyndrome), -Nonbacterial Thrombotic (marantic) endocarditis with arterial emboli, -Disseminated intravascular coagulation -Thrombotic disease complicating cancer is usually a poor prognostic sign. Renal manifestations – 1% - Nephrotic syndrome and - Glomerulonephritis :Harrison's Principles of Internal Medicine, 18e
  61. 61. Eaton-Lambert syndrome. -Autoimmune responses(anti–voltage-gated calcium channel antibodies) -Proximal muscle weakness, usually in lower extremities, -Occasional - autonomic dysfunction -Rarely - cranial nerve symptoms -Frequently - depressed deep tendon reflexes -In contrast to patients with myasthenia gravis, strength improves with serial effort. -Chemotherapy is the initial treatment of choice. :Harrison's Principles of Internal Medicine, 18e
  62. 62. lung cancer-Metastasis  Adrenals - ~50% of cancers  Liver – 30-50%  Brain – 20%  Bone – 20% :Harrison's Principles of Internal Medicine, 18e
  63. 63. The Solitary Pulmonary Nodule:A Systematic Approach  A single discrete pulmonary opacity that is surrounded by normal lung tissue.  Not associated with adenopathy or atelectasis.  Lesions larger than 3cm are almost always malignant.  Solitary pulmonary nodules must be 3cmor less in diameter.  Prompt diagnosis and resection are usually advisable :Fishman’s Pulmonary Diseases and Disorders 4th Edition
  64. 64. Factors influencing assessment of a solitary pulmonary nodule. FACTOR BENIGN Pts Malignant Pts 1.Growth rate No growth on 2 serial xrays at 3 mths interval 10 Definite growth on serial X-rays 10 2.Calcification a)Laminated b)Dense central core c) Diffuse Nodular d) Punctate central 10 10 Uncalcified 4 3.Age <30yrs 9 >40yrs 4 4.Margin of lesion Sharply defined 5 Ill defined 5 5.Size Not a useful factor 0 Larger than 3.5cms 5 6.Density Dense lesion <2cm 4 Low density <2cm 4 7.H/O malignancy None 0 +ve 5 8.Documented hemoptysis None 0 +ve 5 10 10 IACM :Journal Vol.13 April-June 2012
  65. 65. Satisfies 1 of the Lesion rates 10 or ‘10 point’ items more on the ‘Malig for benign ds. nancy Scale’ Patient considered to have benign nodule Find out nature of the lesion. Thoracotomy is indicated Malignant points minus benign points if <10 Fine needle aspiration biopsy (without resorting to thoracotomy) Plan specific therapy Accuracy of assessment was 77.7% in the series of the author(Jain DG ,1988) IACM :Journal Vol.13 April-June 2012
  66. 66. Differential Diagnosis of Solitary Pulmonary Nodules: Malignant tumors Infectious granulomas Bronchogenic carcinoma (adenocarcinoma, large cell, squamous, small cell) Carcinoid Pulmonary lymphoma Tuberculosis Histoplasmosis Coccidioidomycosis Benign tumors Others Hamartoma Adenoma Lipoma Miscellaneous BOOP Abscess Noninfectious granulomas Pseudotumor Spherical pneumonia Pulmonary infarction Arteriovenous malformation Bronchogenic cyst Amyloidoma Rheumatoid arthritis Wegener’s granulomatosis Sarcoidosis Paraffinoma :Fishman’s Pulmonary Diseases and Disorders 4th Edition
  67. 67. Approach to solitory pulmonary nodule New nodule identified on standard CT scanning Benign calcification pattern on CT or stability for 2 yr on archival films yes No further testing No Risk factor for surgery No Does probability of cancer warrant further investigation ? Harrison's Principles of Internal Medicine, 18e
  68. 68. :Harrison's Principles of Internal Medicine, 18e Yes Moderate probability of cancer(10-60%) Low probability of cancer Serial highresolution CT 3, 6, 12, and 24 mo No -ve test Additional testing -PET if nodule> 1 cm in diamete -Contrast- enhanced CT, depending on intitutional expertise -Trans thoracic fineneedle aspiration biopsy if nodule is peripherallly located -Bronchoscopy if air bronchus sign present +ve test Video-assisted thoracoscopic surgery; -examination of mediastinal lymph nodes and frozen section folllowed by lobectomy if nodule is malignant
  69. 69. THANK YOU