Original Research
Nuclear Medicine
January 2008

Nonpalpable Supraclavicular Lymph Nodes in Lung Cancer Patients: Preoperative Characterization with 18F-FDG PET/CT

Abstract

OBJECTIVE. Our purpose was to evaluate the usefulness of integrated 18F-FDG PET/CT in the detection and characterization of nonpalpable supraclavicular lymph node metastasis in patients with the initial diagnosis of lung cancer.
SUBJECTS AND METHODS. This study was conducted from May 2005 to May 2006 and included 32 consecutively registered lung cancer patients in whom supraclavicular lymph nodes were not palpable but were identified on contrast-enhanced CT or exhibited increased FDG uptake on integrated PET/CT. Three patients had bilateral nodes, for a total of 35 nodes in the 32 patients. Results of cytologic analysis of a specimen obtained with sonographically guided fine-needle aspiration (n = 27), normal initial and follow-up sonographic findings (n = 3), and no change in the size of supraclavicular lymph nodes on follow-up sonography (n = 2) were the reference standards. The presence of supraclavicular lymph node metastasis was determined with integrated PET/CT (uptake greater than that of surrounding tissue) and contrast-enhanced CT (node short-axis diameter of 5 mm or more). The diagnostic efficacies of these methods in the detection of supraclavicular lymph node metastasis were compared.
RESULTS. Supraclavicular lymph node metastasis was diagnosed cytologically in 12 (34%) of 35 lesions. The diagnostic accuracies of integrated PET/CT and contrast-enhanced CT in the detection of supraclavicular lymph node metastasis were 71% and 66%, respectively; the difference was not statistically significant. Although the difference was not statistically significant, the sensitivity (92%) and negative predictive value (93%) of integrated PET/CT were higher than those of contrast-enhanced CT.
CONCLUSION. Because of its high sensitivity and negative predictive value, integrated PET/CT is useful in the detection and characterization of nonpalpable supraclavicular lymph nodes in lung cancer patients.

Introduction

Lung cancer is the leading cause of tumor-related death among both men and women worldwide [1]. The optimal management and prognosis of lung cancer rely on the histologic type of tumor, tumor size, regional node involvement, and whether metastasis is present. Accurate assessment of clinical stage at diagnosis is essential for selecting appropriate curative and palliative therapy. Metastasis to supraclavicular lymph nodes in lung cancer is an indicator of inoperable disease [2]. In the TNM system [3] of lung cancer staging, metastasis to this node group is considered N3 disease. Patients with stage IIIB (T0-4N3M0) non-small cell lung cancer have a 3% 5-year survival rate, compared with a 14% 5-year overall survival rate among all patients with lung cancer [1, 3].
Palpation of supraclavicular lymph nodes has been found to be unreliable in several studies [4-7]; palpable supraclavicular nodes are usually affected by metastasis [8]. Several CT and sonographic methods of assessment of nonpalpable supraclavicular lymphadenopathy have been attempted [7, 9-15]. PET with 18F-FDG has been reported to improve the detection of lymph node metastasis and may be more sensitive than other methods because alterations in tissue metabolism generally precede anatomic changes [16]. Integrated FDG PET/CT, by combining morphologic CT data and functional PET data, generally has satisfactory spatial resolution and yields both metabolic and anatomic information. Moreover, integrated FDG PET/CT studies have produced promising initial oncologic imaging results [17-20]. However, the usefulness of integrated FDG PET/CT focused on characterization of nonpalpable supraclavicular lymph node metastasis in lung cancer patients has not been reported, to our knowledge. The purpose of this study was to evaluate the usefulness of integrated FDG PET/CT and contrast-enhanced CT in the detection and characterization of nonpalpable supraclavicular nodal metastasis in patients with the initial diagnosis of lung cancer.

Subjects and Methods

Patient Selection

From May 2005 to May 2006, 870 consecutively registered patients with suspected or proven lung cancer underwent both contrast-enhanced chest CT and integrated whole-body PET/CT examinations. Patients were asked to participate in this study if they met the following inclusion criteria: primary lung cancer suspected on the basis of clinical or radiologic findings, no palpable supraclavicular lymph nodes found at physical examination, identifiable lymph nodes in the supraclavicular area on contrast-enhanced stand-alone CT or increased FDG uptake in the same area on integrated PET/CT. We excluded patients with previous or coexisting malignant disease, patients with a history of cervical or thoracic surgery, patients who had undergone chemotherapy or radiation therapy, and patients not capable of cooperating. For final inclusion in this study, histopathologic proof of primary lung cancer, either from the primary intrathoracic tumor or from an extrapulmonary metastatic lesion, had to be obtained.
Thirty-two patients satisfied the enrollment criteria. The histopathologic diagnosis of primary lung cancer was made at operation in 17 cases, percutaneous needle aspiration biopsy of the primary mass in 12 cases, bronchoscopic biopsy in two cases, and supraclavicular lymph node aspiration biopsy in one case. All patients underwent contrast-enhanced CT of the thorax, upper abdomen, and supraclavicular regions; whole-body integrated PET/CT; and sonographic examination of the supraclavicular regions, in that order. The mean time between CT and PET/CT was 4.8 days (range, 0-15 days). The sonographic examinations were performed on the same day as or the day after the PET/CT examination.

Contrast-Enhanced CT Acquisition and Image Analysis

CT scans were obtained with helical technique with a commercially available machine, mostly an 8-MDCT (LightSpeed Ultra, GE Healthcare) or a 16-MDCT (LightSpeed 16, GE Healthcare) scanner. Scanning was performed from the lower part of the neck, including the supraclavicular region, to the level of the middle portion of the kidneys after IV administration of contrast medium (100 mL of iomeprol, Iomeron 300, Bracco) at a rate of 2 mL/s with a power injector (MCT Plus, Medrad). In all patients, the scanning parameters were 120 kVp; 170-200 mA; beam width, 10 mm; table speed, 13.75 mm per rotation. All image data were reconstructed with a standard algorithm for mediastinal window images, a bone algorithm for lung window images, and a section thickness of 5 mm. Data were interfaced directly to a PACS (Path-speed or Centricity 2.0, GE Healthcare), which displayed all image data on monitors (four monitors, 1,536 × 2,048 image matrices, 8-bit viewable gray scale, 60-foot-lambert luminescence). The monitors were used to view both mediastinal (width, 400 H; level, 20 H) and lung (width, 1,500 H; level, -700 H) window images.
Two experienced thoracic radiologists, who were unaware of integrated FDG PET/CT findings and of any clinical information except that the patients had lung cancer, prospectively read all CT scans by consensus. The supraclavicular nodal area lies above the manubrium on the same image as the clavicle. It is lateral to the medial edge of the common carotid artery and medial to the clavicle and the lateral rib margin [21, 22]. Other landmarks for the central supraclavicular area include the area at or immediately above the junction of the internal jugular and subclavian veins in proximity to the lower scalene muscles and posterolateral to or just below the thyroid gland [9]. On contrast-enhanced CT, metastatic supraclavicular lymph nodes were defined as those with a short-axis diameter of 5 mm or more [7, 9, 10, 15]. Long-axis diameter and the ratio of long-axis to short-axis diameter of the supraclavicular lymph nodes were recorded.

Integrated FDG PET/CT Acquisition and Image Analysis

Details of PET/CT acquisition are described elsewhere [18, 19]. Briefly, the glucose level in peripheral blood was 150 mg/dL or less in all patients. Patients received an IV injection of 10 mCi (370 MBq) of FDG and then rested for more than 45 minutes before scanning was performed. Scans were acquired with a PET/CT system (Discovery LS, GE Healthcare), which consisted of a PET scanner (Advance NXi, GE Healthcare) and an 8-MDCT scanner (LightSpeed Plus, GE Healthcare). CT was performed from the head to the pelvic floor according to a standard protocol with the following settings: 140 kVp; 80 mA; tube rotation time, 0.5 seconds per rotation; pitch, 6; section thickness, 5 mm to match the PET section thickness. Immediately after unenhanced CT, PET was performed in the identical transverse field of view. PET data sets were obtained with an iterative reconstruction with an ordered subset expectation maximization algorithm and by application of segmented attenuation correction (two iterations, 28 subsets) to CT data. Coregistered scans were displayed with eNTEGRA software (GE Healthcare), which enabled image fusion and analysis.
Integrated FDG PET/CT data sets were prospectively evaluated by two nuclear medicine physicians who reached consensus on the findings present. They were unaware of CT findings or any clinical information except that the patients had lung cancer. For qualitative analysis, positive FDG uptake in supraclavicular lymph nodes was considered glucose uptake greater than that of the surrounding tissue. For quantitative analysis, maximum standardized uptake value (SUV) adjusted for the patient's body weight was recorded. The maximum SUV of primary masses and the ratio of maximum SUV of supraclavicular lymph nodes to that of primary masses were recorded.

Sonographic Examination and Sonographically Guided Aspiration Biopsy

All patients underwent middle to lower cervical and supraclavicular sonographic examinations performed with 5- or 7-MHz linear transducers (ATL HDI-5000, Advanced Technology Laboratories). Sonographic examination and sonographically guided fine-needle aspiration were performed by one radiologist. Transverse and sagittal images were obtained from the carotid bifurcation to the sternoclavicular area inferior and lateral to the acromioclavicular joint.
Sonographically guided fine-needle aspiration was performed simultaneously with the sonographic examination in the cases of 27 (77%) of the 35 lesions. A 23-gauge needle and local anesthesia were used. Cytologic smears were evaluated to guarantee that the specimens were diagnostically adequate. Smears were considered diagnostically adequate when they contained either tumor cells or lymphocytes. If specimens were diagnostically inadequate, cytologic sampling was repeated.
In three patients, no supraclavicular abnormality was found on either initial or follow-up sonography performed at 6-month intervals. In the cases of two patients, sonographically guided fine-needle aspiration findings were not available because of the presence of overriding vascular structures. For these two patients, follow-up sonographic findings obtained 12 and 13 months after the initial examination in the absence of adjuvant therapy were used as the reference standard.

Statistical Analysis

Statistical analysis was performed with commercially available software (SAS 8.2, SAS Institute). The accuracy, sensitivity, specificity, and positive and negative predictive values of integrated FDG PET/CT (increased uptake greater than that of surrounding tissue) and contrast-enhanced CT (short-axis diameter) in the diagnosis of supraclavicular lymph node metastasis were assessed with a generalized estimating equation. The diagnostic accuracy, sensitivity, and specificity of the two methods in the diagnosis of supraclavicular lymph node metastasis were compared by use of the McNemar test. The positive and negative predictive values of these methods were compared.
Fig. 1A —55-year-old man with adenocarcinoma of lung and false-negative interpretation on contrast-enhanced CT. Contrast-enhanced CT scan shows supraclavicular lymph node (arrow) not detected at initial interpretation because of beam-hardening artifact due to contrast medium.
Fig. 1B —55-year-old man with adenocarcinoma of lung and false-negative interpretation on contrast-enhanced CT. CT (B), PET (C), and integrated PET/CT (D) scans show increased FDG uptake (arrow) in right supraclavicular lymph node (4.9 mm in short-axis diameter) with maximum standardized uptake value of 4.2.
Fig. 1C —55-year-old man with adenocarcinoma of lung and false-negative interpretation on contrast-enhanced CT. CT (B), PET (C), and integrated PET/CT (D) scans show increased FDG uptake (arrow) in right supraclavicular lymph node (4.9 mm in short-axis diameter) with maximum standardized uptake value of 4.2.
Fig. 1D —55-year-old man with adenocarcinoma of lung and false-negative interpretation on contrast-enhanced CT. CT (B), PET (C), and integrated PET/CT (D) scans show increased FDG uptake (arrow) in right supraclavicular lymph node (4.9 mm in short-axis diameter) with maximum standardized uptake value of 4.2.
Fig. 1E —55-year-old man with adenocarcinoma of lung and false-negative interpretation on contrast-enhanced CT. Photomicrograph of specimen from sonographically guided aspiration biopsy shows malignant cells suggestive of non-small cell carcinoma (H and E, ×200).
A retrospective calculation was made to evaluate the usefulness of maximum SUV of supraclavicular lymph nodes as an indicator of the presence of metastasis on integrated FDG PET/CT. Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated by means of varying the level of maximum SUV that signified a positive finding (cutoff value). The relations between the maximum SUV of supraclavicular lymph nodes and the maximum SUV of primary masses or the short-axis diameter of the nodes on CT were evaluated with Spearman's correlation coefficient. The chi-square test, Fisher's exact test, Student's t test, and Mann-Whitney test were used when associations of various radiologic findings were assessed with presence versus absence of supraclavicular lymph node metastasis. A value of p < 0.05 was considered to indicate a statistically significant difference.

Results

Characteristics of Supraclavicular Lymph Nodes

The characteristics of the patients are shown in Table 1. Thirty-five supraclavicular lymph node lesions were found on either contrast-enhanced CT or PET/CT in 32 patients; three patients had bilateral nodal lesions. Findings at aspiration cytologic examination confirmed the presence of supraclavicular lymph node metastasis in 12 (34%) of the 35 nodal lesions: 11 lesions from 10 patients with non-small cell lung cancer and one from a patient with small cell lung cancer. One (33%) of three patients with non-small cell lung cancer with bilateral supraclavicular lymph node lesions had bilateral positive node findings. The other two patients had positive supraclavicular lymph node findings in either of the bilateral supraclavicular lymph node lesions. The other 23 lesions proved benign. The finding was made at aspiration cytologic examination in 17 of these cases, on the basis of normal initial and follow-up sonographic findings in three cases, and on the basis of no change in lymph node size (without chemotherapy or radiation therapy) for at least 12 months (12, 13, and 13 months) on follow-up sonography in three cases.
TABLE 1: Characteristics of Patients with Primary Lung Cancer (n = 32)
CharacteristicValue
Sex (n) 
    Men19
    Women13
Mean age (y) 
    All patients60 (32-78)
    Men66 (44-78)
    Women51 (32-63)
Cell type of primary lung cancer (n) 
    Small cell lung cancer2
    Non-small cell lung cancer30
        Adenocarcinoma16
        Squamous cell carcinoma9
        Bronchioloalveolar cell carcinoma1
        Pleomorphic carcinoma1
        Large cell neuroendocrine carcinoma1
        Unspecified
2
Note—Values in parentheses are ranges.

Diagnostic Efficacy of Integrated FDG PET/CT and Contrast-Enhanced CT

The sensitivity, specificity, positive and negative predictive values, and accuracy of integrated PET/CT and contrast-enhanced CT in the detection of supraclavicular lymph node metastasis are shown in Table 2. The diagnostic accuracy of integrated PET/CT was slightly higher than that of CT, but the difference was not statistically significant (p = 1.000). The sensitivities (p = 0.360) and specificities (p = 1.000) of the two techniques were not significantly different. The positive predictive values (p = 1.000) and negative predictive values (p = 0.264) also were not significantly different. Integrated PET/CT, however, had a higher sensitivity and negative predictive value and had slightly higher accuracy and positive predictive value than contrast-enhanced CT.
TABLE 2: Diagnostic Efficacy of Integrated PET/CT and Enhanced CT
FindingAccuracySensitivitySpecificityPositive Predictive ValueNegative Predictive Value
18F-FDG uptake on PET/CT71 (25/35)92 (11/12)61 (14/23)55 (11/20)93 (14/15)
Short-axis diameter ≥ 5 mm on CT
66 (23/35)
67 (8/12)
65 (15/23)
50 (8/16)
79 (15/19)
Note—Values are percentages with raw numbers in parentheses.
Fig. 2A —78-year-old man with squamous cell carcinoma of lung and false-positive interpretation on integrated PET/CT. CT (A), PET (B), and PET/CT (C) scans show physiologic muscle uptake (arrow) at scalene muscle with maximum standardized uptake value of 3.6 simulating metastatic lymph node in left supraclavicular area. No abnormality was found on contrast-enhanced CT or sonography.
Fig. 2B —78-year-old man with squamous cell carcinoma of lung and false-positive interpretation on integrated PET/CT. CT (A), PET (B), and PET/CT (C) scans show physiologic muscle uptake (arrow) at scalene muscle with maximum standardized uptake value of 3.6 simulating metastatic lymph node in left supraclavicular area. No abnormality was found on contrast-enhanced CT or sonography.
Fig. 2C —78-year-old man with squamous cell carcinoma of lung and false-positive interpretation on integrated PET/CT. CT (A), PET (B), and PET/CT (C) scans show physiologic muscle uptake (arrow) at scalene muscle with maximum standardized uptake value of 3.6 simulating metastatic lymph node in left supraclavicular area. No abnormality was found on contrast-enhanced CT or sonography.
In the application of a maximum SUV as a cutoff for detecting malignancy in supraclavicular lymph nodes, an SUV of 2.3 appeared to be optimum. When a maximum SUV of 2.3 was used as the threshold for a positive finding (i.e., maximum SUV > 2.3 indicates metastasis), the following diagnostic characteristics were obtained: sensitivity, 75%; specificity, 78%; positive predictive value, 64%; negative predictive value, 86%; and accuracy, 77%.

Causes of False-Negative and False-Positive Interpretations on Integrated FDG PET/CT or Contrast-Enhanced CT

False-negative interpretations of metastatic supraclavicular lymph nodes were made on integrated PET/CT in one patient and contrast-enhanced CT in four patients. A metastatic supraclavicular lymph node with a short-axis diameter of 8.6 mm on CT did not exhibit FDG uptake in the same area on integrated PET/CT. Metastatic supraclavicular lymph nodes were not detected on CT in three patients despite FDG uptake on PET/CT (maximum SUV, 4.2, 4.2, and 2.3) because extensive beam-hardening artifact caused by contrast medium in the subclavian veins precluded identification of nodes in the supraclavicular area (Fig. 1A, 1B, 1C, 1D, 1E). In the fourth patient, supraclavicular lymph nodes exhibited FDG uptake with a maximum SUV of 2.7 on PET/CT but had a short-axis diameter of 4.4 mm on CT.
False-positive interpretations of metastatic supraclavicular lymph nodes were made on integrated PET/CT in the cases of six patients, on contrast-enhanced CT in five, and on both techniques in three cases. In one patient, FDG uptake in the supraclavicular area with a maximum SUV of 3.6 was not found on either CT or sonography and was verified as physiologic muscle uptake (Fig. 2A, 2B, 2C). One patient with adenocarcinoma had a false-positive finding of supraclavicular lymph node metastasis with a maximum SUV of 6.6 on PET/CT and a shortaxis diameter of 5.1 mm on CT. Lymphocytes and fibrous tissues, however, were found at aspiration cytologic examination, and surgical excision of a supraclavicular lymph node confirmed the presence of tuberculous caseating granulomas (Fig. 3A, 3B, 3C, 3D, 3E). The other seven cases with false-positive PET/CT findings were supraclavicular lymph nodes with an average maximum SUV of 2.8 (range, 2.2-4.5). In the seven false-positive interpretations made on contrast-enhanced CT, the mean short-axis diameter of the supraclavicular lymph nodes was 6.3 mm (range, 5.1-7.9 mm).

Correlation Between Node Size, Maximum SUV, and Other Variables

There was no significant correlation between nodal short-axis diameter on CT and maximum SUV on PET (p = 0.219). There also was no significant relation between the maximum SUV of primary masses and that of supraclavicular lymph nodes (p = 0.312). Table 3 shows the statistical assessment of the numeric variables on integrated PET/CT and contrast-enhanced CT according to the presence of metastasis in supraclavicular lymph nodes. Significant differences were observed between the positive and the negative groups of supraclavicular lymph node metastasis in terms of the maximum SUV of supraclavicular lymph nodes (p = 0.001), the ratio of the maximum SUV of supraclavicular lymph nodes to that of primary masses (p = 0.006) on integrated FDG PET/CT, and the ratio of the long-axis (p = 0.002) to the short-axis (p < 0.001) diameter of the nodes on contrast-enhanced CT.
TABLE 3: Statistical Assessment of Measurement Variables on Integrated PET/CT and Enhanced CT According to Presence of Supraclavicular Lymph Node Metastasis
Metastasis in Supraclavicular Lymph Node
VariablePresentAbsentp
Maximum standardized uptake value on integrated PET/CT   
    Supraclavicular lymph node4.9 ± 3.741.3 ± 1.880.001a
    Mass10.4 ± 3.8612.2 ± 9.150.986a
    Supraclavicular lymph node/mass0.6 ± 0.570.3 ± 0.550.006a
Size on enhanced CT   
    Short-axis diameter7.8 ± 1.834.9 ± 1.38< 0.001b
    Long-axis diameter11.7 ± 3.188.0 ± 2.120.002a
    Long-axis diameter/short-axis diameter
1.5 ± 0.37
1.7 ± 0.59
0.469a
a
Mann-Whitney test.
b
Student's t test.

Discussion

Most palpable supraclavicular lymph nodes in patients with lung cancer yield a diagnosis of malignancy [8]. However, examination of the supraclavicular nodes by palpation has been found to be unreliable in several studies [4-7]. In other malignant diseases, such as melanoma [4], esophageal cancer [5], and head and neck cancer [6], sonography and sonographically guided fine-needle aspiration cytologic analysis have proved superior to palpation in the detection and characterization of metastasis in supraclavicular lymph nodes. Twelve percent to 31% of patients presenting with lung cancer and a supraclavicular lymph node with a short-axis diameter of 5 mm or greater have nonpalpable supraclavicular lymph node metastasis at sonographically guided fine-needle aspiration biopsy [9, 13]. In our series, a similar percentage (34%) of nonpalpable supraclavicular nodal metastatic lesions was found.
There have been reports on the successful use of CT to assess for metastatic supraclavicular lymph nodes in patients with esophageal cancer [23] and lung cancer [7, 9]. Using a short-axis-diameter criterion (supraclavicular lymph node with a short-axis diameter ≥ 5 mm), these investigators identified 82-85% sensitivity for supraclavicular lymph node metastasis on CT. In our series (confined to nonpalpable supraclavicular lymph nodes), CT had 67% sensitivity, 65% specificity, and 66% accuracy.
Fig. 3A —63-year-old woman with adenocarcinoma of lung and false-positive interpretation at both integrated PET/CT and contrast-enhanced CT. Contrast-enhanced CT scan shows supraclavicular lymph node (arrow) with short-axis diameter of 5.1 mm in right supraclavicular area.
Fig. 3B —63-year-old woman with adenocarcinoma of lung and false-positive interpretation at both integrated PET/CT and contrast-enhanced CT. CT (B), PET (C), and PET/CT (D) scans show increased FDG uptake (arrow) in right supraclavicular lymph node with maximum standardized uptake value of 6.6.
Fig. 3C —63-year-old woman with adenocarcinoma of lung and false-positive interpretation at both integrated PET/CT and contrast-enhanced CT. CT (B), PET (C), and PET/CT (D) scans show increased FDG uptake (arrow) in right supraclavicular lymph node with maximum standardized uptake value of 6.6.
Fig. 3D —63-year-old woman with adenocarcinoma of lung and false-positive interpretation at both integrated PET/CT and contrast-enhanced CT. CT (B), PET (C), and PET/CT (D) scans show increased FDG uptake (arrow) in right supraclavicular lymph node with maximum standardized uptake value of 6.6.
Fig. 3E —63-year-old woman with adenocarcinoma of lung and false-positive interpretation at both integrated PET/CT and contrast-enhanced CT. Photomicrograph of lymph node biopsy specimen shows chronic granulomatous inflammation with caseation necrosis suggestive of tuberculosis. Lymphocytes and fibrous tissue (not shown) only were found at aspiration cytologic examination. (H and E, ×40)
False-negative and false-positive interpretations on CT can have several causes. First, beam-hardening artifacts caused by contrast medium or bone frequently obscure the supraclavicular area. This problem can be overcome with delayed scans of the supraclavicular area at the sacrifice of additional radiation. Second, normal round and elliptic structures in the base of the neck, including the external and internal jugular veins, vertebral veins, common carotid arteries, and the scalene and longus colli muscles, must be differentiated from supraclavicular lymph nodes [10]. Three patients in our study had sonographic confirmation of normal structures mimicking supraclavicular lymph nodes. Third, short-axis-diameter measurement of a supraclavicular lymph node is not accurate on transverse scans alone. Fourth, metastasis can be present in normal-sized lymph nodes. Finally, borderline-size lymph nodes around the threshold of 5 mm can be variously interpreted as measurement error. In our study, these problems were partly solved by the use of integrated PET/CT.
On qualitative evaluations (nodes with uptake the same as or greater than that of the mediastinal blood pool), the sensitivity, specificity, accuracy, and positive and negative predictive values of integrated FDG PET/CT in the detection of nonpalpable supraclavicular lymph node metastasis were 92%, 61%, 71%, 55%, and 93%, respectively. Although the difference was not statistically significant, integrated PET/CT had a higher sensitivity and negative predictive value than contrast-enhanced CT. The high negative predictive value of 93% may help avoid invasive procedures such as fine-needle aspiration when there is no FDG uptake in a supraclavicular lymph node on integrated PET/CT. However, because supraclavicular lymph nodes are relatively easy to biopsy under sonographic guidance and because the presence of metastatic supraclavicular lymph nodes renders a classification of category N3 in non-small cell lung cancer, the absence of FDG uptake on PET of an enlarged supraclavicular lymph node is unlikely to preclude supraclavicular lymph node biopsy. This supraclavicular lymph node (enlarged supraclavicular node on CT scans but normal on PET) may contain microscopic metastasis unless PET/CT is 100% specific. This supposition is particularly true of patients with mediastinal lymph node metastasis (N2 disease). On the other hand, a relatively high proportion of false-positive cases on integrated PET/CT necessitate additional fine-needle aspiration when FDG uptake is present in supraclavicular lymph nodes on integrated PET/CT.
Another important aspect of imaging the supraclavicular lymph nodes with PET/CT is improved PET/CT detection of supraclavicular lymph nodes not detected with palpation or CT. The PET/CT findings may help locate the appropriate area for biopsy by showing the nodes of increased FDG uptake in the supraclavicular area.
A maximum SUV of 2.3 appeared to be an optimum and most accurate cutoff for the detection of malignant supraclavicular lymph nodes. In quantitative evaluation, accuracy (77% vs 71%) and specificity (78% vs 61%) improved over those of qualitative evaluation, but sensitivity (75% vs 92%) and negative predictive value (93% vs 86%) worsened. Therefore, the maximum SUV cutoff of 2.3 may be applicable when the qualitative evaluation is not conclusive. However, the 2.3 cutoff may not be specific and may not be useful when acquisition parameters other than those in this study are used.
Physiologic muscle uptake and brown fat can cause false-positive results [24-27] (Fig. 2A, 2B, 2C). The pattern of physiologic muscle uptake is typically bilateral, symmetric, fusiform, or elongated and is seldom confused with the presence of malignancy, but asymmetric muscle uptake can occur [28]. Typically, the increased FDG uptake in brown fat is bilateral and symmetric, but it can be asymmetric or focal [29]. Atherosclerotic plaques occasionally manifest as focal areas of increased FDG uptake that can be misinterpreted as areas of malignant growth [30, 31]. The use of integrated FDG PET/CT can help prevent these misinterpretations.
Increased FDG uptake in infectious and inflammatory conditions has been reported. The uptake in these conditions is caused by increased glycolysis in leukocytes, lymphocytes, and macrophages [32]. In our study, there was one false-positive finding of supraclavicular lymph node metastasis with a maximum SUV of 6.6 on PET/CT caused by tuberculous caseating granuloma.
Our study had a few limitations. First, because patients with neither enlarged lymph nodes in the supraclavicular area on CT nor increased FDG uptake in the same area on integrated PET/CT were excluded, both the specificity and accuracy of the techniques examined may have been underestimated with respect to the detection of supraclavicular lymph node metastasis. Second, we did not propose a standardized approach to the physical examination for palpability of the supraclavicular lymph node. Physicians with various levels of experience and varying expertise had performed the physical examinations.
Recognizing metastasis to supraclavicular lymph nodes in lung cancer is important because the presence of supraclavicular lymph node metastasis indicates the presence of inoperable disease. Integrated PET/CT is useful for the detection and characterization of nonpalpable supraclavicular lymph nodes in lung cancer patients because it has a high sensitivity and negative predictive value. However, relatively high rates of false-positive results for supraclavicular lymph node metastasis at integrated PET/CT are reported, and the technique is not perfectly specific. Therefore, neither FDG uptake on PET nor node size on CT should preclude supraclavicular lymph node biopsy if biopsy information about supraclavicular lymph node metastasis is needed to determine treatment.

Footnotes

Address correspondence to K. S. Lee ([email protected]).
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Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: 246 - 252
PubMed: 18094319

History

Submitted: May 3, 2007
Accepted: August 7, 2007

Keywords

  1. CT
  2. lung
  3. lymph node
  4. metastasis
  5. neoplasms
  6. PET/CT

Authors

Affiliations

Yon Mi Sung
Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea.
Present address: Department of Medical Imaging, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
Kyung Soo Lee
Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea.
Byung-Tae Kim
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Seonwoo Kim
Biostatistics Unit, Samsung Biomedical Research Institute, Seoul, Korea.
O Jung Kwon
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Joon Young Choi
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Seoung-Oh Yang
Department of Nuclear Medicine, Eulji Medical Center, Eulji University School of Medicine, Daejeon, Korea.

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