Pulmonary Path II lots of neoplasia

1. Pulmonary Path IIlots of neoplasia December 10, 2008

2. Case I: 62-year old woman with productive cough, fever, chills, and pleuritic chest pain. A 62 year-old woman develops cough productive of green sputum, dyspnea, fever, chills, and pleuritic chest pain. She had a “cold” (stuffy nose, sneezing, sore throat) for the past week. Her past history is negative for any hospitalization or surgery. On exam her temperature is 101F. Oxygen saturation on room air is 89%. On percussion there is dullness over the right upper lung field. On auscultation there are bronchial breath sounds in the right upper lung field. *Sputum gram stain shows few squamous cells, many neutrophils, and Gram positive diplo-cocci. Overall Case Analysis & Notes: We are thinking of something infectious due to fever, chills Get a sputum sample (should not see squamous cells really), chest x-ray See consolidation on CXR

3. Case I: 62-year old woman with productive cough, fever, chills, and pleuritic chest pain. • Identify organ: Lung • Diagnosis: Community-Acquired Pneumonia (MC Strep Pneumo, accounts for 90% of cases of “lobar” pneumonia); also H. Influ, Moraxella Cat (elderly), Staph aureus (IntraVenousDrugsUers), Legionella, Enterbacteriaceae • Describe the characteristic pathologic changes in the specimen. See histology slide—see alveoli with WBC’s, engorged with fluid c. Correlate the clinical findings with the pathology. Fever and chills—acute inflammation (cytokines); Purulent sputum---bronchiolitis; chest pain---pleuritis; recent (likely viral) URI that impaired mucociliary apparatus/pulmonary defense mechanism Complications can include: abscess, empyema, bacteremia

4. Case I: 62-year old woman with productive cough, fever, chills, and pleuritic chest pain. Congestion Red hepatization Gray hepatization Resolution Bronchopneumonia Note the large and small yellow-tan patches (arrows) of pneumonia scattered throughout lung.

6. Case I: 62-year old woman with productive cough, fever, chills, and pleuritic chest pain. Bronchopneumonia=“patchy” consolidation Lobar pneumonia-consolidation of a large portion of lobe or whole lobe Bronchopneumonia The cut surface of the lung reveals large and small, yellow-tan patches (arrows) of pneumonia scattered throughout the lung.

7. Case I: 62-year old woman with productive cough, fever, chills, and pleuritic chest pain. Lobar Pneumonia The "gray hepatization" stops abruptly at the fissure.

8. Case I: 62-year old woman with productive cough, fever, chills, and pleuritic chest pain. • Remember for Zoomify: • What tissue is it? (alveoli, lung) • What is in the alveoli? (neutrophils, lymphocytes, fluid) • See areas of fibrin deposition • Bronchi have inflammatory cells • Pleura has inflammatory cells and is edematous alveoli delineated by engorged septal capillaries alveoli filled with neutrophils

9. Case II: 57 y/o man smoker; hemoptysis • 57-year-old man develops hemoptysis. He has been smoking two packs of cigarettes per day for 30 years. He has had a chronic cough worse in the morning for 10 years. He has had mild dyspnea on exertion in the past 5 years Overall Case Analysis & Notes: DDx: chronic bronchitis, klebsiella pneumonia (rusty sputum), neoplasia What now? CXR, culture sputum we see on CXR: upper lobe cavitating mass where you can see air fluid levels in the cavity; could be cancer, pneumonia, or TB; thick wall around the mass We would probably also get a CT, bronchoscopy (run a tube/scope down into lung to take a look)

10. Case II: 57 y/o man smoker; hemoptysis Squamous cell carcinoma of the lung a. Identify organ: lung Diagnosis: squamous cell b. Describe the characteristic pathologic changes in the specimen. Keratin pearls + intercellular bridgessquamous cell carcinoma of the lung c. Correlate the clinical findings with the pathology. • Smoking history; origin is central bronchi, grows faster than other bronchogenic cancers (small cell, adenocarcinoma) and mets happen later; precursor lesions are bronchial epithelial squamous metaplasia, dysplasia, carcinoma in situ • note that you don’t do surgery on small cell carcinoma—send to oncology • Normal epithelium is ciliated columnar, squamous metaplasia to protect self can lead to dysplasia and advance to cancer! e. What is the most common etiology of this disorder? f. What underlying genetic disorder(s) can contribute to this disorder?

11. Cavitation in lft upper lobe; Could be an abscess, granuloma, mass

12. Bronchogenic carcinoma The opened bronchus contains a carcinoma (arrow). The neoplasm infiltrates adjacent lung (A) and obstructs the lumen, causing retention of secretions distal to the obstruction.

13. Nests of neoplastic squamous cells, cells are Different sizes (pleomorphic) Mitoses Keratinization/keratin pearls- Squamous cell carcinoma Also see intercellular bridges

14. Case III: 69-year-old woman with a “coin lesion” in the periphery of the right lung on x-ray: Adenocarcinoma • 69-year-old woman presents to the emergency room with chest pain. She has no chronic medical problems. She smoked 1 pack of cigarettes during her first two years of college, none since. On physical exam heart, lung, abdominal exams are normal. On chest X-ray there is a “coin lesion” in the periphery of the right lung. Overall Case Analysis & Notes: Normal Ddx: neoplasia, granuloma, infection, etc.

15. Case III: 69-year-old woman with a “coin lesion” in the periphery of the right lung on x-ray: Adenocarcinoma • Identify organ: lung Diagnosis: adenocarcinoma (see glands on histology slide); there should not be glands in lung like that b. Describe the characteristic pathologic changes in the specimen. c. Correlate the clinical findings with the pathology. • Lung tissue is replaced by an infiltrating adenocarcinoma which forms glands. e. What is the most common etiology of this disorder? • Most common lung cancer to arise in women and NON-SMOKERS; but can also be found in smokers; are smaller, peripherally located • 5 year survival is about 10% f. What underlying genetic disorder(s) can contribute to this disorder?

16. Coin Lesion (R field)

17. Adenocarcinoma b/c of glandular formation Malignant cells forming glands

18. Case IV: 51-year-old woman with cough productive of gray-white mucous.   Chest x-ray shows a diffuse infiltrate in the periphery of the right lower lobe. • 51-year-old-woman complains of cough for several weeks. The cough is productive of gray white mucous material. She has never smoked. On physical exam there are decreased breath sounds in the lower right lung field. Chest X-ray shows a diffuse infiltrate in periphery of the right lower lobe. Overall Case Analysis & Notes: • Pneumonia (diffuse); Neoplasia, Miliary Tuberculosis (PPD purified protein derivative) • Ask about recent infection, if fever, fatigued ------------------------------ Miliary tuberculosis (or disseminated TB) is a form of tuberculosis that is characterized by a wide dissemination into the human body and by the tiny size of the lesions (1-5 mm). Its name comes from a distinctive pattern seen on a chest X-ray of many tiny spots distributed throughout the lung fields with the appearance similar to millet seeds, thus the term "miliary" tuberculosis. Miliary TB may infect any number of organs including the lungs, liver, and spleen.

19. Case IV: 51-year-old woman with cough productive of gray-white mucous.   Chest x-ray shows a diffuse infiltrate in the periphery of the right lower lobe. Identify organ: lung & Diagnosis: BRONCHIOALVEOLAR carcinoma, a subtype of adenocarcinoma b. Describe the characteristic pathologic changes in the specimen. Alveolar walls are thickened; hypercellularity; alveoli are filled with desquamated cells and Mphages; large neoplastic cells have abundant cytoplasm and prominent vesicular nuclei c. Correlate the clinical findings with the pathology. e. What is the most common etiology of this disorder? Arises from terminal bronchioles or alveolar walls; grossly—multiple diffuse nodules (pneumonia-like consolidation); involves males and females; Multiple presentations on Xray like multicentric acinar nodules; solitary pulmonary nodule, alveolar cell carcinoma that looks like pneumonia

20. Normal alveoli Alveoli lined by large neoplastic cells

21. Desquamated neoplastic cell Alveoli lined by large neoplastic cells with abundant cytoplasm

22. Case V: 71 year-old man with back pain, hepatomegaly, and enlarged hilar lymph nodes • A-71 year-old man develops progressive chest pain, dyspnea and back pain. He has had a 20 pound unintentional weight loss over 3 months. He smokes and has a 50 pack year smoking history. On physical exam there is hepatomegaly. Chest X-ray shows enlarged hilar and mediastinal lymph nodes. CT scan shows bilaterally enlarged adrenal glands and multiple masses in the liver. • Overall Case Analysis & Notes: • 20 pound unintentional weight loss; smoking 50 pack-year historyworried about cancer • Enlarged hilar and mediastinal lymph nodes support diagnoses of sarcoid and cancer • Bilateral enlarged adrenals and masses in liver support diagnoses of cancer

23. Case V: 71 year-old man with back pain, hepatomegaly, and enlarged hilar lymph nodes: Bronchiogenic Small Cell Carcinoma a. Identify organ: Diagnosis: b. Describe the characteristic pathologic changes in the specimen. Nests of small round/oval cells with scant cytoplasmsmall cell carcinoma (cells 2 to 3x as big as lymphocytes) Neoplasm penetrates the bronchial wall, lying adjacent to strips of hyaline cartilage c. Correlate the clinical findings with the pathology. Smoking=risk factor; hilar or central location, mets are wide, sensitive to chemo but invariably recure, ectopic hormone production may lead to development of paraneoplastic syndomes remember ACTH with small cell e. What is the most common etiology of this disorder? f. What underlying genetic disorder(s) can contribute to this disorder?

24. Case V: 71 year-old man with back pain, hepatomegaly, and enlarged hilar lymph nodes Bronchogenic carcinoma The right lung is bisected into an anterior half (A) and a posterior half (B). The white neoplasm occupies most of the lower lobe and extends into upper lobe. The neoplasm obstructs the right mainstem bronchus. Peribronchial lymph nodes (arrow) contain neoplasm. Centrally located

25. Case V: 71 year-old man with back pain, hepatomegaly, and enlarged hilar lymph nodes Neoplasm is composed of small cells containing dark blue, round nuclei and sparse cytoplasm. These cells resemble (but are not) lymphocytes and are arranged in clusters

26. Case V: 71 year-old man with back pain, hepatomegaly, and enlarged hilar lymph nodes Metastatic Carcinoma Liver parenchyma (cut surface) largely replaced by metastastic carcinoma (yellow arrow) Multiple lobules on liver

27. Genetic mutations in cancer • Dominant oncogene abnormalities (protooncogene) • C-myc overexpression (small cell) • K-Ras mutations (adenocarcinomas) • Recessive Oncogene (tumor suppressor gene) • P53 mutations • Rb gene mutations • 3p deletions • EGFR mutation

28. So What? • Molecular epidemiology: genetic stratification of lung cancer risk • Early detection-specific molecular changes in sputum, blood, bronchial biopsies, brushings, lavage specimens • Chemoprevention • Diagnosis to help with subtype differentiation • Treatment-direct towards molecular targets to get selectivity for the lung cancer and not normal tissue • Prognosis-survival, met potential, probability cancer will respond to chemo