- Email: [email protected]
Imaging of Lung Hamartomas by Multidetector Computed Tomography and Positron Emission Tomography
Concetta De Cicco, MD, Massimo Bellomi, MD, Mirco Bartolomei, MD, Giuseppe Carbone, MD, Giuseppe Pelosi, MD, Giulia Veronesi, MD, Tommaso De Pas, MD, Lorenzo Spaggiari, MD, and Giovanni Paganelli, MD Divisions of Nuclear Medicine, Radiology, Pathology and Laboratory Medicine, Thoracic Surgery, and New Drugs Development Unit, Medical Oncology, European Institute of Oncology, and School of Medicine, University of Milan, Milan, Italy
Background. Hamartomas constitute 8% of solitary lung nodules and 75% of benign nodules. Most are discovered on routine x-ray film and require further evaluation. Computed tomography (CT) is insufficient for a benign versus malignant diagnosis in about 30% of cases. Methods. We retrospectively assessed the ability of CT with contrast and [18F] fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) to diagnose nonmalignancy in 42 consecutive pathologically confirmed hamartomas, with the aim of reducing the number of invasive procedures in future cases. Computed tomography was assessed as probably benign or probably malignant based on one radiologist’s subjective evaluation. The PET/CT images were assessed according to uptake relative to normal parenchyma and mediastinum. Results. Computed tomography was probably benign in 26 cases (62%) and probably malignant in 16 (38%). The PET/CT scan was benign in 34 cases (81% [standard
uptake value available in 16: mean 1.1, SD 0.5]), suspicious in 4 (9.5%), and malignant in 4 (9.5%). The 34 nodules benign by PET/CT had mean size 14.3 mm (SD 7.8) compared with mean 22.7 mm (SD 10) in the 8 nodules malignant/suspicious by PET/CT. Of these 8 nodules, 6 were probably benign by CT and 2 were probably malignant; thus CT and PET/CT concurred on malignancy in only 2 cases. Conclusions. The present study is the first specifically concerned with the CT and PET/CT characteristics of a pathologically confirmed series of lung hamartomas. Our findings support the role of PET/CT in characterizing solitary lung nodules, although about 20% of (mainly large size) hamartomas had uptake characteristics suggesting malignancy.
H
Material and Methods
amartomas constitute 75% of benign lung lesions. Most are discovered incidentally on routine radiography and require computed tomography (CT) for further evaluation. However, in 30% of cases, CT findings clearly indicating a benign lesion (calcifications, fat) are absent, and bronchoscopy, percutaneous biopsy, or open biopsy may be necessary for definitive diagnosis. We retrospectively assessed multidetector CT with contrast findings and [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography-CT (PET/CT) findings in consecutive patients who received these examinations during workup for surgical removal of lung lesions. All cases had pathologically diagnosed hamartoma. Our aim was to delineate the CT and PET/CT characteristics of hamartomas to obtain a profile that may serve to distinguish these lesions from malignant lesions.
(Ann Thorac Surg 2008;86:1769 –73) © 2008 by The Society of Thoracic Surgeons
Patients Records of 42 consecutive patients (24 men and 18 women; mean age, 59 years; range, 33 to 78) with pathologic diagnoses of lung hamartoma after thoracotomy or videothoracoscopy to remove a solitary lung nodule were reviewed. All had been examined by CT and PET/CT in the period January 2001 to May 2007, as part of the workup for an indeterminate nodule discovered in many cases in the ambit of the COSMOS (Continuous Observation of Smoking Subjects) CT screening study [1]. The study was approved by the Ethics Committee of the European Institute of Oncology; patient consent was not required as the study was retrospective and anonymity was maintained.
Computed Tomography Accepted for publication Aug 13, 2008. Address correspondence to Dr De Cicco, Division of Nuclear Medicine, European Institute of Oncology, Via Ripamonti 435, Milan, 20141, Italy; e-mail: [email protected].
© 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
Computed tomography was performed with a Light Speed CT16 (GE Medical Systems, Milwaukee, WI) with the following acquisition parameters: collimation 20 mm; reconstructed slice thickness 2.5 mm; standard reconstruction filter; 120 KVp; 220 to 400 mA (automatic expo0003-4975/08/$34.00 doi:10.1016/j.athoracsur.2008.08.033
GENERAL THORACIC
Imaging of Lung Hamartomas by Multidetector Computed Tomography and Positron Emission Tomography
GENERAL THORACIC
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DE CICCO ET AL IMAGING OF LUNG HAMARTOMAS
Fig 1. Computed tomography after intravenous contrast showing lung nodule in the upper part of the lower right lobe. The nodule has an axial diameter of 36 mm, smooth margin, and irregular hyperdense streaks, but no enhancement. The nodule was considered probably benign.
Ann Thorac Surg 2008;86:1769 –73
five minutes later, PET/CT scans were obtained from base of head to pelvis, with the subject in supine position and arms extended behind the head using a Discovery LS-ST instrument (GE Medical Systems, Waukesha, WI). The CT parameters were 140 kVp, 80 mAs, 5-mm scan width, 4.25-mm intervals, high-sensitivity mode, 15 mm per rotation table speed. Emission image acquisition time was 4 minutes per bed position. Emission data were reconstructed using iterative algorithms and corrected for attenuation using transmission data from CT. Attenuation-corrected images were reconstructed in transaxial, coronal, and sagittal planes. The PET/CT images were reviewed by a nuclear medicine physician blind to the pathology. In some cases, the standardized uptake values normalized to body weight (SUV bw max) was determined. The PET/CT images were interpreted as benign if uptake appeared subjectively less than or equal to normal lung parenchyma, suspicious if uptake was greater than normal parenchyma but less than mediastinum, and malignant if uptake was greater than mediastinum.
Results sure); rotation time 0.8 s; and speed 18.75 mm/rot (pitch 0.938). Scans were started 50 s after the initiation of intravenous injection of 1.5 mg/kg contrast medium, 350 to 370 mg iodine/mL, flow rate 2 mL/s, followed by 50 mL saline at 2 mL/s. A radiologist blind to the pathologic findings reviewed the scans and judged them probably benign or probably malignant based on a combination of lesion size, margins (smooth or irregular), shape (round, oval, lobulated), and internal characteristics (presence of calcifications or fat).
Positron Emission Tomography/Computed Tomography Positron emission tomography/computed tomography was performed 1 to 7 days before surgery. Twenty-seven patients were scanned at our institute, the remaining 15 elsewhere. The [18F]FDG, supplied and qualitycontrolled by IASON Labormedizin Graz-Seiersberg, Austria, was injected intravenously (5.3 MBq/kg). Forty-
Pathology Mean pathologic lesion size was 15.9 mm (SD 8.9 mm; range, 4 to 40 mm). Lesions consisted mainly of chondroid tissue (median 85%; range, 0% to 85%) with varying proportions of fibromyxoid tissue (median 14%; range, 5% to 80%), fat (median 10%; range, 1% to 45%), bronchial-type epithelium (median 8%; range, 2% to 10%), and smooth muscle (median 2%; range, 0% to 15%). Variable lymphoid cell infiltrates were observed in as many as 80% of cases, always accounting for 5% or less of the specimens (median 2%; range, 2% to 5%). No relationship was found between histologic features and imaging findings.
Computed Tomography All 42 lesions were solid and present peripherally; 2 were located close to the mediastinum. Twenty-six nodules
Fig 2. Positron emission tomography (PET)/computed tomography (CT) of same case as in Figure 1. (A) PET image and (B) PET/CT fused image of lesion in the right lobe. The [18F]-fluorodeoxyglucose uptake is evident within the nodule at a level similar to that of the mediastinum (standardized uptake values normalized to body weight ⫽ 2.3). The finding was considered suspicious.
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Table 1. PET/CT Review Outcomes in Relation to CT Review Outcomes in 42 Consecutive Solitary Lung Nodules Pathologically Confirmed as Hamartoma Number of Cases (% of Total)
Median Pathologic Size, mm (Range)
Probably benign
26 (62%)
30.0 (6–45)
Probably malignant
16 (38%)
12.5 (4–25)
Totals
42 (100%)
CT Outcome
CT ⫽ computed tomography;
PET-CT Outcome
Number of Cases
Benign Suspicious Malignant Benign Suspicious Malignant
20 4 2 14 0 2 42
PET ⫽ positron emission tomography.
were in a right lung (11 upper lobe, 11 lower lobe, 4 median lobe), and 16 nodules in the left lung were distributed between the two lobes. Margins were smooth in 30, and irregular in 12. Shape was round in 32, oval in 6, and lobulated in 4. Four nodules (9%) presented calcifications; 13 (31%) were associated with pleural thickening. Twenty-six nodules (62%) were judged probably benign (Fig 1), and 16 (38%), probably malignant.
Positron Emission Tomography/Computed Tomography All PET/CT scans were analyzed visually. The SUV bw max was available in 17 cases. The PET/CT scan was considered benign in 34 (81.0%), suspicious in 4 (9.5%), and malignant in 4 (9.5%; Fig 2). The mean pathologic size of the 8 nodules considered suspicious/malignant was 22.7 mm (SD 10 mm; range, 10 to 40 mm; median 19 mm). The 4 suspicious nodules had a mean size of 30.0 mm (SD 9.1 mm), and the 4 malignant nodes, a size of 15.5 mm (SD 3.6 mm). The SUV was available for only 1 of these 8 nodules (size 40 mm, suspicious, SUV 2.3). The mean size of the 34 nodules considered benign was 14.3 mm (SD 7.8 mm; range, 4 to 45 mm; median 13 mm). For 16 of 34 cases, SUV was available (mean 1.1; SD 0.5; range, 0.4 to 1.7). The PET/CT findings in relation to CT findings are shown in Table 1.
Comment Notwithstanding rapidly improving technology, it is often difficult to determine the malignant versus benign nature of solitary lung nodules identified during routine chest roentgenography or in screening studies with lowdose CT for the early detection of lung cancer in high-risk groups [1]. Follow-up is recommended as the next stage in the workup of indeterminate solitary nodules [2]. Intranodular fat (attenuation, -40 to -120 HU) and popcornlike chondroid calcifications are reliable indicators of hamartoma. However, fat is only identified in approximately 34% of hamartomas, and fat plus calcifications are present in approximately 21% [3]. More generally, several morphologic features and combinations thereof can indicate a benign lesion [3–5] on CT, but again, such features are not present in all benign nodules.
A recent review [6] of the literature indicated that imaging (roentgenography and CT) assessment of nodule features such as size, morphology, and type of opacity can give highly variable results in terms of malignancy prevalence. The risk of malignancy may be as high as 28% for nodules 5 to 10 mm and 20% to 30% for nodules with a smooth margin, and so must be removed. Although surgical removal of nodules by wedge resection or lobectomy has low perioperative mortality [7] and low morbidity when performed by video-assisted thoracoscopy [8], the aim must be to reliably identify benign nodules by noninvasive techniques. Positron emission tomography/CT has emerged as a promising way of characterizing indeterminate lung nodules identified on CT [9 –12]. Yi and colleagues [13] reported that PET/CT was more sensitive and accurate at detecting malignancy than dynamic helical CT and proposed it as the first-line method for evaluating solitary pulmonary nodules. In the present study, we aimed to determine whether the information provided by both CT with contrast and PET/CT was potentially of more use in determining the malignant versus benign nature of solitary lung nodules than either technique alone. We analyzed CT and PET/CT findings in a consecutive series with pathologic diagnosis of hamartoma. All were solitary nodules at first identification, often detected in smokers undergoing low-dose CT screening for the early detection of lung cancer [1]. According to the revised CT screening protocol, such patients receive PET/CT if the lesion is larger than 8 mm. Policies for investigating indeterminate nodules within the screening study evolved as experience was gained. Many patients in this study were operated on when policies for lesion removal differed from those in force today at our institute [1]. We found that CT suggested a benign or probably benign lesion in only 62% of cases, mainly because the nodule lacked the calcifications (only present in 9%) or fat generally considered to indicate nonmalignancy; note, however, that calcification alone may not be sufficient to exclude carcinoma [14]. Use of contrast may make it easier distinguish malignant from benign nodules [11]. However, use of contrast prevented the measurement of density.
GENERAL THORACIC
Ann Thorac Surg 2008;86:1769 –73
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We found that PET/CT provided better results than CT, diagnosing 34 of 42 lesions (81.0%) as benign, and supporting the role of this modality in the characterization of pulmonary nodules. However, it also diagnosed 4 lesions as malignant and another 4 as suspicious. In all 8 of these cases (19%), review of the resected specimens failed to detect pathologic features that might explain high glucose uptake: all were simple chondroid hamartomas. It is noteworthy that by CT, 6 of 8 of these cases were benign. It is also noteworthy that 14 of 16 cases suspicious or malignant by CT were benign by PET/CT. To conclude, the present study is concerned specifically with the CT and PET/CT characteristics of a pathologically confirmed series of lung hamartomas. Our findings support the role of PET/CT in characterizing solitary lung nodules, but reveal that hamartomas, particularly those of large size, may have uptake characteristics suggesting malignancy. The authors thank Mrs Deborah Console for editorial and back office support, and Don Ward for help with the English.
References 1. Veronesi G, Bellomi M, Mulshine JL, et al. Lung cancer screening with low-dose computed tomography: a noninvasive diagnostic protocol for baseline lung nodules. Lung Cancer 2008;61:340 –9. 2. Alberts WM, for the American College of Chest Physicians. Diagnosis and management of lung cancer executive summary: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(Suppl):1–19. 3. Siegelman SS, Khouri NF, Scott WW, et al. Pulmonary hamartoma: CT findings. Radiology 1986;160:313–7.
Ann Thorac Surg 2008;86:1769 –73
4. Oldham HN, Young WG, Sealy WC. Hamartoma of the lung. J Thorac Cardiovasc Surg 1967;53:735– 42. 5. Ledor K, Fish B, Chaise L, Ledor S. CT diagnosis of pulmonary hamartomas. J Comput Assist Tomogr 1981;5:343– 4. 6. Wahidi MM, Govert JA, Goudar RK, Gould MK, McCrory DC, for the American College of Chest Physicians. Evidence for the treatment of patients with pulmonary nodules: when is it lung cancer? ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132(Suppl):94 –107. 7. Landreneau RJ, Sugarbaker DJ, Mack MJ, et al. Wedge resection versus lobectomy for stage I (T1 N0 M0) non-smallcell lung cancer. J Thorac Cardiovasc Surg 1997;113:691– 8. 8. Whitson BA, Andrade RS, Boettcher A, et al. Video-assisted thoracoscopic surgery is more favorable than thoracotomy for resection of clinical stage I nonsmall-cell lung cancer. Ann Thorac Surg 2007;83:1965–70. 9. Gupta NC, Maloof J, Gunel E. Probability of malignancy in solitary pulmonary nodules using fluorine-18-FDG and PET. J Nucl Med 1996;37:943– 8. 10. Christensen JA, Nathan MA, Mullan BP, Hartman TE, Swensen SJ, Lowe VJ. Characterization of the solitary pulmonary nodule: 18F-FDG PET versus nodule-enhancement CT. AJR Am J Roentgenol 2006;187:1361–7. 11. Jeong YJ, Yi CA, Lee KS. Solitary pulmonary nodules: detection, characterization, and guidance for further diagnostic workup and treatment. AJR Am J Roentgenol 2007; 188:57– 68. 12. Veronesi G, Bellomi M, Veronesi U, et al. Role of positron emission tomography scanning in the management of lung nodules detected at baseline computed tomography screening. Ann Thorac Surg 2007;84:959 – 65. 13. Yi CA, Lee KS, Kim BT, et al. Tissue characterization of solitary pulmonary nodule: comparative study between helical dynamic CT and integrated PET/CT. J Nucl Med 2006; 47:443–50. 14. Mahoney MC, Shipley RT, Corcoran HL, Dickson BA. CT demonstration of calcification in carcinoma of the lung. AJR Am J Roentgenol 1990;154:255– 8.
INVITED COMMENTARY In this article, De Cicco and associates [1] retrospectively evaluated 42 patients who underwent surgical resection for benign hamartomas of the lung. The purpose of this study was to evaluate the role of positron emission tomography (PET) and computed tomography (CT) in solitary lung nodules identified by CT scans, and whether this information could obviate the need for surgical resection in future patients. This subject is timely in nature with the increased access and use of CT scans and the present worldwide interest in lung cancer screening protocols. Pulmonary hamartomas are the most common benign tumor of the lung. As such they serve as an obvious platform to evaluate the ability of PET and CT scans to predict benign pathology of solitary lung nodules. By study design, high resolution CT scans and PET with CT scan were evaluated separately, and interpretation of one was blinded to the results of the other. The study design is a reasonable approach when evaluating the value of PET and CT and its ability to predict the benign nature of a solitary nodule. However this design is also a detractor from the perspective © 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
of “real world” patient management. In clinical practice, the thoracic surgeon would evaluate the patient’s clinical history, risk factors, CT scan, and the PET with the CT scan. It is the combination of these factors that leads to appropriate management decisions. The lack of integration of these results led to the high incidence of false positives in the PET with CT scan group. In 42 patients, 8 PET with CT scans, or 19%, were reported as either suspicious (4 scans) or malignant (4 scans). In this group of 8 patients, 6 had CT scans that were correctly interpreted as benign. The patient’s results that are illustrated in Figures 1 and 2 further shows the importance of complete evaluation. Doing so would have likely avoided this PET with CT false positive scan and obviated surgery, which is ultimately the goal. This suggests that while selective use of PET with CT scan may have a role, its routine use, based on the current literature remains inappropriate. Comparisons between being able to determine benign cause using PET with a CT scan and using the CT scan alone reported as 81% and 62%, respectively, must consider that the CT scans were performed with intravenous 0003-4975/08/$34.00 doi:10.1016/j.athoracsur.2008.09.039
Background. Hamartomas constitute 8% of solitary lung nodules and 75% of benign nodules. Most are discovered on routine x-ray film and require further evaluation. Computed tomography (CT) is insufficient for a benign versus malignant diagnosis in about 30% of cases. Methods. We retrospectively assessed the ability of CT with contrast and [18F] fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) to diagnose nonmalignancy in 42 consecutive pathologically confirmed hamartomas, with the aim of reducing the number of invasive procedures in future cases. Computed tomography was assessed as probably benign or probably malignant based on one radiologist’s subjective evaluation. The PET/CT images were assessed according to uptake relative to normal parenchyma and mediastinum. Results. Computed tomography was probably benign in 26 cases (62%) and probably malignant in 16 (38%). The PET/CT scan was benign in 34 cases (81% [standard
uptake value available in 16: mean 1.1, SD 0.5]), suspicious in 4 (9.5%), and malignant in 4 (9.5%). The 34 nodules benign by PET/CT had mean size 14.3 mm (SD 7.8) compared with mean 22.7 mm (SD 10) in the 8 nodules malignant/suspicious by PET/CT. Of these 8 nodules, 6 were probably benign by CT and 2 were probably malignant; thus CT and PET/CT concurred on malignancy in only 2 cases. Conclusions. The present study is the first specifically concerned with the CT and PET/CT characteristics of a pathologically confirmed series of lung hamartomas. Our findings support the role of PET/CT in characterizing solitary lung nodules, although about 20% of (mainly large size) hamartomas had uptake characteristics suggesting malignancy.
H
Material and Methods
amartomas constitute 75% of benign lung lesions. Most are discovered incidentally on routine radiography and require computed tomography (CT) for further evaluation. However, in 30% of cases, CT findings clearly indicating a benign lesion (calcifications, fat) are absent, and bronchoscopy, percutaneous biopsy, or open biopsy may be necessary for definitive diagnosis. We retrospectively assessed multidetector CT with contrast findings and [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography-CT (PET/CT) findings in consecutive patients who received these examinations during workup for surgical removal of lung lesions. All cases had pathologically diagnosed hamartoma. Our aim was to delineate the CT and PET/CT characteristics of hamartomas to obtain a profile that may serve to distinguish these lesions from malignant lesions.
(Ann Thorac Surg 2008;86:1769 –73) © 2008 by The Society of Thoracic Surgeons
Patients Records of 42 consecutive patients (24 men and 18 women; mean age, 59 years; range, 33 to 78) with pathologic diagnoses of lung hamartoma after thoracotomy or videothoracoscopy to remove a solitary lung nodule were reviewed. All had been examined by CT and PET/CT in the period January 2001 to May 2007, as part of the workup for an indeterminate nodule discovered in many cases in the ambit of the COSMOS (Continuous Observation of Smoking Subjects) CT screening study [1]. The study was approved by the Ethics Committee of the European Institute of Oncology; patient consent was not required as the study was retrospective and anonymity was maintained.
Computed Tomography Accepted for publication Aug 13, 2008. Address correspondence to Dr De Cicco, Division of Nuclear Medicine, European Institute of Oncology, Via Ripamonti 435, Milan, 20141, Italy; e-mail: [email protected].
© 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
Computed tomography was performed with a Light Speed CT16 (GE Medical Systems, Milwaukee, WI) with the following acquisition parameters: collimation 20 mm; reconstructed slice thickness 2.5 mm; standard reconstruction filter; 120 KVp; 220 to 400 mA (automatic expo0003-4975/08/$34.00 doi:10.1016/j.athoracsur.2008.08.033
GENERAL THORACIC
Imaging of Lung Hamartomas by Multidetector Computed Tomography and Positron Emission Tomography
GENERAL THORACIC
1770
DE CICCO ET AL IMAGING OF LUNG HAMARTOMAS
Fig 1. Computed tomography after intravenous contrast showing lung nodule in the upper part of the lower right lobe. The nodule has an axial diameter of 36 mm, smooth margin, and irregular hyperdense streaks, but no enhancement. The nodule was considered probably benign.
Ann Thorac Surg 2008;86:1769 –73
five minutes later, PET/CT scans were obtained from base of head to pelvis, with the subject in supine position and arms extended behind the head using a Discovery LS-ST instrument (GE Medical Systems, Waukesha, WI). The CT parameters were 140 kVp, 80 mAs, 5-mm scan width, 4.25-mm intervals, high-sensitivity mode, 15 mm per rotation table speed. Emission image acquisition time was 4 minutes per bed position. Emission data were reconstructed using iterative algorithms and corrected for attenuation using transmission data from CT. Attenuation-corrected images were reconstructed in transaxial, coronal, and sagittal planes. The PET/CT images were reviewed by a nuclear medicine physician blind to the pathology. In some cases, the standardized uptake values normalized to body weight (SUV bw max) was determined. The PET/CT images were interpreted as benign if uptake appeared subjectively less than or equal to normal lung parenchyma, suspicious if uptake was greater than normal parenchyma but less than mediastinum, and malignant if uptake was greater than mediastinum.
Results sure); rotation time 0.8 s; and speed 18.75 mm/rot (pitch 0.938). Scans were started 50 s after the initiation of intravenous injection of 1.5 mg/kg contrast medium, 350 to 370 mg iodine/mL, flow rate 2 mL/s, followed by 50 mL saline at 2 mL/s. A radiologist blind to the pathologic findings reviewed the scans and judged them probably benign or probably malignant based on a combination of lesion size, margins (smooth or irregular), shape (round, oval, lobulated), and internal characteristics (presence of calcifications or fat).
Positron Emission Tomography/Computed Tomography Positron emission tomography/computed tomography was performed 1 to 7 days before surgery. Twenty-seven patients were scanned at our institute, the remaining 15 elsewhere. The [18F]FDG, supplied and qualitycontrolled by IASON Labormedizin Graz-Seiersberg, Austria, was injected intravenously (5.3 MBq/kg). Forty-
Pathology Mean pathologic lesion size was 15.9 mm (SD 8.9 mm; range, 4 to 40 mm). Lesions consisted mainly of chondroid tissue (median 85%; range, 0% to 85%) with varying proportions of fibromyxoid tissue (median 14%; range, 5% to 80%), fat (median 10%; range, 1% to 45%), bronchial-type epithelium (median 8%; range, 2% to 10%), and smooth muscle (median 2%; range, 0% to 15%). Variable lymphoid cell infiltrates were observed in as many as 80% of cases, always accounting for 5% or less of the specimens (median 2%; range, 2% to 5%). No relationship was found between histologic features and imaging findings.
Computed Tomography All 42 lesions were solid and present peripherally; 2 were located close to the mediastinum. Twenty-six nodules
Fig 2. Positron emission tomography (PET)/computed tomography (CT) of same case as in Figure 1. (A) PET image and (B) PET/CT fused image of lesion in the right lobe. The [18F]-fluorodeoxyglucose uptake is evident within the nodule at a level similar to that of the mediastinum (standardized uptake values normalized to body weight ⫽ 2.3). The finding was considered suspicious.
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Table 1. PET/CT Review Outcomes in Relation to CT Review Outcomes in 42 Consecutive Solitary Lung Nodules Pathologically Confirmed as Hamartoma Number of Cases (% of Total)
Median Pathologic Size, mm (Range)
Probably benign
26 (62%)
30.0 (6–45)
Probably malignant
16 (38%)
12.5 (4–25)
Totals
42 (100%)
CT Outcome
CT ⫽ computed tomography;
PET-CT Outcome
Number of Cases
Benign Suspicious Malignant Benign Suspicious Malignant
20 4 2 14 0 2 42
PET ⫽ positron emission tomography.
were in a right lung (11 upper lobe, 11 lower lobe, 4 median lobe), and 16 nodules in the left lung were distributed between the two lobes. Margins were smooth in 30, and irregular in 12. Shape was round in 32, oval in 6, and lobulated in 4. Four nodules (9%) presented calcifications; 13 (31%) were associated with pleural thickening. Twenty-six nodules (62%) were judged probably benign (Fig 1), and 16 (38%), probably malignant.
Positron Emission Tomography/Computed Tomography All PET/CT scans were analyzed visually. The SUV bw max was available in 17 cases. The PET/CT scan was considered benign in 34 (81.0%), suspicious in 4 (9.5%), and malignant in 4 (9.5%; Fig 2). The mean pathologic size of the 8 nodules considered suspicious/malignant was 22.7 mm (SD 10 mm; range, 10 to 40 mm; median 19 mm). The 4 suspicious nodules had a mean size of 30.0 mm (SD 9.1 mm), and the 4 malignant nodes, a size of 15.5 mm (SD 3.6 mm). The SUV was available for only 1 of these 8 nodules (size 40 mm, suspicious, SUV 2.3). The mean size of the 34 nodules considered benign was 14.3 mm (SD 7.8 mm; range, 4 to 45 mm; median 13 mm). For 16 of 34 cases, SUV was available (mean 1.1; SD 0.5; range, 0.4 to 1.7). The PET/CT findings in relation to CT findings are shown in Table 1.
Comment Notwithstanding rapidly improving technology, it is often difficult to determine the malignant versus benign nature of solitary lung nodules identified during routine chest roentgenography or in screening studies with lowdose CT for the early detection of lung cancer in high-risk groups [1]. Follow-up is recommended as the next stage in the workup of indeterminate solitary nodules [2]. Intranodular fat (attenuation, -40 to -120 HU) and popcornlike chondroid calcifications are reliable indicators of hamartoma. However, fat is only identified in approximately 34% of hamartomas, and fat plus calcifications are present in approximately 21% [3]. More generally, several morphologic features and combinations thereof can indicate a benign lesion [3–5] on CT, but again, such features are not present in all benign nodules.
A recent review [6] of the literature indicated that imaging (roentgenography and CT) assessment of nodule features such as size, morphology, and type of opacity can give highly variable results in terms of malignancy prevalence. The risk of malignancy may be as high as 28% for nodules 5 to 10 mm and 20% to 30% for nodules with a smooth margin, and so must be removed. Although surgical removal of nodules by wedge resection or lobectomy has low perioperative mortality [7] and low morbidity when performed by video-assisted thoracoscopy [8], the aim must be to reliably identify benign nodules by noninvasive techniques. Positron emission tomography/CT has emerged as a promising way of characterizing indeterminate lung nodules identified on CT [9 –12]. Yi and colleagues [13] reported that PET/CT was more sensitive and accurate at detecting malignancy than dynamic helical CT and proposed it as the first-line method for evaluating solitary pulmonary nodules. In the present study, we aimed to determine whether the information provided by both CT with contrast and PET/CT was potentially of more use in determining the malignant versus benign nature of solitary lung nodules than either technique alone. We analyzed CT and PET/CT findings in a consecutive series with pathologic diagnosis of hamartoma. All were solitary nodules at first identification, often detected in smokers undergoing low-dose CT screening for the early detection of lung cancer [1]. According to the revised CT screening protocol, such patients receive PET/CT if the lesion is larger than 8 mm. Policies for investigating indeterminate nodules within the screening study evolved as experience was gained. Many patients in this study were operated on when policies for lesion removal differed from those in force today at our institute [1]. We found that CT suggested a benign or probably benign lesion in only 62% of cases, mainly because the nodule lacked the calcifications (only present in 9%) or fat generally considered to indicate nonmalignancy; note, however, that calcification alone may not be sufficient to exclude carcinoma [14]. Use of contrast may make it easier distinguish malignant from benign nodules [11]. However, use of contrast prevented the measurement of density.
GENERAL THORACIC
Ann Thorac Surg 2008;86:1769 –73
GENERAL THORACIC
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DE CICCO ET AL IMAGING OF LUNG HAMARTOMAS
We found that PET/CT provided better results than CT, diagnosing 34 of 42 lesions (81.0%) as benign, and supporting the role of this modality in the characterization of pulmonary nodules. However, it also diagnosed 4 lesions as malignant and another 4 as suspicious. In all 8 of these cases (19%), review of the resected specimens failed to detect pathologic features that might explain high glucose uptake: all were simple chondroid hamartomas. It is noteworthy that by CT, 6 of 8 of these cases were benign. It is also noteworthy that 14 of 16 cases suspicious or malignant by CT were benign by PET/CT. To conclude, the present study is concerned specifically with the CT and PET/CT characteristics of a pathologically confirmed series of lung hamartomas. Our findings support the role of PET/CT in characterizing solitary lung nodules, but reveal that hamartomas, particularly those of large size, may have uptake characteristics suggesting malignancy. The authors thank Mrs Deborah Console for editorial and back office support, and Don Ward for help with the English.
References 1. Veronesi G, Bellomi M, Mulshine JL, et al. Lung cancer screening with low-dose computed tomography: a noninvasive diagnostic protocol for baseline lung nodules. Lung Cancer 2008;61:340 –9. 2. Alberts WM, for the American College of Chest Physicians. Diagnosis and management of lung cancer executive summary: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(Suppl):1–19. 3. Siegelman SS, Khouri NF, Scott WW, et al. Pulmonary hamartoma: CT findings. Radiology 1986;160:313–7.
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INVITED COMMENTARY In this article, De Cicco and associates [1] retrospectively evaluated 42 patients who underwent surgical resection for benign hamartomas of the lung. The purpose of this study was to evaluate the role of positron emission tomography (PET) and computed tomography (CT) in solitary lung nodules identified by CT scans, and whether this information could obviate the need for surgical resection in future patients. This subject is timely in nature with the increased access and use of CT scans and the present worldwide interest in lung cancer screening protocols. Pulmonary hamartomas are the most common benign tumor of the lung. As such they serve as an obvious platform to evaluate the ability of PET and CT scans to predict benign pathology of solitary lung nodules. By study design, high resolution CT scans and PET with CT scan were evaluated separately, and interpretation of one was blinded to the results of the other. The study design is a reasonable approach when evaluating the value of PET and CT and its ability to predict the benign nature of a solitary nodule. However this design is also a detractor from the perspective © 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
of “real world” patient management. In clinical practice, the thoracic surgeon would evaluate the patient’s clinical history, risk factors, CT scan, and the PET with the CT scan. It is the combination of these factors that leads to appropriate management decisions. The lack of integration of these results led to the high incidence of false positives in the PET with CT scan group. In 42 patients, 8 PET with CT scans, or 19%, were reported as either suspicious (4 scans) or malignant (4 scans). In this group of 8 patients, 6 had CT scans that were correctly interpreted as benign. The patient’s results that are illustrated in Figures 1 and 2 further shows the importance of complete evaluation. Doing so would have likely avoided this PET with CT false positive scan and obviated surgery, which is ultimately the goal. This suggests that while selective use of PET with CT scan may have a role, its routine use, based on the current literature remains inappropriate. Comparisons between being able to determine benign cause using PET with a CT scan and using the CT scan alone reported as 81% and 62%, respectively, must consider that the CT scans were performed with intravenous 0003-4975/08/$34.00 doi:10.1016/j.athoracsur.2008.09.039