Clinical Case 3º Curso de Doenças Pulmonares Difusas

1. Clinical Case 3º Curso de Doenças Pulmonares Difusas February 26, 2014

2. Identification • MFSTD • Gender: female • 58 years-old • Caucasian • Retired (textile worker for 23 years)

3. Past medical history • Type 2 diabetes • Dyslipidemia • Osteoporosis • Appendectomy • Medication: acetylsalicylicacid 100mg, alendronatesodium 70mg, calcium carbonate/cholecalciferol 1500mg/400UI, insulintherapy

4. Past medical history • No allergies • No smoking history • No drugs or alcohol consume • No contact with birds or pets • No recent traveling abroad • History of relatives: sister with sarcoidosis

5. History of present illness 2006 . dyspneaonexertion . wheezing . productivecough, whitesputum

6. History of present illness 2006 - CT

7. History of present illness 2006 - CT CT images show a difuse nodular pattern, with some ille-defined nodules in bothlungs; a mosaicpatternisalsoobserved

8. History of present illness 2006 SurgicalLungBiopsy in upperleftlung

9. Patchy peribronchiolar infiltrate of chronic inflammatory cells with associated lymphoid hyperplasia; some interstitial fibrosis..

10. Patchy peribronchiolar infiltrate of chronic inflammatory cells with associated lymphoid hyperplasia.

11. Peribronchiolar infiltrate of chronic inflammatory cells with associated lymphoid hyperplasia; foamy alveolar histiocytes; some scattered giant cells with colesterol clefts.

13. History of present illness 2006 SurgicalLungBiopsy in upperleftlung Chronicbronchiolitiswithlymphoidhyperplasiaandfibrosis JeffreyMyers, M.D.

14. History of present illness 2007 - CT

15. History of present illness 2007 - CT

16. History of present illness 2008 - CT

17. History of present illness 2008 - CT

18. History of present illness 2006 2013 CT: Variations in pulmonary nodules sizeandnumber

19. History of present illness 2008 - A course of corticosteroids was prescribed - No information about dosage or duration - Without clinical or radiological improvement

20. History of present illness 2013 • Patientwasreferred to ourinstitution • No worseningofcomplaints • Goodhealth status • Afebrile, normal bloodpressureand pulse rate • No respiratorydistress • Pulmonaryauscultationwithbibasalinspiratorycrackles

21. 2013 Hospital São João Diagnostic test results High resolution CT Scatteredlung nodules, the largest one in the left upper lobe (13mm); mosaic pattern

22. 2013 Hospital São João Diagnostic test results High resolution CT Scatteredlung nodules, the largest one in the left upper lobe (13mm); mosaic pattern

23. 2013 Hospital São João Diagnostic test results Lung functional tests

24. 2013 Hospital São João Diagnostic test results Arterial blood gas analysis • pH 7.44, PO2 83.5 mmHg; pCO2 45.3 mmHg, HCO3- 30.3 mmol/L, Sat O2 95% Six minute walk test • Oxygendesaturationof 7% (baseline SpO2: 94%) • Distanceof 420 meterswith no stop before 6 minutes Transthoracic echocardiogram • No significantchanges

25. 2013 Hospital São João Diagnostic test results Blood analysis • CBC normal • ACE: 85 U/L (20-70U/L) • Serologicalmarkersagainsthepatitis B, hepatitis C andhumanimmunodeficiencyviruswere negative • Autoantibodies were negative (antinuclear antibodies-ANAs, anti-DsDNA, rheumatoid factor, anti-neutrophil cytoplasmic antibodies – ANCAs, antibodies to Extractable Nuclear Antigen - anti-ENA)

26. 2013 Hospital São João Diagnostic test results Immunoglobulin levels • IgG366 mg/dL(650-1500) • IgG1 337 mg/dL(370-1280); IgG2 <11.0 mg/dL (150-640); • IgG3 0.5 mg/dL(20 – 110); IgG4 <0.3 mg/dL(8-140) • IgA<8 mg/dL(78-312) • IgM44 mg/dL(55-300) • IgD < 3.1 kU/L (< 15) • IgE 2 kU/L (< 114) Commonvariableimmunodeficiency

27. 2013 Hospital São João Diagnostic test results Bronchoscopy • No noticed airways abnormalities • Bronchoalveolarlavage: lymphociticalveolitis(56.4%), mildeosinophilia (1.2%), CD8+predominance • Microbiologicalstudy: Streptococcuspneumoniae • No malignant cells were identified

28. 2013 Hospital São João Diagnostic test results CT - guided transthoracic core lung biopsy • Performed in upper left lobe

29. One adequate fragment of transthoracic lung biopsy Architectural derangement

30. Fibrosis and moderate chronic inflammatory infiltrate Moderate to dense chronic inflammatory infiltrate

31. Organizing pneumonia

32. Diagnosis: Fibrosis, moderate interstitial chronic inflammatory infiltrate and organizing pneumonia (no evidence of lymphoproliferative disease, no features of follicular bronchiolitis) (pathological result of the previous surgical biopsy unknown at this time)

33. Comments How can we interpret the clinical, imagiological and histological picture?

34. Comments 2006 Surgicallungbiopsy: Chronicbronchiolitiswithlymphoidhyperplasiaandfibrosis

35. Comments 2006 2013 CT: pulmonary nodules withvariations in sizeandnumber mosaicpattern

36. Comments 2006 2013 CT: pulmonary nodules withvariations in sizeandnumber mosaicpattern No worseningofcomplaints

37. Comments 2013 CT-guided transthoracic core lung biopsy: Organizing pneumonia, dense inflammatory infiltrate and fibrosis

38. Comments 2013 CT-guided transthoracic core lung biopsy: Organizing pneumonia, dense inflammatory infiltrate and fibrosis Bronchoalveolarlavage: lymphociticalveolitis (56.4%), mildeosinophilia (1.2%), CD8+ predominance

39. Comments 2013 CT-guided transthoracic core lung biopsy: Organizing pneumonia, dense inflammatory infiltrate and fibrosis Bronchoalveolarlavage: lymphociticalveolitis (56.4%), mildeosinophilia (1.2%), CD8+ predominance Commonvariableimmunodeficiency

40. Comments Diagnosis ? Twodifferentdiagnosis in twodifferentsmoments? 2006: Chronicbronchiolitiswithlymphoidhyperplasia 2013: Organizing pneumonia, dense inflammatoryinfiltrateandfibrosisrelated to CVI Two different histological features of the same spectrum of the disease related to CVI?

41. Comments Diagnosis which treatment to choose?