The lung and the Upper Respiratory Tract

1. The lung and the Upper Respiratory Tract Lung Tumors

2. Lung tumors : General features • Most are malignant. • Metastatitc neoplasms are most common.

3. Types • Bronchogenic Carcinoma. • Bronchial carcinoids. • Lymphoma. • Hamartoma

4. Bronchogenic carcinoma • Squamous cell carcinoma ( most common) • Adenocarcinoma • Bronchial derived • Broncheoloalveolar • Larger cell carcinoma • Small cell (oat cell) carcinoma. Non small cell carcinoma

5. 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

6. Molecular pathology • Non-Small Cell Lung Carcinomas (NSCLC) 70-75% of all lung Ca cases: • p16/CDKN2A & K-RAS mutations, • p53 mutation ( inhibit apoptosis). • Small Cell Lung Carcinoma (CSLC) 20-25%, TP53 • & RB gene mutations ( deregulate cell cycle).

7. 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: next

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

9. Micro: nests of polygonal cells with pink cytoplasm and distinct cell borders with intercellular bridges and keratin pearl.

10. 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.

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

12. Adenocarcinoma: The glandular structures formed by this neoplasm + mucin production ( mucin stained purple with PAS)

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

14. Bronchioloalveolar carcinoma is composed of columnar cells that proliferate along the framework of alveolar septae.

15. 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.

16. Gross: This tumor has a soft, lobulated, white to tan appearance. Micro: sheets of blue cells are regular, and round moldednuclei and a moderate amount of eosinophilic cytoplasm. Blue round cells

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

19. Relax your eyes Next topic : Clinical features of tumors

20. Clinical • Common presentation: Cough, hemoptysis, weight loss. • Clubbing of the fingers. • Others: • Due to spread of tumor • Due to paraneoplastic syndromes

21. 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)

22. 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).

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

24. Clinical: Due to paraneoplastic syndromes

25. 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.

26. Bronchial Carcinoid • Origin: Kulchitsy cells: a neuroendocrine cells that line the bronchial mucosa. • Age: mean around 40. • Gross: yellow polypoid mass. • Micro: • LM: Salt pepper. • EM:Dense core neurosecretory granules in their cytoplasm

27. Microscopy Dense core granules Salt pepper

28. Presentation of Carcinoid • Benign carcinoid: • Cough. • Hemoptysis, bronchiectasis. • Recurrent bronchial & pulmonary infections. • Malignant carcinoid: liver mets. and Secret serotonin > carcinoid syndrome: diarrhea and flushing on skin.

29. Hamartoma coin lesion Common Less than 2 cm. Micro: haphazard lung tissue and cartilage. Clinical: Present as a "coin lesion" on X-ray. d/d of coin lesion Granuloma are multiple.

30. Metastatic Cancer to the lungs Multiple variably-sized masses are seen in all lung fields.

31. Next Topic Mesothelioma Pleural effusion

32. Malignant Mesothelioma • Site: The visceral or the parietal pleura. • Carcinogen: asbestosis- amphiboles by reactive free radicals. • Morphology: • Asbestos bodied are found in the tumor. • Lung gets ensheathed by tumor tissue may produce cicatrisation and atelectasis.

33. Diagnosis of malignant mesothelioma

34. Pleural effusion • Empyema- Pus in pleural cavity following abscess. • Chylothorax : Chyle (lymph)= • It is a Milky white fluid due to tumor emboli in lymphatic or in Lymphoma. All patient present with respiratory distress, relieved when the effusion in drained by thoracentesis .

35. Pneumothorax • Def: air in pleural cavity • Types: • Traumatic: Trauma • Spontaneous: rupture of paraseptal bulla • Tension : due to shift of the mediastinum from the midline. Tracheal shifting to other side , and hyperresonant lung on side of injury.

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