Lung Cancer - Rivin

Lung cancer, also known as lung carcinoma, is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung.

1. Lung Cancer W. P. Rivindu H. Wickramanayake Group no. 04a 3 rd Year 2 nd Semester – 2017 October Tbilisi State Medical University, Georgia

2. K ey R isk Factors for Lung C ancer - Risk directly linked to duration and amount of smoking (pack years) 1) Cigarette smoking (85% of lung cancer) - Colorless, odorless gas - Decay product of uranium - Found in soil, accumulates in closed space (basement) 2) Radon (2nd most common cause) - most common ionizing radiation exposure in USA 3) Asbestos

3. C arcinogenicity of Cigarette S moking Contains > 60 carcinogens Polycyclic aromatic hydrocarbons and arsenic are particularly carcinogenic Cancer risk directly increases with duration and amount of smoking (pack years)

4. P resentation of Lung C ancer Average age at presentation is 60. Most common cause of cancer death in USA. Nonspecific presentation - Cough, weight loss, hemoptysis, post obstructive pneumonia

5. Diagnosing Lung Cancer Diagnosis requires biopsy. Imaging reveals solitary nodule (coin-lesion) - growing lesion concerning. Coin lesions also seen in ; - Granulomas - TB, fungus (ex - histoplasma in midwest ) - Bronchial hamartoma - benign tumor of lung tissue + cartilage; often calcified in imaging. - Harmartoma - disorganized mass that grows at same rate as surrounding tissue; made of same cells that makes the tissue.

6. TNM Staging of Lung C ancer 1) T - tumor size Pleural involvement classically seen in adenocarcinoma (adenocarcinoma is peripheral) Obstruction of SVC (superior vena cava syndrome) - distended head and neck veins with edema and blue discoloration of arms and face Involvement of recurrent laryngeal nerve (hoarseness) or phrenic nerve (diaphragmatic paralysis) Horner's - compression of sympathetic chain (ptosis, anhydrosis - in skin, miosis ) - especially if tumor is at apex of lung ( pancoast tumor) 2) N - Spread to hilar and mediastinal lymph nodes 3) M - Unique site of distant metastasis is adrenals (HY) Others - brain, bone, liver

7. P rognosis of Lung Cancer Poor (no effective screening method) - 5 year survival rate is 15%

8. T wo Main Categories of Lung C ancer 1) Small cell carcinoma (15% of all lung carcinoma) - Usually no amenable to surgery (treat with chemotherapy and radiation) 2) Non-small cell carcinoma (85% of all lung carcinoma) Adenocarcinoma (40%) - glands or mucus production Squamous cell carcinoma (30%) - keratin pearls or intercellular bridges Large cell carcinoma (10%) - none of above features seen Carcinoid tumor (5%) - Treat upfront with surgery (doesn't respond well to chemotherapy)

9. D ifferent T ypes of Lung C ancer 1) Small Cell Carcinoma - Treat with Chemotherapy 2) Non-small Cell Carcinoma Subtypes; i . Squamous cell carcinoma Adenocarcinoma Broncheoalveolar carcinoma (Adenocarcinoma in situ) Large cell carcinoma (Bronchial) carcinoid tumor 3) Mesothelioma - Related to asbestos 4) Metastasis - Common origin of metastasis - breast, colon

10. D ifferent Types of Lung C ancer 1) Neuroendocrine (NE) tumor - Small cell carcinoma (poorly differentiated NE cells) - (Bronchial) carcinoid tumor (well differentiated NE cells) 2) Adenocarcinoma - Bronchioalveola r carcinoma (adenocarcinoma in situ) 3) Related to smoking - small, large, squamous, adeno - Squamous cell carcinoma (most common in male smokers - Small cell carcinoma (male smokers) - Adenocarcinoma (most common in female smokers and non-smokers) [ broncheoalveolar carcinoma not associated with smoking] - Large cell carcinoma To Next Page

11. 5) Undifferentiated and poor prognosis - Small cell carcinoma - Large cell carcinoma 4) Paraneoplastic syndrome - Squamous cell carcinoma ( PTHrp ) - Small cell carcinoma (ADH, ACTH, Ab for Ca channel) - Large cell carcinoma (BHCG) 6) Excellent prognosis - Bronchoal veolar carcinoma Continued;

12. T ypes of Cancer 1) Small cell carcinoma Poorly differentiated small cell and very aggressive Arise from neuroendocrine cells ( Kulchitsky cells) Chromogranin + ve (less + ve than carcinoid tumor) Located Centrally Male smokers (99% of small cell carcinoma patients are smokers) Associated with 5A and 1B Produces ACTH Produces ADH Produces Ab for Eaton - Lambert syndrome (presynaptic Ca channel Ab ) ( paraneoplastic syndromes) Anti-neuronal antibody syndrome (limbic encephalitis, cerebellar degeneration, opsoclonus , GI dysmotility , poly radiculopathy) Amplification of myc oncogene LOVES TO GO TO BRAIN - give prophylactic cranial irraditation MOST AGGRESSIVE TYPE OF LUNG CANCER

13. 2) Adenocarcinoma Glands or mucin Located peripherarily Most common tumor in nonsmokers and female smokers Fig: glandular structure in adenocarcinoma

14. 3) Squamous cell carcinoma Keratin pearls or intercellular bridges (by definition) Located centrally Most common tumor in male smokers May produce PTHrp ( paraneoplastic syndrome) Hilar mass from bronchus Associated with double C - HyperCalcemia - due to PTHrp - Cavitation Fig : keratin pearl Fig : intracellular bridge

15. 4) Large cell carcinoma Poorly differentiated and highly anaplastic cells (no keratin pearls, intercellular bridges, glands or mucin ) Smoking associated Located centrally or peripherarily Poor prognosis Poor response to chemotherapy; remove surgically Paraneoplastic - may secrete B-HCG

16. 5) (Bronchial) Carcinoid tumor Well differentiated neuroendocrine cells; chromogranin positive Not related to smoking Central or peripheral (when central, makes polyp like mass in bronchus) MOST COMMON PRIMARY LUNG CANCER IN CHILDREN Low grade malignancy; rarely, can cause carcinoid syndrome - caused due to release of vasoactive substance (mainly serotonin) - flushing, diarrhea, restrictive cardiomyopathy due to endocardial fibrosis Fig: chromogranin positivity

17. 6) Bronchioloalveolar carcinoma (adenocarcinoma in situ) Columnar cells that grow along preexisting bronchioles and alveoli; arise from clara cells Not related to smoking Located periphararily Excellent prognosis Pneumonia like consolidation on imaging Fig: normal alveoli top right ; columnar cells on rest

18. 7) Metastasis Most common source are breast and colon carcinoma Canon-ball nodules on imaging More common than primary tumors

19. 8) Mesothelioma Can see psammoma bodies in biopsy (concentric calcifications - other HY cancer - papillary thyroid, meningioma, papillary serous ovarian) Highly associated with asbestos exposure (lung cancer more common in asbestos exposure) Malignant tumor of mesothelial cells (mesothelium is a membrane of simple squamous cells that lines body cavities: pleura , peritoneum, mediastinum and pericardium) Tumor encases the lung

20. References ; Robbins Pathology – 10 th Edition Pathoma Lecture Notes – 2017 Board Review System – Pathology – 5 th Edition https://library.med.utah.edu/WebPath/LUNGHTML/LUNGIDX.html#9

21. Thank You!  Rivin..®