Is There a Role for PET in the Evaluation of Subcentimeter Pulmonary Nodules? Kemp H. Kernstine, MD, PhD,* Frederic W. Grannis, Jr, MD,* and Arnold J. Rotter, MD † There are little published data available at this time to determine the appropriate role of positron emission tomography (PET) in the evaluation of subcentimeter pulmonary nodules. The sensitivity for malignancy is lower in these smaller lesions, while one would expect the specificity to be higher. Given that the resolution of current generation PET scanners is only 5 to 6 mm, one will be very unlikely to gain useful information from PET for a lesion below 5 mm. For lesions 5 to 10 mm in size, useful information might be gained from PET in those deemed intermediate risk by CT criteria, but this remains to be established. A positive PET in a small, intermediate risk lesion might push one toward biopsy/excision, though a negative PET in such a lesion must be considered to provide no information whatsoever. Even with advances in PET technologies in the future, we feel it is unlikely that PET will evolve a major role in the evaluation of the subcentimeter nodule. Semin Thorac Cardiovasc Surg 17:110-114 © 2005 Elsevier Inc. All rights reserved. KEYWORDS PET, lung cancer, lung mass, solitary pulmonary nodule, screening S mall lung masses are being discovered with increasing frequency given the increasing use of high-quality com- puted tomogram (CT) machines. 1 In the literature, the term solitary pulmonary nodule (SPN) has been used to classify small intraparenchymal lesions that are particularly challeng- ing to diagnose. These have been defined as less than 3 cm in diameter, unassociated with atelectasis, and possessing a CT density greater than the surrounding tissue. 2 In prior de- cades, lesions less than 3 cm were found infrequently and lesions less than 1 cm were rarely found. New developments in the use of CT in lung cancer screening have resulted in the discovery of large numbers of subcentimeter SPNs. In this article we review the limited available evidence regarding the use of positron emission tomography (PET) in the determi- nation of malignancy in these pulmonary nodules. Technological advances have allowed high-precision screen- ing with minimal radiation to the patient. Newly discovered SPNs will be discovered in 23 to 69% of asymptomatic high- risk patients screened by low-dose spiral CT. 3,4,5 The low- dose spiral CT is capable of reproducibly detecting SPNs to a size of 2 mm. 6 In high-risk patients, approximately 90% of newly discovered SPNs are subcentimeter. 7 With the minute size of these lesions, determining the presence of malignancy is a formidable task. Small size renders it difficult to percu- taneously biopsy or to palpate and thus excise these lesions via a minimally invasive approach. The differential diagnosis of these lesions is broad and includes the following: scar, granulomas, inflammatory/in- fectious lesions (sarcoid, tuberculosis, atypical mycobacteria, organizing pneumonia, rheumatoid or other collagen vascu- lar-associated nodules, plasma cell granulomas), primary or secondary malignancy, adenomatoid hyperplasia, vascular, congenital, and traumatic lesions. The presence, degree, and type of calcification, 8 age of the patient, 9 history of smoking, size, 10 density, 11,12 CT contrast enhancement, and volumetric growth on repeated CT 13 of the SPN are all important features in determining the likelihood of the presence of malignancy. However, 40% of SPNs remain indeterminate after thorough CT evaluation, and that rate appears to be higher than this in subcentimeter lesions. 14 The presence of cancer in a subcentimeter nodule is cer- tainly lower than in larger nodules. In the Mayo Lung Trial the incidence of cancer was only 0.69% in screen-detected lesions less than 9 mm, compared with 25% in the 10 to 19 mm, and 33% in the 20 to 29 mm lesions. 15,16,17 However, the very low incidence of malignancy in the Mayo Chest X-ray Trial was influenced by endemic histoplasmosis in that part of the country and the inability to discern subtle lesion *Department of Thoracic Surgery, City of Hope National Medical Center, Duarte, California. †Division of Radiology, City of Hope National Medical Center, Duarte, California. Address reprint requests to Kemp H. Kernstine, MD, PhD, City of Hope National Medical Center, Department of Thoracic Surgery, 1500 East Duarte Road, Warsaw MOB, Suite 2001G, Duarte, California 91010- 3000. E-mail: kkernstine@coh.org 110 1043-0679/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2005.04.004