1. Lung Neoplasm  Lungs frequently are the site of metastases from cancers arising in extrathoracic organs. Primary lung cancer is also a common disease. Roughly 95% of primary lung tumors are carcinomas;  The remaining 5% are carcinoids, mesenchymal malignancies (e.g., fibrosarcomas, leiomyomas), lymphomas, and a few benign lesions.

2. Lung Neoplasm Carcinoma of the lung (also known as “lung cancer”). In USA 30% of men die due to lung cancer. 25% of the women die due to lung cancer. Lung tumor are the leading cause of death among men and women.

3. What is the differential diagnoses of Mass lesion in the Lung

4. Clinical Presentation Mass lesion: incidental, asymptomatic, or causing mass effect Dysfunction of the involved organ Invasion of the adjacent structures Metastasis Paraneoplstic syndromes

5. Hamartoma of lung Not neoplastic, but mass lesion Discrete small peripheral nodule seen incidentally on x-ray on chest Benign, no risk of malignancy Consists of mature tissue in abnormal, disordered organization: cartilage, fat, fibrous tissue, vessels….

7. Four major histologic types of carcinomas of the lung Adenocarcinoma, Squamous cell carcinoma, Small cell carcinoma, Large cell carcinoma Squamous cell and small cell carcinomas show the strongest association with smoking

8. Carcinomas of the lung were classified into two broad groups for therapeutic purposes. Small cell lung cancer (SCLC) Non–small cell lung cancer (NSCLC adenocarcinomas and squamous and large cell carcinomas)

9. All SCLCs have metastasized by the time of diagnosis and hence are not curable by surgery. Therefore, they are best treated by chemotherapy, with or without radiation therapy. NSCLCs were more likely to be resectable and usually responded poorly to chemotherapy.

10. Etiology and Pathogenesis Common gene defects in lung cancer – SCLC: P53, RB mutation – NSLC: P16/CDKN2A – Adenocarcinoma: K-RAS Lung cancer develop through accumulation of genetic defects – Loss of 3p is very early event, occurs as a result of smoking

11. Etiology and Pathogenesis Smoking: – 90% of lung caner occurs in smokers – The risk shows linear increase with the smoking intensity (pack-years) – 60x risk in a person with 40 pack-years smoking – 2x risk in passive smokers Others: asbestos, vinyl chloride… Genetic susceptibility

12. mutagenic effect of carcinogens is conditioned by hereditary (genetic) factors. Metabolic activation via the P-450 monooxygenase enzyme system for conversion into ultimate carcinogens. Persons with specific genetic polymorphisms of P-450 genes have an increased capacity to metabolize procarcinogens derived from cigarette smoke, and thus conceivably incur the greatest risk for development of lung cancer.

13. Small cell carcinoma Most present with advance disease High grade with fast progression Associated with smoking (almost all) Mutation in RB gene. Treatment is palliative Respond to chemotherapy and radiation Non-small cell ca Can present with localized disease Variable behavior, depend on grade Sq ca is related to smoking, Adeno ca is less associated to smoking. Mutation in P16 Treatment can be fro cure Surgery

15. Etiology and Pathogenesis Progression of lesions due to smoking: – Normal respiratory mucosa – Basal cell hyperplasia – Squamous metaplasia – Squamous dysplasia – Carcinoma in-situ – Invasive squamous cell carcinoma

16. Morphology Bronchial epithelium Small mass arising from the bronchial epithelium Invasion of submucosa and underlying lung tissue Pushing and invasive borders Central necrosis, hemorrhage, cavitation Metastasis to lymph nodes: lobar, bronchial, hilar, mediastinal, cervical, supraclavicular Hematogenous spread: brain, liver, adrenal, bone… Body cavity metastasis: pleura

17. Squamous cell carcinoma M>F Central mass, with areas of necrosis, and cavitation Hilar lymphadenopathy Distal obstruction, atelectasis Malignant cells in sputum and bronchoalveolar lavage Grade: well, moderate, poor differentiation Paraneoplstic syndromes

19. Adenocarcinoma Less associated with smoking, More common in females and non smokers. mutations of the epidermal growth factor receptor (EGFR) and K-RAS mutations Usually small, peripheral lung mass with gray gelatinous surface Grade: well, moderate, poor differentiation Metastasize early Special pattern: bronchioloalveolar carcinoma BAC

21. Small cell carcinoma Central mass with hilar and mediastinal lymphadopathy Small cells, nuclear molding, fine chromatin, mitosis, necrosis, neuroendocrine features High grade Respond to chemotherapy and radiation. NSCLCs carry a better prognosis than SCLCs.

23. Clinical Presentation Commonly presents as lung mass with hilar lymphadenopathy, and symptoms related to lung disease If localized: can be asymptomatic, or presents with persistent cough Mass effect: resulting in respiratory dysfunction: cough, dyspnea, chest pain, hemoptysis Invasion of Pleura resulting in pleural effusion or pleuritis. Invasion of mediastal structures and vessels Mestastasis to brain, liver, adrenals….

24. Clinical Presentation Paraneoplastic Syndromes – Hypercalcemia due to PTH-related peptide-  squamous cell carcinoma. – Cushing syndrome due to ACTH secretion – Syndrome of inappropriate ADH secretion SIADH – Neuromuscular syndrome: peripheral neuropathy, polymyositis – Clubbing of fingers – Thrombophlebitis, non-bacterial endocarditis, disseminated intravascular coagulation DIC

25. Special presentation of lung cancer Virchow node: supraclavicular node enlargement due to metastasis Superior vena cava syndrome: obstruction of the SVC by cancer Horner syndrome: ipsilateral enophthalmos, ptosis, meiosis, anhidrosis. It is caused by tumor involving the sympathetic nerves. Pancoast tumor: lung cancer involving the apex and compressing the cerivcal sympathetic plexus.

26. Carcinoid Tumor arising from the endocrine cells (Kulchitsky cells) Mean age 40 years Good prognosis Mass lesion: – Intraluminal mass in large bronchus – Peribronchial mass (collar-button lesion) Metastasis: rare 5-15%

27. Carcinoid Micro: uniform cells with rounded nuclei, salt- and-pepper chromatin Atypical carcinoid: if the tumor cells show mitosis and necrosis 5 year survival: 50-95 %

28. Nasopharyngeal Carcinoma Most common tumor of the nasopharynx More common in male. Increased in Chinese (common in adults) And Africans(children) Strong epidemiologic links to EBV

29. Pathogenesis It is thought that EBV infects the host by first replicating in the nasopharyngeal epithelium and then infecting nearby tontonsillar B lymphocytes. EBV genome is found in virtually all nasopharyngeal carcinomas.

30. The three histologic variants are  keratinizing squamous cell carcinoma,  nonkeratinizing squamous cell carcinoma,  undifferentiated carcinoma. undifferentiated carcinoma is most common and the one most closely linked with EBV. These neoplasms are referred as “lymphoepitheliomas

31. Nasopharyngeal carcinomas invade locally, spread to cervical lymph nodes. metastasize to distant sites. They are radiosensitive, 5-year survival rates of 50% are reported even for patients with advanced cancers.

32. Laryngeal Tumors A variety of non-neoplastic, benign, and malignant neoplasms of epithelial and mesenchymal may arise in the larynx. Majority located on true vocal cords. Risk factors. Cigarette smoking Alcohol Asbestos HPV 6 and 11 association

33. Carcinoma of the larynx represents only 2% of all cancers. It most commonly occurs after age 40 years common in men than in women (with a gender ratio of 7 : 1).

34. About 95% of laryngeal cancers are typical squamous cell carcinomas. The tumor develops directly on the vocal cords (glottic tumors) 60% to 75% above the cords (supraglottic; 25% to 40%) below the cords (5%)

35. Clinical findings Persistent Hoarseness and associated with cervical lymphadenopathy. Treatment –Surgery.