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Original Articles: General Thoracic

Imaging of Lung Hamartomas by Multidetector Computed Tomography and Positron Emission Tomography

^a Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy
^b Division of Radiology, European Institute of Oncology, Milan, Italy
^c Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy
^d Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy
^e New Drugs Development Unit, Medical Oncology, European Institute of Oncology, Milan, Italy
^f School of Medicine, University of Milan, Milan, Italy

Accepted for publication August 13, 2008.

^_* Address correspondence to Dr De Cicco, Division of Nuclear Medicine, European Institute of Oncology, Via Ripamonti 435, Milan, 20141, Italy (Email: concetta.de-cicco{at}ieo.it).

	Abstract

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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.

	Introduction

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Hamartomas 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.

	Material and Methods

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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
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 exposure); 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 quality-controlled by IASON Labormedizin Graz-Seiersberg, Austria, was injected intravenously (5.3 MBq/kg). Forty-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

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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 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.

View larger version (96K): [in this window] [in a new window]   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.

View larger version (42K): [in this window] [in a new window]   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.

	Comment

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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.

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.

	Acknowledgments

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The authors thank Mrs Deborah Console for editorial and back office support, and Don Ward for help with the English.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Lorenzo Spaggiari Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Cicco, C. Articles by Paganelli, G. Search for Related Content PubMed PubMed Citation Articles by De Cicco, C. Articles by Paganelli, G. Related Collections Lung - other Related Article