Differentiation of Benign and Malignant Solitary Pulmonary Nodule: Literature Review

Suresh Tripathi¹, Xuqiu Zhen^2*

¹School of Medicine, South East University, Nanjing, China.
²Department of Radiology Zhongda Hospital, South East University, Nanjing, China.

DOI: 10.4236/alc.2015.42003                

Abstract

The solitary pulmonary nodule (SPN) is frequently seen on chest radiographs and computed tomography (CT), usually the identification is accidental. The overall prevalence of malignancy is relatively low but identification of malignancy of nodule is of prime importance. There are different characters of nodules indicating malignancy, and also the exposure of person to risk factors increases the chances of malignancy of nodule. Chances of malignancy rise with increasing size, the irregular, lobulated border of the nodules is highly associated with higher probability of malignancy and nodules with pure ground grass appearance have higher probability of malignancy, irregularly marginated nodule displaying a corona radiata sign indicating neoplastic infiltration with distortion of neighbouring tissue is almost certainly a malignant nodule. Stippled, punctuate, and eccentric calcifications are suggestive of malignancy. There are 20% - 75% of chances of malignancy if nodule is appeared with ground-glass opacity. Malignant nodules have higher growth rate as compared with benign nodules, malignant nodules usually have doubling time (DT) of 30 - 400 days while DT of more than 450 days is sign of benignity whereas doubling time less than 30 days is usually acute infectious process. The presence of fat within nodule is sign of benignity. Increasing density of the nodule is suggestive of malignancy and requires shorter follow up. Besides the nodule evaluation the chances of malignancy can also be evaluated through the exposure of patient to risk factors like age, current and past smoking status and history of extra thoracic malignancy. The management depends upon various factors mainly three strategies are applied for management including careful observation of nodule, use of diagnostic techniques like CT FNA, PET, and broncoscopy and surgery.

Keywords

Solitary Pulmonary Nodule (SPN), Benign Pulmonary Nodule, Malignant Pulmonary Nodule, CT

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Ost, D., Fein, A.M. and Feinsilver, S.H. (2003) The Solitary Pulmonary Nodule. The New England Journal of Medicine, 348, 2535-2542. http://dx.doi.org/10.1056/NEJMcp012290
[2]	Ost, D.E. and Gould, M.K. (2012) Decision Making in Patients with Pulmonary Nodules. American Journal of Respiratory and Critical Care Medicine, 185, 363-372.
[3]	Wahidi, M.M., Govert, J.A., Goudar, P.K., et al. (2007) Evidence for the Treatment of Patients with Pulmonary Nodules: When Is It Lung Cancer? ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition). Chest, 132, 94S-107S.
[4]	Khan, A., Herman, P.G., Vorwerk, P., Stevens, P., Rojas, K.A. and Graver, M. (1991) Solitary Pulmonary Nodules: Comparison of Classification with Standard, Thin-Section, and Reference Phantom CT. Radiology, 179, 477-481. http://dx.doi.org/10.1148/radiology.179.2.2014295
[5]	Yamashita, K., Matsunobe, S., Tsuda, T., et al. (1995) Solitary Pulmonary Nodules: Preliminary Study of Evaluation with Incremental Dynamic CT. Radiology, 194, 399-405. http://dx.doi.org/10.1148/radiology.194.2.7824717
[6]	Yi, C.A., Lee, K.S., Kim, E.A., Han, J., Kim, H., Kwory, O.J., et al. (2004) Solitary Pulmonary Nodules: Dynamic Enhanced Multi-Detector Row CT Study and Comparison with Vascular Endothelial Growth Factor and Microvessel Density. Radiology, 233, 191-199. http://dx.doi.org/10.1148/radiol.2331031535
[7]	National Lung Screening Trial Research Team, Aberle, D.R., Adams, A.M., et al. (2011) Reduced lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. The New England Journal of Medicine, 365, 395-409. http://dx.doi.org/10.1056/NEJMoa1102873
[8]	Van Klaveren, R.J., Oudkerk, M., Prokop, M., Scholten, E.T., Nackaerts, K., Vernhout, R., van Iersel, C.A., van den Bergh, K.A., van’t Westeinde, S., van der Aalst, C., et al. (2009) Management of Lung Nodules Detected by Volume CT Scanning. The New England Journal of Medicine, 361, 2221-2229. http://dx.doi.org/10.1056/NEJMoa0906085
[9]	Gould, M.K., Fletcher, J., Iannettoni, M.D., et al. (2007) Evaluation of Patients with Pulmonary Nodules: When Is It Lung Cancer? ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition). Chest, 132, 108S-130S.
[10]	Jeong, Y.J., Yi, C.A. and Lee, K.S. (2007) Solitary Pulmonary Nodules: Detection, Characterization, and Guidance for Further Diagnostic Workup and Treatment. American Journal of Roentgenology, 188, 57-68. http://dx.doi.org/10.2214/AJR.05.2131
[11]	Tozaki, M., Ichiba, N. and Fukuda, K. (2005) Dynamic Magnetic Resonance Imaging of Solitary Pulmonary Nodules: Utility of Kinetic Patterns in Differential Diagnosis. Journal of Computer Assisted Tomography, 29, 13-19. http://dx.doi.org/10.1097/01.rct.0000153287.79730.9b
[12]	Henschke, C.I., Yankelevitz, D.F., Naidich, D.P., et al. (2004) CT Screening for Lung Cancer: Suspiciousness of Nodules According to Size on Baseline Scans. Radiology, 231, 164-168. http://dx.doi.org/10.1148/radiol.2311030634
[13]	Darrow, J.C. and Lack, E.E. (1981) Solitary Lung Nodule Due to Dirofilaria immitis (Dog “Heartworm”). Journal of Surgical Oncology, 16, 219-224.
[14]	Siegleman, S.S., Zerhouni, E.A., Leo, F.P., et al. (1980) CT of the Solitary Pulmonary Nodule. American Journal of Roentgenology, 135, 1-13. http://dx.doi.org/10.2214/ajr.135.1.1
[15]	Zwirewich, C.V., Vedal, S., Miller, R.R., et al. (1991) Solitary Pulmonary Nodule: High-Resolution CT and Radiologic-Pathologic Correlation. Radiology, 179, 469-476. http://dx.doi.org/10.1148/radiology.179.2.2014294
[16]	Fishman, A.P. (1988) Pulmonary Disease and Disorders. 2nd Edition, McGraw-Hill, New York, 1947.
[17]	Kim, H.Y., Shim, Y.M., Lee, K.S., et al. (2007) Persistent Pulmonary Nodular Ground-Glass Opacity at Thin-Section CT: Histopathologic Comparisons. Radiology, 245, 267-275. http://dx.doi.org/10.1148/radiol.2451061682
[18]	Aoki, T., Nakata, H., Watanabe, H., et al. (2000) Evolution of Peripheral Adenocarcinomas: CT Findings Correlated with Histology and Tumor Doubling Time. American Journal of Roentgenology, 174, 763-768. http://dx.doi.org/10.2214/ajr.174.3.1740763
[19]	Henschke, C.I., Yankelevitz, D.F., Mirtcheva, R., et al. (2002) CT Screening for Lung Cancer: Frequency and Significance of Part-Solid and Nonsolid Nodules. American Journal of Roentgenology, 178, 1053-1057. http://dx.doi.org/10.2214/ajr.178.5.1781053
[20]	Hasegawa, M., Sone, S., Takashima, S., et al. (2000) Growth Rates of Small Lung Cancers Detected on Mass CT Screening. The British Journal of Radiology, 73, 1252-1259. http://dx.doi.org/10.1259/bjr.73.876.11205667
[21]	Caskey, C.I., Templeton, P.A. and Zerhouni, E.A. (1990) Current Evaluation of the Solitary Pulmonary Nodule. Radiologic Clinics of North America, 28, 511-520.
[22]	Kanauchi, T., Hoshi, T. and Kato, A. (2004) CT Findings of Pulmonary Hamartoma with Special Reference to epithelial-Lined Clefts and Connection with Pulmonary Arteries. Nihon Igaku Hoshasen Gakkai Zasshi, 64, 300-304
[23]	Park, K.Y., Kim, S.J., Noh, T.W., Cho, S.H., Lee, D.Y., Paik, H.C., et al. (2008) Diagnostic Efficacy and Characteristic Features of MRI in Pulmonary Hamartoma: Comparison with CT, MRI and Pathology. Journal of Computer Assisted Tomography, 32, 919-925. http://dx.doi.org/10.1097/RCT.0b013e31815abed4
[24]	Lien, Y.C., Hsu, H.S., Li, W.Y., Wu, Y.C., Hsu, W.H., Wang, L.S., et al. (2004) Pulmonary Hamartoma. Journal of the Chinese Medical Association, 67, 21-26.
[25]	Guo, W., Zhao, Y.P., Jiang, Y.G., Wang, R.W. and Ma, Z. (2008) Surgical Treatment and Outcome of Pulmonary Hamartoma: Retrospective Study of 20-Year Experience. Journal of Experimental & Clinical Cancer Research, 27, 8. http://dx.doi.org/10.1186/1756-9966-27-8
[26]	Takashima, S., Sone, S., Li, F., et al. (2003) Small solitary Pulmonary Nodules (≤1 cm) Detected at Population-Based CT Screening for Lung Cancer: Reliable High-Resolution CT Features of Benign Lesions. American Journal of Roentgenology, 180, 955-964. http://dx.doi.org/10.2214/ajr.180.4.1800955
[27]	Noguchi, M., Morikawa, A., Kawasaki, M., et al. (1995) Small Adenocarcinoma of the Lung. Cancer, 75, 2844-2852. http://dx.doi.org/10.1002/1097-0142(19950615)75:12<2844::AID-CNCR2820751209>3.0.CO;2-#
[28]	Lee, H.J., Goo, J.M., Lee, C.H., Yoo, C.G., Kim, Y.T. and Im, J.G. (2007) Nodular Ground-Glass Opacities on Thin-Section CT: Size Change during Follow-Up and Pathological Results. Korean Journal of Radiology, 8, 22-31. http://dx.doi.org/10.3348/kjr.2007.8.1.22
[29]	Nakata, M., Saeki, H., Takata, I., et al. (2002) Focal Ground-Glass Opacity Detected by Low-Dose Helical CT. Chest, 121, 1464-1467. http://dx.doi.org/10.1378/chest.121.5.1464
[30]	Godoy, M.C. and Naidich, D.P. (2009) Subsolid Pulmonary Nodules and the Spectrum of Peripheral Adenocarcinomas of the Lung: Recommended Interim Guidelines for Assessment and Management. Radiology, 253, 606-622. http://dx.doi.org/10.1148/radiol.2533090179
[31]	Xu, D.M., van Klaveren, R.J., de Bock, G.H., Leusveld, A.L., Dorrius, M.D., Zhao, Y., et al. (2009) Role of Baseline Nodule Density and Changes in Density and Nodule Features in the Discrimination between benign and Malignant Solid Indeterminate Pulmonary Nodules. European Journal of Radiology, 70, 492-498. http://dx.doi.org/10.1016/j.ejrad.2008.02.022
[32]	Herder, G.J., van Tinteren, H., Goldberg, R.P., et al. (2005) Clinical Prediction Model to Characterize Pulmonary Nodules: Validation and Added Value of 18-F-FDG Positron Emission Tomography. Chest, 128, 2490-2496. http://dx.doi.org/10.1378/chest.128.4.2490
[33]	Swensen, S.J., Silverstein, M.D., Ilstrup, D.M., et al. (1997) The Probability of Malignancy in Solitary Pulmonary Nodules, Application to Small Radiologically Indeterminate Nodules. Archives of Internal Medicine, 157, 849-855. http://dx.doi.org/10.1001/archinte.1997.00440290031002
[34]	MacMahon, H., Austin, J.H., Gamsu, G., Herold, C.J., Jett, J.R., Naidich, D.P., Patz Jr., E.F. and Swensen, S.J. (2005) Guidelines for Management of Small pulmonary Nodules Detected on CT Scans: A Statement from the Fleischner Society. Radiology, 237, 395-400. http://dx.doi.org/10.1148/radiol.2372041887
[35]	Ost, D. and Fein, A. (2000) Evaluation and Management of the Solitary Pulmonary Nodule. American Journal of Respiratory and Critical Care Medicine, 162, 782-787. http://dx.doi.org/10.1164/ajrccm.162.3.9812152
[36]	Ost, D. and Fein, A. (2004) Management Strategies for the Solitary Pulmonary Nodule. Current Opinion in Pulmonary Medicine, 10, 272-278. http://dx.doi.org/10.1097/01.mcp.0000130322.11513.c8
[37]	Herder, G.J., Golding, R.P., Hoekstra, O.S., Comans, E.F., Teule, G.J., Postmus, P.E. and Smit, E.F. (2004) The Performance of 18F-Fluorodeoxyglucose Positron Emission Tomography in Small Solitary Pulmonary Nodules. European Journal of Nuclear Medicine and Molecular Imaging, 31, 1231-1236. http://dx.doi.org/10.1007/s00259-004-1552-7
[38]	Weder, W., Schmid, R.A., Bruchhaus, H., Hillinger, S., von Schulthess, G.K. and Steinert, H.C. (1998) Detection of Extrathoracic Metastases by Positron Emission Tomography in Lung Cancer. The Annals of Thoracic Surgery, 66, 886-892.
[39]	Niho, S., Fujii, H., Murakami, K., Nagase, S., Yoh, K., Goto, K., Ohmatsu, H., Kubota, K., Sekiguchi, R., Nawano, S., et al. (2007) Detection of Unsuspected Distant Metastases and/or Regional Nodes by FDG-PET (Corrected) Scan in Apparent Limited-Disease Small-Cell Lung Cancer. Lung Cancer, 57, 328-333. http://dx.doi.org/10.1016/j.lungcan.2007.04.001
[40]	Schreiber, G. and McCrory, D.C. (2003) Performance Characteristics of Different Modalities for Diagnosis of Suspected Lung Cancer: Summary of Published Evidence. Chest, 123, 115S-128S. http://dx.doi.org/10.1378/chest.123.1_suppl.115S
[41]	Freixinet, J.L., Varela, G., Molins, L., Rivas, J.J., Rodríguez-Paniagua, J.M., de Castro, P.L., Izquierdo, J.M. and Torres, J. (2011) Benchmarking in Thoracic Surgery. European Journal Cardio-Thoracic Surgery, 40, 124-129. http://dx.doi.org/10.1016/j.ejcts.2010.10.010
[42]	Matsubara, Y., Takeda, S. and Mashimo, T. (2005) Risk Stratification for Lung Cancer Surgery: Impact of Induction Therapy and Extended Resection. Chest, 128, 3519-3525. http://dx.doi.org/10.1378/chest.128.5.3519