4. vi) ~ 3000 deaths/yr in USA from second hand smoke vii) cigar, pipe also  incidence of cancer, but smaller than cigarettes viii) smokeless tobacco  oral cancers + nicotine addiction b) clinical data i) sequential changes in respiratory epithelium ii) linear correlation between extent or intensity of exposure and worrisome epithelial changes - squamous metaplasia  dysplasia  in situ  invasive www.freelivedoctor.com

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13. b) squamous cell CA begins as area of in situ cytologic dysplasia i) develops along a variety of pathways ii) patterns show gray-white and firm to hard; keratinization (squamous ** pearls), and/or intracellular bridges iii) metastasize outside of the thorax late in its development. Most lung CA metastasize early. iv ) more often found in men v) strong correlation w/ smoking vi) highest frequency of p53 mutations - over expression may precede invasion vi) cavitation (abscess, TB diff. ???) www.freelivedoctor.com

14. viii) p53 staining (i.e., activity) increases as stage of tumor increases - 60-90 % of in situ CA ix) over expression of epidermal growth factor receptor detected in ~ 80% of squamous cell CA c) Distant metastasis of lung CA involve all tissues and organs i) adrenals most often (~ 50%) ii) liver (30-50 %);brain/bone (~20 %) d) Distant metastasis usually first sign of overt lung CA www.freelivedoctor.com

15. e) Adenocarcinoma i) malignant epithelial tumor - mucin production - glandular differentiation ii) most common type of lung CA in women and nonsmokers iii) more peripherally located compared with squamous cell CA iv) several growth patterns - acinar, papillary, bronchioalveolar (only one with distinct features) and solid with mucin production - ~ 80% contain mucin www.freelivedoctor.com

16. v) grow more slowly vs. squamous - metastasize widely and early vi) less frequently associated with smokers (~ 75%) as compared with squamous or small cell CA (~ 98%) vii) K-RAS mutations are seen primarily in adenocarcinomas; p53, RB and p16 mutations, etc seen in squamous cell CA viii) bronchioalveolar CA grow along preexisting structures w/out destruction - “lepidic” growth pattern (butterflies sitting on a fence) www.freelivedoctor.com

17. ix) two subtypes: mucinous and nonmucinous (amenable to surgical resection) f) Small cell CA i) highly malignant tumor ii) grading is inappropriate since all small cell CA are of the HIGH grade iii) strong correlation to cigarette smoking - ~1 % in nonsmokers iv) most aggressive of lung tumors v) metastasize widely and essentially incurable via surgery vi) frequent mutations of p53;RB www.freelivedoctor.com

18. vii) expression of anti-apoptotic gene (i.e., BCL2) in > 90% of tumors; low frequency of expression of pro- apoptotic gene, BAX ** viii) round to oval cells with pleomorphic, hyperchromatic nuclei g) Large cell CA i) undifferentiated malignant epithelial tumor ii) probably represent squamous and adenocarcinoma tumors that are so undifferentiated that they can no longer be identified microscopically www.freelivedoctor.com

19. h) Combined CA i) ~ 10% of all lung CA have combined histology from at lease 2 or more of the preceding CA i) secondary pathology i) obstruction (focal emphysema with partial obstruction); atelectasis with total obstruction ii) pulmonary abscess - bronchiectasis due to decreased drainage iii) compression of vena cava (dusky head and arm edema) www.freelivedoctor.com

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34. c) inflammatory or noninflammatory effusions 1) inflammatory (serous or serofibrinous pleuritis) - TB - abscess - pneumonia - bronchiectasis - RA - SLE - uremia - diffuse systemic infections - metastases (pleural) - radiation therapy www.freelivedoctor.com

35. i) purulent pleural exudate (empyema) - bacterial or mycotic seeding usually resulting from pulmonary infection - lymphatic or hematogenous - subdiaphragmatic or liver abscess bulging into pleura; usually occurring on the right side ii) hemorrhagic pleuritis (sanguineous) - differentiate  hemothorax - presence of tumor cells !! www.freelivedoctor.com

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37. 2. Noninflammatory pleuritis i) hydrothorax - CHF most common cause; usually collects at the base; causing compression and atelectasis of surrounding lung ii) hemothorax (blood in pleura) - fatal complication of ruptured aortic aneurysm / vascular trauma - rare to find inflammatory milieu iii) chylothorax - accumulation of milky lymph - more often confined to left side www.freelivedoctor.com

39. b) more often associated with: i) emphysema ii) asthma iii) TB c) spontaneous idiopathic pneumothorax i) young people ii) rupture of apical blebs iii) recurrent attack common iv) flap valve - when defect allows air to enter but not to escape - results in increasing pressure - “tension pneumothorax” - may compress contralateral lung www.freelivedoctor.com

41. b) solitary (localized) fibrous tumors i) “benign mesothelioma” - soft fibrous tumors mainly in pleura and rarely in lung - remains confined to surface of lung - do not produce pleural effusions - usually benign - tumor cells  CD34+; keratin negative staining (good differential from malignant mesotheliomas) - NO relationship to asbestos exposure !! www.freelivedoctor.com

42. c) Malignant mesothelioma i) arise from either pleura ii) asbestos exposure related iii) long latent period (25-50 yrs) iv) smoking does NOT increase risk - smoking  risk of lung CA in asbestos workers !! v) produces pleural effusions vi) diffuse and covers lung; invades thoracic cavity and structures vii) S & S - chest pain, dyspnea and recurrent pleural effusions viii) outcome poor  death w/in 2 yrs www.freelivedoctor.com

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