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1. Bronchogenic Carcinoma Capt Soe Moe Htun Department of Respiratory Medicine

2. Specific Learning Objectives At the end of this clinical teaching session, the students should be able to

3. Knowledge differentiate the histological types of bronchogenic carcinoma explain the different clinical presentations of bronchogenic carcinoma based on the underlying pathogenesis. recognize the extra pulmonary and pulmonary features of bronchogenic carcinoma. outline the management of bronchogenic carcinoma based on histological types and staging.

4. Skill perform a critical analysis of the symptoms and signs to arrive at a diagnosis and differential diagnoses of bronchogenic carcinoma identify the extra pulmonary features of bronchogenic carcinoma. prioritize the appropriate investigation methods for diagnosis of bronchogenic carcinoma. interpret CXR findings of bronchogenic carcinoma

5. Attitude be aware of the importance of explaining the nature of the condition, the prognosis and line of management to the patient and relatives. be aware of the importance of applying the basic ethical principles for choosing investigations and treatment options.

6. Contents 1. WHO classification of bronchogenic carcinoma 2. Clinical feature of bronchogenic carcinoma 3. Management of bronchogenic carcinoma 4. Ethical consideration in management of patient with bronchogenic carcinoma.

7. Bronchogenic Carcinoma Leading case of cancer death (M/F) Increase in women and decreasing in men. Age: old adult. Etiology: smoking of cigarettes ( amount/ years). Asbestosis Uranium and radiation Air pollution Radon

8. Etiology and Pathogenesis Tobacco Smoking. About 80% of lung cancers occur in active smokers or those who stopped recently.

9. Etiology and Pathogenesis contd ; Industrial Hazards: asbestos arsenic , chromium, Uranium nickel vinyl chloride mustard gas High-dose ionizing radiation

10. Clinical presentations Cough (80 %) haemoptysis (70 %) dyspnoea (60 %) chest pain (40 %) recurrent or slowly resolving pneumonia lethargy , anorexia; weight loss.

11. Squamous cell carcinoma Central tumor Arising from Squamous cell ( often from main bronchus) Smoking is main etiology also caused by radon. p53 mutation and overexpression of epidermal growth-factor receptor very common. Morphology :

12. Squamous cell carcinoma: The neoplasm is very firm and has a pale white to tan cut surface. Central necrosis is frequently seen. Central necrosis

13. Adenocarcinoma Peripheral tumor. Sex: female. Age: much younger person. Types: Bronchial derived : occur in the site of previous scar ( scar carcinoma ). Not clearly linked to smoking. Bronchoalveolar Ca : Not related to smoking. Multiple tumor, present as pneumonia.

14. Adenocarcinoma : peripheral tumor K-RAS mutations are seen primarily in adenocarcinoma .

15. Bronchioloalveolar carcinoma Appears as pneumonic consolidation. Well differentiated tumor: better prognosis.

16. Small Cell Carcinoma: central tumor Central tumor. Aka- oat cell carcinoma Origin: Neuroendocrine argentaffin (Kulchitsky) cells. Smoking is main etiology Gene: p53 and RB tumor suppressor genes + over expression of the anti-apoptotic gene BCL2. Poor prognosis.

17. Large cell carcinoma Micro: large anaplastic cells. Poor prognosis

18. Clinical: Due to spread of tumor Local lymph nodes metastasis; Supraclavicular node (Virchow node). Distant : Brain, Liver ,Bone. Adrenals cortex (Addison’s disease- deficiency of cortical hormones- skin & mucosa hyper - pigmentation )

19. Others Superior Vena caval syndrome ( common in small cell carcinoma, followed by squamous cell Ca. ) Congestion of veins of neck, face: red Engorges jugular vein- edema in arms. Hoarseness: recurrent laryngeal nerve invasion ( with apical tumor ). Acanthosis nigricans: black, thick skin with skin tags= axillae, groin etc ( common in adenocarcinoma ).

20. Clinical: Due to spread of tumor Horner syndrome ( in Pancoast tumor ): Seen in apical tumors due to involvement of cervical sympathetic plexus. Features are: Ipsilateral enophthalmos. Ptosis, Meiosis. Anhidrosis.

21. Clinical: Due to paraneoplastic syndromes Squamous cell carcinoma Secret PTH like hormone > Hypercalcemia → renal calculi Small cell carcinoma Secret ACTH>Cushing syndrome= weight gain, hypertension. Skin pigmentation Secret ADH > SIADH > Hyponatremia= cerebral edema

22. Other Paraneoplastic syndromes in bronchogenic carcinoma Hematologic manifestations (In adenocarcinoma). Migratory thrombophlebitis. Lambert-Eaton myasthenic syndrome ( In Small cell carcinoma: muscle weakness is caused by auto-antibodies directed to the neuronal calcium channel) . Calcitonin , causing hypocalcemia.

23. Investigations Investigations are necessary : to stage the extent of disease to make a tissue diagnosis (differentiate small cell from non-small cell lung cancer (NSCLC) as well as to detail the cell type in NSCLC – increasingly relevant with newer targeted biological agents) and to assess fitness to undergo treatment.

24. CXR : peripheral nodule ; hilar enlargement; consolidation; lung collapse; pleural effusion ; bony secondaries . Cytology : sputum and pleural fluid (send at least 20mL ). Fine needle aspiration or biopsy (peripheral lesions/lymph nodes ). CT to stage the tumour (p176) and guide bronchoscopy . Bronchoscopy : to give histology and assess operability, ± endobronchial ultrasound for assessment and biopsy . 18 F-deoxyglucose PET or PET/CT EBUS scan to help in staging . Radionuclide bone scan : if suspected metastases . Lung function tests : help assess suitability for lobectomy.

25. Management Surgical resection carries the best hope of long-term survival some patients treated with radical radiotherapy and chemotherapy also achieve prolonged remission or cure . Unfortunately, in over 75% of cases, treatment with the aim of cure is not possible, or is inappropriate due to extensive spread or comorbidity. Such patients are offered palliative therapy and best supportive care. Radiotherapy and in some cases chemotherapy can relieve distressing symptoms.

26. Surgery Surgery is performed in early stage non-small cell lung cancer (stage I, II and in selected IIIA) with curative intent . Many patients with stage III disease are treated with chemoradiation with a view to ‘ downstaging ’ disease and render it amenable to surgical resection . Where surgical stagingof resected lung cancer demonstrates nodal involvement, patients require adjuvant chemotherapy.

27. Radiation therapy for cure In selected patients with adequate lung function and early stage NSCLC, high-dose radiotherapy

28. Radiation treatment for symptoms Radiation therapy has a role in palliation of symptoms from lung cancer. Bone and chest wall pain from metastases or direct invasion, haemoptysis , occluded bronchi and superior vena cava obstruction respond favourably to irradiation in the short term. Radiotherapy is also given at the end of chemotherapy to consolidate treatment in small cell lung cancer

29. Prognosis The overall prognosis is very poor around 70% of patients dying within a year of diagnosis and only 6–8% of patients surviving 5 years after diagnosis . The best prognosis is with well differentiated squamous cell tumours that have not metastasised and are amenable to surgical resection.