Differential diagnosis and evaluation of multiple pulmonary nodules
- Jess Mandel, MD
Jess Mandel, MD
- Section Editor — Pulmonary Vascular Disease
- Professor of Medicine
- University of California, San Diego
- Paul Stark, MD
Paul Stark, MD
- Professor of Radiology
- University of California San Diego
- Section Editors
- Nestor L Muller, MD, PhD
Nestor L Muller, MD, PhD
- Section Editor — Pulmonary Imaging
- Professor of Radiology
- University of British Columbia
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
- Deputy Editors
- Geraldine Finlay, MD
Geraldine Finlay, MD
- Senior Deputy Editor — UpToDate
- Deputy Editor — Pulmonary, Critical Care, and Sleep Medicine
- Associate Professor
- Tufts University School of Medicine
- Susanna I Lee, MD, PhD
Susanna I Lee, MD, PhD
- Deputy Editor — Radiology
- Associate Professor of Radiology
- Harvard Medical School
- Massachusetts General Hospital
The etiology of multiple pulmonary nodules can usually be determined with the help of a thorough history and physical examination. However, further testing is sometimes required for diagnosis, which may include imaging tests and/or a biopsy. The differential diagnosis and diagnostic evaluation of multiple pulmonary nodules are reviewed here. The approach to a solitary pulmonary nodule is discussed separately. (See "Diagnostic evaluation and management of the solitary pulmonary nodule".)
Malignant versus benign — Multiple pulmonary nodules may be caused by malignant or benign diseases.
In patients without a known primary malignant tumor, the following characteristics help differentiate multiple malignant nodules from multiple benign nodules:
●Multiple pulmonary nodules that are ≥1 cm in diameter or detected by conventional chest radiography are most likely due to metastatic disease from a malignant solid organ primary tumor [1,2].
●Multiple pulmonary nodules that are <5 mm in diameter, juxtaposed to either the visceral pleura or an interlobar fissure, and detected incidentally, are more likely to be benign lesions, such as granulomata, scars, or intrapulmonary lymph nodes [1-3].
- Ginsberg MS, Griff SK, Go BD, et al. Pulmonary nodules resected at video-assisted thoracoscopic surgery: etiology in 426 patients. Radiology 1999; 213:277.
- Gross BH, Glazer GM, Bookstein FL. Multiple pulmonary nodules detected by computed tomography: diagnostic implications. J Comput Assist Tomogr 1985; 9:880.
- Ahn MI, Gleeson TG, Chan IH, et al. Perifissural nodules seen at CT screening for lung cancer. Radiology 2010; 254:949.
- Ooi GC, Chim CS, Lie AK, Tsang KW. Computed tomography features of primary pulmonary non-Hodgkin's lymphoma. Clin Radiol 1999; 54:438.
- Filly R, Bland N, Castellino RA. Radiographic distribution of intrathoracic disease in previously untreated patients with Hodgkin's disease and non-Hodgkin's lymphoma. Radiology 1976; 120:277.
- Austin JH, Garg K, Aberle D, et al. Radiologic implications of the 2011 classification of adenocarcinoma of the lung. Radiology 2013; 266:62.
- Naidich DP, Bankier AA, MacMahon H, et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology 2013; 266:304.
- Edinburgh KJ, Jasmer RM, Huang L, et al. Multiple pulmonary nodules in AIDS: usefulness of CT in distinguishing among potential causes. Radiology 2000; 214:427.
- Joshi M, Markelova N, Palacio D, Schapira RM. A patient with HIV, dyspnea, and multiple pulmonary nodules: pulmonary Kaposi sarcoma. Chest 2006; 130:1924.
- Libshitz HI, North LB. Pulmonary metastases. Radiol Clin North Am 1982; 20:437.
- Chang AE, Schaner EG, Conkle DM, et al. Evaluation of computed tomography in the detection of pulmonary metastases: a prospective study. Cancer 1979; 43:913.
- Screaton NJ, Ravenel JG, Lehner PJ, et al. Lemierre syndrome: forgotten but not extinct--report of four cases. Radiology 1999; 213:369.
- Casullo J, Semionov A. Reversed halo sign in acute pulmonary embolism and infarction. Acta Radiol 2013; 54:505.
- Dodd JD, Souza CA, Müller NL. High-resolution MDCT of pulmonary septic embolism: evaluation of the feeding vessel sign. AJR Am J Roentgenol 2006; 187:623.
- Kuhlman JE, Fishman EK, Burch PA, et al. CT of invasive pulmonary aspergillosis. AJR Am J Roentgenol 1988; 150:1015.
- Curtis AM, Smith GJ, Ravin CE. Air crescent sign of invasive aspergillosis. Radiology 1979; 133:17.
- Gaeta M, Blandino A, Scribano E, et al. Computed tomography halo sign in pulmonary nodules: frequency and diagnostic value. J Thorac Imaging 1999; 14:109.
- Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology 1985; 157:611.
- Greene RE, Schlamm HT, Oestmann JW, et al. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin Infect Dis 2007; 44:373.
- Chung JH, Godwin JD, Chien JW, Pipavath SJ. Case 160: Pulmonary mucormycosis. Radiology 2010; 256:667.
- Gurney JW, Conces DJ. Pulmonary histoplasmosis. Radiology 1996; 199:297.
- Allen MS. Multiple benign lung tumors. Semin Thorac Cardiovasc Surg 2003; 15:310.
- Harinasuta T, Pungpak S, Keystone JS. Trematode infections. Opisthorchiasis, clonorchiasis, fascioliasis, and paragonimiasis. Infect Dis Clin North Am 1993; 7:699.
- Kagawa FT. Pulmonary paragonimiasis. Semin Respir Infect 1997; 12:149.
- BREM TH, COHN HA. Paragonimus westermanii. Radiology 1946; 46:511.
- Im JG, Whang HY, Kim WS, et al. Pleuropulmonary paragonimiasis: radiologic findings in 71 patients. AJR Am J Roentgenol 1992; 159:39.
- Martínez S, Restrepo CS, Carrillo JA, et al. Thoracic manifestations of tropical parasitic infections: a pictorial review. Radiographics 2005; 25:135.
- Sakai S, Shida Y, Takahashi N, et al. Pulmonary lesions associated with visceral larva migrans due to Ascaris suum or Toxocara canis: imaging of six cases. AJR Am J Roentgenol 2006; 186:1697.
- Okada F, Ono A, Ando Y, et al. Pulmonary computed tomography findings of visceral larva migrans caused by Ascaris suum. J Comput Assist Tomogr 2007; 31:402.
- Fabreguet I, Francis F, Lemery M, et al. A 76-year-old man with multiple pulmonary nodules. Chest 2009; 135:1094.
- Cordier JF, Valeyre D, Guillevin L, et al. Pulmonary Wegener's granulomatosis. A clinical and imaging study of 77 cases. Chest 1990; 97:906.
- Chung MP, Yi CA, Lee HY, et al. Imaging of pulmonary vasculitis. Radiology 2010; 255:322.
- Dauber JH, Kaufman JH, Beswick DR, Rossman MD. Cavitary pulmonary sarcoidosis. Arch Intern Med 1983; 143:1058.
- Swanson KL, Prakash UB, Stanson AW. Pulmonary arteriovenous fistulas: Mayo Clinic experience, 1982-1997. Mayo Clin Proc 1999; 74:671.
- Poole PS, Ferguson EC. Revisiting pulmonary arteriovenous malformations: radiographic and CT-imaging findings and corresponding treatment options. Contemporary Diagnostic Imaging (CDR) 2010; 8:1.
- Stark P, Jacobson F, Shaffer K. Standard imaging in silicosis and coal worker's pneumoconiosis. Radiol Clin North Am 1992; 30:1147.
- Bégin R, Cantin A, Massé S. Recent advances in the pathogenesis and clinical assessment of mineral dust pneumoconioses: asbestosis, silicosis and coal pneumoconiosis. Eur Respir J 1989; 2:988.
- Yang JC, Liu KL. Coal workers' pneumoconiosis with progressive massive fibrosis. CMAJ 2012; 184:E878.
- Baldwin DR, Callister ME, Guideline Development Group. The British Thoracic Society guidelines on the investigation and management of pulmonary nodules. Thorax 2015; 70:794.
- Gould MK, Donington J, Lynch WR, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143:e93S.
- Costello P, Anderson W, Blume D. Pulmonary nodule: evaluation with spiral volumetric CT. Radiology 1991; 179:875.
- Remy-Jardin M, Remy J, Giraud F, Marquette CH. Pulmonary nodules: detection with thick-section spiral CT versus conventional CT. Radiology 1993; 187:513.
- Costello P. Spiral CT of the thorax. Semin Ultrasound CT MR 1994; 15:90.
- Seltzer SE, Judy PF, Adams DF, et al. Spiral CT of the chest: comparison of cine and film-based viewing. Radiology 1995; 197:73.
- Kawel N, Seifert B, Luetolf M, Boehm T. Effect of slab thickness on the CT detection of pulmonary nodules: use of sliding thin-slab maximum intensity projection and volume rendering. AJR Am J Roentgenol 2009; 192:1324.
- de Hoop B, Gietema H, van de Vorst S, et al. Pulmonary ground-glass nodules: increase in mass as an early indicator of growth. Radiology 2010; 255:199.
- Godoy MC, Naidich DP. Subsolid pulmonary nodules and the spectrum of peripheral adenocarcinomas of the lung: recommended interim guidelines for assessment and management. Radiology 2009; 253:606.
- Potter DA, Glenn J, Kinsella T, et al. Patterns of recurrence in patients with high-grade soft-tissue sarcomas. J Clin Oncol 1985; 3:353.
- DIFFERENTIAL DIAGNOSIS
- Malignant versus benign
- Malignant diseases
- Benign diseases
- - Infection
- - Non-infectious inflammatory conditions
- - Pulmonary AVMs
- - Pneumoconioses
- DIAGNOSTIC EVALUATION
- Computed tomography
- - Serial CT scans
- - Tissue sampling
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS