Etiology and Pathogenesis
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1 Lung Tumors
2 Lung Cancer Most common cause of cancer death 27% of all cancer deaths in United States. Most common cancer in men and women Most common between 40 and 70 years of age 2% occurs before age 40
3 Etiology and Pathogenesis Tobacco smoking Amount, tendency to inhale, duration Genetic susceptibility (hereditary factors) Industrial hazards Miners of ra ores, asbestos workers, chromium, arsenic, uranium, nickel, mustrad gas, vinyl chloride
4 Smoking and Lung Cancer Smokers- 10 fold greater risk Heavy smokers- 60 fold greater risk Cessation of smoking for reduces risk; but risk may never return to baseline 96.7% of smokers show some atypical cells in the bronchial tree compared to 0.7% of nonsmoker control subjects
5 Smoking and Lung Cancer Bronchial epithelium shows loss of cilia Basal cell hyperplasia Dysplasia Carcinoma in-situ Association stronger with squamous and small cell carcinoma No experimental animal model
6 Smoking and Lung Cancer Basal cell hyperplasia associated with smoking
7 Smoking and Lung Cancer Squamous metaplasia Squamous dysplasia
8 Lung Cancer Majority are epithelial in origin Bronchogenic carcinoma (90-95%) Bronchial carcinoid (5%) Mesenchymal/miscellaneous (2-5%)
9 Classification of Lung Tumors Bronchogenic Carcinoma Nonsmall cell carcinoma (70-75%) Squamous cell carcinoma (25-40%) Adenocarcinoma (25-40%) Bronchioloalveolar carcinoma Large cell carcinoma (10-15%) Small cell carcinoma (20-25%) Combined patterns (5-10%)
10 Lung Cancer Histology Squamous cell ca Adenoca Small cell ca Large cell ca
11 Classification of Lung Tumors SMALL CELL CARCINOMA Chemotherapy NONSMALL CELL CARCINOMA Surgery
12 Response to Chemotherapy in Small Cell Cancer
13 Classification of Lung Tumors Neuroendocrine Tumors Carcinoid, atypical carcinoid, small cell Soft Tissue/Mesenchymal tumors Localized fibrous tumor, hamartoma Mesothelial Tumors Malignant mesothelioma Lymphoproliferative Diseases Secondary Tumors (Metastatic)
14 Lung Cancer Histogenesis Auerbach theory Dedifferentiation of normal respiratory epithelial cells Yesner theory Small cell carcinoma cell undergoing transformation Sell and Pierce theory Maturation arrest of stem cells
15 Squamous Cell Carcinoma Strong relation to cigarette smoking Marked male predominance (male/female ratio 6.6 to 15:1) At least 50% arise in the major bronchus: centrally located (with both endobronchial and invasive growth) Precursor lesion: Squamous metaplasia/dysplasia
16 Squamous Cell Carcinoma Centrally located, endobronchial fungating mass
17 Squamous Cell Carcinoma Individual cell keratinization, keratin pearls, intercellular bridges Fine needle aspiration Biopsy (FNA)
18 Squamous Cell Carcinoma Individual cell keratinization, keratin pearls, intercellular bridges Surgical biopsy
19 Adenocarcinoma CT scan shows a 5.0cm mass CT guided FNA: Atypical epithelial cell clusters with lumen formation
20 Adenocarcinoma Most common lung ca in women and in nonsmokers Usually peripherally located Histologically vary from well (predominantly gland forming) to poorly (predominantly solid growth) differentiated Precursor lesion: Atypical adenomatous hyperplasia
21 Bronchioloalveolar Carcinoma Well differentiated columnar/cuboidal cells line preserved alveolar septa Lobar consolidation mimicking pneumonia BAC can be seen in all ages Men = women Has a better prognosis
22 Large Cell Carcinoma 10-20% of all cancers Most large cell tumors are peripheral Composed of large cells without glandular or squamous differentiation Common giant cells or clear cells features On EM some differentiation is usually demonstrable
23 Small Cell Carcinoma Highly malignant tumor Usually metastasized at the time of diagnosis Associated with paraneoplastic and endocrine symptoms Strong association with smoking
24 Small Cell Carcinoma Central bulky soft masses with necrosis. Metastases in lymph nodes common.
25 Small Cell Carcinoma Sheets and nests of SMALL cells with scant cytoplasm and nuclear molding Azzopardi effect
26 Carcinoid Tumor Kulchinsky cell (neuroendocrine cell) 5% of all pulmonary neoplasms Regarded as low-grade malignant, 5% metastasize Neural (NSE, synaptophysis) and endocrine (chromogranin, ectopic hormone production) differentiation
27 Carcinoid Tumor Endobronchial usually pedinculated, polypoid lesion which bleeds easily A A. Carcinoid tumor B. Postobstructive pneumonia B
28 Carcinoid Tumor Nests and cords of uniform cells EM: Neurosecretory granules
29 Neuroendocrine Tumors Carcinoid Atypical Carcinoid Small Cell Carcinoma
30 Diagnosis History Chest x-ray Cytology Diagnostic Screening Bronchoscopy/ biopsy Needle biopsy Biopsy of metastatic sites
31 Lung Cancer Diagnosis A B C A. Chest x-ray: Right central mass B. Bronschospy: Fungating white endobronchial mass C. Fine needle aspiration: Squamous cell carcinoma
32 Clinical Features General systemic effects Paraneoplastic symptoms (10% of cases) Hypercalcemia: PTH-related hormone (SqCCa) Cushing syndrome: Adrenocorticotropic hormone SIADH Neuromuscular syndromes: Clubbing, MG Hematologic manifestations: DIC (ACA)
33 Pancoast s Syndrome: Pain in the distribution of the 8 th cervical and 1 st and 2 nd thoracic spinal nerves. Mostly ACAs.
34
35 Benign Lung Tumors Most common benign lesion is a hamartoma Usually discovered as coin lesion on routine chest x- ray Rarely more than 3-4 cm Composed predominantly of mature cartilage Occasionally with cysts lined by respiratory epithelium Admixture of fibrous tissue, fat, blood vessels
36 Well-circumscribed nodule composed of mature cartilage Hamartoma
37 The lung is more often affected by metastatic tumor than primary malignancy Lung Cancer
38 Staging in Lung Cancer Once the diagnosis is made the next step is to stage the patient. Stage I T1-T2 N0 M0 Stage II T1-T2 N1 M0 T3 N0 M0 Stage III T3 N1 M0, N2 (T1-T3) N3 (T1-T4) T4(N0-N3) M0 Stage IV Any T Any N M1
39 Staging in Lung Cancer T1: Primary tumor <3cm T2: Primary tumor >3cm, invasion of pleura, involvement of main bronchus T3: Tumor of any size that directly invades the chest wall, diaphragm, mediastinal pleura, pericardium T4: Tumor of any size that directly invades mediastinum, trachea, carina, esophagus, vertebral body, heart, great vessels, satellite tumor within the ipsilateral primary tumor- lobe of the lung
40 Prognosis/Treatment Non-small Cell CA Stage I: 5 year survival 50% Stage II: 25% Stage III: 5-10% Stage IV: 1% Stage I and II: lobectomy Medically unfit patients, RT is the therapy of choice Stage III: Combinations of surgical resection, CT, RT Stage IV: CT/ hospice care
41 Prognosis/Treatment Small Cell CA Limited Stage (30-40% of cases) Tumor confined to one hemithorax Survival Untreated 12 weeks CT months Extensive stage (60-70% of cases) Survival Untreated 5 weeks CT 7-11 months
42 Pleural Tumors Solitary Fibrous Tumor Benign tumor Confined to the surface of the lung Originates from submesothelial cells - CK (-), CD34 (+)
43 Pleural Tumors: Mesothelioma All are malignant Strong association with asbestos exposure (smoking is NOT a risk factor) Degree of exposure Time interval: 20 years after exposure Prognosis: Poor, 50% survival at 1 yr
44 Mesothelioma Asbestos body in bronchoalveolar washings
45 Mesothelioma Extensive tumor encasing the lung and the heart
46 Mesothelioma A. Papillary B. Epithelial C. Sarcomatoid
47 All the best..
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