WebPath Respiratory Case Studies

1. WebPath Respiratory Case Studies Dr. Spencer Gilbert

2. Laboratory Part I

3. CASE 1: Clinical History: • A 49 year old male with a 25 pack year smoking history presented to you at the homeless clinic with complaints of increasing cough that had gradually been getting worse over the previous six months. He noted that the sputum was blood-tinged on one occasion. He also felt extremely tired. His x-ray showed upper lobe cavitations with nodular infiltrates.

4. Slide 1.1Cavitary lung lesions are seen here grossly.

5. Slide 1.2The lung lesions are seen here microscopically at low power.

6. Slide 1.3The lung lesions are seen here microscopically at medium power.

7. Slide 1.4The lung lesions are seen here microscopically at higher power.

8. Slide 1.5Note the subpleural lesion along with the lesion in the hilar lymph node.

9. Slide 1.6Note the small millet seed sized lesions scattered in the lung parenchyma.

10. Case 1 Questions: • Describe the gross appearance of this lung representative of the disease process in your patient's lungs (Slide 1.1). • Describe the microscopic appearance of the lungs (Slides 1.2 - 1.4). What is the probable diagnosis? • What tests can be performed to diagnose this condition? What additional clinical findings might be present? • Describe the additional gross pathologic patterns for this disease process (Slides 1.5 and 1.6). What is the differential diagnosis?

11. CASE 1: Tuberculosis Answers: • Describe the gross appearance of this lung representative of the disease process in your patient's lungs. There is extensive granulomatous disease involving the lung parenchyma. Mainly upper lobe is involved. The larger tan-white granulomas have caseation with central necrosis and in some areas become almost confluent. • Describe the microscopic appearance of the lungs. What is the probable diagnosis? Granulomatous inflammation is present. The granulomas demonstrate central caseation and surrounding epithelioid macrophages. Some Langhans giant cells are seen. Also contributing to the inflammatory reaction are lymphocytes. The acid fast stain demonstrates many slender red rods consistent in morphology with Mycobacteria. • What tests can be performed to diagnose this condition? What additional clinical findings might be present? A tuberculin skin test is used mainly for screening patients for possible tuberculosis. Sputum samples can be obtained for acid fast smear and culture. This patient's acid fast smear was 3+ positive, and the culture grew Mycobacterium tuberculosis that was sensitive to rifampin, isoniazid, and ethambutol. A chest radiograph will show the extent of pulmonary disease (in this case it was extensive, because of the cavitation). • Describe the additional gross pathologic patterns for this disease process. What is the differential diagnosis? Primary tuberculosis is often seen in children, and is often subclinical. There is a subpleural granuloma and extensive hilar lymph node granulomatous disease (the so-called Ghon complex, as seen in Slide 1.5). In adults, when health status declines, the quiescent infection may reactivate, or the patient may be reinfected, and then secondary tuberculosis is seen. Secondary tuberculosis is what the patient in this case had, because of the extensive upper lobe cavitary disease. When resistance to infection is very poor, a miliary pattern of infection may be seen, with numerous millet seed (1 to 3 mm) sized granulomas scattered extensively throughout the lungs (Slide 1.6). The infection may also disseminate to other organs.

12. CASE 2: Clinical History: • A 50 year old man worked in a foundry (casting metal materials using earthen molds) for thirty years. He was asymptomatic until a few months ago, but now has increasing dyspnea. A routine chest x-ray shows a "snow-storm" appearance.

13. Slide 2.1One of multiple lung nodules is seen here at low power.

14. Slide 2.2One of multiple lung nodules is seen here with polarized light microscopy.

15. Case 2: Questions: • Describe what you see in slides 2.1 and 2.2. What is the probable diagnosis? • How does this lesion form? What are the offending particles seen in Slide 2.2? • How do you explain the lengthy hiatus between exposure and symptomatology? • These patients are at high risk for developing what disease?

16. CASE 2: Silicosis Answers: • Describe what you see in slides 2.1 and 2.2. What is the probable diagnosis? The lesion consists of concentric whirled bundles of hyalinized collagen fibers with scattered black pigment. The pattern is usually random, with some nodules located in perivascular or peribronchiolar location, and others scattered within the lung parenchyma. The lesion in Slide 2.2 is viewed under polarized light, and demonstrates numerous polarizable crystals. This is a characteristic picture of silicosis. • How does this lesion form? What are the offending particles seen in Slide 2.2? The lesion forms in reaction to cellular damage thought to be caused by interaction between SiOH groups on the hydrated surface of the silica crystals, the offending particles, with cellular macromolecules in macrophages, including phospholipids and proteins. There is damage to lipid membranes, with cell injury and death leading to release of a soluble protein factor that stimulates fibroblast proliferation and collagen synthesis. • How do you explain the lengthy hiatus between exposure and symptomatology? Silicosis is a chronic disease that does not manifest itself clinically until 20-40 years after the initial exposure. The reason can be seen by examining the pattern of injury, and realizing that initially the hyalinized nodules will be tiny and insignificant, but that cellular injury continues with ongoing increasing fibrosis and collagen deposition until eventually enough normal lung is damaged to cause symptoms. This ongoing damage does not require continued exposure, rather the residual crystals in the lung cause the continued damage. • These patients are at high risk for developing what disease? Tuberculosis. Patients with silicosis have impaired resistance to tubercle bacilli, possibly on the basis of silica-induced injury to macrophages. 0.5 to 5.0% of all cases of silicosis contract TB, and up to 60% of patients with conglomerate silicosis become infected.

17. CASE 3: Clinical History: • The patient is a 67 year old veteran with a 50 pack year history of smoking who is currently hospitalized for pancreatitis. He developed a productive cough with thick yellow sputum, fever, and hypotension after a week in hospital. He had an elevated WBC count with left shift. A chest radiograph shows increased AP diameter and areas of patchy consolidation.

18. Slide 3.1The lung is seen here grossly with lesions more numerous in upper lung fields.

19. Slide 3.2The microscopic appearance of the upper lung field lesions is seen here.

20. Slide 3.3The gross appearance of a lung with patchy infiltrates on chest radiograph is seen here.

21. Slide 3.4The microscopic appearance of an area of consolidation is seen here at medium power.

22. Slide 3.5The microscopic appearance of an area of consolidation is seen here at higher power.

23. Slide 3.6The microscopic appearance of an area of consolidation is seen here at higher power.

24. Case 3 Questions: • The patient has both a chronic and an acute process. Slides 3.1 and 3.2 demonstrates the gross and microscopic appearance of the chronic process. Slides 3.3 to 3.6 show gross and microscopic findings with the acute process. Describe both processes. • What is the chronic process? How does it develop, and to what in the clinical history is it related? • This represents one form of this type of lung damage. Name the other types, and what their respective etiologies are. • What is the acute process? How might this have developed and/or be related to his hospital course?

25. CASE 3: Centrilobular Emphysema w/Bronchopneumonia Answers • The patient has both a chronic and an acute process. Slides 3.1 and 3.2 demonstrates the gross and microscopic appearance of the chronic process. Slides 3.3 to 3.6 show gross and microscopic findings with the acute process. Describe both processes. Chronic process: The airspaces are dilated grossly, and respiratory bronchioles are dilated microscopically, with preservation of alveolar sacs. The result is the appearance of clubbed septa. • Acute process: There are gross areas of tan-yellow consolidation, and microscopically there are large collections of polymorphonuclear leukocytes in the alveoli along with some hemorrhage. • What is the chronic process? How does it develop, and to what in the clinical history is it related? Centrilobular emphysema. The destructive mechanism is thought to be increased protease activity in the face of decreased protease inhibitors. It is related to smoking. • This represents one form of this type of lung damage. Name the other types, and what their respective etiologies are. The other forms of emphysema are: • Panacinar emphysema, related to the genetic absence or decrease of alpha-1-antitrypsin. The acini are uniformly damaged and dilated, from the respiratory bronchiole to the terminal acinus. • Paraseptal emphysema, in which the proximal airway is normal and only the distal acinus is affected. Greatest in the apices subpleurally, and along connective tissue septa. Etiology is idiopathic. • Irregular emphysema, in which acinus is irregularly involved, and process is associated with scarring. • What is the acute process? How might this have developed and/or be related to his hospital course? The acute process is acute bronchopneumonia. With pancreatitis the patient is already ill, is probably not inspiring deeply, and is a set up for hospital acquired pneumonia. Common bacterial organisms for hospital acquired pneumonias include: Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, E. Coli, Klebsiella, and Hemophilus. The most common organism for community acquired pneumonias is Streptococcus pneumoniae.

26. CASE 4: Clinical History: • A 40 year old female has had a cough that is productive of purulent sputum. On occasion, she notes spots of blood in the sputum. She has been hospitalized for pneumonia twice in the past year. She does not have dyspnea, but she has recently developed wheezing episodes. Laboratory findings include an elevated WBC count with neutrophilia and left shift. Sputum culture grew 3+ Serratia marcescens and 2+ Pseudomonas aeruginosa. A chest radiograph reveals thickened bronchi as seen on end, along with linear streaks in the right middle lobe.

27. Slide 4.1The lung lesion is seen here grossly.

28. Slide 4.2The lung lesion is seen here at low power microscopically.

29. Slide 4.3The lung lesion has adjacent parenchyma seen here microscopically.

30. Questions: • What is the most striking architectural change in the lung? Describe it and the related changes? • What are the possible etiologies of this condition? Further Clinical History: • A 24 year old male had the findings at autopsy shown below. At autopsy his heart weighed 450 grams and had a dilated right heart with right ventricular wall measuring 0.7 cm thick (normal < 0.5 cm).

31. Slide 4.4The lung of a patient with cystic fibrosis is seen here grossly.

32. Slide 4.5The lung of a patient with cystic fibrosis is seen here microscopically at medium power.

33. Slide 4.6The lung of a patient with cystic fibrosis is seen here microscopically at higher power.

34. Slide 4.7The peripheral pulmonary arteries have the appearance shown here.

35. Case 4 Questions: • What do you think is the etiology for his pulmonary findings? What changes do you see in the pulmonary vessels, slide 4.7? How does this relate to autopsy findings? • Do you think he was currently suffering from acute respiratory symptoms when he died? Why or why not?

36. CASE 4: Bronchiectasis Answers: • What is the most striking architectural change in the lung? Describe it and the related changes? There is bronchiectasis, with the bronchi markedly dilated. There has been destruction of the bronchial walls, and there is an intense chronic inflammatory infiltrate around them. Note that although these are "large" bronchi, there is no cartilage present. The epithelial lining is focally eroded, with underlying granulation tissue. There is peribronchial scarring and parenchymal collapse. • What are the possible etiologies of this condition? Multiple possible etiologies, including congenital bronchiectasis, post obstructive, secondary to necrotizing pneumonia (Staphylococcal or TB), immunodeficiency disorders, or the immotile cilia and Kartagener's syndromes.

37. CASE 4: Bronchiectasis Answers: • What do you think is the etiology for his pulmonary findings? What changes do you see in the pulmonary vessels, slide 4.7? How does this relate to autopsy findings? The extensive nature of the bronchiectasis here, along with the young age of the patient, is consistent with cystic fibrosis. This is probably the most common etiology overall for bronchiectasis, but in such cases both lungs are extensively involved. The pulmonary arteries show changes of pulmonary hypertension, as shown by slide 4.7 which highlights a plexiform arteriopathy typical for pulmonary hypertension. There is thickening of arterial and arteriolar walls, and narrowing of lumina. This is related to the relative cardiac hypertrophy, and thickening of the right ventricular wall (normal is up to 0.5 cm thick), indicating a degree of cor pulmonale. • Do you think he was currently suffering from acute respiratory symptoms when he died? Why or why not? Probably, as there are areas of consolidation and acute pneumonia. Depending on the severity of the generalized process throughout the lungs he may or may not have been in severe distress. Many cystic fibrosis patients have chronic infections with Pseudomonas.

38. CASE 5: Clinical History: • The patient is an 84 year old woman who was hospitalized for a broken hip. She spiked a fever on the second hospital day, with cough producing a watery sputum, shaking chills, and marked malaise, but antibiotics were not started and she died within 36 hours of becoming systemically ill. Chest x-ray shows a diffuse consolidation in the left lower lobe. CBC showed an elevated WBC count with increased bands. Blood cultures were reported positive after she died.

39. Slide 5.1The lung is seen here grossly.

40. Slide 5.2The lung is seen here microscopically.

41. Slide 5.3A complicating lesion of the lung --abscess formation-- is seen here microscopically.

42. Case 5: Questions: • What is the process demonstrated in these sections? How does this differ in pattern from what you saw in Case 3? • What organism(s) might have been cultured from her blood, had blood cultures been ordered? • Does the disease process in these sections look severe enough to result in a respiratory death?

43. CASE 5: Lobar Pneumonia Answers: • What is the process demonstrated in these sections? How does this differ in pattern from what you saw in Case 3? These slides show a lobar pneumonia. There is a diffuse infiltrate of acute polymorphonuclear cells in the consolidated lobe. In case 3, the infiltrate showed a patchy pattern. However, the distinction between bronchopneumonia and lobar pneumonia is often not clear, as some organisms cause one pattern in some patients, and another pattern in other patients. Also, treatment with antibiotics can alter the pattern as well. • What organism(s) might have been cultured from her blood, had blood cultures been ordered? Streptococcus pneumoniae causes 95% of the lobar pneumonias, although Klebsiella, Staphylococci, Hemophilus influenze, and some gram negative enteric bacteria (E. Coli, Klebsiella) may also cause it. S. pneumoniae characteristically produces a septic phase within the first 24 to 48 hours during which the organism can readily be cultured from the blood. • Does the disease process in these sections look severe enough to result in a respiratory death? What else might have contributed to her death? Although this looks like a relatively early pneumonia, the patient also was septic, which causes vascular collapse and hypotension. She likely died due to a combination of susceptibility due to old age, shock of trauma, septic shock and pneumonia.

44. CASE 6: Clinical History: • The patient is a 47 year old migrant farm worker who had recently moved from Florida to Southern California. Three weeks after beginning work in the orchards he presented to a local clinic with fever, cough, night sweats and pleuritic chest pain. Chest radiograph revealed segmental infiltrates, some hilar adenopathy and a small pleural effusion.

45. Slide 6.1The lung lesion is seen here microscopically at medium power.

46. Slide 6.2The lung lesion is seen here microscopically at higher power.

47. Slide 6.3The lung lesion is seen here microscopically with Gomori methenamine silver (GMS) stain.

48. Case 6: Questions: • What type of inflammatory process is present? Describe the features of this process. • What is the differential diagnosis? Which of these is most likely given the history? What organism do you see? • How would the histopathology differ if the patient had underlying AIDS? • What proportion of normal hosts exposed to this organism develop clinical symptomatology? What are the possible outcomes/sequelae of this infection?

49. CASE 6: Coccidioidomycosis Answers: • What type of inflammatory process is present? Describe the features of this process. The process is granulomatous. The well-formed granulomas are formed by palisading epithelioid macrophages and chronic inflammatory cells with surrounding fibroblasts and collagen. The macrophages are large pink cells, oval to spindled, which line up around the center, and Langhans giant cells are also seen. • What is the differential diagnosis? Which of these is most likely given the history? What organism do you see? The differential diagnosis includes Mycobacterium tuberculosis, which causes caseating granulomas, and the various invasive fungal organisms that can cause pulmonary disease. In the absence of immune compromise, the possibilities include Histoplasmosis, Cryptococcosis, Blastomycosis, Coccidioidomycosis, and Paracoccidioidomycosis. These each have fairly distinctive morphology on GMS (a silver stain that highlights the walls of fungal organisms in black, on a green background counterstain.) The history and morphology in this case are classic for Coccidioidomycosis. • How would the histopathology differ if the patient had underlying AIDS? If the patient were immunocompromised, particularly with AIDS, the histopathology of Cocci is far less granulomatous and more suppurative (acute inflammatory cells.) • What proportion of normal hosts exposed to this organism develop clinical symptomatology? What are the possible outcomes/sequelae of this infection? Only about 10% of the people exposed develop clinically evident disease. Of those, the vast majority resolve completely either spontaneously or with antifungal treatment. >2 to 4 % may go on to develop systemic dissemination, with worsening pulmonary involvement, and spread to skin, bones, CNS and other organs.

50. CASE 7: Clinical History: • A 37 year old patient known to be infected with the human immunodeficiency virus (HIV) and whose last CD4 lymphocyte count was 75/microliter died in respiratory failure.