Tumors of Respiratory System

1. Tumors of Respiratory System Doç. Dr. Işın Doğan Ekici School of Medicine Department of Pathology

2. Tumors of respiratory system • TUMORS OF LARYNX • Benign -Vocal cord polip -others • Malignant: -SCC -others • LUNG TUMORS • Primary lung tumors • Benign • Malignant • Metastatic lung tumors

3. Lung Tumors • Primary lung tumors • Benign • Malignant • Metastatic lung tumors

4. Primary Lung Tumors

5. Benign lung tumors (WHO Classification) Benign Epithelial Tumors: • Adenomas • Papillomas Soft Tissue Tumors: • Localized fibrous tumor • Chondroma • Congenital peribronchial myofibroblastic tumor • Epitheliod hemangioendothelioma Tumor like lesions: • Tumorlet • Multiple meningoteliod nodules • Langerhans cell histiocytosis • Inflammatory pseudotumor • Localized Organized pneumonia • Amiloid tumor • Hyalinized granuloma • Lymphangioleiomatosis • Micronodular pneumocyte hyperplasia • Endometriosis Others: • Hamartomas • Sclerozing hemangioma • Clear cell tumor

6. Bronchial adenomas • Bronchial adenomas make up 50% of all benign pulmonary tumors. • The use of the term bronchial adenoma should be discouraged because it encompasses several benign and malignant tumors.

7. Mucous gland adenomas • Mucous gland adenomas are true benign bronchial adenomas. • Mucous gland adenomas are also called bronchial cystadenomas, and they arise in the main or local bronchi. • Histologically, they consist of columnar cell–lined cystic spaces with a papillary appearance.

8. Localized fibrous tumor Most frequent benign soft tissue neoplasm of lung. It was historically called as “benign mesothelioma” or “fibroma”. It is generally related to the visceral pleura. Mitotic figures must be <4/10 hpf (high power field)

9. Hamartomas:a focal growth that resembles a neoplasm but results from faulty development in an organ. • Hamartomas are the most common type of benign lung tumor. • They mainly occur in adults but, on occasion, occur in children. • Hamartomas are peripherally located. • Rounded focus of radiopacity (coin lesion). • Grossly, they have a firm marble like consistency. Rarely over 3 to 4 cm in diameter. • Histologically, hamartomas generally consist of the cells normally found in lung such as: epithelial tissue and other tissues such as fat and cartilage.

10. Hamartoma: Rounded focus of radiopacity (coin lesion) rarely over 3 to 4 cm in diameter

13. NOTICE: Carney’s triade: • 1. Gastric epitheloid leiomyosarcoma • 2. Functioning extra-adrenal paraganglioma • 3. Pulmonary chondroma (hamartoma).

14. Primary Malignant Lung Tumors

15. Lung Cancers • Most common visceral malignancy. • 3rd of all cancer deaths are due to lung cancer. • Significant increase in incidence. • Dramatic increase among females. • 90% of lung cancers are related to smoking(passive smoking in 5%).

16. Lung Cancer & Smoking • Depends on (1)duration, (2)amount of daily smoking, (3)deep inhaling: • 10 fold greater risk than non smokers. • 20 fold risk if >40cigarettes per day. • Atypical cells in 96.7% of smokers compared to 0.9% in non smokers. • Significant proportion of over 1200 substances in smoke are carcinogenic (not nicotine). • Initiaters – Benzo[a]pyrenes • Promoters – Phenol derivatives, nitrous compounds • Radioactive substances – Polonium, Carbon14, K40

17. Etiology of Lung Cancer • Tobacco smoking: • the predominant cause of SCLC, as of NSCLC, is tobacco smoking. • Of all histologic types of lung cancer, in fact, SCLC and squamous cell carcinoma have the strongest correlation to tobacco. • Uranium miners: • All types of lung cancers occur with increased frequency in uranium miners, but SCLC is most common. The incidence is increased further in smokers. • Radon: • Exposure to radon, which is an inert gas developing from the decay of uranium.

18. Kiss a non-smoker Enjoy the difference !

19. Molecular Genetics in Lung Cancer • Oncogene dominancy and/or loss or inactivation of tumor suppressor genes plays role in lung cancer; Most common dominant oncogenes in lung cancer are: *C-myc in small cell carcinoma *K-ras in adenocarcinoma Most common deleted or inactive recessive genes in lung cancer are; *p53, retinoblastoma gene and some genes in the short arm of chromosome 3

20. TNM classification of lung tumors • The primary tumor (T) is classified according to its size and local invasion. • Tis : Carcinoma insitu • T1: A tumor 3 cm or less in its greatest dimension, surrounded by lung or visceral pleura, without involvement of the main bronchus, • T2 : A tumor with any of the following features: • Larger than 3 cm in largest dimension • Involvement of the mainstem bronchus more than 2 cm from the carina • Invades the visceral pleura • Associated with atelectasis or post obstructive pneumonitis extending to the hilar region but not involving the entire lung.

21. T3 - A tumor of any size with any of the following features: • Tumor directly invading the chest wall, diaphragm, mediastinal pleura, or parietal pericardium • Tumor associated with atelectasis or obstructive pneumonitis of the entire lung. • T4 - A tumor of any size with any of the following features: • Tumor invading the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina • Any tumor with a malignant pleural or pericardial effusion • Any tumor with satellite tumor nodules within the ipsilateral primary tumor lobe of the lung.

22. N (Lymph node status): • N0: No demonstrable metastasis to the regional lymph nodes • N1: Ipsilateral hilar or peribronchial lymph node involvement • N2: Metastasis to ipsilateral mediastinal or subcarinal lymph nodes • N3: Metastasis to the contralateral mediastinal or hilar lymph nodes, ipsilateral or contralateral scalene, or supraclavicular lymph nodes

23. M: Distant organ metastasis MX: Distant metastasis can not be assessed M1: No distant organ metastatis M2: Distant organ metastasis is positive

24. Stage 0 Stage 1a Stage 1b Stage 2a Stage 2b Stage 3a Stage 3b Stage 4 Tis, N0, M0 T1, N0, M0 T2, N0, M0 T1, N1, M0 T2, N1, M0 T3, N0, M0 T1-3, N2, M0 or T3, N1, M0 Any T, N3, M0, or T3, N2, M0 or T4, any N, M0 Any T, any N, M1 Stage Grouping

25. Squamous cell carcinoma Small cell carcinoma Adenocarcinoma (acinar, papillary, bronchioloalveolar, solid with mucin production) Large cell carcinoma (LC euroendocrine, basaloid, lymphoepithelioma like, clear cell, LC with rhabdoid phenotype) Adenosquamous carcinoma Sarcomatoid carcinoma (pleomorphic, spindle cell, giant cell, carcinosarcoma, pulmonary blastoma) Carcinoid Tumors (typical, atypical) Salivary gland tumors (mucoepidermoid, adenoid cystic, epithelial myoepithelial) Mesenchymal malignant tumors (angiosarcoma, synovial sarcoma...) Lymphoproliferative tumors Miscellaneous tumors (Germ cell tumors, Malignant Melanoma...) Metastatic Tumors WHO Classification of Malignant Lung Tumors

26. Bronchogenic Carcinoma • Squamouscell (epidermoid)carcinoma* 25-45% • Adenocarcinoma 25-40% • Brochial (Acinar, papillary, solid) • Bronchioloalveolar • Small cell carcinoma*20-25% • Oat cell carcinoma (lymphocyte-like) • Intermediate cell • Large cell carcinoma 10-15% • Combined patterns 1% adenoCA+SquamousCA (*) tobacco associated lung cancers

27. In Clinical Oncology Small cell lung cancer (SCLC) is considered distinct from the other lung cancers, called non–small-cell lung cancers (NSCLCs), because of their clinical and biologic characteristics.

28. Small cell lung cancer (SCLC) • Approximately 20% of malignant tumors of the lung are due to small cell carcinoma. • SCLC exhibits aggressive behavior, with rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and frequent association with distinct paraneoplastic syndromes. • Surgery usually plays no role in its management, except in rare situations (<5% of patients) in which it presents at a very early stage as a solitary pulmonary nodule. • Even then, adjuvant chemotherapy after surgical resection is recommended, since SCLC always should be considered a systemic disease.

29. Pathophysiology • Small cell carcinomas arise in peribronchial locations and infiltrate the bronchial submucosa. • Widespread metastases occur early in the course of the disease, with common spread to • mediastinal lymph nodes, • liver, • bones, • adrenal glands, • brain.

30. Histologic Findings • SCLC typically are centrally located, arising in peribronchial locations. • They are thought to arise from Kulchitsky cells. • The tumor is composed of sheets of small, round cells with dark nuclei, scant cytoplasm, fine granular nuclear chromatin, and indistinct nucleoli. • Crush artifact leading to nuclear molding is a common finding, but it is not considered diagnostic. • Very high rates of cell division are observed, and necrosis, sometimes extensive, may be seen. • Because of the central location, the cells exfoliate in sputum and bronchial washings.

31. Small cell BronchogenicCarcinoma:- begins asmucosal growth- firm, gray-white- invades the bronchial mucosa- central necrosis in large ones- may extend to the pleura- metastasis: lymphatics and blood vessels

32. Small Cell Carcinoma of Lung

33. Small Cell Carcinoma of Lung

34. SmallCell Carcinoma (Oat cell carcinoma)

35. Small (oat) Cell Carcinoma This highly malignant tumor has a distinctive cell type. The epithelial cells are generally small, have little cytoplasm and are round or oval and, occasionally, lymphocyte-like (although they are about twice the size of a lymphocyte).

36. Neurosecretory granules can be identified on electron microscopy, and the neuroendocrine nature of the neoplasm is suggested by its frequent association with paraneoplastic syndromes caused by peptide hormones. • Immunohistochemical stains for chromogranin, neuron-specific enolase, and synaptophysin usually are positive. • Approximately 5% of SCLCs exhibit features of mixed small cell and large cell components and, less frequently, may exhibit mixed small cell and squamous cell components.

37. Staging • Almost all solid tumors are staged by utilizing the tumor, node, metastases (TNM) system because it provides important prognostic information and is used to design management plans. • However, the TNM system has failed to provide important prognostic information in patients with SCLC and is useful only in a few patients (<5%).

38. Complications • Tumor lysis syndrome: • Tumor lysis can occur rapidly in patients with SCLC on institution of chemotherapy, especially in extensive-stage disease. • The laboratory features of tumor lysis syndrome (TLS) are • hyperuricemia, • hyperphosphatemia, • hypocalcemia, • hyperkalemia.

39. Spinal cord compression: • A thorough neurologic examination and radiologic evaluation of the spine is indicated with any suspicion of spinal cord compression (neurological deficit). • Hyponatremia • Results from inappropriate secretion of ADH, which results in the inability of the kidneys to excrete free water. • SIADH is reported in 5-10% of patients with SCLC.

40. Paraneoplastic syndromes in Lung Cancers • Production of a variety of peptide hormones • The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) • The syndrome of ectopic adrenocorticotropic hormone (ACTH) production. • Hypercalcemia • Eaton-Lambert syndrome (peripheral neuropathy with myasthenia-like symptoms) • Acanthosis nigricans • Hypertrophic osteoarthropathy.

41. Paraneoplastic syndromes in SCLC

42. Non–small-cell lung cancers (NSCLCs) • Non-small cell cancer requires meticulous staging, because the treatment and prognosis vary widely depending on the stage. • Surgical resection offers patients the best chance for survival. Surgery may be curative for stage I and stage II disease.

43. Pathophysiology • Bronchogenic carcinoma is the most common cancer and the most common cause of cancer-related death in both men and women. • Risk factors for lung cancer include the following: • Cigarette smoking: Smoking increases the risk of bronchogenic carcinoma by 4-120 times. • Exposure to asbestos: Asbestos exposure increases the risk 4- or 5-fold, or as much as 100-fold if the exposed individual is also a smoker. • Fibrosis/Scarring in the Lung: • Peripheral lung cancers are sometimes associated with areas of fibrous scar. In most cases of these "scar cancers," the fibrosis may result from, rather than precede the development of the neoplasia. • As many as 6-12% of patients with idiopathic pulmonary fibrosis develop bronchogenic carcinoma (adenocarcinoma).

44. Exposure to toxic agents:Agents such as arsenic, nickel (squamous cell carcinoma), chromium, and chloromethyl ether (small cell carcinoma) increase the risk. • Exposure to uranium or radon:Exposure to breakdown products of uranium increases the risk of non-small cell carcinoma, too. • Prior lung cancer:Approximately 10-32% of patients who survive resection for lung cancer may develop a second primary lung tumor. • Lung disease:The presence of concomitant chronic obstructive pulmonary disease is a risk factor for lung cancer. • HIV infection:In patients with HIV infection the risk of non-small cell lung carcinoma is increased by 6.5 times.

45. Location • The relative frequency of lung cancer is 3:2 in the right compared with the left lung and in the upper lobe compared with the lower lobe. • Squamous cell carcinomas occur predominantly in a central location. • Adenocarcinoma presents in approximately 50% of patients as a peripheral lesion. • Tumors arising endobronchially are located in segmental or lobar bronchi. • Fewer than 4% of cancers arise in the apex of the upper lobes, and fewer than 1% arise from the trachea.

46. Squamous cell carcinoma (SCC) • SCC accounts for 30-40% of bronchogenic Ca. • strong association with smoking. • centrally located • among all bronchogenic carcinomas, it is most likely to cavitate. • SCC grow intraluminally and are least likely to metastasize distantly (<20% of cases at presentation). • The mode of spread is direct extension to the local lymph nodes.

47. SCC are commonly associated with palmar clubbing and hypertrophic osteoarthropathy. • Hypercalcemia is also commonly observed secondary to a parathormone-like peptide created by the tumor. • Tumors of squamous histology can sometimes elicit a sarcoid reaction in nodes, resulting in nodal enlargement without metastatic spread.

49. Squamous Cell Carcinoma(CT)

50. Squamous Cell Carcinoma The microscopic features are familiar in the form of production of keratin and intercellular bridges in the well-differentiated forms.