Lung Cancer. Ossama Tawfik, MD, PhD Professor, Vice Chairman Director of Anatomic &Surgical Pathology University of Kansas School of Medicine

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1 Lung Cancer Ossama Tawfik, MD, PhD Professor, Vice Chairman Director of Anatomic &Surgical Pathology University of Kansas School of Medicine Alexandria, Egypt July 1-1 3, 2008

2

3 OBJECTIVES Describe and list the main different histologic types of carcinomas of the lung. Describe and list the main clinical and histopathologic features of lung cancer. List factors associated with the different types of lung cancer. Describe and list the main clinical and histopathological features of mesothelioma.

4 Lung Cancer Peak incidence in 6 th and 7 th decades M:F = 2:1

5 Common Risk Factors for Lung Cancer Cigarette smoking Asbestos exposure Radiation Aromatic hydrocarbons Metals: nickel, arsenic, chromate, beryllium Previous history of lung cancer

6 Pathogenesis K-ras mutation, cigarette smoking (nonsmall cell Ca) Myc overexpression (small cell Ca) p53, Rb mutations (small cell Ca, nonsmall cell Ca) bcl-2 expression (SCC- adenoca)

7 Local Clinical Features Cough, dyspnea, hemoptysis, pain, pneumonia, pleural effusion Pancoast tumor (apex of lung) Pancoast syndrome (cervical sympathetic nerves paralysis Horner syndrome endophthalmos, ptosis, miosis, anhidrosis Mediastinal Superior vena cava syndrome Metastasis LNs, brain, bone, liver, ADRENALs Paraneoplastic Syndromes

8 Gross Classification 1. Central group: neoplasms arising in major bronchi, segmental bronchi or divisions up to 1 mm in diameter 2. Peripheral group: neoplasms arising in lung parenchyma where bronchioles are less than 1 mm in diameter

9 Histological Classification of Lung Tumors I. Epithelial tumors A. Benign 1. Papillomas 2. Adenomas B. Dysplasia, CIS

10 C. Malignant, Epithelial 1. Squamous cell carcinoma 2. Small cell carcinoma 3. Adenocarcinoma 4. Large cell carcinoma 5. Adenosquamous carcinoma 6. Carcinoid tumor 7. Others

11 I. Soft Tissue Tumors II. Mesothelioma III. MetastaticTumors IV. Miscellaneous Tumors A. Carcinosarcoma B. Pulmonary blastoma C. Others V. Other Benign Lesions A. Hamartoma

12 Common Lung Cancers Squamous cell carcinoma (25 to 40%) Adenocarcinoma (25 to 40%) Small cell carcinoma (20 to 25%) Large cell carcinoma (10 to 15%)

13 Squamous Cell Carcinoma Clinical Features Hemoptysis, cough Symptoms due to obstruction: recurrent pneumonia, atelectasis Superior vena cava syndrome Pancoast syndrome/pancoast tumor Horner syndrome Hypercalcemia (sec of PTH-like sub)

14 Squamous Cell Carcinoma Closely linked to smoking More frequent in males Usually central in location (75 to 95%)

15 Squamous Cell Carcinoma

16 LUL replaced by tumor LLL bronchus Left mainstem bronchus with tumor

17 Squamous Cell Carcinoma with Cystic cavitary changes

18 Keratin Pearl Desmoplastic (fibrous) stroma of tumor

19 Keratin Pearls in Squamous Cell Carcinoma

20 Intercellular bridges in Squamous Cell Carcinoma

21 MIB-1 Immunostain EGFR Immunostain

22 Squamous Cell Carcinoma Prognosis Clinical stage most important prognostic factor Overall 5 year survival is about 15%

23 Squamous Cell Carcinoma Well, Moderately, poorly differentiated Ca Keratinizing or non keratinizing 90% central - 10% peripheral Carcinoma in situ Association w smoking Paraneoplastic syndrome hypercalcemia Rx: Surgical

24

25 Adenocarcinoma Increasing incidence Usually peripheral (75%) May be associated with scars? Most common type in women

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27 Upper Lobe Adenocarcinoma with Invasion of Chest Wall Peripheral tumor invading rib Cut section of rib & intercostal muscles

28 Adenocarcinoma Histologic Subtypes 1. Acinar adenocarcinoma 2. Solid carcinoma with mucous formation (formerly large cell carcinoma) 3. Papillary adenocarcinoma 4. Bronchiolo-alveolar carcinoma

29 Adenocarcinoma (Acinar Type) Desmoplastic stroma Gland lumens filled with mucinous secretions (gray)

30 Acinar Adenocarcinoma Adenocarcinoma Solid Type

31 Adenocarcinoma (Papillary Type) Papillary structures

32 M:F = 1:1 Bronchioloalveolar Carcinoma Mucinous and Non-mucinous Types 3 growth patterns grossly: 1) Solitary mass (coin lesion) 2) Multiple nodules 3) Multicentric diffuse infiltrate

33 Multicentric BAC

34 Bronchioloaveolar Carcinoma Pre-existent alveolar walls Tumor cells lining up on alveolar walls

35 Adenocarcinoma Prognosis Survival primarily dependent on clinical stage Overall 5 year survival 15-20%

36 Bronchioalveolar Carcinoma Prognosis 5 year survival 42% Worse prognosis for diffuse form

37 Adenocarcinoma Peripherally located Well, moderately, poorly differentiated Primary Vs. metastatic lesions (TTF-1 90%+) Variants: Bronchogenic adenocarcinoma Scar carcinoma Bronchiolo-alveolar carcinoma Others: papillary, solid, mucinous

38

39 Neuroendocrine Tumors of the Lung Mature carcinoid tumor Atypical carcinoid tumor Large-cell neuroendocrine carcinoma Small-cell carcinoma

40 Bronchial Carcinoids Neuroendocrine neoplasm Account for 1-5% of all lung tumors M = F Wide age range; average age 45 yrs

41 Bronchial Carcinoids Three groups: Central carcinoid Peripheral carcinoid Atypical carcinoid

42 Central Bronchial Carcinoid Most frequent type (90% of bronchial carcinoids) Arise in subsegmental or larger bronchi as polypoid exophytic mass projecting into bronchial lumen. Usually invade bronchial wall with variable invasion of adjacent lung

43 Clinical Features of Carcinoid Syndrome Attacks of skin flushing Cyanosis Diarrhea Broncho constriction Sudden hypotension Edema Right-sided heart valve abnormalities

44 Central Carcinoid: Gross and micro H and E

45 H and E Carcinoid Tumor Chromogranin

46 Atypical Carcinoid Tumor Increased mitotic activity (2-10/ 10 HPFs) Tumor necrosis Increased cellularity Nuclear pleomorphism, hyperchromasia, high n/c ration

47 Prognosis of Bronchial Carcinoids 40% metastasize to regional lymph nodes 5-10% metastasize to liver 5 to 10 yr. survival rates: 50-95%

48 Small Cell Carcinoma Oat cell carcinoma Male predominance (M/F 2:1) Closely associated with smoking Usually central in location

49 Small Cell Carcinoma Opened bronchus containing tumor Tumor

50 Small Cell Carcinoma Oat cell type Intermediate type Combined

51 Oat Cell Type

52 Combined Small Cell & Sq.Ca Small cell ca Squamous cell ca

53 Small Cell Carcinoma Frequently associated with paraneoplastic syndrome Majority of tumors are already metastatic at time of diagnosis Treatment of choice: chemotherapy/radiation 5 year survival: 1-4%

54 Common Paraneoplastic Syndromes 1. Cushing's syndrome (ACTH) 2. Inappropriate ADH secretion 3. Carcinoid syndrome 4. Hypercalcemia (PTH) 5. Gynecomastia (Gonadotropin) 6. Acromegaly (GH)

55 Large Cell Carcinoma Poorly differentiated carcinoma without evidence of squamous or glandular differentiation by light microscopy Electron microscopy may show squamous or glandular features

56 Lymphocytes Clusters of large malignant cells

57 Metastatic Neoplasms Lung most frequent site (other than LN) Patterns of Metastasis: 1. Multiple nodules 2. Lymphangitic metastasis 3. Solitary

58 Metastatic Neoplasms Ovarian adenocarcinoma Breast cancer Prostatic cancer Colonic adenocarcinoma Renal carcinoma Melanoma, lymphoma, sarcoma

59 Metastatic Osteosarcoma

60 Metastatic Melanoma

61

62 Malignant Mesothelioma 1. Increasing in frequency 2. Asbestos exposure (20 40 yr lag) 3. Usually have pleural effusion 4. Most frequent in year age group 5. M:F = 2 to 3:1

63 Malignant Mesothelioma: Gross Pleural tumor encasing lung LUL LLL Tumor extending along interlobar fissure Diaphragm with tumor

64 Malignant Mesothelioma: Biphasic Epithelial-like cells Spindle cells

65 Lung Cancer Survival TUMOR TYPE Squamous Cell Ca. Adenocarcinoma Small Cell Carcinoma Large Cell Carcinoma Overall Survival 5 YR. SURVIVAL 15% 15-20% 1-4% 3% 8-10%

66 Metastasis and complications 1. Regional lymph nodes (most cases) 2. Liver 30-50% 3. Adrenal >50% 4. Bone 15-20% 5. Brain 20% Pneumonia Lung abscess Bleeding Effects of metastasis on other organs

67

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