The Solitary Pulmonary Nodule

1. The Solitary Pulmonary Nodule Suneel S. Kumar MD

2. The Solitary Pulmonary Nodule • “Coin lesion” • Defined as < 3 cm • Completely surrounded by lung parenchyma • Lesions > 3 cm called “masses” and often malignant

3. The Solitary Pulmonary Nodule • Incidence of cancer from 10 – 70% • Found on 0.09 to 0.20 % of all CXRs (approximately 1 in 500) • 90% incidental findings • 150,000 SPNs found annually • Increased with incidental findings on CT

4. The Solitary Pulmonary Nodule • Patients with best prognosis are stage IA (T1N0M0) • 61 – 75% 5-year survival following surgical resection • Approximately half of all lung cancers have extrapulmonary spread by time of diagnosis • 5-year survival 10 – 15%

5. The Solitary Pulmonary Nodule • Most SPNs are benign • Primary malignancy found in about 35% • Solitary metastases may account for 23%

6. Neoplasm Infection Inflammation Vascular lesion Post-traumatic Congenital Lung cyst Pulmonary infarct Amyloidosis Rheumatoid nodules Intrapulmonary lymph nodes Plasma cell granulomas Sarcoidosis Mucoid impaction Hematoma Nipple shadow Differential Diagnosis

7. The Solitary Pulmonary Nodule • Since the SPN by definition is a radiographic finding, radiological imaging is intrinsic to the diagnostic workup

8. Radiology • Failure to recognize lung cancer on CXR is one of most frequent causes of missed diagnosis in radiology • Rate of failure to diagnose ranges from 25 – 90% in different studies with different designs • Error rate of 20 – 50% for radiological detection of lung cancer is generally accepted* *Guiss, Cancer 1960;13:91-5

9. Radiology • Study looked back at CXRs in 259 patients with proven NSCLC* • Found 19% incidence of missed diagnosis • Those missed had significantly smaller nodules (median diameter 16 mm), more superimposing structures, and more indistinct borders *Quekel, Chest 1999;115:720-32

10. Radiology • Time of delay in diagnosis was significant at 472 vs 29 days • Resulted in 43% of lesions being upstaged from T1 to T2 during the delay period* *Quekel, Chest 1999;115:720-32

11. Patterns of Margins • Corona radiata sign • Fine linear strands extending 4-5 mm outward • Spiculated on CXRs • 84 – 90% are malignant

12. Patterns of Margins

13. Patterns of Margins Spiculated lipoid pneumonia

14. Patterns of Margins • Scalloped border • Intermediate probability of cancer • Smooth border suggestive of benign diagnosis

15. Other Characteristics • Air bronchograms and pseudocavitation more commonly malignant • Cavitation with thick (>15 mm vs < 5 mm) more often maligant

16. Air Bronchograms

17. Calcification • Suggests benign diagnosis • With CT the reference standard, CXR has sensitivity 50%, specificity 87%, and PPV 93% for identifying calcification

18. Calcification • Laminated or central pattern typical of granuloma

19. Histoplasmoma

20. Popcorn Calcification • Classic “popcorn” pattern often seen in hamartomas • HRCT can show fat and cartilage in half of cases

21. Hamartoma

22. Calcification • Stippled or eccentric patterns • Have been associated with cancer

23. Calcification

24. Rounded Atelectasis

25. Rounded Atelectasis

26. Growth Rate • Volume-doubling time for malignant bronchogenic tumors rarely < 1 month or > 1 year • If considered spherical, 30% increase in diameter represents a doubling of volume

27. Growth Rate • Traditionally, stability of SPN on CXR for 2 years suggested benign disease • Bronchoalveolar cell carcinoma and typical carcinoids occasionally appear stable for more than 2 years • Hamartomas often grow over time • Initial studies were retrospective and reviewed only cases which were resected

28. Growth Rate • One study examined 156 solitary lesions 1 – 14 cm in size • Previous CXR in 74 • Previously documented no growth in 26 • 9 of these were malignant* • Absence of growth over 2 years on CXR has predictive value of 65% for benign lesions *Yankelevitz, Am J Roentgenol 1997;168:325-8

29. Growth Rate • Use of stability predicated on accurate measurement of growth • Thus, it is dependent on resolution of imaging technique • Thin-section high-resolution CT has better estimation of nodule size and growth characteristics

30. Growth Rate • Limit of detectable changes on CXR estimated to be 3 – 5 mm • CT has resolution of 0.3 mm • Reasonable to use two-year stability on CT as a practical guideline

31. Follow-Up • Optimal time not known • Traditionally follow every three months for first year, then six months the second year • Provided CT is used

32. Nonsurgical Approaches • CT Densitometry • Contrast-enhanced CT • Bronchoscopy • Transthoracic fine needle aspiration biopsy • Positron emission tomography

33. CT Densitometry • Involves measurement of attenuation values • Expressed in Hounsfield units, as compared to reference “phantom” • Usually higher for benign nodules • Allows for identification of 35 – 55% of subsequently identified benign lesions

34. CT Densitometry • One large, multicenter trial, only 1 of 66 nodules identified as benign later found to be malignant* • Cutoff used was 264 Hounsfield units • More conventional cutoff is 185, which yielded a higher false negative rate *Zerhouni, Radiology 1986;160:319-27

35. Contrast-Enhanced CT • Degree on enhancement on spiral CT after injection of contrast • One study used an increase in attenuation of 20 Hounsfield units as threshold for malignant lesions • Sensitivity 95-100%, specificity 70-93%* • Awaits further validation • Local expertise varies, and not widely used *Zhang, Radiology 1997;205:471-8

36. Bronchoscopy • Useful for lesions at least 2 cm • Diagnostic yield varies in literature from 20 – 80%, depending on size of nodule and patient population • Yield depends on nodule size and proximity to bronchial tree

37. Bronchoscopy • Yield 10% for < 1.5 cm, and 40 – 60% for > 2 – 3 cm • 70% yield when CT reveals a bronchus leading to lesion

38. Bronchoscopy • Relatively low risk • Overall complication rate 5% • 3% risk of pneumothorax • 1% risk of hemorrhage • 0.24% risk of death

39. Transthoracic FNA • Diagnostic yield up to 95% in peripheral lesions • Higher complication rate • 30% pneumothorax • About 5% of these require chest tube

40. Positron Emission Tomography • Uptake of 18-flurodeoxyglucose used to measure glucose metabolism • Taken up by cells in glycolysis but is bound within cells and cannot enter normal glycolytic pathway • Most tumors have greater uptake of FDG than normal tissue • Due to increased metabolic activity

41. Positron Emission Tomography • Sensitivity for identifying a malignancy is 96.8% and specificity 77.8%* • False negatives can occur • Notable in association with bronchoalveolar carcinoma, carcinoids, and tumors < 1 cm in diameter *Gould, JAMA 2001;285:914-24

42. Positron Emission Tomography • For 450 nodules reviewed in a meta-analysis, mean sensitivity was 93.9% and specificity 85.8% • Median sensitivity 98% and specificity 83.3%* *Gould, JAMA 2001;285:914-24

43. Gould, JAMA 2001;285:914-24

44. Gould, JAMA 2001;285:914-24

45. *Gould, JAMA 2001;285:914-24

46. Positron Emission Tomography • For diagnosis of benign nodules, sensitivity 96% and specificity 88% with 94% accuracy • False positives usually in association with infectious or inflammatory processes

47. Positron Emission Tomography • Resolution is currently 7 – 8 mm • Imaging of nodules < 1 cm unreliable

48. Positron Emission Tomography • May provide staging information • Up to 14% of patients otherwise eligible for surgery have occult extra thoracic disease on whole-body PET

49. PET Images Pieterman, NEJM 2000;343:254-61

50. PET Images Pieterman, NEJM 2000;343:254-61