1. LUNG TUMORS Ch. 12 p (459 – 512) March. 9. 2016

2. LUNG TUMORS Benign, malignant, epithelial, mesenchymal 90% Carcinoma 5% Carcinoids 2-5% Mesenchymal and others BIGGEST USA killer. a peak incidence in the 50s or 60s Only 15% 5 year survival.

6. Types of lung cancer Adenocarcinoma Squamous cell carcinoma Large cell carcinoma Small cell carcinoma NSCLC SCLC On the basis of likelihood of metastases and response to therapies

7. Types of lung cancer

8. Etiology and Pathogenesis Tobacco, (10 - 60 times more in smokers) Secondhand smoke Radiation, asbestos, …..etc. familial clustering (polymorphisms) Genetic mutations Tumor suppressor genes include p53, Rb1, p16.Ch 3p. Oncogenes involved in lung cancer are; c-MYC, KRAS, EGFR, HER-2/neu, c-MET, and c-KIT.

9. Potentially curable asymptomatic cough hemoptysis Presenting symptoms Usually incurable dyspnea chest pain anorexia & weight loss hoarseness bone pain Pleural effusion

11. Positron Emission Tomography–computed tomography The bright red/yellow masses show hypermetabolic areas of with metastases Spine adrenal

12. At diagnosis, >50% have metastases Survival; Overall (all stages) 5ys = 16% Localized disease 5ys = 45% Survival statistics…bad.

13. A precursor epithelial lesion Sq. Dysplasia Sq. CIS Atypical adenomatous hyperplasia (AAH), Adenocarcinoma in situ The term precursor does not imply that progression to cancer will occur in all cases

14. Squamous cell carcinoma Lung carcinomas arise most often in and about the hilus of the lung. About ¾ of the lesions take their origin from 1 st -order, 2 nd -order, and 3 rd -order bronchi

15. Squamous cell carcinoma

16. Dx: Radiology, Cytology & Biopsy Cytologic smears of sputum, bronchial lavage or brushings

17. Squamous cell carcinoma

18. Adenocarcinoma Adenocarcinomas grow more slowly than Sq C ca, but tend to metastasize widely and earlier Most common type in USA, especially in women < 45 years Usually peripheral, associated with scarring less frequently associated with a history of smoking (still, > 75% are in smokers) Sq C Ca or SC Ca(>98% in smokers).

20. Adenocarcinoma

21. aka “bronchioalveolar carcinoma” A rare type of adenocarcinoma 5 year survival better (40%) Grows along existing architecture A precursor epithelial lesion. Adenocarcinoma in situ

22. Adenocarcinoma

23. Adenocarcinoma; involving most of the right lung Consolidation ( * ) similar to those seen with pneumonia. There is a loculated pleural effusion ( ) above the neoplasm, as seen on the left

24. Large cell carcinoma Undifferentiated carcinomas Probably represent undifferentiated Sq C Ca or adenoca.

25. Totally different Ca. Small cells, minimal cytoplasm, “molding” strong relationship to cigarette smoking; only 1% occur in nonsmokers Paraneoplastic syndromes High growth fraction treatment ineffective Median survival (with treatment) = 1 year Small cell carcinoma

29. NSCLC & SCLC

30. Extension to the pleura Spread to LN, tracheal, bronchial, & mediastinal. Distant spread Adenoca & SCL Ca often spread early through the body. While Sq C Ca, metastasizes outside the thorax late Local & Systemic Effects of Lung Tumor

31. Clinical FeaturePathologic Basis Pneumonia, abscess, lobar collapse Tumor obstruction of airway Pleural effusionTumor spread into pleura Hoarseness Vocal cord paralysis Recurrent laryngeal N. invasion DysphagiaEsophageal invasion Diaphragm paralysisPhrenic N. invasion Pancoast syndromeInvolvement of brachial plexus SVC syndromeSVC compression by tumor Horner syndromeSympathetic ganglia invasion Pericarditis, tamponadePericardial involvement Local Effects of Lung Tumor Spread

33. Superior vena cava syndrome in a person with bronchogenic Ca. swelling of his face first thing in the morning (left) and its resolution after being upright all day (right).

34. Pancoast syndrome

35. Horner syndrome Horner syndrome; interruption of the sympathetic nerve supply to the eye, the classic triad of Miosis (constricted pupil), Anhidrosis (loss of hemifacial sweating), partial Ptosis, MAP

36. Pancoast syndrome

37. (ADH), hyponatremia due to inappropriate ADH secretion (ACTH), producing Cushing syndrome Parathormone, hypercalcemia Calcitonin, causing hypocalcemia Gonadotropins, causing gynecomastia Serotonin and bradykinin, associated with the carcinoid syndrome Paraneoplastic Syndromes 1% to 10%

39. Lung Ca.Spread  Local: Pancoast tumor Neck Mediastinum SVC, Ns  Distant spread Lymphatics Bl. (via pulm vein to liver, bone, brain, adrenal Non- Metastatic effects

40. T1 Tumor <3 cm without pleural or main stem bronchus involvement (T1a, <2 cm; T1b, 2–3 cm) T2 Tumor 3–7 cm or involvement of main stem bronchus 2 cm from carina, visceral pleural involvement, or lobar atelectasis (T2a, 3–5 cm; T2b, 5–7 cm) T3 Tumor >7 cm or one with involvement of chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, pericardium, main stem bronchus 2 cm from carina, or entire lung atelectasis, or separate tumor nodule(s) in the same lobe T4 Tumor with invasion of mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina or separate tumor nodules in a different ipsilateral lobe N0 No demonstrable metastasis to regional lymph nodes N1 Ipsilateral hilar or peribronchial nodal involvement N2 Metastasis to ipsilateral mediastinal or subcarinal lymph nodes N3 Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes M0 No distant metastasis M1 Distant metastasis (M1a, separate tumor nodule in contralateral lobe or pleural nodules or malignant pleural effusion; M1b, distant metastasis) International Staging System for Lung Cancer

41. Lung Tumors SCC Limited Stage (LS); (Lung & LN) Extended stage (ES) early metastasis NSCLC Adenocs; slowly growing but early metast SqCCa; Rapid growing but late metastasis Large cell Ca; Slowly growing & late Metas.

42. Treatment Surg. Chemotherapy Radiotherapy Target therapy to the prodcts of mutant genes

43. Bronchial carcinoid

44. OTHER TUMORS

45. Coin lesions Pulmonary hamartoma. islands of cartilage & respiratory epith.

46. METASTATIC TUMORS Metastases to the lungs are more common even than primary lung neoplasms Cannonball lesions

47. PLEURA PLEURITIS PNEUMOTHORAX EFFUSIONS –HYDRO-THORAX –HEMO-THORAX –CHYLO-THORAX MESOTHELIOMAS

48. Malignant tumor of mesothelial cells Most patients have had asbestos exposure Not related to smoking Highly malignant; short survival. Visceral or parietal pleura, pericardium, or peritoneum Mesothelioma

49. Malignant mesothelioma

51.  EM H&E, IMMUNOCHEMISTRY

52. lung carcinoma. A, Gland-forming adenocarcinomaB, Well-diff. sq. c. ca. showing keratinization. C, SCLC with islands of small deeply basophilic cells D, Large cell ca., featuring pleomorphic, anaplastic tumor cells with no sq. or glandular differentiation.

53. PLEURITIS Usual bacteria, viruses, etc. TB “Collagen” diseases, e.g., RA, SLE Uremia Metastatic Infarcts Lung abscesses, empyema

54. PNEUMOTHORAX SPONTANEOUS, TRAUMATIC, THERAPEUTIC OPEN or CLOSED “TENSION” pneumothorax, “valvular” effect “Bleb” rupture Perforating injuries Post needle biopsy

55. EFFUSIONS TRANSUDATE EXUDATE BLOOD LYMPH

56. Mediastinal Tumors SUPERIOR MEDIASTINUM Lymphoma Thymoma Thyroid lesions Metastatic carcinoma Parathyroid tumors

57. Mediastinal Tumors ANTERIOR MEDIASTINUM Thymoma Teratoma Lymphoma Thyroid lesions Parathyroid tumors

58. Mediastinal Tumors POSTERIOR MEDIASTINUM Neurogenic tumors (schwannoma, neurofibroma) Lymphoma Gastroenteric hernia MIDDLE MEDIASTINUM Bronchogenic cyst Pericardial cyst Lymphoma

59. Male Lung & bronchus 4105(12.7%) Bladder 3250 (10%) Leukemia 2618 (8%) NHL 2283(7%) Brain &CNS 2217 (6.9%) Larynx 1998(6%) Colorectal 1545(4.8%) Skin excluding 1342 (4%) Melanoma Stomach 1246(3.9%) Prostate 1081(3.3%) Female Breast 9813 (31%) Leukemia 1858(6 %) Uterus including 1692 (5.3%) Cervix and corpus) Brain &CNS 1654(5.2%) NHL 1499(4.7%) Ovary 1203(3.8%) Colorectal 1191 (3.8%) Skin excluding 1083(3.4%) Melanoma Lung & bronchus 1052((3.3) The 10 leading cancers by gender, site Iraqi Tumor Regestry 2009 J of Oncology

60. Primary site Total No Male No (%) Female No (%) Breast 10277 464(4.5%) 9813(95.5%) Lung & bronchus 5157 4105(79.6%) 1052(20.4%) Leukemia 4476 2618(58.5%) 1858(41.5%) Bladder 4253 3250(76.4%) 1003(23.6%) Brain &CNS 3871 2217(57.3%) 1654(42.7%) NHL 3782 2283(60.4%) 1499(39.6%) Colorectal 2736 1545(56.5%) 1191(43.5%) Larynx 2590 1998(77%) 592(23%) Skin excluding Melanoma 2425 1342(55.4%) 1083(44.6%) Stomach 2108 1246(59%) 862(41%) Uterus including Cervix and corpus) 1692 0 1692 Hodgkin disease 1502 925(61.6%) 577(38.4%) Thyroid 1334 446(33.4%) 888(66.6%) Kidney, pelvis& ureter 1232 754(61%) 478(39%) Ovary 1203 0 1203 Prostate 1081 1081 0 Pancreas 1014 575(56.7%) 439(43.3%) Bone & cartilage 999 58.7(58.8%) 412(41.2%) Liver &bile ducts 637 358(56%) 279(44%) Esophagus 539 342(63.5%) 197(36.5%) Type of cancer by primary tumor site Iraqi Tumor Regestry 2009 J of Oncology